The Role of GIP Receptor in the CNS for the Pathogenesis of Obesity

Authors

Makoto Fukuda

Publication Date

9-1-2021

Journal

Diabetes

DOI

10.2337/dbi21-0001

PMID

34176784

PMCID

PMC8576424

PubMedCentral® Posted Date

6-27-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Blood Glucose, Central Nervous System, Energy Metabolism, Gastric Inhibitory Polypeptide, Humans, Obesity, Receptors, Gastrointestinal Hormone

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) is a hormone produced in the upper gut and secreted to the circulation in response to the ingestion of foods, especially fatty foods. Growing evidence supports the physiological and pharmacological relevance of GIP in obesity. In an obesity setting, inhibition of endogenous GIP or its receptor leads to decreased energy intake, increased energy expenditure, or both, eventually causing weight loss. Further, supraphysiological dosing of exogenous long-lasting GIP agonists alters energy balance and has a marked antiobesity effect. This remarkable yet paradoxical antiobesity effect is suggested to occur primarily via the brain. The brain is capable of regulating both energy intake and expenditure and plays a critical role in human obesity. In addition, the GIP receptor is widely distributed throughout the brain, including areas responsible for energy homeostasis. Recent studies have uncovered previously underappreciated roles of the GIP receptor in the brain in the context of obesity. This article highlights how the GIP receptor expressed by the brain impacts obesity-related pathogenesis.