Local Muscle Microenvironment, Instead of Training Status, Affects Resting IMTG Turnover

Intramyocellular triglyceride (IMTG) level correlates with insulin resistance. Paradoxically, trained humans and obese, sedentary, insulin-resistant humans have high IMTG levels despite discrepant clinical phenotypes. We hypothesize that higher IMTG turnover in trained humans explains this paradox. Methods: Obese, insulin-resistant subjects [n=47, mean (SD), BMI:36.2 kg/m2(5.7), VO2max 25.4 ml/kg/min (5.7)] and lean trained subjects [n=15, BMI:22.2 kg/m2(1.8), VO2max 55ml/kg/min (10.1)] were fasted overnight. Two muscle biopsies (Bx) were acquired during a pulse-chase experiment using [U-13C]palmitate and [9-2H]palmitate infusions (6 h each), overlapping by 1 hour. Bx#1 was performed during the infusion overlap [last hour of 6 h [U-13C]palmitate infusion, 1 hour after starting [9-2H]palmitate. Bx#2 was performed at study conclusion [last hour of [9-2H]palmitate infusion, 6 hours after stopping [U-13C]palmitate]. Palmitate enrichment and concentration were measured. [9-2H]palmitate IMTG incorporation at Bx#1 and [U-13C] IMTG loss at Bx#2 indicated the interplay between plasma and muscle fatty acids. Results: Palmitate IMTG incorporation positively correlated between measures of IMTG turnover and negatively with insulin sensitivity. No correlation seen for VO2max/BMI. Conclusion: Muscle-level IMTG measures dictates higher resting IMTG turnover more than training related phenotype. Disclosure L.S.Chow: Research Support; Dexcom, Inc. A.Bantle: None. A.C.Alvear: None. D.G.Mashek: None. M.D.Jensen: Other Relationship; Novo Nordisk, Elsevier. Funding National Institutes of Health (R01DK098203)