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

Diabetes, ISSN: 1939-327X, Vol: 70, Issue: 9, Page: 1929-1937
2021
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Article Description

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 expendi-ture, or both, eventually causing weight loss. Further, supraphysiological dosing of exogenous long-lasting GIP agonists alters energy balance and has a marked antio-besity 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 through-out 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.

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