The arrestin domain-containing 3 protein regulates body mass and energy expenditure Academic Article uri icon


MeSH Major

  • Adipose Tissue, Brown
  • Arrestins
  • Energy Metabolism
  • Obesity
  • Receptors, Adrenergic, beta
  • Thermogenesis


  • 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.

publication date

  • November 2, 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3216113

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2011.08.011

PubMed ID

  • 21982743

Additional Document Info

start page

  • 671

end page

  • 83


  • 14


  • 5