Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha

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

doi:https://doi.org/10.1016/j.celrep.2014.09.025

Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha

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

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Research output: Contribution to journal › Article › Academic › peer-review

150 Citations (Scopus)

Abstract

High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor alpha (ER alpha) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1 alpha regulates ER alpha 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-1 alpha and ER alpha in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1 alpha depletion with ER alpha overexpression significantly inhibited PA-induced inflammation, confirming that ER alpha is a critical determinant of the anti-inflammatory response. Physiologic relevance of ER alpha-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-1 alpha and ER alpha, promoting inflammation and decrements in myocardial function in a sex-specific way

Original language	English
Pages (from-to)	633-645
Journal	Cell reports
Volume	9
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2014.09.025
Publication status	Published - 2014

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https://doi.org/10.1016/j.celrep.2014.09.025

Cite this

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-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha. Cell reports, 9(2), 633-645. https://doi.org/10.1016/j.celrep.2014.09.025

@article{339e9838ef9a4b45bf9e26969359d140,

title = "Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha",

abstract = "High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor alpha (ER alpha) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1 alpha regulates ER alpha 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-1 alpha and ER alpha in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1 alpha depletion with ER alpha overexpression significantly inhibited PA-induced inflammation, confirming that ER alpha is a critical determinant of the anti-inflammatory response. Physiologic relevance of ER alpha-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-1 alpha and ER alpha, promoting inflammation and decrements in myocardial function in a sex-specific way",

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

year = "2014",

doi = "https://doi.org/10.1016/j.celrep.2014.09.025",

language = "English",

volume = "9",

pages = "633--645",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "2",

}

Morselli, E, Fuente-Martin, E, Finan, B, Kim, M, Frank, A, Garcia-Caceres, C, Navas, CR, Gordillo, R, Neinast, M, Kalainayakan, SP, Li, DL, Gao, Y, Yi, C-X, Hahner, L, Palmer, BF, Tschöp, MH & Clegg, DJ 2014, 'Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha', Cell reports, vol. 9, no. 2, pp. 633-645. https://doi.org/10.1016/j.celrep.2014.09.025

TY - JOUR

T1 - Hypothalamic PGC-1 alpha Protects Against High-Fat Diet Exposure by Regulating ER alpha

AU - Morselli, Eugenia

AU - Fuente-Martin, Esther

AU - Finan, Brian

AU - Kim, Min

AU - Frank, Aaron

AU - Garcia-Caceres, Cristina

AU - Navas, Carlos Rodriguez

AU - Gordillo, Ruth

AU - Neinast, Michael

AU - Kalainayakan, Sarada P.

AU - Li, Dan L.

AU - Gao, Yuanqing

AU - Yi, Chun-Xia

AU - Hahner, Lisa

AU - Palmer, Biff F.

AU - Tschöp, Matthias H.

AU - Clegg, Deborah J.

PY - 2014

Y1 - 2014

N2 - High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor alpha (ER alpha) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1 alpha regulates ER alpha 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-1 alpha and ER alpha in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1 alpha depletion with ER alpha overexpression significantly inhibited PA-induced inflammation, confirming that ER alpha is a critical determinant of the anti-inflammatory response. Physiologic relevance of ER alpha-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-1 alpha and ER alpha, promoting inflammation and decrements in myocardial function in a sex-specific way

AB - High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor alpha (ER alpha) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1 alpha regulates ER alpha 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-1 alpha and ER alpha in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1 alpha depletion with ER alpha overexpression significantly inhibited PA-induced inflammation, confirming that ER alpha is a critical determinant of the anti-inflammatory response. Physiologic relevance of ER alpha-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-1 alpha and ER alpha, promoting inflammation and decrements in myocardial function in a sex-specific way

U2 - https://doi.org/10.1016/j.celrep.2014.09.025

DO - https://doi.org/10.1016/j.celrep.2014.09.025

M3 - Article

C2 - 25373903

SN - 2211-1247

VL - 9

SP - 633

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JO - Cell reports

JF - Cell reports

IS - 2

ER -