Carnitine palmitoyltransferase‐1 activity and sensitivity to malonyl‐CoA in insulin‐sensitive and in insulin‐resistant rhesus monkeys

Obese non‐diabetic (non‐DM) insulin‐resistant monkeys are characterized by low insulin activation of skeletal muscle (SM) glycogen synthase, low SM lipoprotein lipase (LPL) activity, high adipose tissue LPL activity and high SM triglyceride (TG) compared to younger leaner insulin‐sensitive monkeys. Interestingly, older calorie‐restricted (CR) monkeys that are as insulin sensitive as younger animals have higher SM‐TG and SREPB‐1 expression than young lean monkeys. In order to determine whether insulin resistance and/or calorie restriction affected SM fatty acid oxidation (FA OX) we determined SM carnitine palmitoyltransferase‐1 (CPT‐1) activity and sensitivity (IC50) of CPT to malonyl‐CoA (M‐CoA) in 4 groups (n=6 each) of adult monkeys: young lean (13% body fat (BF), 9 yrs old), non‐DM insulin‐resistant (32% BF, 17 yrs old), type 2 diabetic (DM) (30% BF, 22 yrs old) and CR (21% BF, 20 yrs old). CPT‐1 activity was lower (p<0.05) in the obese non‐DM monkeys (104±19 pmol/min·mg protein) compared to the young lean (234±62) and DM (226±48) monkeys. CR tended to have lower CPT‐1 activity (115±29) than the young lean (p=0.06) and DM (p=0.08) monkeys. IC50 was not different between the groups. There was a positive correlation between fasting plasma glucose and CPT‐1 activity in the DM monkeys (r=0.85; p<0.05). CPT‐1 activity was inversely correlated to % BF in the monkeys without DM (r=−0.49, p<0.05, n=18). We conclude that obese non‐DM insulin‐resistant monkeys have low basal SM CPT‐1 activity that may be indicative of low SM FA OX rate in these animals. Whether CPT‐1 activity and FA OX rate are dysregulated in the DM (high CPT but low FA OX) and CR (low CPT but high FA OX) monkeys remains to be determined.