Peroxisome proliferator-activated receptor-alpha deficiency does not alter insulin sensitivity in mice maintained on regular or high-fat diet: hyperinsulinemic-euglycemic clamp studies.

Abstract

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.

• Authors: Martin Haluzik, Oksana Gavrilova, Derek LeRoith
• Journal: Endocrinology (Endocrinology) Vol. 145 Issue 4 Pg. 1662-7 (Apr 2004) ISSN: 0013-7227 [Print] United States
• PMID: 14670996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Dietary Fats
• Insulin
• Intercellular Signaling Peptides and Proteins
• Proteins
• Receptors, Cytoplasmic and Nuclear
• Transcription Factors
• Glucose

Topics

• Adiponectin
• Adipose Tissue (metabolism)
• Adipose Tissue, Brown (metabolism)
• Animals
• Dietary Fats (administration & dosage)
• Glucose (metabolism)
• Glucose Clamp Technique
• Insulin (blood)
• Insulin Resistance (physiology)
• Intercellular Signaling Peptides and Proteins
• Liver (metabolism)
• Male
• Mice
• Mice, Knockout
• Muscles (metabolism)
• Proteins (metabolism)
• Receptors, Cytoplasmic and Nuclear (deficiency)
• Transcription Factors (deficiency)
• Weight Gain (drug effects)