Metabolic Profiling of Mice with Deletion of the Orphan G Protein-Coupled Receptor, GPR37L1

Margaret A Mouat; Brendan P Wilkins; Eileen Ding; Hemna Govindaraju; James L J Coleman; Robert M Graham; Nigel Turner; Nicola J Smith

doi:10.3390/cells11111814

Metabolic Profiling of Mice with Deletion of the Orphan G Protein-Coupled Receptor, GPR37L1

Cells. 2022 Jun 1;11(11):1814. doi: 10.3390/cells11111814.

Authors

Margaret A Mouat^{1

2}, Brendan P Wilkins¹, Eileen Ding³, Hemna Govindaraju³, James L J Coleman², Robert M Graham², Nigel Turner^{3

4}, Nicola J Smith¹

Affiliations

¹ Orphan Receptor Laboratory, School of Medical Sciences, Faculty of Medicine & Health, UNSW Sydney, Kensington, NSW 2052, Australia.
² Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
³ Mitochondrial Bioenergetics Laboratory, School of Medical Sciences, Faculty of Medicine & Health, UNSW Sydney, Kensington, NSW 2052, Australia.
⁴ Cellular Bioenergetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.

Abstract

Understanding the neurogenic causes of obesity may reveal novel drug targets to counter the obesity crisis and associated sequelae. Here, we investigate whether the deletion of GPR37L1, an astrocyte-specific orphan G protein-coupled receptor, affects whole-body energy homeostasis in mice. We subjected male Gpr37l1^-/- mice and littermate wildtype (Gpr37l1^+/+, C57BL/6J background) controls to either 12 weeks of high-fat diet (HFD) or chow feeding, or to 1 year of chow diet, with body composition quantified by EchoMRI, glucose handling by glucose tolerance test and metabolic rate by indirect calorimetry. Following an HFD, Gpr37l1^-/- mice had similar glucose handling, body weight and fat mass compared with wildtype controls. Interestingly, we observed a significantly elevated respiratory exchange ratio in HFD- and chow-fed Gpr37l1^-/- mice during daylight hours. After 1 year of chow feeding, we again saw no differences in glucose and insulin tolerance or body weight between genotypes, nor in energy expenditure or respiratory exchange ratio. However, there was significantly lower fat mass accumulation, and higher ambulatory activity in the Gpr37l1^-/- mice during night hours. Overall, these results indicate that while GPR37L1 may play a minor role in whole-body metabolism, it is not a viable clinical target for the treatment of obesity.

Keywords: G protein-coupled receptor; GPR37L1; metabolism; orphan GPCR; phenotype.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Body Weight
Glucose / metabolism
Male
Mice
Mice, Inbred C57BL
Obesity* / metabolism
Receptors, G-Protein-Coupled* / genetics
Receptors, G-Protein-Coupled* / metabolism

Substances

Gpr37l1protein, mouse
Receptors, G-Protein-Coupled
Glucose

Associated data

figshare/10.6084/m9.figshare.19656741

Grants and funding

This work was supported in part by a National Heart Foundation of Australia Future Leader Fellowship (101153, N.J.S.), funding from the National Health and Medical Research Council (N.T.) and an Australian Government Research Training Program Scholarship to M.A.M.