Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

Area of Science:

• Metabolic regulation
• Endocrinology
• Molecular biology

Background:

• Hepatic glucose release is crucial for maintaining blood glucose homeostasis, especially during fasting.
• Hormonal regulation precisely controls plasma glucose levels.
• The role of specific fasting-induced hormones in hepatic glucose regulation requires further elucidation.

Purpose of the Study:

• To identify and characterize novel fasting-induced hormones that modulate hepatic glucose release.
• To investigate the mechanism of action of the identified hormone.
• To assess the therapeutic potential of targeting this hormone in metabolic disorders.

Main Methods:

• Identification of a novel protein hormone (Asprosin) from profibrillin cleavage.
• Measurement of circulating Asprosin levels in humans and mice.
• Investigation of Asprosin's signaling pathway in the liver (G protein-cAMP-PKA).
• Assessment of Asprosin's effect on glucose and insulin levels following immunologic or genetic ablation.

Main Results:

• Asprosin, a C-terminal cleavage product of profibrillin, is secreted by white adipose tissue.
• Asprosin activates the G protein-cAMP-PKA pathway in the liver, stimulating glucose release.
• Pathologically elevated Asprosin levels are observed in insulin-resistant humans and mice.
• Loss of Asprosin function leads to significant glucose and insulin reduction due to decreased hepatic glucose release.

Conclusions:

• Asprosin is a novel glucogenic protein hormone that plays a key role in regulating hepatic glucose release.
• Therapeutic targeting of Asprosin may offer a promising strategy for managing type II diabetes and metabolic syndrome.