Long-term high-fat-diet feeding induces skeletal muscle mitochondrial biogenesis in rats in a sex-dependent and muscle-type specific manner

Gastrocnemius and soleus muscles of male and female Wistar rats of 2 months of age fed with a high-fat-diet (HFD) or a low fat diet for 26 weeks were used. Mitochondrial biogenesis and oxidative damage markers, oxidative capacity and antioxidant defences were analyzed. Serum insulin sensitivity parameters and the levels of proteins involved in adiponectin signaling pathway were also determined.HFD feeding induced mitochondrial biogenesis in both sexes, but to a higher degree in male rats. Although HFD female rats showed greater antioxidant protection and maintained a better insulin sensitivity profile than their male counterparts, both sexes showed an impaired response to adiponectin, which was more evident in gastrocnemius muscle.We conclude that HFD rats may induce skeletal muscle mitochondrial biogenesis as an attempt to compensate the deleterious consequences of adiponectin and insulin resistance on oxidative metabolism, and that the effects of HFD feeding are sex-dependent and muscle-type specific.Insulin resistance is a major risk factor for developing type 2 diabetes, which is caused by the inability of insulin-target tissues to respond properly to insulin [1], and in whose aetiology mitochondrial dysfunction is thought to play a crucial role [2,3]. Skeletal muscle is the main tissue responsible for the insulin-stimulated disposal of glucose and is the main contributor to the development of insulin resistance in type 2 diabetes [4].Skeletal muscle is a heterogeneous tissue made up of different contractile fibre types, in which the relative importance of glycolysis and mitochondrial oxidative phosphorylation for energy production varies. Glycolytic muscles are mainly composed of fast twitch or fast glycolytic fibres and generate energy by means of anaerobic metabolic processes, whereas oxidative muscles have a high proportion of slow twitch or slow oxidative fibres, are very resistant to fatigue and obtain energy through oxidative metabolic processes [5,6]. Un