Haploinsufficiency in the PPAR{alpha} and LDL receptor genes leads to gender- and age-specific obesity and hyperinsulinemia
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621 (Japan) and Department of Nutritional Science, Nagano Prefectural College, Nagano 380-8525 (Japan)
- Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621 (Japan)
- Department of Hygiene and Medical Genetics, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621 (Japan)
- Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621 (Japan)
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621 (Japan)
- Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892 (United States)
When preparing peroxisome proliferator-activated receptor (PPAR){alpha}:low-density lipoprotein receptor (LDLR) (-/-) double knockout mice, we unexpectedly found a unique gender- and age-specific obesity in the F1 generation, PPAR{alpha} (+/-):LDLR (+/-), even in mice fed standard chow. Body weights of the male heterozygous mice increased up to about 60 g at 75 weeks of age, then decreased by about 30 g at 100 weeks of age. More than 95% of the heterozygous mice between 35- and 75-week-olds were overweight. Of interest, the obese heterozygous mice also exhibited hyperinsulinemia correlating with moderate insulin resistance. Hepatic gene expression of LDLR was lower than expected in the heterozygous mice, particularly at 50 and 75 weeks of age. In contrast, the hepatic expression of PPAR{alpha} was higher than expected in obese heterozygous mice, but decreased in non-obese older heterozygous mice. Modulated expression of these genes may be partially associated with the onset of the hyperinsulinemia.
- OSTI ID:
- 20854571
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 350, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2006.09.048; PII: S0006-291X(06)02076-6; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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