title: The arrestin domain-containing 3 protein regulates body mass and energy expenditure.
abstract: A human genome-wide linkage scan for obesity identified a linkage peak on chromosome 5q13-15. Positional cloning revealed an association of a rare haplotype to high body-mass index (BMI) in males but not females. The risk locus contains a single gene, "arrestin domain-containing 3" (ARRDC3), an uncharacterized α-arrestin. Inactivating Arrdc3 in mice led to a striking resistance to obesity, with greater impact on male mice. Mice with decreased ARRDC3 levels were protected from obesity due to increased energy expenditure through increased activity levels and increased thermogenesis of both brown and white adipose tissues. ARRDC3 interacted directly with β-adrenergic receptors, and loss of ARRDC3 increased the response to β-adrenergic stimulation in isolated adipose tissue. These results demonstrate that ARRDC3 is a gender-sensitive regulator of obesity and energy expenditure and reveal a surprising diversity for arrestin family protein functions.
authors: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. parth@alum.mit.edu
authors: Parth
authors: P
authors: Patwari
authors: Valur
authors: V
authors: Emilsson
authors: Eric E
authors: EE
authors: Schadt
authors: William A
authors: WA
authors: Chutkow
authors: Samuel
authors: S
authors: Lee
authors: Alessandro
authors: A
authors: Marsili
authors: Yongzhao
authors: Y
authors: Zhang
authors: Radu
authors: R
authors: Dobrin
authors: David E
authors: DE
authors: Cohen
authors: P Reed
authors: PR
authors: Larsen
authors: Ann Marie
authors: AM
authors: Zavacki
authors: Loren G
authors: LG
authors: Fong
authors: Stephen G
authors: SG
authors: Young
authors: Richard T
authors: RT
authors: Lee
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D015992:Body Mass Index; D002895:Chromosomes, Human, Pair 5; D015331:Cohort Studies; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012737:Sex Factors; D015398:Signal Transduction; D022722:Thermogenesis / Q000235:genetics*
chemical_list: C508469:ARRDC3 protein, human; C570236:ARRDC3 protein, mouse; D000318:Adrenergic beta-Agonists; D019390:Arrestins; D011943:Receptors, Adrenergic, beta