Adipose Is a Conserved Dosage-Sensitive Antiobesity Gene

Jae Myoung Suh, Daniel Zeve, Renee McKay, Jin Seo, Zack Salo, Robert Li, Michael Wang, Jonathan M. Graff

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Adipose (Adp) is an evolutionarily conserved gene isolated from naturally occurring obese flies homozygous for an adp mutation. Here we show that the anti-obesity function of Adp (worm Y73E7A.9, fly adp, and murine Wdtc1) is conserved from worms to mammals. Further, Adp appears to inhibit fat formation in a dosage-sensitive manner. Adp heterozygous flies and Adp heterozygous mutant mice are obese and insulin resistant, as are mice that express a dominant negative form of Adp in fat cells. Conversely, fat-restricted Adp transgenic mice are lean and display improved metabolic profiles. A transient transgenic increase in Adp activity in adult fly fat tissues reduces fat accumulation, indicating therapeutic potential. ADP may elicit these anti-adipogenic functions by regulating chromatin dynamics and gene transcription, as it binds both histones and HDAC3 and inhibits PPARγ activity. Thus Adp appears to be involved in an ancient pathway that regulates fat accumulation.

Original languageEnglish (US)
Pages (from-to)195-207
Number of pages13
JournalCell Metabolism
Volume6
Issue number3
DOIs
StatePublished - Sep 5 2007

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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