Whole-body protein anabolic response is resistant to the action of insulin in obese women.
BACKGROUND
Obesity is associated with insulin resistance of glucose and lipid metabolism.


OBJECTIVE
We sought to determine the effects of obesity on the insulin sensitivity of protein metabolism.


METHODS
Whole-body [(13)C]leucine and [(3)H]glucose kinetics were measured in 9 lean and 10 obese women in the postabsorptive state and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp.


RESULTS
In the postabsorptive state, the leucine endogenous rate of appearance (catabolism), normalized for fat-free mass, was 11% greater and the nonoxidative rate of disappearance (synthesis) was 8% greater in the obese than in the lean women, but net balance was 29% more negative (P < 0.05). Clamp amino acid and glucose infusion rates were significantly lower in the obese women than in the lean women (0.65 +/- 0.02 compared with 0.85 +/- 0.04 and 5.7 +/- 0.3 compared with 9.1 +/- 0.5 mg x kg fat-free mass(-1) x min(-1), respectively; P < 0.0001 for both), and their rates correlated positively (r = 0.635, P = 0.005). During hyperinsulinemia, synthesis was stimulated less and net leucine balance was much lower in the obese women than in the lean women (-0.08 +/- 0.06 and 0.30 +/- 0.03 mumol x kg fat-free mass(-1) x min(-1), respectively; P < 0.0001). The percentage change in net leucine balance correlated negatively with all adiposity indexes. Plasma free fatty acids were less suppressed and the respiratory quotient was lower in the obese women than in the lean women.


CONCLUSIONS
Obese women show a blunted protein anabolic response to hyperinsulinemia that is consistent with resistance to the action of insulin on protein concurrent with that on glucose and lipid metabolism.
Chevalier
Stéphanie
S
McGill Nutrition and Food Science Centre, McGill University Health Centre-Royal Victoria Hospital, Montreal, Canada.
Marliss
Errol B
EB
Morais
José A
JA
Lamarche
Marie
M
Gougeon
Réjeanne
R
D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000097:blood; D015992:Body Mass Index; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
D000597:Amino Acids, Branched-Chain; D011506:Proteins; D005947:Glucose