TE ROLE OF S100B IN MULTIPLE SCLEROSIS: FROM A BIOMARKER TO A THERAPEUTIC TARGET

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Leptin Resistance and the Neuro-Adipose Connection

Publication . Barateiro, Andreia; Mahú, Ines; Domingos, Ana I.

Obesity is a public health concern affecting both genders at all ages around the world. The worldwide prevalence of obesity is rapidly increasing and has nearly doubled between 1980 and 2016. Consequently, it places a large financial burden on the economy due to the increased morbidity and mortality, as well as the reduced quality of life and development of chronic diseases. Obesity is typically characterized by excessive amounts of the hormone leptin, a cytokine-like molecule produced in white adipose tissue (WAT) that is secreted into the systemic circulation. The circulating levels of leptin are proportional to the amount of fat and function as the afferent signal in a negative feedback loop that seeks to maintain body fat in a very narrow range of variation. Leptin has a central role in body weight homeostasis due to its inhibition of food intake inhibition and stimulation of energy expenditure. The effect of leptin on body weight is attributed to its action in a specific brain region, the hypothalamus. Hence, leptin is released by adipocytes in proportion to the size of fat depots, enters the circulation, and reaches the central nervous system by crossing the blood-brain barrier (BBB) through receptor-mediated endocytosis in which it acts mainly through the arcuate nucleus of the hypothalamus to mediate most of its actions. Specifically, leptin modulates the activity of two types of neurons to inhibit appetite, through production of anorexigenic peptides by the pro-opiomelanocortin (POMC) neurons and suppression of the orexigenic agouti-related protein (AgRP) neurons. Besides acting on the hypothalamus to suppress appetite, leptin also induces lipolysis in WAT and thermogenesis in brown adipose tissue (BAT) and browning of WAT, via the activation of the sympathetic nervous system (SNS). However, in most obese subjects, despite its high serum levels, leptin fails to perform its physiological functions and consequently fails to reduce weight. This effect has been coined as leptin resistance.

2017-03-06Journal article

Open access