The Arrestin Domain-Containing 3 Protein Regulates Body Mass and Energy Expenditure

被引：112

作者：

Patwari, Parth ^{[1
]}

Emilsson, Valur ^{[5
]}

Schadt, Eric E. ^{[6
]}

Chutkow, William A. ^{[1
]}

Lee, Samuel ^{[1
]}

Marsili, Alessandro ^{[2
]}

Zhang, Yongzhao ^{[3
,4
]}

Dobrin, Radu ^{[7
]}

Cohen, David E. ^{[3
,4
]}

Larsen, P. Reed ^{[2
]}

Zavacki, Ann Marie ^{[2
]}

Fong, Loren G. ^{[8
]}

Young, Stephen G. ^{[8
]}

Lee, Richard T. ^{[1
,9
]}

机构：

[1] Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Div Endocrinol, Dept Med, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Div Gastroenterol, Dept Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

[5] Iceland Heart Assoc, IS-201 Kopavogur, Iceland

[6] Pacific Biosci, Menlo Pk, CA 94025 USA

[7] Merck Res Lab, Rahway, NJ 07065 USA

[8] Univ Calif Los Angeles, Dept Cardiol, Los Angeles, CA 90095 USA

[9] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

来源：

CELL METABOLISM | 2011年 / 14卷 / 05期

关键词：

BROWN ADIPOSE-TISSUE; HUMAN OBESITY; ADAPTIVE THERMOGENESIS; SUSCEPTIBILITY LOCUS; METABOLIC SYNDROME; RECEPTOR; MICE; GENE; DEFICIENCY; DIET;

D O I：

10.1016/j.cmet.2011.08.011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 alpha-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 beta-adrenergic receptors, and loss of ARRDC3 increased the response to beta-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.

引用

页码：671 / 683

页数：13

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