King Grub
2014-04-04, 08:14
Context/Objective:
The aim of the study was to evaluate the regulation of fuel partitioning and energy metabolism in skeletal muscle during lipid overfeeding in healthy men.
Design/Participants/Intervention: Thirty-nine healthy volunteers were overfed for 56 days with a high-fat diet (3180 kJ/day). Energy metabolism (indirect calorimetry) was characterized in fasting state and during a test meal before and at the end of the diet. Skeletal muscle biopsies were taken at D0 and D56. Main outcome measures: Change in gene expression, mitochondrial respiration, NAD+ content and acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in skeletal muscle.
Results:
Overfeeding increased body weight (+2.6kg) and fat mass concomitantly with a shift in the use of substrates as energy fuel towards preferential oxidation of carbohydrates instead of lipids. Changes in lipid metabolic gene expression supported this observation, with a reduction in pyruvate dehydrogenase kinase 4 expression that could be the consequences of increased NAD+ concentration and reduced deacetylase activity of the sirtuins, as supported by hyperacetylation of PGC-1α after overfeeding. Interestingly, this reduction of SIRT1-PGC-1α pathway was associated with increased mitochondrial gene expression and higher respiration rate under these conditions.
Conclusion:
Adaptation to lipid overfeeding and regulation of fuel partitioning in human muscle appear to rely on a dissociation between the regulatory functions of the SIRT-PGC-1α pathway on fatty acid oxidation and on mitochondrial regulation. This may facilitate lipid storage during a period of positive energy balance while maintaining mitochondrial functions and oxidative capacities.
J Clin Endocrinol Metab. 2014 Mar 31. Regulation of Energy Metabolism and Mitochondrial Function in Skeletal Muscle during Lipid Overfeeding in Healthy Men.
The aim of the study was to evaluate the regulation of fuel partitioning and energy metabolism in skeletal muscle during lipid overfeeding in healthy men.
Design/Participants/Intervention: Thirty-nine healthy volunteers were overfed for 56 days with a high-fat diet (3180 kJ/day). Energy metabolism (indirect calorimetry) was characterized in fasting state and during a test meal before and at the end of the diet. Skeletal muscle biopsies were taken at D0 and D56. Main outcome measures: Change in gene expression, mitochondrial respiration, NAD+ content and acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in skeletal muscle.
Results:
Overfeeding increased body weight (+2.6kg) and fat mass concomitantly with a shift in the use of substrates as energy fuel towards preferential oxidation of carbohydrates instead of lipids. Changes in lipid metabolic gene expression supported this observation, with a reduction in pyruvate dehydrogenase kinase 4 expression that could be the consequences of increased NAD+ concentration and reduced deacetylase activity of the sirtuins, as supported by hyperacetylation of PGC-1α after overfeeding. Interestingly, this reduction of SIRT1-PGC-1α pathway was associated with increased mitochondrial gene expression and higher respiration rate under these conditions.
Conclusion:
Adaptation to lipid overfeeding and regulation of fuel partitioning in human muscle appear to rely on a dissociation between the regulatory functions of the SIRT-PGC-1α pathway on fatty acid oxidation and on mitochondrial regulation. This may facilitate lipid storage during a period of positive energy balance while maintaining mitochondrial functions and oxidative capacities.
J Clin Endocrinol Metab. 2014 Mar 31. Regulation of Energy Metabolism and Mitochondrial Function in Skeletal Muscle during Lipid Overfeeding in Healthy Men.