Short-term high fat-feeding results in morphological and metabolic adaptations in the skeletal muscle of C57BL/6J mice

Abstract

The prevalence of the metabolic syndrome (MS) is rapidly increasing all over the world. Consequently, there is an urgent need for more effective intervention strategies. Both animal and human studies indicate that lipid oversupply to skeletal muscle can result in insulin resistance, which is one of the characteristics of the MS. C57BL/6J mice were fed a low-fat (10 kcal%) palm oil diet or a high-fat (45 kcal%; HF) palm oil diet for 3 or 28 days. By combining transcriptomics with protein and lipid analyses we aimed to better understand the molecular events underlying the early onset of the MS. Short-term HF feeding led to altered expression levels of genes involved in a variety of biological processes including morphogenesis, energy metabolism, lipogenesis, and immune function. Protein analysis showed increased levels of the myosin heavy chain, slow fiber type protein, and the complexes I, II, III, IV, and V of the oxidative phosphorylation. Furthermore, we observed that the main mitochondrial membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, contained more saturated fatty acids. Altogether, these results point to a morphological as well as a metabolic adaptation by promoting a more oxidative fiber type. We hypothesize that after this early positive adaptation, a continued transcriptional downregulation of genes involved in oxidative phosphorylation will result in decreased oxidative capacity at a later stage. Together with increased saturation of phospholipids of the mitochondrial membrane this can result in decreased mitochondrial function, which is a hallmark observed in insulin resistance and Type 2 diabetes.

Morphological changes in the fast vs slow fiber profiles of the urethras of diabetic pregnant rats

“…Our finding of an increased number of type I (slow-type) fibers could be related to the abundant availability of lipids. 21 Changes in a muscle's fiber composition are often associated with glucose metabolism, diabetes and obesity. 22 Since muscle is an important site for glucose uptake, reduced muscle mass and changes in a muscle's fiber type composition may directly impair acute glucose utilization.…”

Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

“…The results obtained in these animal models are mostly in agreement with those obtained in human studies. The most used protocol to induce insulin resistance is overfeeding with high-fat/high-sugar diets in rats (Chanseaume et al 2006, Gomes et al 2012, Crescenzo et al 2013, Warren et al 2014 or 233:1 in mice (de Wilde et al 2008, Shelley et al 2009, Yuzefovych et al 2013, however, models of genetic obesity were also used (Holmström et al 2012). However, other observations report discrepant results, showing that high-fat feeding in rats was associated with no variation (Atgié et al 1993, De Feyter et al 2008a or even a higher mitochondrial capacity (Hancock et al 2008), and IR could be related to incomplete intramitochondrial β-oxidation (Koves et al 2008).…”

The nutrigenomic investigation of C57BL/6N mice fed a short-term high-fat diet highlights early changes in clock genes expression

“…Most studies were based on long-term HF feeding treatments; however, also short-term effects should be evaluated to understand which are the first ''alarm bells'' for the development of a pre-disease condition, the so-called metabolic syndrome (de Wilde et al 2008;Sasaki et al 2010;Isken et al 2010). This syndrome has attracted much attention, because it seems to be caused by an excess of nutrients (Kimokoti and Brown 2011).…”