Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue

Grzegorz Godlewski, Tony Jourdan, G. Szanda, Joseph Tam, Resat Cinar, Judith Harvey-White, Jie Liu, Bani Mukhopadhyay, Pál Pacher, Fong Ming Mo, Douglas Osei-Hyiaman, George Kunos

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Abstract

We report an unexpected link between aging, thermogenesis and weight gain via the orphan G protein-coupled receptor GPR3. Mice lacking GPR3 and maintained on normal chow had similar body weights during their first 5 months of life, but gained considerably more weight thereafter and displayed reduced total energy expenditure and lower core body temperature. By the age of 5 months GPR3 KO mice already had lower thermogenic gene expression and uncoupling protein 1 protein level and showed impaired glucose uptake into interscapular brown adipose tissue (iBAT) relative to WT littermates. These molecular deviations in iBAT of GPR3 KO mice preceded measurable differences in body weight and core body temperature at ambient conditions, but were coupled to a failure to maintain thermal homeostasis during acute cold challenge. At the same time, the same cold challenge caused a 17-fold increase in Gpr3 expression in iBAT of WT mice. Thus, GPR3 appears to have a key role in the thermogenic response of iBAT and may represent a new therapeutic target in age-related obesity.

Original languageEnglish
Article number14953
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Oct 12 2015

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Brown Adipose Tissue
Phenotype
Body Temperature
Body Weight
Thermogenesis
G-Protein-Coupled Receptors
Energy Metabolism
Weight Gain
Proteins
Homeostasis
Obesity
Hot Temperature
Gene Expression
Weights and Measures
Glucose
Therapeutics

ASJC Scopus subject areas

  • General

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Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue. / Godlewski, Grzegorz; Jourdan, Tony; Szanda, G.; Tam, Joseph; Cinar, Resat; Harvey-White, Judith; Liu, Jie; Mukhopadhyay, Bani; Pacher, Pál; Ming Mo, Fong; Osei-Hyiaman, Douglas; Kunos, George.

In: Scientific Reports, Vol. 5, 14953, 12.10.2015.

Research output: Contribution to journalArticle

Godlewski, G, Jourdan, T, Szanda, G, Tam, J, Cinar, R, Harvey-White, J, Liu, J, Mukhopadhyay, B, Pacher, P, Ming Mo, F, Osei-Hyiaman, D & Kunos, G 2015, 'Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue', Scientific Reports, vol. 5, 14953. https://doi.org/10.1038/srep14953
Godlewski, Grzegorz ; Jourdan, Tony ; Szanda, G. ; Tam, Joseph ; Cinar, Resat ; Harvey-White, Judith ; Liu, Jie ; Mukhopadhyay, Bani ; Pacher, Pál ; Ming Mo, Fong ; Osei-Hyiaman, Douglas ; Kunos, George. / Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue. In: Scientific Reports. 2015 ; Vol. 5.
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