The influence of Glucose-dependent Insulinotropic Polypeptide (GIP) on human adipose tissue and fat metabolism: Implications for obesity, type 2 diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD)

Nov 24, 2019Peptides

How Glucose-Dependent Insulinotropic Polypeptide (GIP) affects human fat tissue and fat metabolism, with links to obesity, type 2 diabetes, and fatty liver disease

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Abstract

Antagonizing the actions of GIP in mice prevented diet-induced obesity and improved insulin sensitivity.

GIP and GLP-1 are incretin hormones released in response to nutrient intake.
GIP has significant biological effects beyond insulin secretion, particularly in fat metabolism.
The long-term effects of GIP on fat metabolism and adipose tissue are uncertain.
Combining GIP and GLP-1 agonists has led to weight reduction and improved blood sugar control in people with type 2 diabetes.
Research is ongoing into the potential benefits of both GIP agonists and antagonists for obesity, type 2 diabetes, and non-alcoholic fatty liver disease.

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Glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide (GLP-1) are the two incretin hormones secreted by the enteroendocrine system in response to nutrient ingestion. Compared with GLP-1, GIP is less well studied as a hormone or as a potential pharmacological treatment. Beyond its insulinotropic effects in the pancreas, GIP has important biological actions in many other tissues but its role in dietary fat metabolism and lipid storage in adipose tissue has been most studied. It is still unclear if such effects of GIP on adipose tissue/fat metabolism are protective or deleterious in the long term. Antagonising GIP actions through genetic and chemical disruption in mice models prevented diet induced obesity and improved insulin sensitivity. Whilst such effects of GIP antagonism are yet to be evaluated in humans, recent studies using combined GIP and GLP-1 agonists have shown weight reduction and improved glycaemic control in people with type 2 diabetes (T2D). Therapeutic manipulation of GIP physiology is intriguing in that both agonists and antagonists of GIP are being investigated to explore their potential weight-reducing and other metabolic benefits in people with obesity, T2D and non-alcoholic fatty liver disease (NAFLD). This review will discuss the physiological effects of GIP on fat metabolism in human adipose and other non-adipose tissues such as liver, pancreas, skeletal muscle and heart, describe where the actions of GIP may contribute to the pathophysiology of obesity, T2D and NAFLD and finally describe the therapeutic implications of GIP antagonism and agonism in these conditions.

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The influence of Glucose-dependent Insulinotropic Polypeptide (GIP) on human adipose tissue and fat metabolism: Implications for obesity, type 2 diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD)

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