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.