Journal
MOLECULAR ENDOCRINOLOGY
Volume 23, Issue 11, Pages 1787-1798Publisher
OXFORD UNIV PRESS INC
DOI: 10.1210/me.2009-0073
Keywords
-
Categories
Funding
- National Institutes of Health [HL42630, HL077145, DK067320]
- National Science Council Taiwan [96-23-2-B-006-001]
- National Cheng Kung University Landmark Project
Ask authors/readers for more resources
Mutations and polymorphisms in PPARG have been linked to adiposity and partial lipodystrophy in humans. However, how disturbances in PPARG lead to depot-specific effects on adipose tissue, as shown by the characteristic aberrant fat distribution in patients, remains unclear. By manipulating the 3'-untranslated region of the Pparg gene, we have generated mice with peroxisome proliferator-activated receptor gamma (PPAR gamma) gene expression ranging from 25% to 100% normal. Basal levels of PPAR gamma transcripts between 50% and approximately 100% had no significant effect on body weight, fat mass, and insulin sensitivity. In contrast, mice with 25% normal PPAR gamma expression exhibited reduced body weight and total fat mass, insulin resistance, and dyslipidemia. Interestingly, fat mass was selectively reduced in perigonadal depot without significant changes in inguinal and other depots. Expression of adipogenic factor CCAAT enhancer binding protein-alpha and some other metabolic genes containing peroxisome proliferator response element were reduced in a perigonadal depot-specific fashion. This was further associated with depot-specific reduction in the expression of adipokines, increased expression of TNF alpha, and increased ectopic lipid deposition in muscles. Together, these results underscore the differential sensitivity of the individual fat depots on PPAR gamma availability as an underlying mechanism of partial lipodystrophy. (Molecular Endocrinology 23: 1787-1798, 2009)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available