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

Eugenia Morselli, Esther Fuente-Martin, Brian Finan, Min Kim, Aaron Frank, Cristina Garcia-Caceres, Carlos Rodriguez Navas, Ruth Gordillo, Michael Neinast, Sarada P. Kalainayakan, Dan L. Li, Yuanqing Gao, Chun Xia Yi, Lisa Hahner, Biff F. Palmer, Matthias H. Tschöp, Deborah J. Clegg

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

High-fat diets (HFDs) lead to obesityand 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,wedemonstrate 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, promotinginflammation and decrements in myocardial function in a sex-specific way.

Original languageEnglish (US)
Pages (from-to)633-645
Number of pages13
JournalCell Reports
Volume9
Issue number2
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Morselli, E., Fuente-Martin, E., Finan, B., Kim, M., Frank, A., Garcia-Caceres, C., Navas, C. R., Gordillo, R., Neinast, M., Kalainayakan, S. P., Li, D. L., Gao, Y., Yi, C. X., Hahner, L., Palmer, B. F., Tschöp, M. H., & Clegg, D. J. (2014). Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα. Cell Reports, 9(2), 633-645. https://doi.org/10.1016/j.celrep.2014.09.025