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 language | English |
|---|---|
| Pages (from-to) | 1010-1021 |
| Number of pages | 12 |
| Journal | Journal of Clinical Investigation |
| Volume | 122 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2012 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - FOSL2 promotes leptin gene expression in human and mouse adipocytes
AU - Wrann, Christiane D.
AU - Eguchi, Jun
AU - Bozec, Aline
AU - Xu, Zhao
AU - Mikkelsen, Tarjei
AU - Gimble, Jeffrey
AU - Nave, Heike
AU - Wagner, Erwin F.
AU - Ong, Shao En
AU - Rosen, Evan D.
PY - 2012/3/1
Y1 - 2012/3/1
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI58431
DO - 10.1172/JCI58431
M3 - Article
VL - 122
SP - 1010
EP - 1021
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 3
ER -