High-Fat Diet Augments the Effect of Alcohol on Skeletal Muscle Mitochondrial Dysfunction in Mice.

Ahmed Ismaeel,Emma Fletcher,Athanasios Z Jamurtas,Abigail Tice,Jennifer Steiner,Dimitrios Miserlis,Panagiotis Koutakis,Evlampia Papoutsi,Joseph A Laudato,Lara S Hwa

doi:10.3390/nu14051016

Abstract

Previous studies have shown that chronic heavy alcohol consumption and consumption of a high-fat (HF) diet can independently contribute to skeletal muscle oxidative stress and mitochondrial dysfunction, yet the concurrent effect of these risk factors remains unclear. We aimed to assess the effect of alcohol and different dietary compositions on mitochondrial activity and oxidative stress markers. Male and female mice were randomized to an alcohol (EtOH)-free HF diet, a HF + EtOH diet, or a low-Fat (LF) + EtOH diet for 6 weeks. At the end of the study, electron transport chain complex activity and expression as well as antioxidant activity and expression, were measured in skeletal muscles. Complex I and III activity were diminished in muscles of mice fed a HF + EtOH diet relative to the EtOH-free HF diet. Lipid peroxidation was elevated, and antioxidant activity was diminished, in muscles of mice fed a HF + EtOH diet as well. Consumption of a HF diet may exacerbate the negative effects of alcohol on skeletal muscle mitochondrial health and oxidative stress.

Highlights

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines heavy alcohol use as consumption of >3 or 4 drinks per day, or >7 or 14 drinks per week, for females and males, respectively [1]
All mice were individually housed in the Biomedical Research Facility (BRF) vivarium at Florida State University (FSU) for at least 1 week prior to the start of the experiment
Alcohol consumption across the treatment groups over the duration of the experiment were similar, irrespective of whether the data were analyzed per sex or combined (Supplemental Table S2)

Summary

Introduction

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines heavy alcohol use as consumption of >3 or 4 drinks per day, or >7 or 14 drinks per week, for females and males, respectively [1]. Chronic heavy alcohol consumption affects health via various mechanisms, including adverse effects on several organs and tissues. These effects have mostly been studied in the brain, heart, liver, and pancreas [3], skeletal muscle dysfunction, referred to as alcoholic myopathy, can occur in up to 50% of alcoholic patients [4]. High-resolution respirometry experiments show impaired respiration and increased reactive oxygen species (ROS) production in alcohol-treated myotubes and in skeletal muscle fibers from alcohol-fed mice [7]

Objectives

Methods

Results