PuSH - Publication Server of Helmholtz Zentrum München

Gray, S.L.* ; Nora, E.D.* ; Grosse, J.* ; Manieri, M.* ; Stöger, T. ; Medina-Gomez, G.* ; Burling, K.* ; Wattler, S.* ; Russ, A.* ; Yeo, G.S.* ; Chatterjee, V.K.* ; O'Rahilly, S.* ; Voshol, P.J.* ; Cinti, S.* ; Vidal-Puig, A.*

Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice.

Diabetes 55, 2669-2677 (2006)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Peroxisome proliferator-activated receptor (PPAR)γ is a key transcription factor facilitating fat deposition in adipose tissue through its proadipogenic and lipogenic actions. Human patients with dominant-negative mutations in PPARγ display lipodystrophy and extreme insulin resistance. For this reason it was completely unexpected that mice harboring an equivalent mutation (P465L) in PPARγ developed normal amounts of adipose tissue and were insulin sensitive. This finding raised important doubts about the interspecies translatability of PPARγ-related findings, bringing into question the relevance of other PPARγ murine models. Here, we demonstrate that when expressed on a hyperphagic ob/ob background, the P465L PPARγ mutant grossly exacerbates the insulin resistance and metabolic disturbances associated with leptin deficiency, yet reduces whole-body adiposity and adipocyte size. In mouse, coexistence of the P465L PPARγ mutation and the leptin-deficient state creates a mismatch between insufficient adipose tissue expandability and excessive energy availability, unmasking the deleterious effects of PPARγ mutations on carbohydrate metabolism and replicating the characteristic clinical symptoms observed in human patients with dominant-negative PPARγ mutations. Thus, adipose tissue expandability is identified as an important factor for the development of insulin resistance in the context of positive energy balance. © 2006 by the American Diabetes Association.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 55, Issue: 10, Pages: 2669-2677 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)