Metabolomic analysis reveals altered skeletal muscle amino acid and fatty acid handling in obese humans

Abstract

Objective: Investigate the effects of obesity and high-fat diet (HFD) exposure on fatty acid oxidation and TCA cycle intermediates and amino acids in skeletal muscle to better characterize energy metabolism.

Methods: Plasma and skeletal muscle metabolomic profiles were measured from lean and obese males before and after a 5-day HFD in the 4 h postprandial condition.

Results: At both time points, plasma short-chain acylcarnitine species (SCAC) were higher in the obese subjects, while the amino acids glycine, histidine, methionine, and citrulline were lower in skeletal muscle of obese subjects. Skeletal muscle medium-chain acylcarnitines (MCAC) C6, C8, C10:2, C10:1, C10, and C12:1 increased in obese subjects, but decreased in lean subjects, from pre- to post-HFD. Plasma content of C10:1 was also decreased in the lean but increased in the obese subjects from pre- to post-HFD. CD36 increased from pre- to post-HFD in obese but not lean subjects.

Conclusions: Lower skeletal muscle amino acid content and accumulation of plasma SCAC in obese subjects could reflect increased anaplerosis for TCA cycle intermediates, while accumulation of MCAC suggests limitations in β-oxidation. These measures may be important markers of or contributors to dysregulated metabolism observed in skeletal muscle of obese humans.

Fig. 1

Data are skeletal muscle amino acid and TCA cycle intermediates/organic acids in lean and obese individuals, before and after a 5-day HFD. Skeletal muscle measures were taken in the post-prandial state following a single high fat meal. Measures were made for content of amino acids (A), and TCA cycle intermediates and organic acids (B). Data are mean ± SEM. Data are significant at P<0.05. # indicates significant phenotype effect and ∞ indicates significant interaction effect.

Fig. 2

Data are plasma amino acids in lean and obese individuals, before and after a 5-day HFD. Plasma measures were taken in the post-prandial state following a single high fat meal. Measures were made for content of amino acids. Data are mean ± SEM. Data are significant at P<0.05. # indicates significant phenotype effect.

Fig. 3

Data are skeletal muscle acylcarnitine species in lean and obese individuals, before and after a 5- day HFD. Skeletal muscle measures were taken in the post-prandial state following a single high fat meal. Measures were made for content of free carnitine/CoA species (A), SCAC (B), MCAC (C), and LCAC (D). Data are mean ± SEM. Data are significant at P<0.05. # indicates significant phenotype effect, f indicates significant HFD effect, and ∞ indicates significant interaction effect.

Fig. 4

Data are plasma acylcarnitine species in lean and obese individuals, before and after a 5-day HFD. Plasma measures were taken in the post-prandial state following a single high fat meal. Measures were made for content of free carnitine/CoA species (A), SCAC (B), MCAC (C), and LCAC (D). Data are mean ± SEM. Data are significant at P<0.05. # indicates significant phenotype effect, ƒ indicates significant HFD effect, and ∞ indicates significant interaction effect.

Fig. 5

Data are skeletal muscle mRNA content for genes involved in β-oxidation and mitochondrial biogenesis in lean and obese individuals, before and after a 5-day HFD. Skeletal muscle biopsy measures were taken in the post-prandial state following a single high fat meal. Data are mean ± SEM. Data are significant at P<0.05. # indicates significant phenotype effect, ∞ indicates significant interaction effect.