Reg3γ: current understanding and future therapeutic opportunities in metabolic disease

• Published in: Experimental & molecular medicine 2023, 55(0), , pp.1672-1677
• Main Authors: Shin, Jae Hoon, Bozadjieva-Kramer, Nadejda, Seeley, Randy J.
• Format: Article
• Language: English
• Subjects: 631/443/319/1557; 64/110; 64/60; 692/699/2743/137/773; Animals; Antimicrobial peptides; Bacteria - metabolism; Bactericidal activity; Biomedical and Life Sciences; Biomedicine; Diabetes mellitus (non-insulin dependent); Dietary supplements; Digestive system; Gastrointestinal Microbiome; Gastrointestinal surgery; Gastrointestinal tract; Immune response; Intestinal microflora; Medical Biochemistry; Metabolic Diseases - drug therapy; Metabolic disorders; Mice; Microbiomes; Microbiota; Molecular Medicine; Pancreatitis-Associated Proteins - metabolism; Peptides; Review; Review Article; Small intestine; Stem Cells; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-023-01054-5

Regenerating family member gamma, Reg3γ (the mouse homolog of human REG3A), belonging to the antimicrobial peptides (AMPs), functions as a part of the host immune system to maintain spatial segregation between the gut bacteria and the host in the intestine via bactericidal activity. There is emerging evidence that gut manipulations such as bariatric surgery, dietary supplementation or drug treatment to produce metabolic benefits alter the gut microbiome. In addition to changes in a wide range of gut hormones, these gut manipulations also induce the expression of Reg3γ in the intestine. Studies over the past decades have revealed that Reg3γ not only plays a role in the gut lumen but can also contribute to host physiology through interaction with the gut microbiota. Herein, we discuss the current knowledge regarding the biology of Reg3γ, its role in various metabolic functions, and new opportunities for therapeutic strategies to treat metabolic disorders. Metabolic diseases: Role of antimicrobial peptide found in small intestine An antimicrobial peptide, Reg3γ found in the small intestine may be a vital link between gut microbiota and metabolic regulation, and understanding its activity may inform future therapeutics. Reg3γ protects the host by keeping gut bacteria from passing into other organs. Questions remain regarding the role of Reg3γ in metabolic disorders. Randy Seeley at the University of Michigan, Ann Arbor, USA, and co-workers reviewed understanding of the biological roles of Reg3γ. Its production is boosted in infections as part of the host immune response, and it can confer beneficial effects in multiple organs. However, Reg3γ is downregulated in metabolic disorders such as obesity and type 2 diabetes. Stimulating the gut to generate high levels of Reg3γ can improve gut function, but also affect metabolic regulation in mice. Analogs designed to mimic Reg3γ may have therapeutic advantages.