Effects of the POMC System on Glucose Homeostasis and Potential Therapeutic Targets for Obesity and Diabetes

Abstract

The hypothalamus is indispensable in energy regulation and glucose homeostasis. Previous studies have shown that pro-opiomelanocortin neurons receive both central neuronal signals, such as α-melanocyte-stimulating hormone, β-endorphin, and adrenocorticotropic hormone, as well as sense peripheral signals such as leptin, insulin, adiponectin, glucagon-like peptide-1, and glucagon-like peptide-2, affecting glucose metabolism through their corresponding receptors and related signaling pathways. Abnormalities in these processes can lead to obesity, type 2 diabetes, and other metabolic diseases. However, the mechanisms by which these signal molecules fulfill their role remain unclear. Consequently, in this review, we explored the mechanisms of these hormones and signals on obesity and diabetes to suggest potential therapeutic targets for obesity-related metabolic diseases. Multi-drug combination therapy for obesity and diabetes is becoming a trend and requires further research to help patients to better control their blood glucose and improve their prognosis.

Keywords:

• POMC neurons
• central signals
• peripheral signals
• glucose homeostasis
• obesity
• diabetes

Abbreviations

ARC, the arcuate nucleus; AMPK, AMP-activated protein kinase; CB1R, cannabinoid receptor 1; CNS, central nervous system; ERK1/2, extracellular signal-regulated protein kinases 1 and 2; FoxO1, forkhead box protein O1; GLP-1, glucagon-like peptide-1; GLP-1R, GLP-1 receptor; GLP-2, glucagon-like peptide-2; GLP-2R, GLP-2 receptor; HFD, high-fat diet; HIF, hypoxia inducible factor; HIF1α, HIF-1-alpha; IRS, insulin receptor substrate; JAK/STAT, Janus kinase/signal transducer and activator of transcription; KATP, ATP sensitive potassium; LKB1, liver kinase B1; Sirt6, Sirtuin 6; MC3R, melanocortin-3 receptor; MC4R, melanocortin 4 receptor; MCH, melanin-enhanced hormone; MCHR1, melanin-enhanced hormone receptor 1; mTOR/S6K, the mechanistic target of rapamycin/S6 kinase; NF-κB, nuclear factor-kappa B; NPY, neuropeptide Y; OX-1R, OX-A receptor type 1; POMC, pro-opiomelanocortin; SHP2-MAPK, src homology region 2-containing protein tyrosine phosphatase 2-mitogen-activated protein kinase; SIRT1, Sirtuin 1; SRC-2, steroid receptor coactivator-2; TGF-β, transforming growth factor-β; TLR4, toll-like receptor-4; α-MSH, α-melanocyte-stimulating hormone; β-endorphin, beta-endorphin; 5-HT2CR, serotonin 2C receptor.

Acknowledgments

The coauthors thank the National Natural Science Foundation of China (81973378, 82073909), Research Project Supported by Shanxi Scholarship Council of China (2020-0172) for their support.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.