Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective

Overview

Journal Nutrients

Date 2021 Jan 28

PMID 33503878

Citations 21

Authors

Joanna Michalowska

Ewa Miller-Kasprzak

Pawel Bogdanski

Affiliations

Soon will be listed here.

Abstract

The prevalence of obesity continues to grow rapidly worldwide, posing many public health challenges of the 21st century. Obese subjects are at major risk for serious diet-related noncommunicable diseases, including type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Understanding the mechanisms underlying obesity pathogenesis is needed for the development of effective treatment strategies. Dysregulation of incretin secretion and actions has been observed in obesity and related metabolic disorders; therefore, incretin-based therapies have been developed to provide new therapeutic options. Incretin mimetics present glucose-lowering properties, together with a reduction of appetite and food intake, resulting in weight loss. In this review, we describe the physiology of two known incretins-glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and their role in obesity and related cardiometabolic disorders. We also focus on the available and incoming incretin-based medications that can be used in the treatment of the above-mentioned conditions.

Citing Articles

Secretagogin Is Highly Expressed in Enteroendocrine K Cells and Plays a Critical Role in Nutrient-Induced GIP Secretion.

Liu X, Liu X, Hu Y, Wang X, Yang X, Yan B J Endocr Soc. 2025; 9(3):bvaf022.

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Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients.

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Association between polymorphisms of glucagon-like peptide-1 receptor gene and susceptibility to osteoporosis in Chinese postmenopausal women.

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Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Exploring Their Impact on Diabetes, Obesity, and Cardiovascular Health Through a Comprehensive Literature Review.

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Management of Metabolic-Associated Fatty Liver Disease/Metabolic Dysfunction-Associated Steatotic Liver Disease: From Medication Therapy to Nutritional Interventions.

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References

Polyzos S, Kountouras J, Mantzoros C . Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism. 2018; 92:82-97. DOI: 10.1016/j.metabol.2018.11.014. View

Larsen M, Torekov S . Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes?. J Diabetes Res. 2017; 2017:7583506. PMC: 5610892. DOI: 10.1155/2017/7583506. View

Bergmann N, Gasbjerg L, Heimburger S, Krogh L, Dela F, Hartmann B . No Acute Effects of Exogenous Glucose-Dependent Insulinotropic Polypeptide on Energy Intake, Appetite, or Energy Expenditure When Added to Treatment With a Long-Acting Glucagon-Like Peptide 1 Receptor Agonist in Men With Type 2 Diabetes. Diabetes Care. 2020; 43(3):588-596. DOI: 10.2337/dc19-0578. View

Joao A, Reis F, Fernandes R . The incretin system ABCs in obesity and diabetes - novel therapeutic strategies for weight loss and beyond. Obes Rev. 2016; 17(7):553-72. DOI: 10.1111/obr.12421. View

Sofogianni A, Filippidis A, Chrysavgis L, Tziomalos K, Cholongitas E . Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update. World J Hepatol. 2020; 12(8):493-505. PMC: 7475780. DOI: 10.4254/wjh.v12.i8.493. View

Greenwell A, Chahade J, Ussher J . Cardiovascular biology of the GIP receptor. Peptides. 2019; 125:170228. DOI: 10.1016/j.peptides.2019.170228. View

de Luis D, Pacheco D, Aller R, Izaola O . Role of the rs6923761 gene variant in glucagon-like peptide 1 receptor gene on cardiovascular risk factors and weight loss after biliopancreatic diversion surgery. Ann Nutr Metab. 2014; 65(4):259-63. DOI: 10.1159/000365975. View

Kalra S, Das A, Sahay R, Baruah M, Tiwaskar M, Das S . Consensus Recommendations on GLP-1 RA Use in the Management of Type 2 Diabetes Mellitus: South Asian Task Force. Diabetes Ther. 2019; 10(5):1645-1717. PMC: 6778554. DOI: 10.1007/s13300-019-0669-4. View

Brown E, Cuthbertson D, Wilding J . Newer GLP-1 receptor agonists and obesity-diabetes. Peptides. 2018; 100:61-67. DOI: 10.1016/j.peptides.2017.12.009. View

10.

Zhang Q, Wu K, He J, Zeng Y, Greenbaum J, Xia X . Novel Common Variants Associated with Obesity and Type 2 Diabetes Detected Using a cFDR Method. Sci Rep. 2017; 7(1):16397. PMC: 5703959. DOI: 10.1038/s41598-017-16722-6. View

11.

Naslund E, Gutniak M, Skogar S, Rossner S, Hellstrom P . Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr. 1998; 68(3):525-30. DOI: 10.1093/ajcn/68.3.525. View

12.

Wharton S, Lau D, Vallis M, Sharma A, Biertho L, Campbell-Scherer D . Obesity in adults: a clinical practice guideline. CMAJ. 2020; 192(31):E875-E891. PMC: 7828878. DOI: 10.1503/cmaj.191707. View

13.

Smith N, Hackett T, Galli A, Flynn C . GLP-1: Molecular mechanisms and outcomes of a complex signaling system. Neurochem Int. 2019; 128:94-105. PMC: 7081944. DOI: 10.1016/j.neuint.2019.04.010. View

14.

Rizzo M, Nikolic D, Patti A, Mannina C, Montalto G, McAdams B . GLP-1 receptor agonists and reduction of cardiometabolic risk: Potential underlying mechanisms. Biochim Biophys Acta Mol Basis Dis. 2018; 1864(9 Pt B):2814-2821. DOI: 10.1016/j.bbadis.2018.05.012. View

15.

Jall S, Sachs S, Clemmensen C, Finan B, Neff F, DiMarchi R . Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice. Mol Metab. 2017; 6(5):440-446. PMC: 5404097. DOI: 10.1016/j.molmet.2017.02.002. View

16.

Reddon H, Gerstein H, Engert J, Mohan V, Bosch J, Desai D . Physical activity and genetic predisposition to obesity in a multiethnic longitudinal study. Sci Rep. 2016; 6:18672. PMC: 4698633. DOI: 10.1038/srep18672. View

17.

Daousi C, Wilding J, Aditya S, Durham B, Cleator J, Pinkney J . Effects of peripheral administration of synthetic human glucose-dependent insulinotropic peptide (GIP) on energy expenditure and subjective appetite sensations in healthy normal weight subjects and obese patients with type 2 diabetes. Clin Endocrinol (Oxf). 2009; 71(2):195-201. DOI: 10.1111/j.1365-2265.2008.03451.x. View

18.

Musso G, Gambino R, Pacini G, De Michieli F, Cassader M . Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver. Am J Clin Nutr. 2009; 89(2):558-67. DOI: 10.3945/ajcn.2008.26720. View

19.

Scott R, Scott L, Magi R, Marullo L, Gaulton K, Kaakinen M . An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. Diabetes. 2017; 66(11):2888-2902. PMC: 5652602. DOI: 10.2337/db16-1253. View

20.

Li P, Tiwari H, Lin W, Allison D, Chung W, Leibel R . Genetic association analysis of 30 genes related to obesity in a European American population. Int J Obes (Lond). 2013; 38(5):724-9. PMC: 3909018. DOI: 10.1038/ijo.2013.140. View