PPAR{alpha} is a key regulator of hepatic FGF21
- Center for Endocrinology, Metabolism, and Diabetes, Department of Medicine, M63, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm (Sweden)
- Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm (Sweden)
- Division of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm (Sweden)
- Molecular Nutrition Unit, Department of Biosciences and Nutrition, NOVUM, Karolinska Institutet, Huddinge, SE-141 86 Stockholm (Sweden)
- Center for Endocrinology, Metabolism, and Diabetes, Department of Medicine, M63, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm (Sweden) and Molecular Nutrition Unit, Department of Biosciences and Nutrition, NOVUM, Karolinska Institutet, Huddinge, SE-141 86 Stockholm (Sweden)
The metabolic regulator fibroblast growth factor 21 (FGF21) has antidiabetic properties in animal models of diabetes and obesity. Using quantitative RT-PCR, we here show that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPAR{alpha}). Fasting or treatment of mice with the PPAR{alpha} agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPAR{alpha} deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPAR{alpha} levels, displayed 12-fold increased hepatic FGF21 mRNA levels. The potential importance of PPAR{alpha} for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPAR{alpha} response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPAR{alpha} in humans will be of great interest.
- OSTI ID:
- 20991506
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 360, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2007.06.068; PII: S0006-291X(07)01308-3; Copyright (c) 2007 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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