As a peripherally derived hormone, asprosin actively crosses the blood-brain barrier (BBB) to exert central effects on metabolic and behavioral regulation.
It stimulates the liver to release glucose into the bloodstream during fasting, ensuring energy availability, and influences appetite and body weight regulation by acting on hypothalamic neurons.
[1] The discovery of asprosin’s role as a fasting-induced glucogenic hormone, stimulating hepatic glucose release, stemmed from the observation of low plasma insulin levels in the two patients.
[2] To further investigate the condition, Chopra and colleagues developed a mouse model carrying the MPL mutation, which faithfully phenocopied the human disorder.
[2] These mice exhibited the same features as the patients, including low plasma asprosin levels, extreme thinness, reduced appetite, and resistance to diet-induced obesity and diabetes.
This model confirmed the role of asprosin in regulating appetite and body weight through its orexigenic effects on hypothalamic neurons and demonstrated its broader implications in metabolic health.
Since furin is expressed in a plethora of cell lines and tissues, the presence or lack of this enzyme does not narrow down the possible locations of asprosin secretion.
[22] This finding underscores a remarkable duality in asprosin’s function: it regulates both thirst and appetite by acting on the same receptor, PTPRD, while engaging distinct neuronal populations to orchestrate these vital survival behaviors.
[5][29] In a test of pharmacologic asprosin depletion in animals, preliminary results raised the possibility of its use, therapeutically, in treating type 2 diabetes and obesity.
[30] For instance, Chopra and coworkers observed that when monoclonal antibodies targeting asprosin were injected into diabetic mice, blood glucose and insulin levels improved.
[5][31] Mishra and colleagues have demonstrated that anti-asprosin mAbs (monoclonal antibody) are a dual-effect therapy that targets the two key pillars of metabolic syndrome – overnutrition and plasma glucose burden .
Specifically, anti-asprosin mAbs have been shown to reduce blood glucose, appetite, and body weight in various diet-induced and genetic models of metabolic syndrome.