The impact of a short-term high-fat diet on mitochondrial respiration, reactive oxygen species production, and dynamics in oxidative and glycolytic skeletal muscles of young rats.

Jean-Philippe Leduc-Gaudet,Jocelyne Mercier,David E Andrich,Olivier Reynaud,François Chabot,David H St-Pierre,Gilles Gouspillou

doi:10.14814/phy2.13548

Abstract

Multiple aspects of mitochondrial function and dynamics remain poorly studied in the skeletal muscle of pediatric models in response to a short‐term high‐fat diet (HFD). This study investigated the impact of a short‐term HFD on mitochondrial function and dynamics in the oxidative soleus (SOL) and glycolytic extensor digitorum longus (EDL) muscles in young rats. Young male Wistar rats were submitted to either HFD or normal chow (NCD) diets for 14 days. Permeabilized myofibers from SOL and EDL were prepared to assess mitochondrial respiration and reactive oxygen species (ROS) production. The expression and content of protein involved in mitochondrial metabolism and dynamics (fusion/fission) were also quantified. While no effects of HFD was observed on mitochondrial respiration when classical complex I and II substrates were used, both SOL and EDL of rats submitted to a HFD displayed higher basal and ADP‐stimulated respiration rates when Malate + Palmitoyl‐L‐carnitine were used as substrates. HFD did not alter ROS production and markers of mitochondrial content. The expression of CPT1b was significantly increased in SOL and EDL of HFD rats. Although the expression of UCP3 was increased in SOL and EDL muscles from HFD rats, mitochondrial coupling efficiency was not altered. In SOL of HFD rats, the transcript levels of Mfn2 and Fis1 were significantly upregulated. The expression and content of proteins regulating mitochondrial dynamics was not modulated by HFD in the EDL. Finally, DRP1 protein content was increased by over fourfold in the SOL of HFD rats. Taken altogether, our findings show that exposing young animals to short‐term HFD results in an increased capacity of skeletal muscle mitochondria to oxidize fatty acids, without altering ROS production, coupling efficiency, and mitochondrial content. Our results also highlight that the impact of HFD on mitochondrial dynamics appears to be muscle specific.

Highlights

Obesity is one of the major risk factors for the development of metabolic disorders such as insulin resistance, type 2 diabetes Mellitus (T2DM), nonalcoholic liver disease, and atherosclerosis (Dedoussis et al 2007)
There was no significant difference in energy expenditure between both groups (Fig. 1D).No difference in the absolute and relative weights of the SOL and extensor digitorum longus (EDL) muscles was observed between high-fat diets (HFD) and NCD rats (Fig. 1E and F)
When mitochondria were treated with complex I substrates, no difference in basal and maximal mitochondrial respiration was observed between HFD and NCD groups in both SOL and EDL muscles (Fig. 2A and B)

Summary

Introduction

Obesity is one of the major risk factors for the development of metabolic disorders such as insulin resistance, type 2 diabetes Mellitus (T2DM), nonalcoholic liver disease, and atherosclerosis (Dedoussis et al 2007). The incidence of obesity is estimated at 17% (Pulgaron and Delamater 2014), whereas cases of T2DM increased by 14% between 2000 and 2008 in US children and adolescents (May et al 2012) Because of this alarming epidemiological trend, there is a critical need to determine the effects of HFD on mitochondrial function in the skeletal muscle using relevant pediatric animal models. This is further supported by the fact that mitochondrial dysfunction were reported in the skeletal muscle of insulin-resistant obese adolescents (Slattery et al 2014)

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