Relationship between visceral adiposity and intramyocellular lipid content in two rat models of insulin resistance.
High visceral adiposity and intramyocellular lipid levels (IMCL) are both associated with the development of type 2 diabetes. The relationship between visceral adiposity and IMCL levels was explored in diet- and glucocorticoid-induced models of insulin resistance. In the diet-induced model, lean and fa/fa Zucker rats were fed either normal or high-fat (HF) chow over 4 wk. Fat distribution, IMCL content in the tibialis anterior (TA) muscle (IMCL(TA)), and whole body insulin resistance were measured before and after the 4-wk period. The HF diet-induced increase in IMCL(TA) was strongly correlated with visceral fat accumulation and greater glucose intolerance in both groups. The increase in IMCL(TA) to visceral fat accumulation was threefold greater for fa/fa rats. In the glucocorticoid-induced model, insulin sensitivity was impaired with dexamethasone. In vivo adiposity and IMCL(TA) content measurements were combined with ex vivo analysis of plasma and muscle tissue. Dexamethasone treatment had minimal effects on visceral fat accumulation while increasing IMCL(TA) levels approximately 30% (P < 0.05) compared with controls. Dexamethasone increased plasma glucose by twofold and increased the saturated fatty acid content of plasma lipids [fatty acid (CH2)n/omegaCH3 ratio +15%, P < 0.05]. The lipid composition of the TA muscle was unchanged by dexamethasone treatment, indicating that the relative increase in IMCL(TA) observed in vivo resulted from a decrease in lipid oxidation. Visceral adiposity may influence IMCL accumulation in the context of dietary manipulations; however, a "causal" relationship still remains to be determined. Dexamethasone-induced insulin resistance likely operates under a different mechanism, i.e., independently of visceral adiposity.
Discovery Technologies Area, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA 02139, USA.
M
M
Korach-André
J
J
Gao
J S
JS
Gounarides
R
R
Deacon
A
A
Islam
D
D
Laurent
D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014781:Viscera
D001786:Blood Glucose; D004041:Dietary Fats; D005938:Glucocorticoids; D008055:Lipids; D003907:Dexamethasone