TY - JOUR
T1 - Evidence for increased and insulin-resistant lipolysis in skeletal muscle of high-fat-fed rats
AU - Guo, Zeng Kui
AU - Zhou, Lianzhen
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/6
Y1 - 2004/6
N2 - The metabolic and isotopic profiles of glycerol in skeletal muscle were examined using awake, fasted lean and high-fat-induced obese rats, and hyperinsulinemic-euglycemic clamp was performed to assess the effect of insulin. During the clamp, Intralipid (no heparin; Fresnius Kabi Clayton, Clayton, NC), free fatty acids, glycerol, and glucose were coinfused to maintain their respective basal plasma levels in both groups. At steady-state, [U- 14C]glycerol was infused intravenously for 120 minutes followed by muscle biopsy. The classical phenotypic characteristics of obesity, namely, reduced insulin-stimulated glucose uptake, a failure to suppress systemic lipolysis by insulin, and elevated plasma fatty acid concentration, were observed in the obese rats. Novel observations showed that in the basal state, the isotopic specific activity (S.A.) of glycerol (dpm/nmol) in gastrocnemius (0.03 v 0.12), soleus (0.05 v 0.12), and tibialis anterior (0.03 v 0.12) was significantly lower (all P < .003) in obese than in lean rats despite similar concentrations, indicating an active basal intramyocellular lipolysis. In addition, the lipolysis appeared resistant to insulin because the suppression of muscle glycerol during the clamp was 8%, 12%, and 8% in obese compared to 67%, 71%, and 63% in the lean control for gastrocnemius (P = .001), soleus (P = .007), and tibialis anterior (P = .004), respectively. The active intracellular lipolysis likely disturbs metabolic functions that may contribute to insulin resistance.
AB - The metabolic and isotopic profiles of glycerol in skeletal muscle were examined using awake, fasted lean and high-fat-induced obese rats, and hyperinsulinemic-euglycemic clamp was performed to assess the effect of insulin. During the clamp, Intralipid (no heparin; Fresnius Kabi Clayton, Clayton, NC), free fatty acids, glycerol, and glucose were coinfused to maintain their respective basal plasma levels in both groups. At steady-state, [U- 14C]glycerol was infused intravenously for 120 minutes followed by muscle biopsy. The classical phenotypic characteristics of obesity, namely, reduced insulin-stimulated glucose uptake, a failure to suppress systemic lipolysis by insulin, and elevated plasma fatty acid concentration, were observed in the obese rats. Novel observations showed that in the basal state, the isotopic specific activity (S.A.) of glycerol (dpm/nmol) in gastrocnemius (0.03 v 0.12), soleus (0.05 v 0.12), and tibialis anterior (0.03 v 0.12) was significantly lower (all P < .003) in obese than in lean rats despite similar concentrations, indicating an active basal intramyocellular lipolysis. In addition, the lipolysis appeared resistant to insulin because the suppression of muscle glycerol during the clamp was 8%, 12%, and 8% in obese compared to 67%, 71%, and 63% in the lean control for gastrocnemius (P = .001), soleus (P = .007), and tibialis anterior (P = .004), respectively. The active intracellular lipolysis likely disturbs metabolic functions that may contribute to insulin resistance.
UR - http://www.scopus.com/inward/record.url?scp=3042816313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042816313&partnerID=8YFLogxK
U2 - 10.1016/j.metabol.2003.11.029
DO - 10.1016/j.metabol.2003.11.029
M3 - Article
C2 - 15164331
AN - SCOPUS:3042816313
SN - 0026-0495
VL - 53
SP - 794
EP - 798
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 6
ER -