Peroxisome proliferator-activated receptor-alpha deficiency does not alter insulin sensitivity in mice maintained on regular or high-fat diet: hyperinsulinemic-euglycemic clamp studies.
Chronic peroxisome proliferator-activated receptor (PPAR)-alpha activation improves glucose metabolism in rodent models of insulin resistance and diabetes; however, PPAR-alpha deficiency was also reported to protect against high-fat diet (HFD)-induced insulin resistance. The aim of this study was to clarify the role of PPAR-alpha in the development of insulin resistance using PPAR-alpha knockout (KO) mice and wild-type controls (WT). Both WT and PPAR-alpha KO mice on HFD gained significantly more weight relative to chow-fed groups and displayed an increase in insulin levels and a decrease in adiponectin levels. Hyperinsulinemic-euglycemic clamp performed in the nonfasting state demonstrated that HFD caused a marked reduction in whole body, muscle, and white and brown adipose tissue glucose uptake in both WT and PPAR-alpha KO mice relative to chow-fed groups. Suppression of endogenous glucose production during the clamp was markedly blunted in both WT and PPAR-alpha KO HFD-fed mice, indicating liver insulin resistance. The magnitude of HFD-induced changes in the clamp parameters of insulin sensitivity was comparable in PPAR-alpha KO and WT mice. In conclusion, these data show that PPAR-alpha deficiency does not alter insulin sensitivity in mice fed normal chow diet and does not protect against HFD-induced insulin resistance as measured by hyperinsulinemic-euglycemic clamp in nonfasted state.
Haluzik
Martin
M
Third Department of Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic. mhalu@lf1.cuni.cz
Gavrilova
Oksana
O
LeRoith
Derek
D
D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency*; D014157:Transcription Factors / Q000172:deficiency*; D015430:Weight Gain / Q000187:drug effects
D052242:Adiponectin; D004041:Dietary Fats; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D005947:Glucose