Abstract
Alcohol is a myotoxin that disrupts skeletal muscle function and metabolism, but specific metabolic alternations following a binge and the time course of recovery remain undefined. The purpose of this work was to determine the metabolic response to binge alcohol, the role of corticosterone in this response, and whether nutrient availability mediates the response. Female mice received saline (control) or alcohol (EtOH) (5 g/kg) via intraperitoneal injection at the start of the dark cycle. Whole body metabolism was assessed for 5 days. In a separate cohort, gastrocnemius muscles and liver were collected every 4 h for 48 h following intoxication. Metyrapone was administered before alcohol and gastrocnemius was collected 4 h later. Lastly, alcohol-treated mice were compared with fed or fasted controls. Alcohol disrupted whole body metabolism for multiple days. Alcohol altered the expression of genes and proteins in the gastrocnemius related to the promotion of fat oxidation (Pparα, Pparδ/β, AMPK, and Cd36) and protein breakdown (Murf1, Klf15, Bcat2). Changes to select metabolic genes in the liver did not parallel those in skeletal muscle. An alcohol-induced increase in circulating corticosterone was responsible for the initial change in protein breakdown factors but not the induction of FoxO1, Cebpβ, Pparα, and FoxO3. Alcohol led to a similar, but distinct metabolic response when compared with fasting animals. Overall, these data show that an acute alcohol binge rapidly disrupts macronutrient metabolism including sustained disruption to the metabolic gene signature of skeletal muscle in a manner similar to fasting at some time points.NEW & NOTEWORTHY Herein, we demonstrate that acute alcohol intoxication immediately alters whole body metabolism coinciding with rapid changes in the skeletal muscle macronutrient gene signature for at least 48 h postbinge and that this response diverges from hepatic effects and those of a fasted animal.