FOSL2 promotes leptin gene expression in human and mouse adipocytes

Christiane D. Wrann, Jun Eguchi, Aline Bozec, Zhao Xu, Tarjei Mikkelsen, Jeffrey Gimble, Heike Nave, Erwin F. Wagner, Shao En Ong, Evan D. Rosen

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Abstract

The adipocyte-derived hormone leptin is a critical regulator of many physiological functions, ranging from satiety to immunity. Surprisingly, very little is known about the transcriptional pathways that regulate adipocyte-specific expression of leptin. Here, we report studies in which we pursued a strategy integrating BAC transgenic reporter mice, reporter assays, and chromatin state mapping to locate an adipocyte-specific cis-element upstream of the leptin (LEP) gene in human fat cells. Quantitative proteomics with affinity enrichment of protein-DNA complexes identified the transcription factor FOS-like antigen 2 (FOSL2) as binding specifically to the identified region, a result that was confirmed by ChIP. Knockdown of FOSL2 in human adipocytes decreased LEP expression, and overexpression of Fosl2 increased Lep expression in mouse adipocytes. Moreover, the elevated LEP expression observed in obesity correlated well with increased FOSL2 levels in mice and humans, and adipocyte-specific genetic deletion of Fosl2 in mice reduced Lep expression. Taken together, these data identify FOSL2 as a critical regulator of leptin expression in adipocytes.

Original languageEnglish
Pages (from-to)1010-1021
Number of pages12
JournalJournal of Clinical Investigation
Volume122
Issue number3
DOIs
Publication statusPublished - Mar 1 2012

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Leptin
Adipocytes
Gene Expression
Antigens
Proteomics
Transgenic Mice
Chromatin
Immunity
Transcription Factors
Obesity
Hormones
DNA
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wrann, C. D., Eguchi, J., Bozec, A., Xu, Z., Mikkelsen, T., Gimble, J., ... Rosen, E. D. (2012). FOSL2 promotes leptin gene expression in human and mouse adipocytes. Journal of Clinical Investigation, 122(3), 1010-1021. https://doi.org/10.1172/JCI58431

FOSL2 promotes leptin gene expression in human and mouse adipocytes. / Wrann, Christiane D.; Eguchi, Jun; Bozec, Aline; Xu, Zhao; Mikkelsen, Tarjei; Gimble, Jeffrey; Nave, Heike; Wagner, Erwin F.; Ong, Shao En; Rosen, Evan D.

In: Journal of Clinical Investigation, Vol. 122, No. 3, 01.03.2012, p. 1010-1021.

Research output: Contribution to journalArticle

Wrann, CD, Eguchi, J, Bozec, A, Xu, Z, Mikkelsen, T, Gimble, J, Nave, H, Wagner, EF, Ong, SE & Rosen, ED 2012, 'FOSL2 promotes leptin gene expression in human and mouse adipocytes', Journal of Clinical Investigation, vol. 122, no. 3, pp. 1010-1021. https://doi.org/10.1172/JCI58431
Wrann, Christiane D. ; Eguchi, Jun ; Bozec, Aline ; Xu, Zhao ; Mikkelsen, Tarjei ; Gimble, Jeffrey ; Nave, Heike ; Wagner, Erwin F. ; Ong, Shao En ; Rosen, Evan D. / FOSL2 promotes leptin gene expression in human and mouse adipocytes. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 3. pp. 1010-1021.
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