Would-be-worlds of adipobiology in the exposome of globesity

The obesity epidemic has become global meriting the term of "globesity". At the heart of it lies our increasing sedentary lifestyle together with detrimental dietary habits. The genetic background, in particular, our "thrifty genes" also take part of the responsibility for this pandemia. Interestingly, mounting epidemiological evidence links obesity with increases in intrauterine influences, epigenetics, viruses, microbiota, climate changes, sleep debt, and xenobiotics including endocrine disruptors, among others. In this respect, it may be worthwhile to consider that all these factors, that conform our lifelong exposure profile or "exposome", may be partly contributing to the global obesity epidemic. Consequently, an exposomic approach underlines the need for biomonitoring of xenobiotics accumulation in human body, particularly in adipose tissue. It may be time to try to better identify these potential drivers and stimulate analysis on the impact of the "exposome" in light of the increasing overweight and obesity trends.Adipobiology 2012; 4: 107-110

Role of ghrelin gene-derived peptides in the control of energy balance and cardiometabolic homeostasis

The human GHRL gene encodes a 117-aminoacid peptide, preproghrelin that is proteolytically processed to yield two peptides: ghrelin and obestatin. Ghrelin is secreted to the bloodstream in two major forms, acylated ghrelin (with an n-octanoylation in the third serine residue) and desacyl ghrelin (the form lacking n-octanoylation). Ghrelin acylation, promoted by ghrelin O-acyltransferase (GOAT), is essential for binding to the growth hormone (GH) secretagogue receptor (GHS-R) 1a and for the main endocrine functions of acylated ghrelin, including the stimulation of GH release, induction of food intake and stimulation of adipogenesis. Although devoid of binding to GHS-R 1a, desacyl ghrelin also displays orexigenic and adipogenic actions, whereas the role of obestatin in the regulation of energy balance remains unclear. The discovery of the widespread distribution of ghrelin and its receptor in the cardiovascular system opened a new research field in the role of ghrelin in the control of blood pressure and myocardial function. Indeed, ghrelin inhibits the apoptosis of cardiomyocytes and endothelial cells, ameliorates left ventricular function and reduces fibrosis after myocardial injury in experimental models. In humans, ghrelin improves endothelial function by increasing nitric oxide (NO) bioavailability, normalizes the altered balance between endothelin-1 and NO in patients with metabolic syndrome and exerts performance-enhancing effects on myocardial function of patients with chronic heart failure. This review focuses on advances in cardiometabolic effects of ghrelin gene-derived products in rodents and humans, and the possible role of ghrelin as a therapeutic molecule for treating cardiometabolic diseases.Adipobiology 2011; 3: 21-30

Adipopharmacology of inflammation and insulin resistance

Among the rapidly expanding list of factors synthesized and released by white adipose tissue, the range of cytokines, chemokines and other signaling proteins, collectively termed adipokines, are of particular interest to better understand the pathogenesis of low-grade systemic inflammation associated with obesity. An overwhelming body of evidence further links high circulating concentrations of inflammatory biomarkers with the development of insulin resistance and the progression to type 2 diabetes mellitus. The secretory pattern of adipose tissue characteristic of obesity comprises an increase in pro-inflammatory adipokines together with a decrease in adipokines with anti-inflammatory, cardioprotective and insulin sensitizing actions. These molecules exerts local autocrine and paracrine effects on white adipose tissue physiology at the same time as having systemic effects on other organs. A number of factors derived not only from adipocytes but also from infiltrated macrophages and mast cells, which have been shown to accompany morbid adiposity, further contribute to inflammation and insulin resistance. The evolving notion of adipose tissue as an immuno-modulatory organ together with the improving knowledge of how inflammation exerts a (counter)regulatory action on glucose and lipid metabolism are opening up new therapeutic opportunities for applying anti-inflammatory strategies to counterbalance the detrimental consequences of excess adiposity and its comorbidities.Biomedical Reviews 2006; 17: 43-51

Physiology and pathophysiology of aquaporins

Aquaporins (AQPs) are water channels that facilitate a rapid transport of water, across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol. Thirteen aquaporins (AQP0-12) have been identified so far in mammalian tissues. The disruption of the genes encoding aquaporins in transgenic mice has revealed their implication in physiological and pathophysiological processes, including renal water absorption, neural function, digestion, tumor angiogenesis, and reproduction. A subset of aquaporins that transport both water and glycerol, the 'aquaglyceroporins', regulate glycerol content in epidermal, fat and other tissues, and are involved in skin hydration, fat metabolism and gluconeogenesis. Better understanding of the exact mechanisms and regulation of aquaporins might be useful for designing potential drug targets against different metabolic disorders, such as stroke, glaucoma, brain edema, cancer, diabetes and obesity.Adipobiology 2010; 2: 9-22