Adipose is a conserved dosage-sensitive antiobesity gene.
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 PPARgamma activity. Thus Adp appears to be involved in an ancient pathway that regulates fat accumulation.
Suh
Jae Myoung
JM
Department of Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, NB5.118, Dallas, TX 75390-9133, USA.
Zeve
Daniel
D
McKay
Renee
R
Seo
Jin
J
Salo
Zack
Z
Li
Robert
R
Wang
Michael
M
Graff
Jonathan M
JM
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000517:prevention & control; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009765:Obesity / Q000235:genetics* / Q000517:prevention & control; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D000099186:Histone Deacetylase 3; D043743:Ubiquitin-Protein Ligase Complexes
D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D006655:Histone Deacetylases; D006657:Histones; D007328:Insulin; D011506:Proteins; D000099186:Histone Deacetylase 3; C527990:Wdtc1 protein, mouse; D043743:Ubiquitin-Protein Ligase Complexes; C490481:adp protein, Drosophila; C527991:adpr-1 protein, C elegans