Leptin is a hormone primarily produced by the adipose tissue in proportion to the size of fat stores, with a primary function in the control of lipid reserves. Besides adipose tissue, leptin is also produced by other tissues, such as the stomach, placenta, and mammary gland. Altogether, leptin exerts a broad spectrum of short, medium, and long-term regulatory actions at the central and peripheral levels, including metabolic programming effects that condition the proper development and function of the adipose organ, which are relevant for its main role in energy homeostasis. Comprehending how leptin regulates adipose tissue may provide important clues to understand the pathophysiology of obesity and related diseases, such as type 2 diabetes, as well as its prevention and treatment. This review focuses on the physiological and long-lasting regulatory effects of leptin on adipose tissue, the mechanisms and pathways involved, its main outcomes on whole-body physiological homeostasis, and its consequences on chronic diseases.

A main challenge in nutritional studies is the valid and reliable assessment of food intake, as well as its effects on the body. Generally, food intake measurement is based on self-reported dietary intake questionnaires, which have inherent limitations. They can be overcome by the use of biomarkers, capable of objectively assessing food consumption without the bias of self-reported dietary assessment. Another major goal is to determine the biological effects of foods and their impact on health. Systems analysis of dynamic responses may help to identify biomarkers indicative of intake and effects on the body at the same time, possibly in relation to individuals’ health/disease states. Such biomarkers could be used to quantify intake and validate intake questionnaires, analyse physiological or pathological responses to certain food components or diets, identify persons with specific dietary deficiency, provide information on inter-individual variations or help to formulate personalized dietary recommendations to achieve optimal health for particular phenotypes, currently referred as “precision nutrition.” In this regard, holistic approaches using global analysis methods (omics approaches), capable of gathering high amounts of data, appear to be very useful to identify new biomarkers and to enhance our understanding of the role of food in health and disease.

Previous studies suggest that sex hormones could be responsible, at least in part, for the gender-dependent thermogenesis found in the adrenergic control of brown adipose tissue (BAT) under control conditions and in response to diet and cold. Catecholamines, as well as several hormones, including sex hormones, may alter the function or expression of different adrenoceptor subtypes in brown adipocytes in vivo, and a confirmation could be provided by in vitro experiments. Therefore, the effect of testosterone, 17 beta-estradiol, progesterone, and norepinephrine (NE) on adrenergic receptor (AR) gene expression (alpha 2A-, beta 1-, -, and beta 3-AR) and lipolytic activity was investigated in differentiated brown adipocytes in culture. We report that the expression of each AR subtype gene was distinctively regulated by NE and sex hormones in brown adipocytes. Testosterone-treated cells had lower lipolytic activity and increased expression of antilipolytic receptors alpha 2A-AR. Both 17 beta-estradiol and progesterone decreased alpha 2A-AR expression and alpha 2A/beta 3-AR protein ratio, but progesterone had higher potency than 17 beta-estradiol, increasing beta-AR levels, mainly beta 3-AR expression, and enhancing lipolysis stimulated by NE. In conclusion, our results support the idea that male and female sex hormones, as a part of the hormonal environment of BAT, have direct and opposite effects on the AR balance and lipolytic activity, and they might play a role in the gender dimorphism for the recruitment process in BAT.

Hypothalamus is crucial in the control of energy intake and expenditure in mammals, presenting two interconnected populations of neurons producing orexigenic NPY/AgRP (neuropeptide Y; agouti related peptide) and anorexigenic POMC/CART (pro-opiomelanocortin; cocaine and amphetamine regulated transcript) neuropeptides. We aimed to shed more light on the response and sensitivity in the production of these neuropeptides to face nutritional changes, particularly food deprivation, and on the signals that regulate them. Male Wistar rats were fasted for 0, 4, 8 and 24h and refed for 3h after 8h fasting. mRNA levels of gastric and adipose tissue (retroperitoneal, mesenteric and inguinal) leptin, and of hypothalamic NPY, AgRP, POMC, CART, leptin receptor, SOCS3 (suppressor of cytokine signaling 3) and insulin receptor were analyzed. Gastric and circulating leptin, and circulating insulin, glucose and ghrelin were also determined. The only neuropeptide mRNAs that responded (increasing) to the short-term periods of fasting used were those of NPY (transiently) and AgRP, and these changes were accompanied by an increase in leptin receptor mRNA levels and by a decrease in adipose and gastric leptin expression and in the circulating levels of leptin, insulin and glucose, but without changes in circulating ghrelin. The elevation in AgRP and leptin receptor mRNA levels and the drop in circulating leptin were not reverted with refeeding. It is suggested that the induction of expression of the orexigenic molecules in NPY/AgRP neurons is an early event upon fasting, related with changes in leptin, insulin and glucose levels, but with the role of leptin signaling in particular.