Regulation of hepatic PPAR{gamma}2 and lipogenic gene expression by melanocortin
- Department of Physiology, University of Manitoba, 730 William Avenue, Winnipeg, MB, R3E 3J7 (Canada)
- Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, R3E 3J7 (Canada)
The central melanocortin system regulates hepatic lipid metabolism. Hepatic lipogenic gene expression is regulated by transcription factors including sterol regulatory element-binding protein 1c (SREBP-1c), carbohydrate responsive element-binding protein (ChREBP), and peroxisome proliferator-activated receptor {gamma}2 (PPAR{gamma}2). However, it is unclear if central melanocortin signaling regulates hepatic lipogenic gene expression through the activation of these transcription factors. To delineate the molecular mechanisms by which the melanocortin system regulates hepatic lipid metabolism, we examined the effect of intracerebroventricular injection of SHU9119, a melanocortin receptor antagonist, on hepatic expression levels of genes involved in lipid metabolism in mice. SHU9119 treatment increased hepatic triglyceride content and mRNA levels of lipogenic genes, SREBP-1c, and PPAR{gamma}2, whereas it did not cause any changes in hepatic ChREBP mRNA levels. These findings suggest that reduced central melanocortin signaling increases hepatic lipid deposition by stimulating hepatic lipogenic gene expression at least partly through the activation of SREBP-1c and PPAR{gamma}2.
- OSTI ID:
- 21217102
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 376, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.08.162; PII: S0006-291X(08)01729-4; Copyright (c) 2008 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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