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PMID:21982743

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Citation

Patwari, P, Emilsson, V, Schadt, EE, Chutkow, WA, Lee, S, Marsili, A, Zhang, Y, Dobrin, R, Cohen, DE, Larsen, PR, Zavacki, AM, Fong, LG, Young, SG and Lee, RT (2011) The arrestin domain-containing 3 protein regulates body mass and energy expenditure. Cell Metab. 14:671-83

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.

Links

PubMed PMC3216113 Online version:10.1016/j.cmet.2011.08.011

Keywords

Adipose Tissue, Brown/metabolism; Adipose Tissue, White/metabolism; Adrenergic beta-Agonists/pharmacology; Animals; Arrestins/genetics; Arrestins/metabolism; Body Mass Index; Chromosomes, Human, Pair 5; Cohort Studies; Energy Metabolism/genetics; Female; Genetic Loci; Humans; Iceland/epidemiology; Linkage Disequilibrium; Male; Mice; Mice, Knockout; Obesity/epidemiology; Obesity/genetics; Obesity/metabolism; Receptors, Adrenergic, beta/metabolism; Sequence Homology, Amino Acid; Sex Factors; Signal Transduction; Thermogenesis/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:ARRD3

involved_in

GO:0120163: negative regulation of cold-induced thermogenesis

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q7TPQ9

P

Seeded From UniProt

complete

MOUSE:ARRD3

acts_upstream_of_or_within

GO:0001659: temperature homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3877613

P

Seeded From UniProt

complete

MOUSE:ARRD3

acts_upstream_of_or_within

GO:0031651: negative regulation of heat generation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3877613

P

  • regulates_o_occurs_in:(EMAPA:19209)|regulates_o_occurs_in:(EMAPA:35926)

Seeded From UniProt

complete

MOUSE:ARRD3

acts_upstream_of_or_within

GO:0060613: fat pad development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3877613

P

  • results_in_development_of:(EMAPA:35340)

Seeded From UniProt

complete

MOUSE:ARRD3

acts_upstream_of_or_within

GO:0071878: negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3877613

P

Seeded From UniProt

complete

MOUSE:ARRD3

acts_upstream_of_or_within

GO:0090327: negative regulation of locomotion involved in locomotory behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3877613

P

Seeded From UniProt

complete

MOUSE:ARRD3

involved_in

GO:0120163: negative regulation of cold-induced thermogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ARRD3

enables

GO:0031699: beta-3 adrenergic receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ARRD3

involved_in

GO:0120163: negative regulation of cold-induced thermogenesis

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q7TPQ9

P

Seeded From UniProt

complete


See also

References

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