Increasing Dietary Fat Elicits Similar Changes in Fat Oxidation and Markers of Muscle Oxidative Capacity in Lean and Obese Humans

Abstract

In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m2, age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m2, 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity.

Twenty-Four Hour Total and Dietary Fat Oxidation in Lean, Obese and Reduced-Obese Adults with and without a Bout of Exercise

“…In a previous study, we had also observed no difference between obese and lean subjects in 24-hr RQ, fat oxidation and muscle oxidative capacity in response to a dietary intervention (low-fat vs. high-fat isocaloric diet) [35]. While studies examining short-term responses to metabolic challenges have demonstrated reduced fat oxidation in obese individuals [36]–[38], our observations that over 24-hr obese subjects can increase fat oxidation in response to a high-fat diet or a bout of exercise does not support the idea of a mitochondrial defect in fat oxidation in these people.…”

Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle

“…In contrast, overfeeding with HF/LC diet increased the activity of this pathway indicating that low carbohydrate content may be sufficient for its activation. In a recent study, Bergouignan et al [ 25 ] have demonstrated that a short-term isocaloric high fat diet enhanced deacetylation of PGC1α and phosphorylation of AMPK in skeletal muscle of lean and obese individuals. In the current study, we demonstrated This document was downloaded for personal use only.…”

Fatty acid type–specific regulation of SIRT1 does not affect insulin sensitivity in human skeletal muscle

“…Consumption of both a hypercaloric (11) and an isocaloric (12) HFD with similar proportions of saturated, mono, and polyunsaturated fatty acids (FAs) for 2–5 d led to deacetylation of peroxisome proliferator–activated receptor 7, coactivator 1α (PGC‐1α) in human skeletal muscle. The deacetylation of PGC‐1α could be due to increased activity of the type III NAD + ‐dependent deacetylase SIRT1 acting as a key upstream deacetylase of PGC‐αa (13).…”

“…To this end, SIRT1 was shown to induce mitochondrial and lipid oxidative gene expression during glucose restriction in myotubes (14). Moreover, induction of mitochondrial and FA oxidative gene transcription was observed after 2–5 d of an HFD in human skeletal muscle (12, 15). Together, these findings propose a possible role of SIRT1 in the metabolic adaptations to HFDs.…”