There and Back Again: Leptin Actions in White Adipose Tissue

Abstract

Leptin is a hormone discovered almost 30 years ago with important implications in metabolism. It is primarily produced by white adipose tissue (WAT) in proportion to the amount of fat. The discovery of leptin was a turning point for two principle reasons: on one hand, it generated promising expectations for the treatment of the obesity, and on the other, it changed the classical concept that white adipose tissue was simply an inert storage organ. Thus, adipocytes in WAT produce the majority of leptin and, although its primary role is the regulation of fat stores by controlling lipolysis and lipogenesis, this hormone also has implications in other physiological processes within WAT, such as apoptosis, browning and inflammation. Although a massive number of questions related to leptin actions have been answered, the necessity for further clarification facilitates constantly renewing interest in this hormone and its pathways. In this review, leptin actions in white adipose tissue will be summarized in the context of obesity.

Keywords: leptin; obesity; white adipose tissue.

Figure 1

Factors implicated in circulating leptin levels. Leptin is secreted mainly by white adipose tissue. Leptin levels are correlated with the amount of fat (reflecting the amount of energy stored), and with changes in caloric intake. Other factors can regulate the circulating leptin levels. Glucose, insulin, estrogens and some inflammatory cytokines (acute effect) promote leptin secretion (left); catecholamines or adrenergic agonists, thyroid hormones, androgens and inflammatory cytokines inhibit the secretion of this hormone (right). Fat mass and leptin levels are significantly affected by gender and by menopausal status, where the leptin levels can decrease; leptin levels in females are higher than in males. This sexual dimorphism is due, at least in part, to the suppressive effect of androgens on leptin [78].

Figure 2

Leptin actions in white adipose tissue. White adipose tissue (WAT) is composed of by adipocytes, among other cells types. White adipocytes are cells with capacity to store lipids in a large droplet. WAT adipose tissue is more than a reservoir, as it also serves as an endocrine organ that produce and release several adipocytokines with effects in obesity, including leptin. Leptin has several effects in WAT, in direct or indirect mechanisms. Thus, leptin can promote adipogenesis, lipolysis or browning in this tissue. Recently, leptin actions in immune system have sparked the interest in the field; briefly, this hormone stimulates the production of pro-inflammatory cytokines and it is implicated in adipose tissue macrophages (ATMs) polarization. Also, leptin stimulates the apoptotic adipocyte process, another promising area since fat loss could be achieved by decreasing the number of adipocytes through apoptosis.