Intermittent binge-like ethanol exposure during adolescence attenuates the febrile response by reducing brown adipose tissue thermogenesis in rats.

Ethanol (EtOH) consumption is a primary health risk worldwide, which generally starts during adolescence in a binge pattern (i.e., the episodic consumption of high amounts). Binge EtOH consumption can lead to modifications of the innate and adaptive immune responses, including fever. The present study evaluated the febrile response that was induced by lipopolysaccharide (LPS) and prostaglandins E2 (PGE2) and the mechanisms of thermoregulation in adolescent rats that were exposed to EtOH in a binge-like pattern. Male Wistar rats were treated with an intraperitoneal (i.p.) injection of EtOH or saline on postnatal days (PND) 25, 26, 29, 30, 33, 34, 37, and 38. On PND 51, they received a pyrogenic challenge with LPS (i.p.) or PGE2 (intracerebroventricular) to induce a febrile response. Interscapular brown adipose tissue (BAT) mass and uncoupling protein (UCP) activity in isolated mitochondria were evaluated on PND 51. The rats were then subjected to cold challenges to analyze adaptive thermogenesis. Intermittent EtOH exposure during adolescence impaired the LPS- and PGE2-induced febrile response 12 days after the end of EtOH exposure. Ethanol exposure decreased interscapular BAT mass, oxygen consumption, and UCP activity in isolated mitochondria, resulting in an impairment in thermogenesis at 5 °C. No morphological changes in BAT were observed. These findings indicate that binge-like EtOH exposure during adolescence impairs thermoregulation by reducing BAT mass and function. This reduction may last for a prolonged period of time after the cessation of EtOH exposure and may affect both cold defenses and the febrile response during the development of infectious diseases.

Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse.

The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through ß-adrenergic receptors (AR). Here, we wished to define the role played by the ARß3 isoform in this process. This study focused on the ARß3 knockout mice (ARß3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). ARß3KO mice defend core temperature during cold exposure (4°C for 5 h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, ARß3KO mice kept on a high-fat diet (HFD; 40% fat) for 8 weeks exhibited greater susceptibility to diet-induced obesity, markedly increased epididymal adipocyte area with clear signs of inflammation. The HFD-induced glucose intolerance was similar in both groups but serum hypertriglyceridemia and hypercholesterolemia were less intense in ARß3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in ARß3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, ARß3 inactivation does not affect BAT thermogenesis but increases susceptibility to diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation.