Gpr75 Deficiency Attenuates High Fat Diet-Driven Obesity and Glucose Intolerance

Author

Sakib Hossain, NYMCFollow

Date of Award

5-22-2023

Document Type

Doctoral Dissertation - Open Access

Degree Name

Doctor of Philosophy

Department

Pharmacology

First Advisor

Michal L Schwartzman

Abstract

Recently, a collaboration between Regeneron Pharmaceuticals and the Schwartzman-Garcia labs at New York Medical College published an exome sequencing study of individuals across the United Kingdom, United States, and Mexico which concluded that individuals possessing non-functioning, truncated mutations to the orphan g protein coupled receptor (GPCR), GPR75, had lower BMI and 54% reduced likelihood of obesity. The present study was undertaken to fully characterize the metabolic phenotype of Gpr75 deficient mice when fed a high fat diet (HFD) and explore potential mechanisms by which GPR75 activation links to increased adiposity and decreased glucose tolerance. After 14 weeks of HFD-feeding we observed significant differences in weight gain, with male and female wild-type mice gaining double the amount of weight as the transgenic mice. Surprisingly, mice with Gpr75 deficiency show no differences in caloric intake compared to wild-type animals throughout the feeding period. In contrast, whole-body energy expenditure calculated from volume of oxygen consumption (VO₂) and carbon dioxide (VCO₂) production decreased in response to HFD-feeding for wild-type animals, while remaining unchanged compared to baseline for transgenic animals. This correlated with increased expression of mitochondrial uncoupling proteins (UCPs) in different adipose tissue depots, whose role in diet-induced obesity prevention is well documented.

Recommended Citation

Hossain, Sakib, "Gpr75 Deficiency Attenuates High Fat Diet-Driven Obesity and Glucose Intolerance" (2023). NYMC Student Theses and Dissertations. 55.
https://touroscholar.touro.edu/nymc_students_theses/55