Asprosin is a protein hormone discovered in 2016. It acts as a messenger within the body’s communication network, regulating energy balance and influencing how the body manages fuel resources. Understanding asprosin’s functions offers insights into human health and disease.
Biological Origin of Asprosin
Asprosin originates primarily from white adipose tissue, commonly known as fat cells, which produce and secrete this hormone. The genetic blueprint for asprosin is found within the FBN1 gene, which provides instructions for creating a larger precursor protein called profibrillin-1.
Profibrillin-1 undergoes an enzymatic cutting process by furin, yielding two products. One is fibrillin-1, a component of connective tissues. The other is asprosin, a 140-amino acid protein that circulates as a hormone. This mechanism ensures a single gene contributes to both structural components and circulating signals.
How Asprosin Regulates Metabolism
Asprosin functions as a fasting hormone, signaling the body when energy reserves are low. When blood sugar levels decrease, asprosin is released from white adipose tissue into the bloodstream. It then travels to the liver, where it prompts the release of stored glucose.
This action in the liver helps maintain stable blood glucose levels, supplying energy to organs like the brain. Asprosin achieves this by activating a signaling pathway involving cyclic adenosine monophosphate (cAMP) via the OLFR734 receptor on liver cells. Asprosin also travels to the hypothalamus in the brain, where it signals to increase appetite, acting like a low-fuel warning light. It activates AgRP neurons and suppresses POMC neurons, which regulate hunger and satiety.
Connection to Metabolic and Genetic Disorders
Elevated asprosin levels are associated with several metabolic disorders. Individuals with obesity, insulin resistance, and type 2 diabetes often exhibit chronically high circulating asprosin. The continuous signal from excess asprosin to release glucose can overwhelm the body’s ability to manage blood sugar, contributing to these conditions and exacerbating metabolic imbalance.
Asprosin is also linked to Polycystic Ovary Syndrome (PCOS), a common endocrine disorder in women, where higher asprosin levels correlate with insulin resistance. Conversely, Neonatal Progeroid Syndrome (NPS) is a rare genetic condition characterized by too little asprosin. Patients with NPS often present with symptoms such as extremely low body fat, reduced appetite, and a lean body composition, alongside low blood glucose and insulin levels.
The study of NPS patients, who have FBN1 gene mutations leading to profoundly decreased asprosin, was instrumental in the hormone’s discovery. These individuals provided direct evidence of asprosin’s role in fat accumulation and metabolic regulation. Understanding the consequences of both excess and deficiency of asprosin offers insights into the complex interplay of hormones in metabolic health.
Future Therapeutic Applications
The discovery of asprosin’s role in metabolism opens several avenues for future medical interventions. One promising area involves developing treatments that block or neutralize asprosin’s activity. Monoclonal antibodies designed to target asprosin have shown potential in preclinical studies, demonstrating the ability to lower blood sugar, reduce appetite, and promote weight loss in animal models of obesity and type 2 diabetes. These antibodies aim to counteract the effects of excess asprosin.
Conversely, researchers are exploring whether administering asprosin could be beneficial in conditions characterized by dangerously low blood sugar or insufficient appetite. This approach presents a possibility for addressing specific metabolic challenges. Furthermore, asprosin’s levels in the blood could serve as a biomarker. Monitoring asprosin concentrations might help doctors diagnose or track the progression of metabolic diseases, including type 2 diabetes and its complications like diabetic kidney disease.