Despite discrepant phenotypes, the insulin resistant (IR) and trained states have high levels of intramyocellular lipid. We hypothesize that higher muscle lipid turnover in the trained state may explain this discrepancy.
Obese, IR subjects and trained subjects were fasted overnight (Table1). To characterize muscle lipid turnover, we conducted a pulse-chase experiment using sequential [U-13C]palmitate and [9-2H]palmitate infusions (6 h each) with a 1 hour overlap to label endogenous and exogenous FFA pools. Biopsy#1 (Bx#1 -s/p 14 hr fast) was performed at the time of the overlap (last hour of the 6 h [U-13C]palmitate infusion, after 1 h of starting the [9-2H]palmitate). Bx#2 was performed at the study conclusion (last hour of the [9-2H]palmitate infusion-s/p 20 hr fast). Plasma and muscle samples were analyzed for palmitate enrichment and concentration.
Regardless of phenotype, muscle triglyceride (IMTG) synthesis at Bx#1 was not different as assessed by either [U-13C]palmitate or [9-2H]palmitate; IMTG synthesis assessed by [9-2H]palmitate was 9-fold higher than [U-13C]palmitate. At Bx#2, IMTG breakdown as assessed by [U-13C]palmitate was similar between groups, whereas [9-2H]palmitate showed IMTG synthesis in the obese, IR group and IMTG breakdown in the trained group.
IMTG synthesis was higher with recent (1 hour) FFA exposure than more prolonged (6 hour) FFA exposure supporting separate FFA pools in lipid utilization.
L.S. Chow: None. D.G. Mashek: None. M.D. Jensen: None.
National Institutes of Health (R01DK098203, UL1TR000114)