The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly heritable trait. However, despite reports from recent genome-wide association studies, only a small proportion of the overall heritability of BMI is known to be lurking within the human genome. Other non-genetic heritable traits may contribute to BMI. The gut microbiome is an excellent candidate, implicating complex interlinks with hypothalamic control of appetite and metabolism via entero-endocrine, autonomic, and neuro-humeral pathways. The neonatal gut microbiome derived from the mother via transgenerational transmission (vaginal delivery and breastfeeding) tends to have a permanence within the gut. Conversely, non-maternally derived gut microbiota manifest mutability that responds to changes in lifestyle and diet. We should all strive to optimize our lifestyles and ensure a diet that is replete with varied and unprocessed plant-based foods to establish and nurture a healthy gut microbiome. Women of reproductive age should optimize their gut microbiome, particularly pre-conception, ante- and postnatally to enable the establishment of a healthy neonatal gut microbiome in their offspring. Finally, we should redouble our efforts to educate the populace on the pathogenesis of obesity, and the role of heritable (but modifiable) factors such as the gut microbiome. Such renewed understanding and insights would help to promote the widespread adoption of healthy lifestyles and diets, and facilitate a transition from our current dispassionate and stigmatized societal approach towards people living with obesity towards one that is epitomized by understanding, support, and compassion.

Gut-produced glucagon-like peptide-1 (GLP-1) and pancreas-made amylin robustly reduce food intake by directly or indirectly affecting brain activity. While for both peptides a direct action in the hindbrain and the hypothalamus is likely, few studies examined their impact on whole brain activity in rodents and did so evaluating male rodents under anesthesia. However, both sex and anesthesia may significantly alter the influence of feeding controlling molecules on brain activity. Therefore, we investigated the effect of GLP-1 and amylin on brain activity and functional connectivity (FC) in awake adult male and female rats using resting-state functional magnetic resonance imaging (rsfMRI). We further examined the relationship between the altered brain activity or connectivity and subsequent food intake in response to amylin or GLP-1. We observed sex divergent effects of amylin and GLP-1 on the brain activity and FC patterns. Most importantly correlation analysis between FC and feeding behavior revealed that different brain areas potentially drive reduced food intake in male and female rats. Our findings underscore the distributed and distinctly sex divergent neural network engaged by each of these anorexic peptides and suggest that different brain areas may be the primary drivers of the feeding outcome in male and female rats. Moreover, prominent activity and connectivity alterations observed in brain areas not typically associated with feeding behavior in both sexes may either indicate novel feeding centers or alternatively suggest the involvement of these substances in behaviors beyond feeding and metabolism. The latter question is of potential translational significance as analogues of both amylin and GLP-1 are clinically utilized.

Traditional diet management for type 2 diabetes (T2DM) is often complex and effortful to sustain. Nudging offers low-effort and automatic approaches to dietary behaviour change yet remains underexplored in T2DM. This study evaluated the independent and combined 6-month effects of nudging education (NE) and nudging tableware (NT) on HbA1c, along with other secondary health outcomes, among adults with T2DM and overweight/obesity, compared to their non-nudge counterparts (control education, CE; control tableware, CT).

A 2 × 2 factorial cluster RCT was conducted in 12 primary healthcare settings in China (pre-registered as ChiCtr2100044471). Participants were randomly assigned to the nudging education group (NE + CT), the nudging tableware group (CE + NT), the combined group (NE + NT) or the full-control group (CE + CT) for 1 month. The primary outcome was HbA1c. Secondary outcomes included dietary behaviours, metabolic indicators, and psychological health. Generalized linear mixed models were used for analysis.

A total of 284 participants (mean age, 52.28 years; 54.3% male) were randomly assigned and included in the analysis. After 6 months, NE and NT independently led to HbA1c reductions (-0.76%, p < 0.001; -0.33%, p = 0.042, vs. controls), with an additive but non-interactive effect when combined, resulting in a 1.04% reduction (p < 0.001) in the combined group. They also improved total calorie, macronutrient, and vegetable intake, FBG, plasma lipids, and BMI. NE additionally reduced diabetes distress and enhanced self-efficacy.

Both NE and NT improved dietary and metabolic outcomes without increasing the psychological burden. The combined group showed the greatest benefits. Findings highlighted the importance of considering automatic processes in diabetes management.

In everyday life, dietary decisions are made in response to real foods, such as at the grocery store or cafe. In stark contrast, decision-making studies in the laboratory typically measure responses to food stimuli presented as two-dimensional pictures or computer images, with the assumption that artificial displays are adequate substitutes for their real-world counterparts. Yet accumulating evidence challenges this view, including studies showing that willingness-to-pay (WTP) is higher for foods displayed as real objects versus images -a phenomenon known as the "real object advantage" in valuation. Here, we examined whether the "real object advantage" is modulated by accessibility to the stimuli, subjective food preference, or interactions between these factors. Participants placed monetary bids on snack foods displayed as real objects or computer images. Critically, on half of the trials, a transparent barrier was positioned between the participant and the stimulus. Linear mixed-effects modeling analysis revealed that, overall, WTP was ∼7 % higher for foods displayed as real objects versus images; however, this effect emerged only for foods of moderate (but not strong) preference strength. WTP was also higher when the stimuli appeared unoccluded versus behind the barrier, but this was equally so for real objects and images, suggesting that the barrier's effect on valuation was not related to stimulus actability. Our findings suggest that while eliminating perceived barriers to a good can bolster valuation regardless of display format, presenting real foods may nevertheless increase valuation and encourage healthy dietary choices.

Non-nutritive sweeteners (NNSs) are used to reduce caloric intake by replacing sugar with compounds that are sweet but contain little or no calories. In this study, we investigate how non-nutritive sweetener sucralose to promote acute food intake in the fruit fly Drosophila melanogaster. Our results showed that acute exposure to NNSs sweetness induces a robust hyperphagic response in flies. Cellular and molecular dissection of this acute effect revealed the requirement of a reward pathway comprising of sweet taste neurons, octopaminergic neurons, and NPF neurons which drive increased food intake in response to sucralose. These data provide mechanistic insight into how NNSs can increase food intake, information that may help us better understand how artificially sweeteners may impact our physiology.

Nucleus accumbens (NAc) dopamine D1 receptor-expressing neurons are known to be critical for processing reward and regulating food intake. However, the role of D2-expressing neurons in this nucleus remains less understood. This study employed optogenetic manipulations to investigate the role of NAc D2-expressing neurons in reward processing and sucrose consumption. Optogenetic activation of these neurons decreased sucrose preference (at 20 Hz), disrupted licking patterns (particularly at 8 and 20 Hz), and increased self-stimulation. Conversely, synchronizing stimulation with the animal licking rhythm mitigated licking disruption and even increased sucrose intake, suggesting a rewarding effect. Furthermore, 20 Hz stimulation (but not 8 Hz) induced place preference in a real-time place preference (RTPP) test. In contrast, inhibiting D2 neurons produced a negative hedonic state, although not reaching complete aversion, influencing food choices in specific contexts. For instance, while the RTPP test per se was not sensitive enough to observe place aversion when mice could choose between consuming a high-fat diet (HFD) pellet in a context associated with or without inhibition of D2 neurons, they preferred to consume HFD on the non-inhibited side. This suggests that the palatability of HFD can unmask (but also overshadow) the negative hedonic state associated with D2 neuron inhibition. A negative reinforcement paradigm further confirmed the active avoidance behavior induced by D2 neuron inhibition. In conclusion, NAc D2 neuron inhibition induces a negative hedonic state, while activation has a dual effect-it is rewarding yet disrupts licking behavior-highlighting its complex role in reward and consummatory behavior. Importantly, self-paced stimulation, where the animal controls the timing of the stimulation through its licking behavior, offers a more efficient and natural approach for stimulating NAc activity.

Aging is the main risk factor for developing cognitive impairments and associated neurodegenerative diseases. However, environmental factors, including nutritional health, are likely to promote or reduce cognitive impairments and neurodegenerative pathologies. An intricate relationship exists between maternal nutrition and adult eating behavior, metabolic phenotype, and cognitive abilities.

The objective of the present review was to collect available data, suggesting a link between maternal overnutrition and the latter impairment of cognitive functions in the progeny, and to relate this relationship with Alzheimer's disease (AD). Indeed, cognitive impairments are major behavioral signs of AD. We first reviewed studies showing an association between unbalanced maternal diet and cognitive impairments in the progeny in humans and rodent models. Then we looked for cellular and molecular hallmarks which could constitute a breeding ground for AD in those models. With this end, we focused on synaptic dysfunction, altered neurogenesis, neuroinflammation, oxidative stress, and pathological protein aggregation. Finally, we proposed an indirect mechanism linking maternal unbalanced diet and progeny's vulnerability to cognitive impairments and neurodegeneration through promoting metabolic diseases. We also discussed the involvement of progeny's gut microbiota in the maternal diet-induced vulnerability to metabolic and neurodegenerative diseases.

Further investigations are needed to fully decipher how maternal diet programs the fetus and infant brain. Addressing this knowledge gap would pave the way to precise nutrition and personalized medicine to better handle cognitive impairments in adulthood.

Food pleasantness is largely based on the palatability of food and is linked to taste. Along with homeostatic and cognitive control, it forms part of the control of food intake (hedonic control), and does not only correspond to the pleasure that can be described of food intake. There are many factors that cause variations in eating pleasantness between individuals, such as age, sex, culture, co-morbidities, treatments, environmental factors or the specific characteristics of foods. The control of food intake is based on four determinants: conditioned satiety, the reward system, sensory specific satiety and alliesthesia. These four determinants follow one another over time, in the per-prandial and inter-prandial periods, and complement one another. There are many cerebral areas involved in the hedonic control of food intake. The most involved brain areas are the orbitofrontal and anterior cingulate cortices, which interact with deep neural structures (amygdala, striatum, substantia nigra) for the reward circuit, with the hippocampi for memorising pleasant foods, and even with the hypothalamus and insula, brain areas more recently involved in the physiology of food pleasantness. Changes in brain activity secondary to modulation of food pleasantness can be measured objectively by recording taste-evoked potentials, an electroencephalography technique with very good temporal resolution.

Obesity is a major risk factor for noncommunicable diseases and is associated with a reduced life expectancy of up to 20 years, as well as with other consequences such as unemployment and increased economic burden for society. It is a multifactorial disease, and physiopathology of obesity involves dysregulated calorie utilization and energy balance, disrupted homeostasis of appetite and satiety, lifestyle factors including sedentary lifestyle, lower socioeconomic status, genetic predisposition, epigenetics, and environmental factors. Some endocrine-disrupting chemicals (EDCs) have been proposed as "obesogens" that stimulate adipogenesis leading to obesity. In this review, definition of obesogens, their adverse effects, underlying mechanisms, and metabolic implications will be updated and discussed.

Disruption of lipid homeostasis by EDCs involves multiple mechanisms including increase in the number and size of adipocytes, disruption of endocrine-regulated adiposity and metabolism, alteration of hypothalamic regulation of appetite, satiety, food preference and energy balance, and modification of insulin sensitivity in the liver, skeletal muscle, pancreas, gastrointestinal system, and the brain. At a cellular level, obesogens can exert their endocrine disruptive effects by interfering with peroxisome proliferator-activated receptors and steroid receptors. Human exposure to chemical obesogens mainly occurs by ingestion and, to some extent, by inhalation and dermal uptake, usually in an unconscious manner. Persistent pollutants are lipophilic features; thus, they bioaccumulate in adipose tissue.

Although there are an increasing number of reports studying the effects of obesogens, their mechanisms of action remain to be elucidated. In addition, epidemiological studies are needed in order to evaluate human exposure to obesogens.

A growing literature suggests manipulating dietary protein status decreases sweet consumption in rodents and in humans. Underlying neurocircuit mechanisms have not yet been determined, but previous work points towards hedonic rather than homeostatic pathways. Here we hypothesized that a history of protein restriction reduces sucrose seeking by altering mesolimbic dopamine signaling in mice. We tested this hypothesis using established behavioral tests of palatability and conditioned reward, including the palatability contrast and conditioned place preference (CPP) tests. We used modern optical sensors for measuring real-time nucleus accumbens (NAc) dopamine dynamics during voluntary sucrose consumption, via fiber photometry, in male C57/Bl6J mice maintained on low-protein high-carbohydrate (LPHC) or control (CON) diet for ∼5 weeks. Our results showed that a history of protein restriction decreased the consumption of a sucrose 'dessert' in sated mice by ∼50% compared to controls [T-test, p < 0.05]. The dopamine release in NAc during sucrose consumption was reduced, also by ∼50%, in LPHC-fed mice compared to CON [T-test, p < 0.01]. Furthermore, LPHC-feeding blocked the sucrose-conditioned place preference we observed in CON-fed mice [paired T-test, p < 0.05], indicating reduced sucrose reward. This was accompanied by a 33% decrease in neuronal activation of the NAc core, as measured by c-Fos immunolabeling from brains collected directly after the CPP test [T-test, p < 0.05]. Together, these findings advance our mechanistic understanding of how dietary protein restriction decreases the consumption of sweets-by inhibiting the incentive salience of a sucrose reward, together with reduced sucrose-evoked dopamine release in NAc.

Childhood obesity represents a significant public health concern, imposing a substantial burden on the healthcare system. Furthermore, weight-loss programs often exhibit reduced effectiveness in adults who have a history of childhood obesity. Therefore, early intervention against childhood obesity is imperative. Presently, the primary method for diagnosing childhood obesity relies on body mass index (BMI), yet this approach has inherent limitations. Leptin, a satiety hormone produced by adipocytes, holds promise as a superior tool for predicting both childhood and subsequent adulthood obesity. In this review, we elucidate the tools employed for assessing obesity in children, delve into the biological functions of leptin, and examine the factors governing its expression. Additionally, we discuss maternal and infantile leptin levels as predictors of childhood obesity. By exploring the relationship between leptin levels and weight loss, we present leptin as a potential indicator of the effectiveness of obesity interventions.

Due to relationships between diet and health including obesity, there is a need to examine the explanatory power of factors that motivate people to (over or under) eat. In a previous investigation, a four-factor subscale-based model of eating behaviour traits (EBTs) was developed which identified individual differences in psychological factors influencing motivations to eat and some residual uncertainties. The current study used a data-driven and theory-driven approach, including individual items to refine and extend previous EBT models. The aim was to examine and validate the domain structure of a framework for EBTs. The analysis used two samples including a representative sample of the UK population (n = 2010, 51% female, 49% male, 18-88 years), and members of a weight management program (n = 2317, 96.6% female, 2.8% male, 21-84 years), who completed 5 questionnaires including 10 EBTs. The results found some support for a 6-factor model, encompassing reactive eating, negative emotional eating, positive emotional eating, restricted eating, homeostatic eating, and body-food choice congruence (data-driven model) or eating for health (theory-driven model). There were differences between the data-driven model and the theory-driven model regarding the 6th factor. Additionally, the data-driven model did not distinguish between eating for pleasure and reactive eating. The models demonstrated that the eating behaviour factors were significantly associated with BMI category. Overall, this research contributes to a more structured understanding of the dimensions of motivation underlying EBTs, emphasising the utility of this framework for identifying at-risk individuals and tailoring interventions to meet specific individual needs.

Microglia are the macrophages of the central nervous system (CNS), implying their role in maintaining brain homeostasis. To achieve this, these cells are sensitive to a plethora of endogenous and exogenous signals, such as neuronal activity, cellular debris, hormones, and pathological patterns, among many others. More recent research suggests that microglia are highly responsive to nutrients and dietary variations. In this context, numerous studies have demonstrated their significant role in the development of obesity under calorie surfeit. Because many reviews already exist on this topic, we have chosen to present the state of our reflections on various concepts put forth in the literature, bringing a new perspective whenever possible. Our literature review focuses on studies conducted in the arcuate nucleus of the hypothalamus, a key structure in the control of food intake. Specifically, we present the recent data available on the modifications of microglial energy metabolism following the consumption of an obesogenic diet and their consequences on hypothalamic neuron activity. We also highlight the studies unraveling the mechanisms underlying obesity-related sexual dimorphism. The review concludes with a list of questions that remain to be addressed in the field to achieve a comprehensive understanding of the role of microglia in the regulation of body energy metabolism. This article is part of the Special Issue on "Microglia".

A growing literature suggests manipulating dietary protein status decreases sweet consumption in rodents and in humans. Underlying neurocircuit mechanisms have not yet been determined, but previous work points towards hedonic rather than homeostatic pathways. Here we hypothesized that a history of protein restriction reduces sucrose seeking by altering mesolimbic dopamine signaling.

We tested this hypothesis using established behavioral tests of palatability and motivation, including the 'palatability contrast' and conditioned place preference (CPP) tests. We used modern optical sensors for measuring real-time nucleus accumbens (NAc) dopamine dynamics during sucrose consumption, via fiber photometry, in male C57/Bl6J mice maintained on low-protein high-carbohydrate (LPHC) or control (CON) diet for ∼5 weeks.

A history of protein restriction decreased the consumption of a sucrose 'dessert' in sated mice by ∼50% compared to controls [T-test, p< 0.05]. The dopamine release in NAc during sucrose consumption was reduced, also by ∼50%, in LPHC-fed mice compared to CON [T-test, p< 0.01]. Furthermore, LPHC-feeding blocked the sucrose-conditioned place preference we observed in CON-fed mice [paired T-test, p< 0.05], indicating reduced motivation. This was accompanied by a 33% decrease in neuronal activation of the NAc core, as measured by c-Fos immunolabeling from brains collected directly after the CPP test.

Despite ongoing efforts to promote healthier dietary habits, adherence to recommendations aimed at reducing the intake of added sugars and processed sweets remains challenging. This study highlights chronic dietary protein restriction as a nutritional intervention that suppresses the motivation for sucrose intake, via blunted sucrose-evoke dopamine release in NAc.

The term emotional eating (EE) describes the tendency to eat as an automatic response to negative emotions and has been linked to anxiety and depression, common symptoms among the university population. The EE tendencies have also been associated with excessive internet use and an increase in alcohol intake among young university students.

The aim of this study is to examine the relationship between the tendency towards EE and other health-compromising behaviors, such as excessive internet use or high alcohol intake. Additionally, it aims to investigate the association of these risky behaviors with the participants' performance level in a virtual reality (VR) task that assesses their executive functioning, and to assess impulsivity and levels of anxiety and depression.

The results associate EE with excessive internet (r = 0.332; p < 0.01). use but not with alcohol consumption. Alcohol consumption was not associated with anxiety, depression, or impulsivity, but it was related to altered executive functions in the VR task: flexibility and working memory explained 24.5% of the variance. By contrast, EE and internet overuse were not related to executive function but were associated with impulsivity, depression, and anxiety. Impulsivity and depressive symptoms accounted for 45% of the variance in EE. Depression, trait anxiety and impulsivity explained 40.6% of the variance in internet overuse.

The results reveal distinct patterns of psychological and neuropsychological alterations associated with alcohol consumption compared to emotional eating (EE) and excessive internet use. These findings underscore significant differences in the contributing factors between addictions and other substance-free addictive behaviors. For a deeper understanding of the various contributing factors to EE in college students, further research is recommended.

Greed, the insatiable and excessive desire and striving for more even at the expense of others, may be directed toward various goods. In this article, we propose that greed may be conceptualized as a domain-specific construct. Based on a literature review and an expert survey, we identified 10 domains of greed which we operationalized with the DOmain-SPEcific Greed (DOSPEG) questionnaire. In Study 1 (N = 725), we found support for the proposed structure and convergent validity with related constructs. Bifactor-(S-1) models revealed that generic greed is differentially related to the greed domains, indicating that generic greed primarily captures a striving for money and material things. In the second study (N = 591), we found that greed domains had incremental validity beyond generic greed with regard to corresponding criteria assessed via self- and other-reports. We conclude that greed can be conceptualized as a domain-specific construct and propose an onion model reflecting this structure.

The number of individuals experiencing sleep loss has exponentially risen over the past decades. Extrapolation of laboratory findings to the real world suggests that females are more affected by extended wakefulness and circadian misalignment than males are. Therefore, long-term effects such as sleep and metabolic disorders are likely to be more prevalent in females than in males. Despite emerging evidence for sex differences in key aspects of sleep-wake and circadian regulation, much remains unknown, as females are often underrepresented in sleep and circadian research. This narrative review aims at highlighting 1) how sex differences systematically impinge on the sleep-wake and circadian regulation in humans, 2) how sex differences in sleep and circadian factors modulate metabolic control, and 3) the relevance of these differences for precision medicine. Ultimately, the findings justify factoring in sex differences when optimizing individually targeted sleep and circadian interventions in humans.

Previous work demonstrated the beneficial effect of T6 dermatomal stimulation by the percutaneous method in managing obesity. However, a simple, cost-effective, and feasible intervention stimulating the dermatome can be a potential solution for obesity care.

The objective of this study was to find the effect of transcutaneous electrical nerve stimulation (TENS) of T6 dermatome on appetite and weight loss in obese individuals.

In this prospective single-arm experimental study, 20 obese patients received TENS treatment of T6 dermatome for 30 min, once a week and for 12 weeks. Outcome measures such as appetite level in the visual analog scale (VAS), weight in kg, and basal metabolic index (BMI) in kg/m2 were assessed at baseline, 12 weeks -post-intervention, and at 8 weeks of follow-up.

A statistically significant difference in all the variables was found from baseline to 12 weeks of intervention (P < 0.001) and maintained till 8 weeks of follow-up. From pre- to post-treatment, the effect size for appetite reduction was large (>1) while for weight and BMI loss was (0.14, 0.16), respectively small. Additionally, a weak correlation was found between pre- and follow-up appetite and weight loss (r = 0.25, P = 0.294).

Twelve weeks of TENS treatment of T6 dermatome showed a positive effect in reducing appetite with sustained reduction up to 8 weeks of follow-up even after completion of the intervention. However, in the absence of dietary modification, TENS treatment was associated with low effect sizes weight and BMI loss.

The interest in new 5-HT₆ agents stems from their ability to modulate cognition processing, food motivation and anxiety-like behaviors. While these findings come primarily from rodent studies, no studies on primates have been published. Furthermore, our understanding of where and how they act in the brain remains limited. Although the striatum is involved in all of these processes and expresses the highest levels of 5-HT₆ receptors, few studies have focused on it. We thus hypothesized that 5-HT6 receptor blockade would influence food motivation and modulate behavioral expression in non-human primates through striatal 5-HT6 receptors. This study thus aimed to determine the effects of acute administration of the SB-258585 selective 5-HT6 receptor antagonist on the feeding motivation and behaviors of six male macaques. Additionally, we investigated potential 5-HT6 targets using PET imaging to measure 5-HT6 receptor occupancy throughout the brain and striatal subregions. We used a food-choice task paired with spontaneous behavioral observations, checking 5-HT6 receptor occupancy with the specific PET imaging [18F]2FNQ1P radioligand. We demonstrated, for the first time in non-human primates, that modulation of 5-HT6 transmission, most likely through the striatum (the putamen and caudate nucleus), significantly reduces food motivation while exhibiting variable, weaker effects on behavior. While these results are consistent with the literature showing a decrease in food intake in rodents and proposing that 5-HT6 receptor antagonists can be used in obesity treatment, they question the antagonists' anxiolytic potential.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, constitutes a metabolic disorder frequently associated with obesity and insulin resistance (IR). Furthermore, women with PCOS often suffer from excessive anxiety and depression, elicited by low self-esteem due to obesity, acne, and hirsutism. These mood disorders are commonly associated with food cravings and binge eating. Hypothalamic signaling regulates appetite and satiety, deteriorating excessive food consumption. However, the hypothalamic function is incapable of compensating for surplus food in women with PCOS, leading to the aggravation of obesity and a vicious circle. Hyperandrogenism, IR, the reduced secretion of cholecystokinin postprandially, and leptin resistance defined by leptin receptors' knockout in the hypothalamus have been implicated in the pathogenesis of hypothalamic dysfunction and appetite dysregulation. Diet modifications, exercise, and psychological and medical interventions have been applied to alleviate food disorders, interrupting the vicious circle. Cognitive-behavioral intervention seems to be the mainstay of treatment, while the role of medical agents, such as GLP-1 analogs and naltrexone/bupropion, has emerged.

High-fat diets cause obesity in male mice; however, the underlying mechanisms remain controversial. Here, three contrasting ideas were assessed: hedonic overdrive, reverse causality, and passive overconsumption models.

A total of 12 groups of 20 individually housed 12-week-old C57BL/6 male mice were exposed to 12 high-fat diets with varying fat content from 40% to 80% (by calories), protein content from 5% to 30%, and carbohydrate content from 8.4% to 40%. Body weight and food intake were monitored for 30 days after 7 days at baseline on a standard low-fat diet.

After exposure to the diets, energy intake increased first, and body weight followed later. Intake then declined. The peak energy intake was dependent on both dietary protein and carbohydrate, but not the dietary fat and energy density, whereas the rate of decrease in intake was only related to dietary protein. On high-fat diets, the weight of food intake declined, but despite this average reduction of 14.4 g in food intake, they consumed, on average, 357 kJ more energy than at baseline.

The hedonic overdrive model fit the data best. The other two models were not supported.

Habitual consumption of highly palatable foods when not in metabolic need (HPF eating) is linked to obesity. High HPF consumption is also linked to mental health disorder (MHD) symptoms. Mindfulness-based interventions are popular treatments for obesity and MHDs, but little is known about the relationship between trait mindfulness and motive-based HPF eating. Therefore, a total of 927 young adults completed a survey that included the Palatable Eating Motives Scale-7 (which identifies Coping-, Reward enhancement-, Social-, and Conformity-eating), the Mindful Attention Awareness Scale, the Perceived Stress Scale, and demographic and body mass index (BMI) questions. An MHD questionnaire allowed a comparison of HPF eating between participants with and without various MHDs. Regressions revealed that Coping-eating was independently associated with lower mindfulness and also greater perceived stress, higher BMI, and female sex. Of these variables, only lower mindfulness was independently associated with Reward-, Social-, and Conformity-eating. Coping- and Reward-eating were more frequent in participants with versus without an anxiety disorder, depression, ADD/ADHD, and PTSD. Coping-eating was also more frequent in participants with body dysmorphic disorder. These findings warrant investigations in participants with clinically validated diagnoses for DSM-specific MHDs. Results from such investigations and the uncovered nature of associations between motive-specific HPF eating and trait mindfulness could provide novel targets to improve mindfulness-based interventions for obesity and MHDs.

Food addiction refers to a condition in which individuals exhibit addictive-like behaviors toward food, like those observed in substance abuse. Although still debated, evidence supporting the validity and usefulness of the concept of food addiction is growing. Food addiction is particularly associated with obesity and eating disorders involving binge eating. This study discusses the cases of two adolescent patients who presented with anorexia nervosa. During the recovery phase of anorexia nervosa, binge eating was observed, and the patterns of binge eating significantly differed between patients, with and without food addiction. Therefore, healthcare professionals treating eating disorders should be aware of food addiction and modify their treatment strategies accordingly.

Intermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis.

In this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples.

Our results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes.

There was dynamical alteration of BGM axis (the communication of E. coli with specific brain regions) during the weight loss under the IER.

Bulimia nervosa (BN) is an eating disorder characterized by recurrent binge eating and compensatory behaviors. The thalamus plays a crucial role in the neural circuitry related to eating behavior and needs to be further explored in BN.

In this study, 49 BN patients and 44 healthy controls (HCs) were recruited. We applied the fractional amplitude of low-frequency fluctuation to investigate regional brain activity in the thalamus and functional connectivity (FC) to examine the synchronization of activity between thalamic subregions and other brain regions in both groups. All results underwent false discovery rate (p < 0.05, FDR correction) correction. Pearson correlation analysis was performed to assess the relationship between the patients' abnormal clinical performance and the thalamic alterations (p < 0.05, FDR correction).

We found no significant differences in neural activity between BN patients and HCs in the sixteen thalamic subregions. However, compared to the HCs, the individuals with BN showed decreased FC between the thalamic subregions and several regions, including the bilateral prefrontal cortex, right inferior parietal lobule, right supplementary motor area, right insula, cingulate gyrus and vermis. Additionally, BN patients showed increased FC between the thalamic subregions and visual association regions, primary sensorimotor cortex, and left cerebellum. These altered FC patterns in the thalamus were found to be correlated with clinical variables (the frequency of binge eating/purging per week and external eating behavior scale scores) in the BN group. All results have passed FDR correction.

Our study provides evidence that there is disrupted FC between thalamic subregions and other brain regions in BN patients during resting state. These regions are primarily located within the frontoparietal network, default mode network, somatosensory, and visual network. These findings elucidate the neural activity characteristics underlying BN and suggest that thalamic subregions have potential as targets for future neuromodulation interventions.

The aim of this study was to assess brain functional alterations in BN patients with affective disorders and their association with maladaptive eating behaviors.

A total of 42 BN patients with affective disorders (anxiety and depression) and 47 healthy controls (HCs) were enrolled in this study. The resting-state fMRI data were analyzed for functional changes as indicated by regional homogeneity based on Kendall's coefficient of concordance (KCC-ReHo) and seed-based functional connectivity (FC). A principal component analysis (PCA) model was used to identify the commonalities within the behavioral questionnaires from the BN group.

Patients in the BN group showed decreased ReHo in the bilateral middle frontal gyrus (MFG) and right supramarginal gyrus (SMG). Additionally, the BN group showed increased FC between the left MFG and the right inferior temporal gyrus (ITG); decreased FC between the right MFG and the bilateral insula and the left middle temporal gyrus (MTG); and decreased FC between the right SMG and the left superior temporal gyrus (STG) and right inferior frontal gyrus (IFG). In the FC-behavior association analysis, the second principal component (PC2) was negatively correlated with FC between the left MFG and the right ITG.

Based on a brain functional analysis (ReHo and FC), this study revealed significant aberrant changes in the frontal-temporal regions of BN patients with affective disorders. These regions, which serve as fronto-temporal circuitry, are associated with restraint and emotional eating behaviors. Our findings shed new light on the neural mechanisms underlying the condition.

Behaviour change interventions for weight management have found varied effect sizes and frequent weight re-gain after weight loss. There is interest in exploring whether differences in eating behaviour can be used to develop tailored weight management programs. This secondary analysis of an 18-month weight maintenance randomised controlled trial (RCT) aimed to investigate the association between individual variability in weight maintenance success and change in eating behaviour traits (EBT). Data was analysed from the NoHoW trial (Scott et al., 2019), which was designed to measure processes of change after weight loss of ≥5% body weight in the previous year. The sample included 1627 participants (mean age = 44.0 years, SD = 11.9, mean body mass index (BMI) = 29.7 kg/m2, SD = 5.4, gender = 68.7% women/31.3% men). Measurements of weight (kg) and 7 EBTs belonging to domains of reflective, reactive, or homeostatic eating were taken at 4 time points up to 18-months. Increases in measures of 'reactive eating' (binge eating, p < .001), decreases in 'reflective eating' (restraint, p < .001) and changes in 'homeostatic eating' (unlimited permission to eat, p < .001 and reliance on hunger and satiety cues, p < .05) were significantly and independently associated with concomitant weight change. Differences in EBT change were observed between participants who lost, maintained, or re-gained weight for all EBTs (p < .001) except for one subscale of intuitive eating (eating for physical reasons, p = .715). Participants who lost weight (n = 322) exhibited lower levels of reactive eating and higher levels of reflective eating than participants who re-gained weight (n = 668). EBT domains can identify individuals who need greater support to progress in weight management interventions. Increasing reflective eating and reducing reactive eating may enhance weight management success.

Melanocortin 4 receptor (MC4R) activity in the hypothalamus is crucial for regulation of metabolism and food intake. The peptide ligands for the MC4R are associated with feeding, energy expenditure, and also with complex behaviors that orchestrate energy intake and expenditure, but the downstream neuroanatomical and neurochemical targets associated with these behaviors are elusive. In addition to strong expression in the hypothalamus, the MC4R is highly expressed in the medial prefrontal cortex, a region involved in executive function and decision-making.

Using viral techniques in genetically modified male mice combined with molecular techniques, we identify and define the effects on feeding behavior of a novel population of MC4R expressing neurons in the infralimbic (IL) region of the cortex.

Here, we describe a novel population of MC4R-expressing neurons in the IL of the mouse prefrontal cortex that are glutamatergic, receive input from melanocortinergic neurons, and project to multiple regions that coordinate appetitive responses to food-related stimuli. The neurons are stimulated by application of MC4R-specific peptidergic agonist, THIQ. Deletion of MC4R from the IL neurons causes increased food intake and body weight gain and impaired executive function in simple food-related behavior tasks.

Together, these data suggest that MC4R neurons of the IL play a critical role in the regulation of food intake in male mice.

Binge-Eating Disorder (BED) involves anticipatory craving and urges, subjective loss-of-control during binge-eating episodes, and post-feeding psychological distress and guilt. Evidence indicates neurocognitive dysfunctions contribute to BED onset, maintenance, and treatment response. However, an integrated understanding of how cognitive processes underpin BED symptomology is lacking. We utilised a multi-stage decision-making model defining ten cognitive processes underpinning Preference Formation, Choice Implementation, Feedback Processing, and Flexibility/Shifting, to comprehensively review research published since 2013. We used preregistered PICOS criteria to assess 1966 articles identified from PubMed, PsycInfo, and Scopus database searches. This yielded 50 studies reporting behavioural cognitive tasks outcomes, comparing individuals with BED to controls with normal and higher weight. Meta-analyses revealed a unique profile of cognitive dysfunctions that spanned all decision-making stages. Significant deficits were evident in Uncertainty Evaluation, Attentional Inhibition, Choice Consistency, and Cognitive Flexibility/Set-shifting. We propose a novel model of dysfunctional decision-making processes in BED and describe their role in binge-eating behaviour. We further highlight the potential for cognitive interventions to target these processes and address the significant treatment gap in BED.

Body weight gain in combination with metabolic alterations has been observed after deep brain stimulation (DBS) of subthalamic nucleus (STN) in patients with Parkinson's disease (PD), which potentially counteracts the positive effects of motor improvement. We aimed to identify stimulation-dependent effects on motor activities, body weight, body composition, energy metabolism, and metabolic blood parameters and to determine if these alterations are associated with the local impact of DBS on different STN parcellations. We assessed 14 PD patients who underwent STN DBS (PD-DBS) before as well as 6- and 12-months post-surgery. For control purposes, 18 PD patients under best medical treatment (PD-CON) and 25 healthy controls (H-CON) were also enrolled. Wrist actigraphy, body composition, hormones, and energy expenditure measurements were applied. Electrode placement in the STN was localized, and the local impact of STN DBS was estimated. We found that STN DBS improved motor function by ~ 40% (DBS ON, Med ON). Weight and fat mass increased by ~ 3 kg and ~ 3% in PD-DBS (all P ≤ 0.005). fT3 (P = 0.001) and insulin levels (P = 0.048) increased solely in PD-DBS, whereas growth hormone levels (P = 0.001), daily physical activity, and VO2 during walking were decreased in PD-DBS (all P ≤ 0.002). DBS of the limbic part of the STN was associated with changes in weight and body composition, sedentary activity, insulin levels (all P ≤ 0.040; all r ≥ 0.56), and inversely related to HOMA-IR (P = 0.033; r = - 0.62). Daily physical activity is decreased after STN DBS, which can contribute to weight gain and an unfavorable metabolic profile. We recommend actigraphy devices to provide feedback on daily activities to achieve pre-defined activity goals.

This study was designed to explore relationship of perceived depression, anxiety and stress (DAS) levels and hedonic hunger in adults.

A cross-sectional survey included questions about some socio-demographic characteristics, Power of Food Scale (PFS-Tr) and Depression Anxiety Stress Scales (DASS-21) was sent via an online platform. Self-reported weight and height were also questioned. A total of 4112 adult volunteers between the ages of 18-65 years participated in this study. 72.3% of them were female.

The prevalence of moderate to extremely severe depression, anxiety, and stress was reported as 31%, 34% and 13% respectively. Hedonic hunger and perceived DAS levels were higher in females (p < 0.001). Hedonic hunger was positively correlated with perceived DAS (p < 0.001). While body mass index (BMI) was positively associated with PFS-Tr total score, food available and food present; negatively associated with food tasted. Body mass index was negatively correlated with perceived DAS. Hedonic hunger and perceived DAS levels decreased with increasing age. Females were more prone to both hedonic hunger and perceived DAS. About one in three participants reported moderate to extremely severe levels of depression and anxiety. Greater perceived DAS levels are associated with hedonic hunger. Underweight individuals had higher levels of perceived DAS.

To our knowledge, this is the first study to examine the prevalence and predictors of perceived DAS levels and hedonic hunger in the Turkish adult population. The findings of the study suggest that the predictors such as age, sex and BMI are a part of psychological well-being and hedonic hunger.

Previous research has suggested that there is an association between impulsivity, assessed via self-report measures and behaviourally, and disinhibited eating patterns, but it remains unclear which specific dimension of impulsivity is the most salient in this relationship. Furthermore, it remains uncertain whether any such associations would extend to actual eating behaviours and food consumption.

The present study aimed to examine whether impulsivity, assessed both behaviourally and via self-report, is associated with self-reported disinhibited and actual eating behaviour in a controlled eating task.

70 women from a community sample (aged 21-35) completed the Disinhibition subscale of the Three Factor Eating Questionnaire (TFEQ), the Barratt Impulsiveness Scale (BIS-11), the Matching Familiar Figures Task (MFFT-20), and a behavioural food consumption task.

Bivariate correlational analyses revealed significant associations between self-report measure of impulsivity, the scores on the MFFT-20 (assessing reflection impulsivity), and self-report measure of disinhibited eating. All these measures were associated with overall food consumption in a taste task, with reflection impulsivity, that is poor ability to reflect on information before making a decision, having the strongest association with the amount of food consumed. Self-reported impulsivity was most strongly associated with disinhibited eating. Partial correlations controlling for BMI and age did not diminish any significant correlations within these relationships.

Significant associations between both trait and behavioural (reflection) impulsivity, and self-reported disinhibited eating and actual eating behaviour were demonstrated. The implications of these findings on uncontrolled eating patterns in real life are discussed.

Behavioral processes through which lifestyle interventions influence risk factors for type 2 diabetes (T2DM), e.g., body weight, are not well-understood. We examined whether changes in psychological dimensions of eating behavior during the first year of lifestyle intervention would mediate the effects of intervention on body weight during a 9-year period.

Middle-aged participants (38 men, 60 women) with overweight and impaired glucose tolerance (IGT) were randomized to an intensive, individualized lifestyle intervention group (n = 51) or a control group (n = 47). At baseline and annually thereafter until nine years body weight was measured and the Three Factor Eating Questionnaire assessing cognitive restraint of eating with flexible and rigid components, disinhibition and susceptibility to hunger was completed. This was a sub-study of the Finnish Diabetes Prevention Study, conducted in Kuopio research center.

During the first year of the intervention total cognitive (4.6 vs. 1.7 scores; p < 0.001), flexible (1.7 vs. 0.9; p = 0.018) and rigid (1.6 vs. 0.5; p = 0.001) restraint of eating increased, and body weight decreased (-5.2 vs. -1.2 kg; p < 0.001) more in the intervention group compared with the control group. The difference between the groups remained significant up to nine years regarding total (2.6 vs. 0.1 scores; p = 0.002) and rigid restraint (1.0 vs. 0.4; p = 0.004), and weight loss (-3.0 vs. 0.1 kg; p = 0.046). The first-year increases in total, flexible and rigid restraint statistically mediated the impact of intervention on weight loss during the 9-year study period.

Lifestyle intervention with intensive and individually tailored, professional counselling had long-lasting effects on cognitive restraint of eating and body weight in middle-aged participants with overweight and IGT. The mediation analyses suggest that early phase increase in cognitive restraint could have a role in long-term weight loss maintenance. This is important because long-term weight loss maintenance has various health benefits, including reduced risk of T2DM.

The calcium-sensing receptor (CaSR) is abundantly expressed in gastrointestinal mucosa and participates in the regulation of feeding by affecting hormone secretion. Studies have demonstrated that the CaSR is also expressed in feeding-related brain areas, such as the hypothalamus and limbic system, but the effect of the central CaSR on feeding has not been reported. Therefore, the aim of this study was to explore the effect of the CaSR in the basolateral amygdala (BLA) on feeding, and the potential mechanism was also studied. CaSR agonist R568 was microinjected into the BLA of male Kunming mice to investigate the effects of the CaSR on food intake and anxiety-depression-like behaviours. The enzyme-linked immunosorbent assay (ELISA) and fluorescence immunohistochemistry were used to explore the underlying mechanism. Our results showed that microinjection of R568 into the BLA could inhibit both standard and palatable food intake in mice for 0-2 h, induce anxiety-depression-like behaviours, increase glutamate levels in the BLA, and activate dynorphin and gamma-aminobutyric acid neurons through the N-methyl-D-aspartate receptor and thus reduce the content of dopamine in the arcuate nucleus of the hypothalamus (ARC) and ventral tegmental area (VTA), respectively. Our findings suggest that activation of the CaSR in the BLA inhibited food intake and caused anxiety-depression-like emotions. The reduced dopamine levels in the VTA and ARC via glutamatergic signals are involved in these functions of CaSR.

. There is a growing global interest in the evaluation of food reward, necessitating the adaptation of culturally appropriate instruments for use in empirical studies. This work presents the development and validation of a culturally adapted French version of the Leeds Food Preference Questionnaire (LFPQ-fr).

. The LFPQ-fr was developed and validated in healthy-weight adults using the following systematic approach: i) selection and validation of appropriate food pictures; ii) linguistic translation of liking and wanting constructs in the target population (n=430; 81% female; 42.2 ± 12.7 years); iii) validation of the sensitivity and reliability of the task performed in a fasted state and in response to a standardized test meal (n=50; 50% female; 30.0 ± 8.4 years).

. During the first and second phases, the nutritional and perceptual validation of culturally appropriate food pictures and pertinent reward constructs, respectively, was demonstrated in a healthy-weight French sample. Findings from the third phase indicated that all food reward components were sensitive to the test meal and showed moderate to high agreement in both fasted (Lin's CCC =.72-.94) and fed (Lin's CCC = .53-.80) appetitive states between visit 1 (V1) and visit (V2). Except for explicit liking fat bias, all primary outcomes were statistically consistent in fasted and fed states between V1 and V2. Changes in fat and taste biases in response to a standardized meal for all primary outcomes were also consistent between V1 and V2 except for explicit liking fat bias (Lin's CCC = .49- .72).

. The LFPQ-fr developed and tested in this study is a reproducible and reliable method to assess food reward in both the fasted and fed states in a healthy-weight French population.

Dysfunctional glucose sensing in homeostatic brain regions such as the hypothalamus is interlinked with the pathogenesis of obesity and type 2 diabetes mellitus. However, the physiology and pathophysiology of glucose sensing and neuronal homeostatic regulation remain insufficiently understood. To provide a better understanding of glucose signaling to the brain, we assessed the responsivity of the hypothalamus (i.e., the core region of homeostatic control) and its interaction with mesocorticolimbic brain regions in 31 normal-weight, healthy participants. We employed a single-blind, randomized, crossover design of the intravenous infusion of glucose and saline during fMRI. This approach allows to investigate glucose signaling independent of digestive processes. Hypothalamic reactivity and connectivity were assessed using a pseudo-pharmacological design and a glycemia-dependent functional connectivity analysis, respectively. In line with previous studies, we observed a hypothalamic response to glucose infusion which was negatively related to fasting insulin levels. The observed effect size was smaller than in previous studies employing oral or intragastric administration of glucose, demonstrating the important role of the digestive process in homeostatic signaling. Finally, we were able to observe hypothalamic connectivity with reward-related brain regions. Given the small amount of glucose employed, this points toward a high responsiveness of these regions to even a small energy stimulus in healthy individuals. Our study highlights the intricate relationship between homeostatic and reward-related systems and their pronounced sensitivity to subtle changes in glycemia.

Serotonin modulates many motivated behaviours via multiple receptor subtypes. Agonists at 5-HT_2C receptors have potential for treating behavioural problems associated with obesity and drug use. In this work we examined the impact of the 5-HT_2C receptor agonist lorcaserin on several motivated behaviours related to feeding, reward and waiting impulsivity, and on neuronal activation in key brain areas mediating those behaviours. In male C57BL/6J mice effects of lorcaserin (0.2, 1 and 5mg/kg) were examined on feeding, and on operant responding for a palatable reward. Feeding was reduced only at 5mg/kg, whereas operant responding was reduced at 1mg/kg. At a much lower dose range lorcaserin 0.05-0.2mg/kg also reduced impulsive behaviour measured as premature responding in the 5-choice serial reaction time (5-CSRT) test, without affecting attention or ability to perform the task. Lorcaserin induced Fos expression in brain regions related to feeding (paraventricular nucleus and arcuate nucleus), reward (ventral tegmental area), and impulsivity (medial prefrontal cortex, VTA) although these effects did not show the same differential sensitivity to lorcaserin as the behavioural measures. These results indicate a broad profile of action of 5-HT_2C receptor stimulation on brain circuitry and on motivated behaviours, but with clear evidence of differential sensitivity across behavioural domains. This is exemplified by that fact that impulsive behaviour was reduced at a much lower dose range than was feeding behaviour. Along with previous work, and some clinical observations, this work supports the idea that 5-HT_2C agonists may be useful for behavioural problems associated with impulsivity.

The availability of hyper-palatable foods (HPF) increased over the past three decades worldwide, a period when eating disorders (ED) and obesity have become global public health concerns. The present study aimed to assess HPF consumption during binge and non-binge meals in a representative sample of adults with and without ED from a metropolitan city in Brazil. A total of 2297 individuals were interviewed in their homes by trained lay interviewers to assess the presence of binge eating disorder (BED), bulimia nervosa (BN), and recurrent binge eating (RBE). Information on their food consumption in objective and subjective binge eating episodes (OBE and SBE, respectively), as well as in the 24 h food recall were obtained. Individuals from the general population consumed 56% of their total calories from HPF. In non-binge meals, people with BN consumed substantially fewer calories from HPF than BED (63% vs. 48%) and RBE (63% vs. 48%) groups. During OBE, participants consumed an average of 70% of the calories from HPF, with no between-group differences. During SBE, subjects with BN consumed substantially fewer calories from HPF than those with BED (76% vs. 50%). In conclusion, HPF were highly consumed by the Brazilian population. However, there was a greater impact on BED and RBE subjects and during binge eating episodes.

Few have studied the associations between rs9939609 genotypes in the obesity candidate locus FTO and energy and nutrient intakes and meal frequencies in adults with severe obesity. We are unaware of studies that have assessed adherence to key dietary recommendations in this population, at least in Norway. Increased knowledge of genotype associations with dietary factors could improve personalized obesity therapy.

The present study aimed to explore how the rs9939609 genotypes associate with dietary variables and adherence to key dietary recommendations in a sample of adults with severe obesity.

A cross-sectional observation study designed to have similar numbers of participants with genotypes TT, AT, and AA included 100 patients (70% women) with median (25th, 75th percentile) age 42 (32, 50) y and BMI 42.8 (39.5, 46.4) kg/m2. We assessed intakes of food groups, energy, and macro- and micronutrients from three 24-h dietary recalls and meal frequencies. Genotype associations were analyzed using regression analyses. Reported intakes were evaluated against national diet recommendations.

Using a significance level of 0.01, we found no genotype associations with energy intake, energy density, adherence to recommendations, or meal frequency but tendencies of associations with energy adjusted protein intake (AA > AT, P = 0.037; AT > TT, P = 0.064), food groups milk and cream (AT > TT, P = 0.029), and Mixed dishes (AA > TT, P = 0.039). Few participants complied with recommendations for intakes of whole grains (21%), fruits and vegetables (11%), and fish (37%); however, 67% followed the recommendation to limit added sugar. Less than 20% had recommended intakes of vitamin D and folate.

In our patients with severe obesity, we found tendencies of associations between the FTO rs9939609 genotypes and diet but no significant associations at the 0.01 level and below. Few met key food-based diet recommendations, suggesting that the food habits in this population pose an increased risk of nutrient deficiencies. Curr Dev Nutr 2023;xx:xx.

Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the lowest for major surgery. Because there are not nearly enough surgeons to implement bariatric surgery on a global scale, intensive research efforts have begun to identify its mechanisms of action on a molecular level in order to replace surgery with targeted behavioral or pharmacological treatments. To date, however, there is no consensus as to the critical mechanisms involved.

The purpose of this non-systematic review is to evaluate the existing evidence for specific molecular and inter-organ signaling pathways that play major roles in bariatric surgery-induced weight loss and metabolic benefits, with a focus on Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), in both humans and rodents.

Gut-brain communication and its brain targets of food intake control and energy balance regulation are complex and redundant. Although the relatively young science of bariatric surgery has generated a number of hypotheses, no clear and unique mechanism has yet emerged. It seems increasingly likely that the broad physiological and behavioral effects produced by bariatric surgery do not involve a single mechanism, but rather multiple signaling pathways. Besides a need to improve and better validate surgeries in animals, advanced techniques, including inducible, tissue-specific knockout models, and the use of humanized physiological traits will be necessary. State-of-the-art genetically-guided neural identification techniques should be used to more selectively manipulate function-specific pathways.

The role of physical activity (PA) in the regulation of body weight is still a major topic of debate. This may be because studies have essentially focused on the effects of moderate/vigorous PA (MVPA) on body weight while overlooking the other components of PA, namely, light-intensity PA (LPA, daily life activities) and sedentary behaviors (SB, too much sitting). In this review, we will (i) describe the history of changes in PA behaviors that occurred with modernization; (ii) review data from cross-sectional and longitudinal studies that examined the associations between PA, SB, and measures of obesity; (iii) review interventional studies that investigated the effects of changes in PA and SB on body weight and adiposity; and (iv) discuss experimental studies that addressed potential biological mechanisms underlying the effects of PA and SB on weight regulation. Overall recent findings support the importance of considering all components of PA to better understand the regulation of energy balance and suggest an important role for LPA and SB in addition to MVPA on body weight regulation. Longitudinal large-scale rigorous studies are needed to advance our knowledge of the role of PA/SB in combating the obesity epidemic.