Human leptin: from an adipocyte hormone to an endocrine mediator

Abstract

Leptin is a mainly adipocyte-secreted protein that was discovered 5 years ago. Most of the research following this discovery focused on the role of leptin in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more and more data are emerging that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function as a metabolic and neuroendocrine hormone. It is now clear that it is especially involved in glucose metabolism, as well as in normal sexual maturation and reproduction. Besides this, interactions with the hypothalamic±pituitary±adrenal, thyroid and GH axes and even with haematopoiesis and the immune system have also been described. It has been shown that leptin secretion by the adipocyte is partly regulated by other hormones, such as insulin, cortisol, and sex steroids, mainly testosterone. Also, other hormones like thyroid hormone and GH are possibly involved in leptin synthesis. Leptin itself exerts effects on different endocrine axes, mainly on the hypothalamic±pituitary±gonadal axis and on insulin metabolism, but also on the hypothalamic±pituitary±adrenal, thyroid and GH axes.Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation.

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

“…3 More recently, another trait of human obesity, that is, hyperleptinaemia, has been extensively investigated. 4,5 Leptin, the ob gene product, reduces food intake and increases energy expenditure in rodents, 5 in whom defects in the ob gene or its receptors lead to severe obesity. 4 In humans, obesity mutations in the ob gene are uncommon 4 and an expanded fat mass (FM) is associated with hyperleptinaemia and leptin resistance, 6,7 which improves with weight loss.…”

“…4,5 Leptin, the ob gene product, reduces food intake and increases energy expenditure in rodents, 5 in whom defects in the ob gene or its receptors lead to severe obesity. 4 In humans, obesity mutations in the ob gene are uncommon 4 and an expanded fat mass (FM) is associated with hyperleptinaemia and leptin resistance, 6,7 which improves with weight loss. 8 As leptin increases basal metabolic rate, several studies have investigated the relationship between leptin and thyroid hormones, with conflicting results.…”

The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

“…quently found to have inverse correlations with body mass index (BMI), waist circumference, waist-hip-ratio (WHR), amount of visceral fat as well as with serum levels of leptin, insulin and free fatty acids [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. These markers of obesity and insulin resistance also show correlations with the cardiovascular risk factors of the metabolic syndrome [1,12].…”

“…Due to these complex interrelationships it is not clear to what extent mutual interactions of direct or indirect nature exist between androgens and adipose tissue, insulin sensitivity and cardiovascular risk factors. It seems that testosterone has a diminishing effect on leptin secretion while this hormone can simultaneously induce LH production in the pituitary and suppress testicular steroidogenesis [18]. Complicating this further, concentrations of sex hormone binding globulin (SHBG) are negatively related to body fat content, which is putatively mediated by insulin [10,23,24,25].…”

Voluntary physical activity counteracts the proliferative tumor growth microenvironment created by adipose tissue via high-fat diet feeding in female rats

“…LEP is predominately produced by white adipose tissue and its level in the peripheral circulation is directly proportional to BMI (Wauters et al. 2000). LEP activates several intracellular pathways implicated in breast carcinogenesis, including the phosphoinositide‐3/Akt kinase signaling pathway (Garofalo and Surmacz 2006; Jarde et al.…”