Regulation of energy metabolism and mitochondrial function in skeletal muscle during lipid overfeeding in healthy men.
Study Goal
The researchers aimed to evaluate how lipid overfeeding regulates fuel partitioning and energy metabolism in skeletal muscle of healthy men.
Results Summary
Overfeeding increased body weight and fat mass, shifted substrate use toward carbohydrate oxidation, reduced NAD(+) concentration, and hyperacetylated PGC-1α, but paradoxically increased mitochondrial gene expression and respiration rates.
Population
Thirty-nine healthy male volunteers
Effective Dosage
3180 kJ/day (high-fat diet)
Duration
56 days
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
overfeeding with a high-fat diet (3180 kJ/d) | increase | body weight | healthy men | +2.6 kg | increased | #1 |
overfeeding with a high-fat diet (3180 kJ/d) | increase | fat mass | healthy men | - | increased | #2 |
overfeeding with a high-fat diet (3180 kJ/d) | increase | use of substrates as energy fuel | healthy men | toward preferential oxidation of carbohydrates instead of lipids | shifted | #3 |
overfeeding with a high-fat diet (3180 kJ/d) | decrease | pyruvate dehydrogenase kinase 4 expression | healthy men | - | reduction in | #4 |
overfeeding with a high-fat diet (3180 kJ/d) | decrease | NAD(+) concentration | healthy men | - | decreased | #5 |
overfeeding with a high-fat diet (3180 kJ/d) | decrease | deacetylase activity of the sirtuins | healthy men | - | reduced | #6 |
overfeeding with a high-fat diet (3180 kJ/d) | increase | PGC-1α | healthy men | - | hyperacetylation of | #7 |
overfeeding with a high-fat diet (3180 kJ/d) | decrease | sirtuin PGC-1α pathway | healthy men | - | reduction of the | #8 |
overfeeding with a high-fat diet (3180 kJ/d) | increase | mitochondrial gene expression | healthy men | - | increased | #9 |
overfeeding with a high-fat diet (3180 kJ/d) | increase | respiration rate | healthy men | - | higher | #10 |
CONTEXT/OBJECTIVE: The aim of this study was to evaluate the regulation of the 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/d). Energy metabolism (indirect calorimetry) was characterized in the fasting state and during a test meal before and at the end of the diet. Skeletal muscle biopsies were taken at day 0 and day 56. MAIN OUTCOME MEASURES: Change in gene expression, mitochondrial respiration, nicotinamide adenine dinucleotide (NAD(+)) content, and acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in skeletal muscle was measured. RESULTS: Overfeeding increased body weight (+2.6 kg) and fat mass concomitantly with a shift in the use of substrates as energy fuel toward 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 decreased NAD(+) concentration and reduced deacetylase activity of the sirtuins, as supported by hyperacetylation of PGC-1α after overfeeding. Interestingly, this reduction of the sirtuin 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 sirtuin-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.