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Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling

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posted on 2023-05-18, 10:56 authored by Fernandez-Rojo, MA, Gongora, M, Fitzsimmons, RL, Martel, N, Martin, SD, Nixon, SJ, Brooks, AJ, Ikonomopoulou, MP, Martin, S, Lo, HP, Stephen MyersStephen Myers, Restall, C, Ferguson, C, Pilch, PF, McGee, SL, Anderson, RL, Waters, MJ, Hancock, JF, Grimmond, SM, Muscat, GEO, Parton, RG
Caveolae and caveolin-1 (CAV1) have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1-/- mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1-/- mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1) hepatic lipid homeostasis and (2) nuclear hormone receptor (PPARα, FXRα, and SHP) and bile acid signaling.

History

Publication title

Cell Reports

Volume

4

Pagination

238-247

ISSN

2211-1247

Department/School

School of Nursing

Publisher

Elsevier Inc.

Place of publication

United States

Rights statement

Copyright 2013 The Authors Licenced under Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) http://creativecommons.org/licenses/by-nc-nd/3.0/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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