• Aquaporins
• oil body
• oleosin
• polyamine depletion
• salt stress

• metabolic syndrome
• nutraceutical
• obesity
• polyamine
• type 2 diabetes

• Humans
• Metabolic Syndrome/metabolism
• Diabetes Mellitus, Type 2/metabolism
• Obesity/metabolism
• Microbiota
• Probiotics/therapeutic use

• R01 AR078414 NIAMS NIH HHS
• R01 MH125103 NIMH NIH HHS
• T90 DE021985 NIDCR NIH HHS

Despite overt insulin resistance, adipocytes of genetically obese Zucker rats accumulate the excess of calorie intake in the form of lipids.

To investigate whether factors can replace or reinforce insulin lipogenic action by exploring glucose uptake activation by hydrogen peroxide, since it is produced by monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) in adipocytes.

³H-2-deoxyglucose uptake (2-DG) was determined in adipocytes from obese and lean rats in response to insulin or MAO and SSAO substrates such as tyramine and benzylamine. ¹⁴C-tyramine oxidation and binding of imidazolinic radioligands [³H-Idazoxan, ³H-(2-benzofuranyl)-2-imidazoline] were studied in adipocytes, the liver, and muscle. The influence of in vivo administration of tyramine + vanadium on glucose handling was assessed in lean and obese rats.

2-DG uptake and lipogenesis stimulation by insulin were dampened in adipocytes from obese rats, when compared to their lean littermates. Tyramine and benzylamine activation of hexose uptake was vanadate-dependent and was also limited, while MAO was increased and SSAO decreased. These changes were adipocyte-specific and accompanied by a greater number of imidazoline I₂ binding sites in the obese rat, when compared to the lean. In vitro, tyramine precluded the binding to I₂ sites, while in vivo, its administration together with vanadium lowered fasting plasma levels of glucose and triacylglycerols in obese rats.

The adipocytes from obese Zucker rats exhibit increased MAO activity and imidazoline binding site number. However, probably as a consequence of SSAO down-regulation, the glucose transport stimulation by tyramine is decreased as much as that of insulin in these insulin-resistant adipocytes. The adipocyte amine oxidases deserve more studies with respect to their putative contribution to the management of glucose and lipid handling.

• Obesity
• Adipocyte
• Amine oxidases
• Imidazoline binding sites
• Creatine kinase B
• Idazoxan
• Lipogenesis
• Hydrogen peroxide
• Glucose uptake

• Cancer
• Cell proliferation
• Diet
• Diseases
• Immune system
• Metabolism
• Nervous system
• Polyamines

• Alkyl and Aryl Transferases/genetics
• Alkyl and Aryl Transferases/metabolism
• Animals
• Carboxy-Lyases/genetics
• Carboxy-Lyases/metabolism
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Fertility/physiology
• Gastrointestinal Diseases/genetics
• Gastrointestinal Diseases/metabolism
• Gastrointestinal Diseases/physiopathology
• Gene Expression Regulation
• Humans
• Hydrolases/genetics
• Hydrolases/metabolism
• Mammals
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/physiopathology
• Neurodegenerative Diseases/genetics
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/physiopathology
• Oxidoreductases Acting on CH-NH Group Donors/genetics
• Oxidoreductases Acting on CH-NH Group Donors/metabolism
• Polyamines/administration & dosage
• Polyamines/metabolism
• Polyamines/pharmacology

• BIO-267 Junta de Andalucía
• P12-CTS-1507 Junta de Andalucía
• BIO2014-56092-R Ministerio de Economía, Industria y Competitividad, Gobierno de España

The polyamines putrescine, spermidine, and spermine are widely distributed polycationic compounds essential for cellular functions. Intracellular polyamine pools are tightly regulated by a complex regulatory mechanism involving de novo biosynthesis, catabolism, and transport across the plasma membrane. In mammals, both the production of polyamines and their uptake from the extracellular space are controlled by a set of proteins named antizymes and antizyme inhibitors. Dysregulation of polyamine levels has been implicated in a variety of human pathologies, especially cancer. Additionally, decreases in the intracellular and circulating polyamine levels during aging have been reported. The differences in the polyamine content existing among tissues are mainly due to the endogenous polyamine metabolism. In addition, a part of the tissue polyamines has its origin in the diet or their production by the intestinal microbiome. Emerging evidence has suggested that exogenous polyamines (either orally administrated or synthetized by the gut microbiota) are able to induce longevity in mice, and that spermidine supplementation exerts cardioprotective effects in animal models. Furthermore, the administration of either spermidine or spermine has been shown to be effective for improving glucose homeostasis and insulin sensitivity and reducing adiposity and hepatic fat accumulation in diet-induced obesity mouse models. The exogenous addition of agmatine, a cationic molecule produced through arginine decarboxylation by bacteria and plants, also exerts significant effects on glucose metabolism in obese models, as well as cardioprotective effects. In this review, we will discuss some aspects of polyamine metabolism and transport, how diet can affect circulating and local polyamine levels, and how the modulation of either polyamine intake or polyamine production by gut microbiota can be used for potential therapeutic purposes.

• aging
• diet
• gut microbiota
• metabolism
• obesity
• polyamines

• HbA1c
• case-control
• diabetes
• insulin
• polyamines

• PI14-00696; PI17-00855 Instituto de Salud Carlos III
• PI-0096-2017 Andalusian Health Public System

• Arginase
• Arginine
• Hypertension
• Obesity

Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue (WAT) is an active endocrine organ, with a crucial influence on whole-body homeostasis. WAT dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease, and some cancers. Among the regulators of WAT physiology, the calcium-sensing receptor (CaSR) has arisen as a potential mediator of WAT dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that CaSR activation in the visceral (i.e., unhealthy) WAT is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to CaSR activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in WAT plays a key role in the development of WAT dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that CaSR may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

• CaSR
• adipocyte
• adipose tissue dysfunction
• inflammation
• obesity
• preadipocyte

• Animals
• Arginase/metabolism
• Aspartate Aminotransferases/blood
• Carbon Tetrachloride/toxicity
• Chemical and Drug Induced Liver Injury/drug therapy
• Chemical and Drug Induced Liver Injury/enzymology
• Male
• Rats
• Rats, Long-Evans
• Spermine/therapeutic use
• Triglycerides/blood

• Animals
• Arginine/administration & dosage
• Biogenic Polyamines/metabolism
• Diet
• Male
• Mice