GLP-1 and energy balance: an integrated model of short-term and long-term control
- PMID: 21647189
- PMCID: PMC4231434
- DOI: 10.1038/nrendo.2011.77
GLP-1 and energy balance: an integrated model of short-term and long-term control
Abstract
Glucagon-like peptide 1 (GLP-1), a peptide secreted from the intestine in response to nutrient ingestion, is perhaps best known for its effect on glucose-stimulated insulin secretion. GLP-1 is also secreted from neurons in the caudal brainstem, and it is well-established that, in rodents, central administration of GLP-1 potently reduces food intake. Over the past decade, GLP-1 has emerged not only as an essential component of the system that regulates blood glucose levels but also as a viable therapeutic target for the treatment of type 2 diabetes mellitus. However, although GLP-1 receptor agonists are known to produce modest but statistically significant weight loss in patients with diabetes mellitus, our knowledge of how endogenous GLP-1 regulates food intake and body weight remains limited. The purpose of this Review is to discuss the evolution of our understanding of how endogenous GLP-1 modulates energy balance. Specifically, we consider contributions of both central and peripheral GLP-1 and propose an integrated model of short-term and long-term control of energy balance. Finally, we discuss this model with respect to current GLP-1-based therapies and suggest ongoing research in order to maximize the effectiveness of GLP-1-based treatment of obesity.
Conflict of interest statement
D. A. Sandoval declares an association with the following company: Ethicon. D. A. D’Alessio declares an association with the following companies: Amylin, Johnson and Johnson, MannKind, Merck, Novo Nordisk, Sanofi-Aventis, Takeda. R. J. Seeley declares an association with the following companies: Alkermes, Amylin, Eli Lilly, Johnson and Johnson, MannKind, Merck, Novo Nordisk, Roche, Zafgen. See the article online for details of the relationships. J. G. Barrera declares no competing interests.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4231434/bin/nihms639983f1.gif)
Similar articles
-
Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates.Diabetes Obes Metab. 2016 Dec;18(12):1176-1190. doi: 10.1111/dom.12735. Epub 2016 Aug 15. Diabetes Obes Metab. 2016. PMID: 27377054 Free PMC article.
-
Team Players or Opponents: Coadministration of Selective Glucagon and GLP-1 Receptor Agonists in Obese Diabetic Monkeys.Endocrinology. 2018 Aug 1;159(8):3105-3119. doi: 10.1210/en.2018-00399. Endocrinology. 2018. PMID: 29992313
-
Glucagon-like peptide 1 (GLP-1).Mol Metab. 2019 Dec;30:72-130. doi: 10.1016/j.molmet.2019.09.010. Epub 2019 Sep 30. Mol Metab. 2019. PMID: 31767182 Free PMC article. Review.
-
The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications.Diabetes Obes Metab. 2014 Jan;16(1):9-21. doi: 10.1111/dom.12119. Epub 2013 May 26. Diabetes Obes Metab. 2014. PMID: 23617798 Review.
-
Running on mixed fuel-dual agonistic approach of GLP-1 and GCG receptors leads to beneficial impact on body weight and blood glucose control: A comparative study between mice and non-human primates.Diabetes Obes Metab. 2018 Aug;20(8):1836-1851. doi: 10.1111/dom.13212. Epub 2018 Jun 25. Diabetes Obes Metab. 2018. PMID: 29938884 Free PMC article.
Cited by
-
Dichotomous effect of dietary fiber in pediatrics: a narrative review of the health benefits and tolerance of fiber.Eur J Clin Nutr. 2024 Jul;78(7):557-568. doi: 10.1038/s41430-024-01429-5. Epub 2024 Mar 13. Eur J Clin Nutr. 2024. PMID: 38480843 Review.
-
Satiety: a gut-brain-relationship.J Physiol Sci. 2024 Feb 17;74(1):11. doi: 10.1186/s12576-024-00904-9. J Physiol Sci. 2024. PMID: 38368346 Free PMC article. Review.
-
The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission.JCI Insight. 2023 Jun 22;8(12):e170671. doi: 10.1172/jci.insight.170671. JCI Insight. 2023. PMID: 37192005 Free PMC article.
-
Contribution of the microbiome for better phenotyping of people living with obesity.Rev Endocr Metab Disord. 2023 Oct;24(5):839-870. doi: 10.1007/s11154-023-09798-1. Epub 2023 Apr 29. Rev Endocr Metab Disord. 2023. PMID: 37119391 Free PMC article. Review.
-
Acute changes in systemic glycemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis.Cell Rep. 2022 Nov 22;41(8):111698. doi: 10.1016/j.celrep.2022.111698. Cell Rep. 2022. PMID: 36417883 Free PMC article.
References
-
- Moran TH, Kinzig KP. Gastrointestinal satiety signals II. Cholecystokinin. Am J Physiol Gastrointest Liver Physiol. 2004;286:G183–G188. - PubMed
-
- Benoit SC, Clegg DJ, Seeley RJ, Woods SC. Insulin and leptin as adiposity signals. Recent Prog Horm Res. 2004;59:267–285. - PubMed
-
- Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87:1409–1439. - PubMed
-
- Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132:2131–2157. - PubMed
-
- Parker HE, Reimann F, Gribble FM. Molecular mechanisms underlying nutrient-stimulated incretin secretion. Expert Rev Mol Med. 2010;12:e1. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous