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Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2003 Nov 25; Vol. 100 (24), pp. 14457-62. Date of Electronic Publication: 2003 Nov 05. - Publication Year :
- 2003
-
Abstract
- Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor, which controls adipocyte differentiation. We targeted with homologous recombination the PPAR gamma 2-specific exon B, resulting in a white adipose tissue knockdown of PPAR gamma. Although homozygous (PPAR gamma hyp/hyp) mice are born with similar weight as the WT mice, the PPAR gamma hyp/hyp animals become growth retarded and develop severe lipodystrophy and hyperlipidemia. Almost half of these PPAR gamma hyp/hyp mice die before adulthood, whereas the surviving PPAR gamma hyp/hyp animals overcome the growth retardation, yet remain lipodystrophic. In contrast to most lipodystrophic models, the adult PPAR gamma hyp/hyp mice only have mild glucose intolerance and do not have a fatty liver. These metabolic consequences of the lipodystrophy are relatively benign because of the induction of a compensatory gene expression program in the muscle that enables efficient oxidation of excess lipids. The PPAR gamma hyp/hyp mice unequivocally demonstrate that PPAR gamma is the master regulator of adipogenesis in vivo and establish that lipid and glucose homeostasis can be relatively well maintained in the absence of white adipose tissue.
- Subjects :
- Adipose Tissue pathology
Animals
Female
Gene Targeting
Homozygote
Lipodystrophy genetics
Lipodystrophy pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
RNA, Messenger genetics
RNA, Messenger metabolism
Receptors, Cytoplasmic and Nuclear genetics
Receptors, Cytoplasmic and Nuclear metabolism
Transcription Factors genetics
Transcription Factors metabolism
Adipose Tissue metabolism
Lipodystrophy metabolism
Muscles metabolism
Receptors, Cytoplasmic and Nuclear deficiency
Transcription Factors deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 100
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 14603033
- Full Text :
- https://doi.org/10.1073/pnas.2336090100