Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
diet-induced obesity | decrease | protein synthesis | - | - | may contribute to impairments | #1 |
diet-induced obesity | decrease | mitochondrial respiration | - | - | may contribute to decreased | #2 |
diet-induced obesity and insulin resistance | neutral | mitochondrial respiration | - | - | impact on mitochondrial energetics is controversial | #3 |
high-fat diet | increase | insulin resistance | C57BL/6J mice | - | induced | #4 |
pioglitazone-enriched diet | increase | insulin sensitivity | C57BL/6J mice | - | to restore | #5 |
Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial, with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin resistance was induced in C57BL/6J mice using 4 wk of a high-fat compared with a low-fat diet. For 8 additional weeks, diets were enriched with pioglitazone to restore insulin sensitivity compared with nonenriched control low-fat or high-fat diets. Skeletal muscle mitochondrial protein synthesis was measured using deuterium oxide labeling during