Acute physical exercise increases leptin‐induced hypothalamic extracellular signal‐regulated kinase1/2 phosphorylation and thermogenesis of obese mice

Abstract

The obesity is a result of energy imbalance and the increase in thermogenesis seems an interesting alternative for the treatment of this disease. The mechanism of energy expenditure through thermogenesis is tightly articulated in the hypothalamus by leptin. The hypothalamic extracellular signal-regulated kinase-1/2 (ERK1/2) is a key mediator of the thermoregulatory effect of leptin and mediates the sympathetic signal to the brown adipose tissue (BAT). In this context, physical exercise is one of the main interventions for the treatment of obesity. Thus, this study aimed to verify the effects of acute physical exercise on leptin-induced hypothalamic ERK1/2 phosphorylation and thermogenesis in obese mice. Here we showed that acute physical exercise reduced the fasting glucose of obese mice and increased leptin-induced hypothalamic p-ERK1/2 and uncoupling protein 1 (UCP1) content in BAT ( P < 0.05). These molecular changes are accompanied by an increased oxygen uptake (VO ) and heat production in obese exercised mice ( P< 0.05). The increased energy expenditure in the obese exercised animals occurred independently of changes in spontaneous activity. Thus, this is the first study demonstrating that acute physical exercise can increase leptin-induced hypothalamic ERK1/2 phosphorylation and energy expenditure of obese mice.

Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases

“…Animals lacking muscle ERK1/2 displayed muscle weakness with a mixture of modest fiber atrophy and loss [77]. In hypothalamus, ERK1/2 suppress appetite and promote energy expenditure in the periphery [89,91,94].…”

“…Inhibition of ERK1/2 reduces the ability of leptin to stimulate the sympathetic signal of the hypothalamus to brown adipose tissue, resulting in lower heat production [89]. Acute physical exercise also increases leptin-induced hypothalamic phospho-ERK1/2, associated with higher BAT UCP1 content and heat production in obese mice [91]. The increase in ERK1/2 phosphorylation is likely to depend on the intensity of the physical exercise.…”

Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases

“…Chronic exercise would have a similar effect on UCP-1 expression, as seen in Wistar rats [194,199], and would be accompanied by an increase in carnitine palmitoyltransferase II, the mitochondrial F1 ATP synthase α-chain, and mitochondrial malate dehydrogenase 2. In terms of cell signaling, chronic exercise increases SIRT1 expression, PGC1α, and activation of AMPK by phosphorylation (Thr172/183) in the skeletal muscles of rats [200].…”

“…Physical exercise would thus be beneficial, at least partly, by augmenting the mitochondrial uncoupling-driven thermogenesis (and thus energy expenditure). As an example, acute physical exercise leads to an increase in BAT UCP-1 protein expression in HFD-treated (High Fat Diet) Swiss mice [194] and ICR (Institute of Cancer Research) mice [195]. The importance of UCP-1 expression was illustrated in a recent study performed in Ucp1 −/− C57BL/6J female mice, showing an increased sensitivity to Western diet [172].…”

“…The importance of UCP-1 expression was illustrated in a recent study performed in Ucp1 −/− C57BL/6J female mice, showing an increased sensitivity to Western diet [172]. The acute exercise effect on thermogenesis can be explained by a potentiation of leptin-induced hypothalamic ERK1/2 phosphorylation, which stimulates BAT thermogenic function [194]. In WAT, physical exercise seems to promote the opposite effect.…”