Liver X receptors are regulators of adipocyte gene expression but not differentiation

Sarah Hummasti; Bryan A. Laffitte; Michael A. Watson; Cristin Galardi; Lily C. Chao; Lakshman Ramamurthy; John T. Moore; Peter Tontonoz

Journal of Lipid Research (Apr 2004)

Liver X receptors are regulators of adipocyte gene expression but not differentiation

Sarah Hummasti,
Bryan A. Laffitte,
Michael A. Watson,
Cristin Galardi,
Lily C. Chao,
Lakshman Ramamurthy,
John T. Moore,
Peter Tontonoz

Affiliations

Sarah Hummasti: Molecular Biology Institute, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of California, Los Angeles, CA 90095; High Thoughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709; Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709
Bryan A. Laffitte: Molecular Biology Institute, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of California, Los Angeles, CA 90095; High Thoughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709; Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709
Michael A. Watson: Molecular Biology Institute, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of California, Los Angeles, CA 90095; High Thoughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709; Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709
Cristin Galardi: Molecular Biology Institute, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of California, Los Angeles, CA 90095; High Thoughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709; Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709
Lily C. Chao: Molecular Biology Institute, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of California, Los Angeles, CA 90095; High Thoughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709; Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709
Lakshman Ramamurthy: Molecular Biology Institute, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of California, Los Angeles, CA 90095; High Thoughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709; Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709
John T. Moore: Molecular Biology Institute, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of California, Los Angeles, CA 90095; High Thoughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709; Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709
Peter Tontonoz: Molecular Biology Institute, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of California, Los Angeles, CA 90095; High Thoughput Biology, GlaxoSmithKline, Research Triangle Park, NC 27709; Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709

Journal volume & issue: Vol. 45, no. 4
pp. 616 – 625

Abstract

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The liver X receptors α and β (LXRα and LXRβ) have been shown to play important roles in lipid homeostasis in liver and macrophages, however, their function in adipose tissue is not well defined. Both LXRs are highly expressed in fat, and the expression of LXRα increases during adipogenesis. Furthermore, LXRα expression is induced by peroxisome proliferator-activated receptor γ (PPARγ), the master regulator of fat cell differentiation. Here we investigate the role of LXRs in adipocyte differentiation and gene expression and their potential crosstalk with the PPARγ pathway. We demonstrate that LXR agonists have no significant effect on the differentiation of 3T3-F442A or 3T3-L1 preadipocytes in vitro and do not alter the expression of differentiation-linked PPARγ target genes in vivo. Moreover, retroviral expression of LXRα in NIH-3T3 cells does not alter the adipogenic potential of these cells and neither augments nor inhibits the action of PPARγ. However, transcriptional profiling studies reveal that LXRs are important regulators of adipocyte gene expression. We identify the multifunction lipid carrier protein apolipoprotein D and the lipogenic protein Spot 14 as LXR responsive genes both in vitro and in vivo.Thus, although LXRs do not influence adipocyte differentiation per se, these receptors are likely to play an important role in the modulation of lipid metabolism in adipocytes.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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