Mitochondrial Acyl‐CoA synthase activity is related to intramyocellular triglyceride and oxidative capacity in lean and obese rhesus monkeys

Abstract

Acyl‐CoA synthase (ACS) plays a pivotal role in fatty acid metabolism by activating long‐chain fatty acids for either lipid synthesis or lipid oxidation. Older obese, type 2 diabetic (DM) and chronically calorie‐restricted (CR) monkeys have higher intramuscular triglyceride (IMTG) compared to younger lean monkeys. We sought to determine whether (1) obese, DM and/or CR monkeys have reduced ACS activity and (2) ACS activity is associated with IMTG and/or oxidative capacity (citrate synthase [CS]). Fasting ACS and CS activities were measured in mitochondria isolated from skeletal muscle (vastus lateralis) in 4 groups of monkeys: young lean (9 yrs, 13% body fat, n=9), obese non‐DM (17 yrs, 32% body fat, n=7), obese DM (22 yrs, 30% body fat, n=8) and CR (20 yrs, 21% body fat, n=6). ACS activity was 37% lower in the obese non‐DM (54 ± 21 pmol/min/mg protein, p<0.05) and 48% lower in the CR (45 ± 10, p<0.05) compared to the normal monkeys (86 ± 16), but only 10% lower in the DM monkeys (77 ± 16, NS). ACS activity was strongly associated with CS activity (r=0.68, p<0.0001); IMTG was inversely related to ACS activity (r=−0.58, p<0.005) and CS activity (r=−0.61, p=0.002). We conclude that low ACS activity leads to low mitochondrial oxidative capacity, resulting in high IMTG. The mechanisms for the reduced ACS activity in obese and CR monkeys and near‐normal ACS activity in the DM monkeys warrant further study.