Heart failure with preserved ejection fraction (HFpEF) is a major subtype of heart failure, primarily characterized by a normal or mildly reduced left ventricular ejection fraction along with left ventricular diastolic dysfunction. Recent studies have shown that the prevalence of HFpEF is higher in women than that in men, particularly in postmenopausal women. Concurrently, it has been observed that the incidence of risk factors contributing to HFpEF (such as obesity, hypertension, diabetes, and atrial fibrillation) also notably increases post-menopause, affecting the incidence of HFpEF. This review aimed to examine the relationship between estrogen and risk factors associated with HFpEF, clarifying the underlying mechanisms through which estrogen affects these risk factors from epidemiological and pathophysiological perspectives. This review also provides a comprehensive understanding of the association between estrogen and the risk factors for HFpEF, thus helping explore potential targets for HFpEF treatment.

Central obesity is a well-known risk factor of numerous disease. Numerous indicators are developed for central obesity measurement, among them, abdominal volume index (AVI), reflecting total volume of the abdomen, precisely estimates the visceral fat volume. As a relatively new health measure and potent prognostic marker of metabolic disturbances, no study is available to investigate its role in cardio-metabolic health and oxidized LDL among obese young adults. In the current study we aimed to evaluate the association between abdominal volume index (AVI) with cardio-metabolic profile including serum lipids, glycemic markers of serum glucose, hemoglobin (Hb) A1C, insulin, oxidized LDL and blood pressure among young obese adults.

Two hundred twenty young adults aged 18 to 25 years old with overweight or obesity were enrolled in the current study. Anthropometric measurements were done and AVI were calculated. Biochemical variables including serum total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglyceride (TG), glycemic markers, including fasting serum glucose (FBS), insulin, hemoglobin (Hb) A1C and blood pressure were also measured with an automatic analyzer.

Participants in the third tertiles of AVI had higher body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) (p < 0.001 for all). Among biochemical variables, oxidized LDL, TG and HDL demonstrated significant associations across AVI tertiles in the first and second models, with higher oxidized LDL and TG and lower HDL levels observed in higher AVI tertiles (p < 0.05). Moreover, those at the highest AVI tertiles showed significantly higher odds ratios for elevated cardio-metabolic index and systolic and diastolic blood pressures compared to the first tertiles (p < 0.05).

In the current study, we comprehensively investigated the association between AVI with cardio-metabolic health in young obese adults and accordingly, AVI was unfavorably associated with metabolic health among obese adults. Further studies are needed to elaborate the underlying mechanisms.

Not applicable.

Obesity is a major global health issue, driving high morbidity and mortality rates. The body roundness index (BRI), which includes waist circumference, offers a more accurate measure of visceral and total body fat. However, despite evidence of BRI's effectiveness in predicting obesity-related diseases, national-level data, especially from non-Western populations like China, remain limited.

This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS), a large, nationally representative cohort of Chinese adults, to examine the temporal trends of BRI, identify associated risk factors, and investigate the longitudinal associations between BRI and cardiovascular disease (CVD) outcomes. BRI was calculated using height and waist circumference measurements. Temporal trends and risk factors were analyzed cross-sectionally, while longitudinal associations were examined using Cox proportional hazards models adjusted for confounders. Mediation analyses were conducted to assess the role of intermediate factors such as hypertension and diabetes in the relationship between BRI and CVD.

A total of 12,902 participants were included for risk factor analysis, 10,525 for longitudinal analysis, and 7,310 for cumulative analysis. BRI continued to rise slowly across survey cycles but was higher in women, older adults, and urban residents. Multivariable analysis identified age, alcohol consumption, elevated blood pressure, and diabetes as positive predictors of BRI, while male sex, rural residence, and smoking were negatively associated. Higher baseline BRI was significantly associated with increased CVD risk (HR: 1.44, 95% CI: 1.22-1.69), stroke (HR: 1.49, 95% CI: 1.12-1.98), and heart disease (HR: 1.47, 95% CI: 1.22-1.77). Cumulative BRI similarly predicted increased risks of CVD, stroke, and heart disease. Mediation analysis showed that hypertension accounted for 20.69% of the association between BRI and CVD risk.

BRI is a robust predictor of CVD risk. Targeting hypertension and other metabolic conditions could mitigate the elevated CVD risk associated with high BRI in Chinese adults. These findings underscore the importance of incorporating BRI into public health strategies to better manage obesity-related health risks in China.

This Review focuses on currently available literature describing sex differences in skeletal muscle metabolism in humans, as well as highlighting current research gaps within the field. These discussions serve as a call for action to address the current lack of sufficient sex-balanced studies in skeletal muscle research, and the resulting limitations in understanding sex-specific physiological and pathophysiological responses. Although the participation of women in studies has increased, parity between the sexes remains elusive, affecting the validity of conclusions drawn from studies with limited numbers of participants. Changes in skeletal muscle metabolism contribute to the development of metabolic disease (such as type 2 diabetes mellitus), and maintenance of skeletal muscle mass is a key component for health and the ability to maintain an independent life during ageing. Exercise is an important factor in maintaining skeletal muscle health and insulin sensitivity, and offers promise for both prevention and treatment of metabolic disease. With the increased realization of the promise of precision medicine comes the need to increase patient stratification and improve the understanding of responses in different populations. In this context, a better understanding of sex-dependent differences in skeletal muscle metabolism is essential.

The expression of BDNF in both neuronal and non-neuronal cells is influenced by various stimuli, including prenatal developmental factors and postnatal conditions such as estrogens, dietary habits, and lifestyle factors like obesity, blood pressure, and aging. Central BDNF plays a crucial role in modulating how target tissues respond to these stimuli, influencing the pathogenesis of hypertension, mitigating obesity, and protecting neurons from aging. Thus, BDNF serves as a dynamic mediator of environmental influences, reflecting an individual's unique history of exposure. Estrogens, on the other hand, regulate various processes to maintain overall physiological well-being. Through nuclear estrogen receptors (ERα, ERβ) and the membrane estrogen receptor (GPER1), estrogens modulate transcriptional processes and signaling events that regulate the expression of target genes, such as ERα, components of the renin-angiotensin system (RAS), and hormone-sensitive lipase. Estrogens are instrumental in maintaining the set point for blood pressure and energy balance. BDNF and estrogens work cooperatively to prevent obesity by favoring lipolysis, and counteractively regulate blood pressure to adapt to the environment. Estrogen deficiency leads to menopause in women with low central BDNF level. This review delves into the complex mechanisms involving BDNF and estrogen, especially in the context of hypertension and obesity, particularly among postmenopausal women. The insights gained aim to inform the development of comprehensive therapeutic strategies for these prevalent syndromes affecting approximately 68% of adults.

Considering sex-specific factors has become an increasingly recognized area for research and practice, in the field of clinical nutrition, there is insufficient evidence regarding differences in clinical presentation, treatment response, and side effects of nutritional therapy among female and male patients.

We hypothesized that the clinical presentation, response to nutritional therapy, and side effects from the intervention would differ in the two sexes.

This secondary analysis investigated differences among female and male patients at risk for malnutrition regarding initial presentation, clinical outcomes, and treatment response in patients included in the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial comparing individualized nutritional support to usual care.

Of 2028 patients included in the trial, 964 were females and 1064 were males. The nutritional history and clinical presentation of female patients was different: they consumed less food and had a greater loss of appetite than the male population. Male patients had higher risk for mortality at 180 d [27% compared with 19%; adjusted hazards ratio (HR): 1.35; 95% CI: 1.12, 1.63] and further adverse clinical outcomes. However, there was no difference in the effect of nutritional support on mortality among female and male patients (HR: 0.76; 95% CI: 0.45, 1.27, compared with HR: 0.81; 95% CI: 0.54, 1.21, respectively; P-interaction = 0.939).

Results of this multicenter randomized trial suggest that multimorbid female inpatients have a different clinical presentation and are more prone to loss of appetite and reduced daily dietary intake than male inpatients. Importantly, the favorable response to nutritional interventions was similar in both sexes. This trial was registered at clinicaltrials.gov as NCT02517476.

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species. The degree to which LC activity is homogenous across these factors, however, has never been assessed due to the small sample size of individual studies. Here, we pool data from 20 laboratories (1,855 neurons) and show diversity across both intrinsic and extrinsic factors such as species, age, sex and brain state. We use a negative binomial regression model to compare activity from male monkeys, and rats and mice of both sexes that were recorded across brain states from brain slices ex vivo or under different anesthetics or during wakefulness in vivo. LC activity differed due to complex interactions of species, sex, and brain state. The LC became more active during aging, independent of sex. Finally, in contrast to the foundational principle that all species express two distinct LC firing modes ("tonic" or "phasic"), we discovered great diversity within spontaneous LC firing patterns. Different factors were associated with higher incidence of some firing modes. We conclude that the activity of the evolutionarily-ancient LC is not conserved. Inherent differences due to age and species-sex-brain state interactions have implications for understanding the role of LC in species-specific naturalistic behavior, as well as in psychiatric disorders, cardiovascular disease, immunology, and metabolic disorders.

It was previously shown in striatal slices obtained from male rats that insulin excites cholinergic interneurons and increases dopamine (DA) release via α4β2 nicotinic receptors on DA terminals. The effect of insulin on DA release was blocked either by maintaining rats on a high sugar-high fat (HS-HF) diet that induced hyperinsulinemia and nucleus accumbens (NAc) insulin receptor insensitivity, or applying the α4β2 antagonist DHβE. In vivo, NAc shell insulin inactivation decreased a glucose lick microstructure parameter indicative of hedonic impact in male and female rats, and prevented flavor-nutrient learning, tested only in males. The HS-HF diet decreased hedonic impact in males but not females, and prevented flavor-nutrient learning, tested only in males. The present study extends testing to more fully assess the translation of brain slice results to the behaving rat. Insulin inactivation by antibody microinjection in NAc shell was found to decrease the number of lick bursts emitted and average lick burst size, measures of incentive motivation and hedonic impact respectively, for a wide range of glucose concentrations in male and female rats. In contrast, the HS-HF diet decreased these lick parameters in males but not females. Follow-up two-bottle choice tests for 10 % versus 40 % glucose showed decreased intake of both concentrations by males but increased intake of 40 % glucose by females. In a further set of experiments, it was predicted that α4β2 receptor blockade would induce the same behavioral effects as insulin inactivation. In females, DHβE microinjection in NAc shell decreased both lick parameters for glucose as predicted, but in males only the number of lick bursts emitted was decreased. DHβE also decreased the number of lick bursts emitted for saccharin by females but not males. Finally, DHβE microinjection in NAc shell decreased flavor-nutrient learning in both sexes. The few discrepancies seen with regard to the hypothesized insulin-nicotinic-dopaminergic regulation of behavioral responses to nutritive sweetener, and its inhibition by HS-HF diet, are discussed with reference to sex differences in DA dynamics, female resistance to diet-induced metabolic morbidities, and extra-striatal cholinergic inputs to NAc.

Growing evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) is significantly higher in men versus women. Increased prevalence is observed in postmenopausal women, suggesting that age and sex (hormones) influence MASLD development and progression. Molecular data further reveal that sex regulates the innate immune responses with an essential role in MASLD progression. To date, there has been limited focus on the role of innate immune sexual dimorphism in MASLD, and differences between men and women are not considered in the current drug discovery landscape. In this review, we summarize the sex disparities and innate immune sexual dimorphism in MASLD pathogenesis. We further highlight the importance of harnessing sexual dimorphism in identifying therapeutic targets, developing pharmacological therapies, and designing (pre-) clinical studies for the personalized treatment for MASLD.

The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism (MOSH) with emerging evidence on the role of testosterone therapy. We aim to provide an updated and practical approach towards its management. We did a comprehensive literature search across MEDLINE (via PubMed), Scopus, and Google Scholar databases using the keywords "MOSH" OR "Obesity-related hypogonadism" OR "Testosterone replacement therapy" OR "Selective estrogen receptor modulator" OR "SERM" OR "Guidelines on male hypogonadism" as well as a manual search of references within the articles. A narrative review based on available evidence, recommendations and their practical implications was done. Although weight loss is the ideal therapeutic strategy for patients with MOSH, achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world practice. Therefore, androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to obesity. However, there is conflicting evidence for the appropriate use of testosterone replacement therapy (TRT), and it can also be associated with complications. This evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with MOSH. Before starting testosterone replacement in functional hypogonadism of obesity, it would be desirable to initiate lifestyle modification to ensure weight reduction. TRT should be coupled with the management of other comorbidities related to obesity in MOSH patients. Balancing the risks and benefits of TRT should be considered in every patient before and during long-term management.

Psychological research frequently encounters criticism regarding the representativeness of the samples under study, highlighting concerns about the external validity of the obtained results. Here, we conducted a comprehensive survey of all the quantitative samples from the journal Body Image for 2021 (n = 149 samples). Our primary objective was to examine the extent to which the sampled populations deviated from the population at large, which could potentially compromise the generalizability of findings. We identified that a substantial number of these samples came from student populations (n = 44) and the majority were from the United States, United Kingdom, and Australia. Only a small number of samples (n = 9) employed direct measurements of body mass index (BMI), while the majority relied on self-reported data (n = 93). For a subset of samples in the journal, which were drawn from the general population, we compared whether these differed from population reference values in terms of age and BMI. Using Monte Carlo simulations, we found that samples tended to be younger and score lower on BMI than reference values obtained from the broader population. Samples drawn from female university students also tended to be lower on BMI than age-matched reference samples. We discuss the implications of our findings and make recommendations on sampling and inference. We conclude that a clearer specification of the parameters or conditions under which findings are expected to generalise has the potential to enhance the overall rigor and validity of this field of research.

Obesity is often associated with aging. However, the mechanism of age-related obesity is unknown. The melanocortin-4 receptor (MC4R) mediates leptin-melanocortin anti-obesity signaling in the hypothalamus. Here, we discovered that MC4R-bearing primary cilia of hypothalamic neurons progressively shorten with age in rats, correlating with age-dependent metabolic decline and increased adiposity. This "age-related ciliopathy" is promoted by overnutrition-induced upregulation of leptin-melanocortin signaling and inhibited or reversed by dietary restriction or the knockdown of ciliogenesis-associated kinase 1 (CILK1). Forced shortening of MC4R-bearing cilia in hypothalamic neurons by genetic approaches impaired neuronal sensitivity to melanocortin and resulted in decreased brown fat thermogenesis and energy expenditure and increased appetite, finally developing obesity and leptin resistance. Therefore, despite its acute anti-obesity effect, chronic leptin-melanocortin signaling increases susceptibility to obesity by promoting the age-related shortening of MC4R-bearing cilia. This study provides a crucial mechanism for age-related obesity, which increases the risk of metabolic syndrome.

The findings from previous epidemiological studies of the association between regional body fat and depressive symptoms have been unclear. We aimed to determine the association between the body fat in different regions and depressive symptoms based on data from the National Health and Nutrition Examination Survey (NHANES).

This study included 3393 participants aged ≥ 20 years from the NHANES performed during 2011-2018. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The fat mass (FM) was measured in different regions using dual-energy X-ray absorptiometry to determine the total FM, trunk FM, arm FM, and leg FM. The FM index (FMI) was obtained by dividing the FM in kilograms by the square of the body height in meters. Weighted data were calculated in accordance with analytical guidelines. Linear logistic regression models were used to quantify the association between regional FMI and depressive symptoms. Univariate and stratified analyses were also performed.

The participants in this study comprised 2066 males and 1327 females. There were 404 (11.91%) participants with depressive symptoms, who were aged 40.89 ± 11.74 years and had a body mass index of 30.07 ± 7.82 kg/m². A significant association was found between total FMI and depressive symptoms. In the fully adjusted multivariate regression model, a higher total FMI (odds ratio = 2.18, 95% confidence interval [CI] = 1.08-4.39) was related to a higher risk of depressive symptoms, while increased total FMI (β = 1.55, 95% CI = 0.65-2.44, p = 0.001), trunk FMI (β = 0.57, 95% CI = 0.04-1.10, p = 0.036), and arm FMI (β = 0.96, 95% CI = 0.33-1.59, p = 0.004) were significantly associated with PHQ-9 (Patient Health Questionnaire-9) scores, whereas the leg FMI was not (p = 0.102). The weighted association between total FMI and depressive symptoms did not differ significantly between most of the subpopulations (all p values for interaction > 0.05). The risk of having depression was higher in individuals who were non-Hispanic Whites, smokers, drinkers, obese, and had diabetes and thyroid problems (p < 0.05).

These findings suggest that the population with a higher regional FMI is more likely to have depressive symptoms, especially in those who also have an increased total FMI. The association is more pronounced in individuals who are smokers, drinkers, obese, and have diabetes and thyroid problems.

In Abidjan, Côte d'Ivoire's largest city, obesity rates among women are increasing, posing a major health challenge, especially for the working generation. Merchants represent 64.3% of working women and are a typical occupation for women with low- and middle-income. Health literacy is used to prevent and overcome chronic diseases and can be used as anti-obesity measures.

The aim of this study was to examine the relationship between obesity, health literacy, and weight perception among women merchants in Abidjan.

In this cross-sectional study, we conducted a complete enumeration survey among women merchants in a market in Abidjan from December 2020 to December 2021. In addition to anthropometric measurements, structured face-to-face interviews were conducted. The participants were asked about their weight perception, weight management behaviors, and sociodemographic attributes. They also responded to the Health Literacy Questionnaire (HLQ). Data were tabulated using descriptive statistics, and multiple logistic regression analysis was performed to examine obesity's association with HLQ scales, weight perception, and weight management behaviors.

Of the 873 participants, 259 (29.7%) were obese; 82% of them underestimated their weight. Obesity was associated with a higher rate of HLQ1 (Feeling understood and supported by health care providers) (odds ratio [OR] = 2.926, confidence interval [CI]:1.450-5.901, p = .03), a lower score of HLQ3 (Actively managing my health) (OR = 0.343, CI:0.165-0.716, p = 0.004), a lower rate of accurate weight perception (OR = 0.145, CI: 0.093-0.224, p < .001), and a lower rate of eating at least three meals per day (OR = 0.401, CI:0.260-0.617, p < .001).

Findings from this study of Abidjan women merchants include obese participants' lack of a proactive attitude toward personal health management, and the association of factors such as inaccurate weight perception and eating fewer than three meals per day with obesity. These finding have important implications for future anti-obesity measures. [HLRP: Health Literacy Research and Practice. 2024;8(2):e102-e112.].

Recent research suggests a possible association between midlife obesity and an increased risk of dementia in later life. However, the underlying mechanisms remain unclear. Little is known about the relationship between body mass index (BMI) and hippocampal subfield atrophy. In this study, we aimed to explore the associations between BMI and hippocampal subfield volumes and cognitive function in non-demented Chinese older adults. Hippocampal volumes were assessed using structural magnetic resonance imaging. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A total of 66 participants were included in the final analysis, with 35 females and 31 males. We observed a significant correlation between BMI and the hippocampal fissure volume in older females. In addition, there was a negative association between BMI and the RBANS total scale score, the coding score, and the story recall score, whereas no significant correlations were observed in older males. In conclusion, our findings revealed sex-specific associations between BMI and hippocampal subfield volumes and cognitive performance, providing valuable insights into the development of effective interventions for the early prevention of cognitive decline.

Studies have shown that Caveolin gene polymorphisms (CAV-1) are involved in chronic diseases, such as metabolic syndrome. Moreover, the dietary insulin index (DII) and dietary insulin load (DIL) have been shown to potentially elicit favorable effects on cardiovascular disease (CVD) risk. Therefore, this study sought to investigate the effect of DII DIL and CAV-1 interaction on CVD risk factors.

This cross-sectional study consisted of 333 overweight and obese women aged 18-48 years. Dietary intakes, DII, and DIL were evaluated using the 147-item food frequency questionnaire (FFQ). Serum profiles were measured by standard protocols. The CAV-1 rs 3,807,992 and anthropometric data were measured by the PCR-RFLP method and bioelectrical impedance analysis (BIA), respectively. Participants were also divided into three groups based on DII, DIL score, and rs3807992 genotype.

This comparative cross-sectional study was conducted on 333 women classified as overweight or obese. Participants with A allele for the caveolin genotype and higher DII score showed significant interactions with high-density lipoprotein (HDL) (P for AA = 0.006 and P for AG = 0.019) and CRI-I (P for AA < 0.001 and P for AG = 0.024). In participants with AA genotype and greater DII score, interactions were observed in weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, CRI-II, fat-free mass (FFM), and skeletal muscle mass (SMM) (P < 0.079). Those with higher DIL scores and AA genotype had higher weight (P = 0.033), FFM (P = 0.022), and SMM (P = 0.024). In addition, DIL interactions for waist/hip ratio (WHR), waist circumference (WC), triglyceride (TG), CRI-I, and body fat mass (BFM) among individuals with AA genotype, while an HDL interaction was observed in individuals with AG and AA (P < 0.066).

The findings of the present study indicate that people who carry the caveolin rs3807992 (A) allele and have greater DII and DIL scores are at higher risk for several cardiovascular disease and metabolic syndrome biomarkers. These results highlight that diet, gene variants, and their interaction, should be considered in the risk evaluation of developing CVD.

Obesity represents an important public health concern, being one of the leading causes of death worldwide. It is a multifactorial disease with many underlying intertwined causes, including genetic, environmental and behavioral factors. Notably, metabolism-disrupting chemicals (MDCs) can alter the set point control of metabolism, affecting the development and function of the adipose tissue. Epidemiological studies have reported associations between human exposure to MDCs and several altered metabolic endpoints. It is also noteworthy that sex and gender represent important risk factors in the development of obesity. Different sex-related biological and physiological characteristics influence individual susceptibility, whereas gender represents a critical component in determining the different exposure scenarios. Although some advancements in the treatment of obesity have been achieved in preclinical and clinical studies, the obesity pandemic continues to increase worldwide. The present study performed a systematic review of recent studies considering the effects of MDCs on obesity, with a specific focus on sex- and gender-related responses. This review highlighted that MDCs could differently affect men and women at different stages of life even though the number of studies evaluating the association between obesity and MDC exposure in relation to sex and gender is still limited. This evidence should urge researchers to carry out studies considering sex and gender differences. This is essential for developing sex-/gender-tailored prevention strategies to improve public health policies and reduce exposure.

The goal of this study was to identify mediators in peri-lymphatic adipose tissue (PLAT) that are altered in obese versus lean Zucker rats, with focus on potential sex differences MAIN METHODS: Mesenteric PLAT was analyzed with protein and lncRNA arrays. Additional RT-PCR confirmation was performed with epididymal/ovarian fat.

MCP-1, TCK-1, Galectin-1, Galectin-3, and neuropilin-1 were elevated in PLAT from obese rats of both sexes. However, 11 additional proteins were elevated only in obese males while 24 different proteins were elevated in obese females. Profiling of lncRNAs revealed lean males have elevated levels of NEAT1, MALAT1 and GAS5 compared to lean females. NEAT1, MALAT1, and GAS5 were significantly reduced with obesity in males but not in females. Another lncRNA, HOTAIR, was higher in lean females compared to males, and its levels in females were reduced with obesity. Obese rats of both sexes had similar histologic findings of mesenteric macrophage crown-like structures and hepatocyte fat accumulation.

While obese male and female Zucker rats both have increased inflammation, they have distinct signals. Future studies of the proteome and lncRNA landscape of obese males vs. females in various animal models and in human subjects are warranted to better guide development of therapeutics for obesity-induced inflammation.

The prevalence of obesity is increasing among men, and this population remains under-represented in lifestyle and weight management interventions. The current study aims to explore the experiences of men living with obesity (body fat ≥25 %) toward a 12-week supervised online exercise platform. Ten men were interviewed for this qualitative study. Semi-structured, open-ended phone interviews were conducted, and the transcripts were thematically coded using the qualitative data analysis Nvivo QSR software package. The research findings are illustrated using quotes from participants. The results were organized into two main themes: those that removed barriers to exercise and those that improved the enablers of exercise. Eliminating barriers included not purchasing specialized equipment or travelling to a gym facility. The enablers to their success with the program included the structured format of the circuit program and having supervised sessions. By removing barriers and enhancing enablers, the 12-week online exercise circuit program increased compliance to and success of the exercise program for men living with obesity. Future research should explore the long-term effects of an online program for men living with obesity and its appeal beyond COVID-19.

Dementia is a clinical syndrome characterized by progressive impairment of cognitive and functional abilities. As currently applied treatments for dementia can only delay the progression of dementia and cannot fundamentally cure it, much attention is being paid to reducing its incidence by preventing the associated risk factors. Cardiovascular and metabolic diseases are well-known risk factors for dementia, and many studies have attempted to prevent dementia by treating these risk factors. Growing evidence suggests that sex-based factors may play an important role in the pathogenesis of dementia. Therefore, a deeper understanding of the differences in the effects of drugs based on sex may help improve their effectiveness. In this study, we reviewed sex differences in the impact of therapeutics targeting risk factors for dementia, such as cardiovascular and metabolic diseases, to prevent the incidence and/or progression of dementia.

Colorectal cancer ranks third in global cancer prevalence and stands as the second leading cause of cancer-related mortalities. With obesity recognized as a pivotal risk factor for colorectal cancer, the potential protective role of bariatric surgery, especially laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy, has garnered attention.

To investigate the Roux-en-Y gastric bypass (RYGB) vs sleeve gastrectomy (SG) effect on colorectal cancer incidence in obese individuals.

A systematic review and meta-analysis of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Seventeen studies with a total of 12497322 patients were included. The primary outcome was the relative risk (RR) of developing colorectal cancer in obese patients who underwent weight loss surgery compared to those who did not. Secondary outcomes included determining the RR for colon and rectal cancer separately and subgroup analyses by gender and type of weight loss surgery.

The meta-analysis revealed a 54% reduction in colorectal cancer risk in morbidly obese patients who underwent bariatric surgery compared to those who did not. A significant 46% reduction in colorectal cancer risk was observed among female patients. However, no significant differences were found in the meta-analysis for various types of bariatric surgery, such as SG and RYGB.

This meta-analysis reveals weight loss surgery, regardless of type, reduces colorectal cancer risk, especially in women, as indicated by RR and hazard ratio assessments. Further validation is essential.

Obesity is a major health concern that is associated with altered gene transcription in the hypothalamus. However, the mechanisms controlling this gene expression dysregulation remain largely unknown. DNA 5-hydroxymethylation (5-hmC) is a potent transcriptional activator that is expressed at 10 times higher levels in the brain than the periphery. Despite this, no study has examined if DNA 5-hmC is altered in the brain following exposure to obesogenic diets or contributes to abnormal weight gain over time. Here, we used a rodent diet-induced obesity model in combination with quantitative molecular assays and CRISPR-dCas9 manipulations to test the role of hypothalamic DNA 5-hmC in abnormal weight gain in male and female rats. We found that males, but not females, have decreased levels of DNA 5-hmC in the hypothalamus following exposure to a high fat diet, which directly correlate with increased body weight. Short-term exposure to a high fat diet, which does not result in significant weight gain, resulted in decreased hypothalamic DNA 5-hmC levels, suggesting these changes occur prior to obesity development. Moreover, decreases in DNA 5-hmC persist even after the high fat diet is removed, though the extent of this is diet-dependent. Importantly, CRISPR-dCas9-mediated upregulation of DNA 5-hmC enzymes in the male, but not female, ventromedial nucleus of the hypothalamus significantly reduced the percentage of weight gained on the high fat diet relative to controls. These results suggest that hypothalamic DNA 5-hmC is an important sex-specific regulator of abnormal weight gain following exposure to high fat diets.

To assess the impact of longitudinal adolescent sleep duration on adult C-reactive protein (CRP), waist-to-height ratio (WtHR), and body mass index (BMI) by race.

Participants (N = 2,399; Mage = 15.7; 40.2% male; 79.2% White, 20.8% Black; Grades 7-12 at Wave I) from the Add Health database provided self-reported sleep duration in Waves I-IV. During Wave V, CRP, WtHR, and BMI were objectively measured. Trajectory analysis was performed using a group-based modeling approach. Chi-square test determined racial differences between groups. General linear models determined relationships between trajectory group, race, and group/race interaction with Wave V CRP, WtHR, and BMI.

Three sleep trajectories emerged: Group 1 "shortest" (24.4%), Group 2 "stable recommended" (67.6%), and Group 3 "varied" (8%). Black individuals and older individuals were more likely to be in Group 1 compared with Group 2. Regardless of race, individuals with patterns of sleep duration increasing to above what is recommended across waves (Group 3) had elevated CRP. Individuals with stable patterns of adequate sleep (Group 2) had lower WtHR. Black individuals with consistently stable patterns of adequate sleep duration had lower BMI compared to those with low sleep duration.

Black individuals were more likely to obtain chronically short sleep during the transition from adolescence to adulthood, highlighting a significant health disparity. Poor longitudinal sleep predicted elevated CRP and WtHR. Sleep only impacted BMI for Black individuals. This may relate to racial differences in BMI measurement.

The prevalence of obesity, a disorder linked to numerous comorbidities and metabolic complications, has recently increased dramatically worldwide and is highly prevalent in men, even at a young age. Compared to female patients, men with obesity more frequently have delayed diagnosis, higher severity of obesity, increased mortality rate, and only a minority of obese male patients are successfully treated, including with bariatric surgery. The aim of this review was to present the current state of knowledge about the clinical and therapeutic implications of obesity diagnosed in males.

Research in preclinical models indicates that estrogens are neuroprotective and positively impact cognitive aging. However, clinical data are equivocal as to the benefits of menopausal estrogen therapy to the brain and cognition. Pre-existing cardiometabolic disease may modulate mechanisms by which estrogens act, potentially reducing or reversing protections they provide against cognitive decline. In the current review we propose mechanisms by which cardiometabolic disease may alter estrogen effects, including both alterations in actions directly on brain memory systems and actions on cardiometabolic systems, which in turn impact brain memory systems. Consideration of mechanisms by which estrogen administration can exert differential effects dependent upon health phenotype is consistent with the move towards precision or personalized medicine, which aims to determine which treatment interventions will work for which individuals. Understanding effects of estrogens in both healthy and unhealthy models of aging is critical to optimizing the translational link between preclinical and clinical research.

Clinical studies on effects of marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) on lipoprotein-lipid components and glucose-insulin homeostasis have shown conflicting results, which may partly be explained by differential responses in females and males. However, we have lacked data on sexual dimorphism in the response of cardiometabolic risk markers following increased consumption of n-3 or n-6 PUFAs.

To explore sex-specific responses after n-3 (EPA + DHA) or n-6 (LA) PUFA supplementation on circulating lipoprotein subfractions, standard lipids, apolipoproteins, fatty acids in red blood cell membranes, and markers of glycemic control/insulin sensitivity among people with abdominal obesity.

This was a randomized double-blind crossover study with two 7-week intervention periods separated by a 9-week washout phase. Females (n = 16) were supplemented with 3 g/d of EPA + DHA (fish oil) or 15 g/d of LA (safflower oil), while males (n = 23) received a dose of 4 g/d of EPA + DHA or 20 g/d of LA. In fasting blood samples, we measured lipoprotein particle subclasses, standard lipids, apolipoproteins, fatty acid profiles, and markers of glycemic control/insulin sensitivity.

The between-sex difference in relative change scores was significant after n-3 for total high-density lipoproteins (females/males: -11%*/-3.3%, p = 0.036; *: significant within-sex change), high-density lipoprotein particle size (+2.1%*/-0.1%, p = 0.045), and arachidonic acid (-8.3%*/-12%*, p = 0.012), and after n-6 for total (+37%*/+2.1%, p = 0.041) and small very-low-density lipoproteins (+97%*/+14%, p = 0.021), and lipoprotein (a) (-16%*/+0.1%, p = 0.028). Circulating markers of glucose-insulin homeostasis differed significantly after n-3 for glucose (females/males: -2.1%/+3.9%*, p = 0.029), insulin (-31%*/+16%, p < 0.001), insulin C-peptide (-12%*/+13%*, p = 0.001), homeostasis model assessment of insulin resistance index 2 (-12%*/+14%*, p = 0.001) and insulin sensitivity index 2 (+14%*/-12%*, p = 0.001), and quantitative insulin sensitivity check index (+4.9%*/-3.4%*, p < 0.001).

We found sex-specific responses after high-dose n-3 (but not n-6) supplementation in circulating markers of glycemic control/insulin sensitivity, which improved in females but worsened in males. This may partly be related to the sex differences we observed in several components of the lipoprotein-lipid profile following the n-3 intervention.

https://clinicaltrials.gov/, identifier [NCT02647333].

We recently devised continuous "sex-scores" that sum up multiple quantitative traits, weighted by their respective sex-difference effect sizes, as an approach to estimating polyphenotypic "maleness/femaleness" within each binary sex. To identify the genetic architecture underlying these sex-scores, we conducted sex-specific genome-wide association studies (GWASs) in the UK Biobank cohort (females: n = 161,906; males: n = 141,980). As a control, we also conducted GWASs of sex-specific "sum-scores", simply aggregating the same traits, without weighting by sex differences. Among GWAS-identified genes, while sum-score genes were enriched for genes differentially expressed in the liver in both sexes, sex-score genes were enriched for genes differentially expressed in the cervix and across brain tissues, particularly for females. We then considered single nucleotide polymorphisms with significantly different effects (sdSNPs) between the sexes for sex-scores and sum-scores, mapping to male-dominant and female-dominant genes. Here, we identified brain-related enrichment for sex-scores, especially for male-dominant genes; these findings were present but weaker for sum-scores. Genetic correlation analyses of sex-biased diseases indicated that both sex-scores and sum-scores were associated with cardiometabolic, immune, and psychiatric disorders.

Data from NHANES 2001-2018 were used to examine the relationship between metabolism score for visceral fat (METS-VF) and asthma prevalence.

We assessed the association between METS-VF and asthma disease using multiple logistic regression analysis from the National Health and Nutrition Examination Survey (NHANES), 2001-2018, followed by subgroup analysis for sensitive populations. To determine whether METS-VF and asthma disease had a non-linear relationship, smooth curve fitting was used, and threshold effect analysis was used to verify the relationship.

Among the 36,876 participants, 4,919 self-reported having asthma. When all confounders were controlled for, a positive association was found between METS-VF and asthma prevalence (OR = 1.27, 95% CI: 1.22,1.32), and this positive association was stronger with elevated METS-VF (P for trend = 0.01). According to the smooth curve fitting analysis, METS-VF and asthma prevalence do not have a linear relationship. The double-segmented threshold effect analysis suggested a negative correlation but no statistically significant difference between METS-VF less than 5.24 and asthma prevalence (OR = 0.60, 95% CI: 0.33, 0.91). Besides, other METS-VF showed positive associations with asthma prevalence before and after the effective inflection point. According to subgroup analysis, METS-VF is associated with asthma prevalence among participants aged 40 - 59, male, Mexican American, with hypertension and diabetes, and without asthma history.

A positive correlation between METS-VF and asthma was observed and this positive correlation was non-linear, and participants with METS-VF above 5.24 should be cautious about the high risk of asthma. The relationship should be given more attention to participants who are aged 40-59 years old, male, Mexican American, have hypertension, diabetes, and who do not have a family history of asthma.

Depression is highly prevalent (6% 1-year prevalence) and is the second leading cause of disability worldwide. Available treatment options for depression are far from optimal, with response rates only around 50%. This is most likely related to a heterogeneous clinical presentation of major depression disorder (MDD), suggesting different manifestations of underlying pathophysiological mechanisms. Poorer treatment outcomes to first-line antidepressants were reported in MDD patients endorsing an "atypical" symptom profile that is characterized by preserved reactivity in mood, increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity. In recent years, evidence has emerged that immunometabolic biological dysregulation is an important underlying pathophysiological mechanism in depression, which maps more consistently to atypical features. In the last few years human microbial residents have emerged as a key influencing variable associated with immunometabolic dysregulations in depression. The microbiome plays a critical role in the training and development of key components of the host's innate and adaptive immune systems, while the immune system orchestrates the maintenance of key features of the host-microbe symbiosis. Moreover, by being a metabolically active ecosystem commensal microbes may have a huge impact on signaling pathways, involved in underlying mechanisms leading to atypical depressive symptoms. In this review, we discuss the interplay between the microbiome and immunometabolic imbalance in the context of atypical depressive symptoms. Although research in this field is in its infancy, targeting biological determinants in more homogeneous clinical presentations of MDD may offer new avenues for the development of novel therapeutic strategies for treatment-resistant depression.

This meta-analysis aimed to assess the association between the empirical dietary index for hyperinsulinemia (EDIH) and cancer mortality risk. We performed a comprehensive search across the online literature up to November 2022 databases. Then, hazard ratio (H.R.) and 95% confidence intervals (CI) were extracted. A total of 14 and seven cohort studies that reported H.R. for the risk of cancer incidence and cancer mortality respectively were included. The pooled H.R. (95% CI) of the association between EDIH and cancer incidence was 1.13 (1.05-1.23) in overall meta-analyses, 1.15 (1.08-1.22) in female subgroups, 1.27 (1.14-1.41) in digestive cancer subgroups, and 1.15 (1.07-1.24) in breast cancer subgroups. Also, the pooled H.R. (95% CI) of the association between EDIH and incidence of cancer mortality was 1.19 (1.13-1.26) in overall meta-analyses, 1.23 (1.13-1.34) in males, 1.18(1.10-1.28) in females, and 1.20 (1.13-1.27) in studies conducted on all cancers as an outcome. Our findings revealed that a higher EDIH was significantly associated with an increased risk of cancer incidence, particularly in females, digestive cancers, and breast cancer. Also, a higher EDIH score was related to a higher risk of cancer mortality overall in both male and female subgroups and with all cancers.

The common C-allele of rs13266634 (c.973C>T or p.Arg325Trp) in SLC30A8 (ZNT8) is associated with increased risk of type 2 diabetes. While previous studies have examined the correlation of the variant with insulin and glucose metabolism, the effects of this variant on insulin and lipid responses after a lipid challenge in humans remain elusive. The goal of this study was to determine whether the C-allele had an impact on an individual's risk to metabolic syndromes in U.S. adults.

We studied the genotypes of rs13266634 in 349 individuals aged between 18 and 65 y with BMI ranging from 18.5 to 45 kg/m². The subjects were evaluated for insulin, glucose, HbA1c, ghrelin, and lipid profiles before and after a high-fat mixed macronutrient tolerance test (MMTT).

We found that the effects of variants rs13266634 on glucose and lipid metabolism were sex-dimorphic, greater impact on males than on females. Insulin incremental area under the curve (AUC) after MMTT was significantly decreased in men with the CC genotype (p < 0.05). Men with the CC genotype also had the lowest fasting non-esterified fatty acid (NEFA) concentrations. On the other hand, the TT genotype was associated with a slower triglyceride removal from the circulation in men after MMTT. The reduced triglyceride removal was also observed in subjects with BMI ≥ 30 carrying either the heterozygous or homozygous T-allele. Nevertheless, the SNP had little effect on fasting or postprandial blood glucose and cholesterol concentrations.

We conclude that the CC genotype negatively affects insulin response after MMTT while the T-allele may negatively influence lipolysis during fasting and postprandial blood triglyceride removal in men and obese subjects, a novel finding in this study.

Previous work has shown that exposure to a high fat diet dysregulates the protein degradation process in the hypothalamus of male rodents. However, whether this occurs in a sex-independent manner is unknown. The objective of this study was to determine the effects of a short-term obesogenic diet on the ubiquitin-proteasome mediated protein degradation process in the hypothalamus of female rats.

We fed young adult female rats a high fat diet or standard rat chow for 7 weeks. At the end of the 7th week, animals were euthanized and hypothalamus nuclear and cytoplasmic fractions were collected. Proteasome activity and degradation-specific (K48) ubiquitin signaling were assessed. Additionally, we transfected female rats with CRISPR-dCas9-VP64 plasmids in the hypothalamus prior to exposure to the high fat diet in order to increase proteasome activity and determine the role of reduced proteasome function on weight gain from the obesogenic diet.

We found that across the diet period, females gained weight significantly faster on the high fat diet than controls and showed dynamic downregulation of proteasome activity, decreases in proteasome subunit expression and an accumulation of degradation-specific K48 polyubiquitinated proteins in the hypothalamus. Notably, while our CRISPR-dCas9 manipulation was able to selectively increase some forms of proteasome activity, it was unable to prevent diet-induced proteasome downregulation or abnormal weight gain.

Collectively, these results reveal that acute exposure to an obesogenic diet causes reductions in the protein degradation process in the hypothalamus of females.

Obesity is caused by a prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated3,4. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.

Exposure to stress early in life has been associated with adult-onset comorbidities such as chronic pain, metabolic dysregulation, obesity, and inactivity. We have established an early-life stress model using neonatal maternal separation (NMS) in mice, which displays evidence of increased body weight and adiposity, widespread mechanical allodynia, and hypothalamic-pituitary-adrenal axis dysregulation in male mice. Early-life stress and consumption of a Western-style diet contribute to the development of obesity; however, relatively few preclinical studies have been performed in female rodents, which are known to be protected against diet-induced obesity and metabolic dysfunction. In this study, we gave naïve and NMS female mice access to a high-fat/high-sucrose (HFS) diet beginning at 4 wk of age. Robust increases in body weight and fat were observed in HFS-fed NMS mice during the first 10 wk on the diet, driven partly by increased food intake. Female NMS mice on an HFS diet showed widespread mechanical hypersensitivity compared with either naïve mice on an HFS diet or NMS mice on a control diet. HFS diet-fed NMS mice also had impaired glucose tolerance and fasting hyperinsulinemia. Strikingly, female NMS mice on an HFS diet showed evidence of hepatic steatosis with increased triglyceride levels and altered glucocorticoid receptor levels and phosphorylation state. They also exhibited increased energy expenditure as observed via indirect calorimetry and expression of proinflammatory markers in perigonadal adipose. Altogether, our data suggest that early-life stress exposure increased the susceptibility of female mice to develop diet-induced metabolic dysfunction and pain-like behaviors.

Metabolic dysregulation frequently co-occurs with obesity, which has been shown to be a risk factor for lower extremity osteoarthritis (OA). We evaluated the association between metabolic syndrome (MetS), alone and in combination with obesity, and hip OA.

In two parallel cross-sectional analyses, we studied 403 women from the Study of Osteoporotic Fractures (SOF) and 2354 men from the Osteoporotic Fractures in Men (MrOS) study. We used multivariable logistic regression to evaluate associations of obesity (body mass index ≥30 kg/m2 ) and/or MetS (three of five National Cholesterol Education Program Adult Treatment Panel III criteria) with clinical hip OA, defined as a modified Croft score of 2 or more or total hip replacement, and pain or limited range of motion. Our analysis adjusted for demographics.

Approximately 3.5% of SOF women and 5.4% of MrOS men had clinical hip OA. Among women, obesity was not associated with hip OA, yet those with MetS had a 365% higher odds of hip OA (95% CI: 1.37-15.83). Among men, those who had obesity had a 115% higher odds of hip OA (95% CI: 1.39-3.32), yet MetS was not associated with hip OA. There was no interaction between MetS, obesity, and hip OA in either women or men.

In women, but not in men, MetS was associated with hip OA. In men, but not in women, obesity was associated with hip OA. These findings suggest that mechanical effects of obesity may predominate in the pathogenesis of hip OA in men, whereas metabolic effects predominate in women.