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Morselli, E.* ; Fuente-Martin, E. ; Finan, B. ; Kim, M.* ; Frank, A.* ; García-Cáceres, C. ; Navas, C.R.* ; Gordillo, R.* ; Neinast, M.* ; Paretzke, H.G.* ; Li, D.L.* ; Gao, Y. ; Yi, C.-X. ; Hahner, L.* ; Palmer, B.F.* ; Tschöp, M.H. ; Clegg, D.J.*

Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα.

Cell Rep. 9, 633-645 (2014)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor α (ERα) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 9, Issue: 2, Pages: 633-645 Article Number: , Supplement: ,
Publisher Cell Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)