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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 languageAmerican English
Article number14953
JournalScientific Reports
Volume5
DOIs
StatePublished - 12 Oct 2015

Bibliographical note

Funding Information:
This study was supported by funds from the intramural research program of National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

Fingerprint

Dive into the research topics of 'Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue'. Together they form a unique fingerprint.

Cite this