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Originally published In Press as doi:10.1194/jlr.M600116-JLR200 on September 11, 2006

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Journal of Lipid Research, Vol. 47, 2640-2646, December 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Acute hyperinsulinemia inhibits intramyocellular triglyceride synthesis in high-fat-fed obese rats

ZengKui Guo1, Lianzhen Zhou and Michael D. Jensen

Endocrine Research Unit, Mayo Foundation, Rochester, MN 55905

Published, JLR Papers in Press, September 11, 2006.

1 To whom correspondence should be addressed. e-mail: guo.zengkui{at}mayo.edu

Hyperinsulinemia is common in obesity, but whether it plays a role in intramyocellular triglyceride (imcTG) buildup is unknown. In this study, hyperinsulinemic-euglycemic clamp experiments were performed in overnight-fasted lean and high-fat-fed obese rats, awake, to determine the effect of insulin on imcTG synthesis (incorporation of [14C]glycerol, [14C]glucose, and [3H]oleate). Insulin infusion at 25 (low insulin) and 100 (high insulin) pmol/kg/min increased plasma insulin by 5- and 16-fold, respectively, whereas plasma and intramyocellular glycerol, FFAs, triglycerides, and glucose levels were maintained at their basal levels by co-infusion of exogenous glycerol, FFAs, and triglycerides at fixed rates and glucose at varying rates. In obese rats, insulin suppressed incorporation of glycerol into the imcTG-glycerol moiety dose dependently (P < 0.01–P < 0.001) in gastrocnemius and tibialis anterior, but only the high insulin suppressed it in soleus (P < 0.05). The low insulin suppressed glucose incorporation into imcTG-glycerol in all three muscles (P = 0.01–P < 0.01). However, the low insulin did not affect (P > 0.05) and the high insulin suppressed (P < 0.05–P < 0.01) fatty acid incorporation into imcTG in all three muscles. Insulin also suppressed glycerol incorporation in lean rats (P < 0.01–P < 0.04). On the other hand, imcTG pool size was not affected by insulin (P > 0.05). These observations suggest that acute hyperinsulinemia inhibits imcTG synthesis and thus does not appear to promote imcTG accumulation via the synthetic pathway, at least in the short term.

Supplementary key words muscle • triglycerides • insulin • obesity

Abbreviations: FG, fast-twitch glycolytic; FOG, fast-twitch oxidative-glycolytic; G3P, glycerol 3-phosphate; imcTG, intramyocellular triglyceride; SA, specific activity; SO, slow-twitch oxidative


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