Skeletal Muscle Adaption to 5 days of High-Fat Feeding in Humans

Skeletal muscle is highly involved in macronutrient metabolism. To maintain proper energy metabolism and physiology, skeletal muscle must adapt to nutrient supply. Thus, diet macronutrient composition is an important modulator of skeletal muscle metabolism. Evidence from rodent and human models show high-fat diets contribute to impaired insulin signaling, as well as decreased fatty acid and glucose oxidation. Utilizing proteomic analysis of metabolic proteins in humans may lead to the mechanism behind skeletal muscle adaption to macronutrient composition, potentially providing the groundwork for characterizing the etiology of high-fat feeding induced metabolic disease. The objective of this study was to compare the substrate oxidation patterns and the levels of metabolic proteins in the fasted skeletal muscle of lean, healthy males that either increased fatty acid oxidation in response to the high-fat diet, termed responders, or males that decreased fatty acid oxidation, termed non-responders. We employed a controlled feeding study design, where the participants served as their own controls. Following a 2-week control diet (30% fat, 55% carbohydrate and 15% protein), participants came to the lab fasted overnight and a muscle biopsy was taken from their vastus lateralis muscle. Participants were then placed on a 5-day high-fat diet (50% fat [45% saturated fat], 35% carbohydrate, and 15% protein). Following this diet, participants again came to the lab fasted overnight and another muscle biopsy was taken from their vastus lateralis muscle. Both the control and the high-fat diets were isocaloric to habitual diets. Muscle from the biopsies were utilized for substrate metabolism measures and mass spectrometry. We did not observe any significant differences in glucose oxidation between responders and non-responders, prior to or following the high-fat diet. Our proteomic analysis identified 81 proteins and protein subunits involved in substrate metabolism but only 6 were differentially regulated by the high-fat diet. Independent of the high-fat diet, compared to non-responders, responders contained an overall higher content of protein subunits belonging to Complex I and ATP synthase. The findings from this study suggest that adaption to high-fat feeding is individual specific and proteomic changes alone cannot explain high-fat feeding induced metabolic changes.