Peroxisome proliferator-activated receptor-alpha deficiency protects aged mice from insulin resistance induced by high-fat diet.
OBJECTIVE
Insulin resistance is a central feature of the metabolic syndrome and progressively increases with age, resulting in excessively high incidence of type II diabetes in the elderly population. Peroxisome proliferator-activated receptor-alpha (PPARalpha) is widely expressed in insulin target tissues, including those of the liver, kidney, and muscle, where it mediates expression of genes promoting fatty acid beta-oxidation. The aim of this study was to evaluate the potential role of PPARalpha in insulin resistance in aging mice induced by a high-fat diet.


METHODS
We used male PPARalpha knockout (KO) mice and wild-type (WT) littermates that were 18 months old. Animals were fed with a high-fat diet (HFD) for 4 weeks, and metabolic parameters associated with insulin sensitivity were assessed.


RESULTS
Following HFD treatment, WT mice showed more severe insulin resistance than did mice lacking the PPARalpha gene, as assessed by both the glucose tolerance test (GTT) and insulin tolerance test (ITT). In addition, WT mice exhibited significantly higher HOMA-IR, plasma total cholesterol levels and urinary albumin-creatinine ratio but less liver weight than did PPARalpha KO mice.


CONCLUSIONS
These data suggest that PPARalpha gene deficiency may protect aged mice from developing insulin resistance and albuminuria induced by a HFD.
Cha
Dae Ryong
DR
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn. 37232-2372, USA.
Han
Jee Young
JY
Su
Dong Ming
DM
Zhang
Yahua
Y
Fan
Xuefeng
X
Breyer
Matthew D
MD
Guan
Youfei
Y
D000375:Aging; D000419:Albuminuria; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage*; D005215:Fasting / Q000097:blood; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D047493:PPAR alpha / Q000172:deficiency*
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D047493:PPAR alpha; D002784:Cholesterol; D003404:Creatinine