Energy Regulation Mechanism and Therapeutic Potential of Asprosin
- 16 March 2020
- journal article
- review article
- Published by American Diabetes Association in Diabetes
- Vol. 69 (4), 559-566
- https://doi.org/10.2337/dbi19-0009
Abstract
Genetic studies of patients with neonatal progeroid syndrome led to the discovery of the novel fasting-induced, glucogenic, and orexigenic hormone named asprosin, the C-terminal cleavage product of profibrillin. Upon secretion, asprosin travels to the liver, where it exerts a glucogenic effect through OR4M1, an olfactory G-protein–coupled receptor. It also crosses the blood-brain barrier to stimulate appetite-modulating neurons in the arcuate nucleus of the hypothalamus, exerting an orexigenic effect via an as yet unidentified receptor. Specifically, it stimulates appetite by activating orexigenic AgRP neurons and inhibiting anorexigenic POMC neurons. Studies have also focused on the therapeutic potential of inhibiting asprosin for treatment of obesity and type 2 diabetes, both of which are characterized by high levels of circulating asprosin. It has been shown that anti-asprosin monoclonal antibodies reduce blood glucose, appetite, and body weight, validating asprosin as a therapeutic target. Current work aims to uncover key features of the asprosin biology such as the identification of its neuronal receptor, identification of the secretion mechanism from adipose tissue, and development of anti-asprosin monoclonal antibodies as diabetes and obesity therapies.Keywords
This publication has 41 references indexed in Scilit:
- Severe congenital lipodystrophy and a progeroid appearance: Mutation in the penultimate exon of FBN1 causing a recognizable phenotypeAmerican Journal of Medical Genetics Part A, 2013
- Mechanisms of insulin resistance in obesityFrontiers of Medicine, 2013
- Further evidence for a marfanoid syndrome with neonatal progeroid features and severe generalized lipodystrophy due to frameshift mutations near the 3? end of the FBN1 geneAmerican Journal of Medical Genetics Part A, 2011
- Progeroid facial features and lipodystrophy associated with a novel splice site mutation in the final intron of the FBN1 geneAmerican Journal of Medical Genetics Part A, 2011
- Marfan syndrome with neonatal progeroid syndrome‐like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1‐geneAmerican Journal of Medical Genetics Part A, 2010
- Body fat distribution and metabolic variables in patients with neonatal progeroid syndromeAmerican Journal of Medical Genetics Part A, 2007
- The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a reviewObesity Reviews, 2006
- Profibrillin‐1 maturation by human dermal fibroblasts: Proteolytic processing and molecular chaperonesJournal of Cellular Biochemistry, 2003
- Growth and maturation in Marfan syndromeAmerican Journal of Medical Genetics, 2002
- Processing of the Fibrillin-1 Carboxyl-terminal DomainOnline Journal of Public Health Informatics, 1999