Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species dependent: potent tissue-specific effects of medium-chain fatty acids

Abstract

Objective: Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action.

Research design and methods: C57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4-5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured.

Results: Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P < 0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20-50%, P < 0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet-fed controls; however; the increase in oxidative capacity was substantially greater in MCFA-fed animals (50-140% versus low-fat-fed controls, P < 0.01). The MCFA diet induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic enzymes. In rats, isocaloric feeding of MCFA or LCFA high-fat diets induced hepatic insulin resistance to a similar degree; however, insulin action was preserved at the level of low-fat diet-fed controls in muscle and adipose from MCFA-fed animals.

Conclusions: MCFAs reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance in the liver. Dietary supplementation with MCFAs may therefore be beneficial for preventing obesity and peripheral insulin resistance.

FIG. 1.

Glucose tolerance test in overnight-fasted low-fat (LF) (●), MCFA (○)-, and LCFA ()-fed mice. A: Blood glucose levels after an intraperitoneal glucose load (2 g/kg). B: Incremental areas under the curve as an indicator of glucose clearance. Data represent the means ± SE of 5–11 mice. *P < 0.01 vs. low fat; †P < 0.01 vs. low fat and MCFAs.

FIG. 2.

Oxidative enzyme activity in skeletal muscle and liver from mice fed the low-fat (LF) (■), MCFA (□), and LCFA () diets. Data represent the means ± SE of 5–6 mice. *P < 0.01 vs. low fat and LCFAs; †P < 0.01 vs. low fat.

FIG. 3.

Immunoblots for markers of mitochondrial metabolism and biogenesis in skeletal muscle and liver from mice fed the low-fat (LF), MCFA, and LCFA diets. Equal amounts of muscle lysates (10–20 μg protein) were resolved by SDS-PAGE and immunoblotted with specific antibodies for PGC-1α, CPT-1, UCP3, and mitochondrial respiratory chain subunits. Densitometric analysis (relative to low-fat controls) for n = 6 animals is presented. *P < 0.05; †P < 0.01 vs. low fat; ‡P < 0.05; §P < 0.01 vs. MCFAs.

FIG. 4.

Immunoblots for enzymes involved in lipogenesis in liver from mice fed the low-fat (LF), MCFA, and LCFA diets. Equal amounts of liver lysates (10–20 μg protein) were resolved by SDS-PAGE and immunoblotted with specific antibodies for FAS, ACC, and SCD-1.