Lipid oxidation is reduced in obese human skeletal muscle

Abstract

The purpose of this study was to discern cellular mechanisms that contribute to the suppression of lipid oxidation in the skeletal muscle of obese individuals. Muscle was obtained from obese [body mass index (BMI), 38.3 +/- 3.1 kg/m(2)] and lean (BMI, 23.8 +/- 0.9 kg/m(2)) women, and fatty acid oxidation was studied by measuring (14)CO(2) production from (14)C-labeled fatty acids. Palmitate oxidation, which is at least partially dependent on carnitine palmitoyltransferase-1 (CPT-1) activity, was depressed (P < 0.05) by approximately 50% with obesity (6.8 +/- 2.2 vs. 13.7 +/- 1.4 nmole CO(2).g(-1).h(-1)). The CPT-1-independent event of palmitoyl carnitine oxidation was also depressed (P < 0.01) by approximately 45%. There were significant negative relationships (P < 0.05) for adiposity with palmitate (r = -0.76) and palmitoyl carnitine (r = -0.82) oxidation. Muscle CPT-1 and citrate synthase activity, an index of mitochondrial content, were also significantly (P < 0.05) reduced ( approximately 35%) with obesity. CPT-1 (r = -0.48) and citrate synthase (r = -0.65) activities were significantly (P < 0.05) related to adiposity. These data suggest that lesions at CPT-1 and post-CPT-1 events, such as mitochondrial content, contribute to the reduced reliance on fat oxidation evident in human skeletal muscle with obesity.

Intramyocellular lipid accumulation is associated with permanent relocation ex vivo and in vitro of fatty acid translocase (FAT)/CD36 in obese patients

“…Mitochondrial function is not impaired in type 2 diabetes Several studies have provided evidence of mitochondrial dysfunction in skeletal muscle of type 2 diabetic, prediabetic and obese participants [1,8,9,11,12,36]. In our study the measure of oxidative capacity and of citrate synthase activity clearly argues against mitochondrial or cellular dysfunction as a confounding variable in lipid accumulation of muscle from type 2 diabetic patients.…”

Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity?

“…Kim et al [32] showed that CS activity was significantly reduced in the vastus lateralis of obese subjects, suggesting that the low mitochondrial content in the skeletal muscle of these subjects contributed to their decrease in muscle oxidative capacity.…”

Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)γ3 results in increased oxidative capacity and glucose uptake in human primary myotubes

“…), 1 mmol/l carnitine and 12.5 mmol/l HEPES. Incubation medium was then transferred to a 24 dual-well Teflon trapping plate [37] and the reaction terminated by adding 70% perchloric acid (wt/vol.). During 1 h incubation at 25°C, 14 CO 2 was trapped in 1 mol/l sodium hydroxide and quantified by liquid scintillation counting.…”