TY - JOUR
T1 - Acute hyperinsulinemia inhibits intramyocellular triglyceride synthesis in high-fat-fed obese rats
AU - Guo, Zeng Kui
AU - Zhou, Lianzhen
AU - Jensen, Michael D.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
KW - Insulin
KW - Muscle
KW - Obesity
KW - Triglycerides
UR - http://www.scopus.com/inward/record.url?scp=33845574590&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845574590&partnerID=8YFLogxK
U2 - 10.1194/jlr.M600116-JLR200
DO - 10.1194/jlr.M600116-JLR200
M3 - Article
C2 - 16966492
AN - SCOPUS:33845574590
SN - 0022-2275
VL - 47
SP - 2640
EP - 2646
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 12
ER -