Protein Kinase C Epsilon Deletion in Adipose Tissue,but Not in Liver,Improves Glucose Tolerance

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A Dangerous Duo in Adipose Tissue: High-Mobility Group Box 1 Protein and Macrophages

High-mobility group box 1 (HMGB1) protein first made headlines 40 years ago as a non-histone nuclear protein that regulates gene expression. Not so long ago, it was also shown that HMGB1 has an additional surprising function. When released into the extracellular milieu, HMGB1 triggers an inflammatory response by serving as an endogenous danger signal. The pro-inflammatory role of HMGB1 is now well-established and has been associated with several diseases, including sepsis, rheumatoid arthritis, and atherosclerosis. Yet very little is known about its role in obesity, wherein adipose tissue is typified by a persistent, smoldering inflammatory response instigated by high macrophage infiltrate that potentiates the risk of obesity-associated comorbidities. This mini-review focuses on the putative causal relationship between HMGB1 and macrophage pro-inflammatory activation in pathologically altered adipose tissue associated with obesity.     

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

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 ₂) 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.