Identification of a New Adipogenic and Inflammogenic Hormone, Asprosin
Aprosin helps treat fat metabolism at one of its key biological nodes without having to rely on appetite suppression or increase
Obesity is a leading cause of preventable death worldwide. While diet and exercise are the simplest cures for this disease, in some cases, patients may need weight-loss drugs. These treatments may be helpful in cases where the patient must meet a certain weight to safely use exercise equipment or become a candidate for gastric bypass surgical procedures. Additionally, patients who manage diabetes may also benefit from a new drug that help to regulate their appetite, blood glucose release, and adipose metabolism. In contrast, there are individuals who have genetic disorders that prevent or severely reduce adipose deposition and regulation, such as in lipodystrophies like Neonatal Progeroid Syndrome (NPS). Many organs are involved in the regulation of glucose and adipose metabolism and fat deposition in the body, presenting a significant scientific challenge.
Currently, there are only five FDA-approved weight loss drugs available in the U.S. Two of the drugs work to suppress appetite by mimicking the hormone glucagon-like peptide 1 (GLP-1). Orlistat (Xenical) helps by working in the gut to prevent fat absorption from food that is consumed. The other FDA-approved weight loss treatments are drugs that were developed to treat other disorders but are known to suppress appetite. About half of the medications are available by injection only. Many of these drugs come with adverse side effects that can heavily outweigh the benefits of taking the medication and may only be used for a short period of time. Currently, there is only one FDA-approved drug, Metreleptin, a leptin replacement therapy, used to treat lipodystrophy.
The researchers have identified a peptide hormone that is cleaved from the C-terminus of the protein profibrillin, from the gene fibrillin-1 (FBN1). FBN1 mutations can cause Marfan Syndrome and lipodystrophies such as NPS. This peptide hormone, which the researchers have termed asprosin, is responsible for regulating glucose homeostasis. Asprosin was found to be secreted by white adipose tissue, where it circulates into the blood stream to reach the liver and activate glucose release. Using a combination of in vitro cultured human adipocytes, differentiated from human dermal fibroblasts from unaffected and NPS-affected patients, and mouse models, the researchers found that asprosin is capable of regulating glucose release and hepatic lipid deposition.
Administration of synthesized asprosin peptide is sufficient to cause a release in glucose and an increase in insulin in mice, which would help excess glucose be converted into lipids and stored as fat, ultimately helping an individual to gain weight.
Administration of an antibody to block circulating asprosin could be used to help prevent glucose release and suppress adipose generation, helping an individual to lose weight. Asprosin administration or reduction could also be used to help in the regulation of circulating blood glucose, aiding diabetic patients to maintain greater control over their blood glucose levels.
Stage of Development
This technology has been validated using in vitro human cell culture and in vivo mouse models. A genetic condition validates the hypothesis of the therapy and how it works. In addition, a tool antibody to asprosin has also been developed.
Romere, C., Duerrschmid, C., Bournat, J., Constable, P., Jain, M., Xia, F., Saha, P.K., Del Solar, M., Zhu, B., York, B., Sarkar, P., Rendon, D.A., Gaber, M.W., LeMaire, S.A., Coselli, J.S., Milewicz, D.M., Sutton, V.R., Butte, N.F., Moore, D.D., Chopra, A.R. (2016). Asprosin, a fasting-induced glucogenic protein hormone. Cell 165, 566-579 doi: 10.1016/j.cell.2016.02.063
Duerrschmid C, He Y, Wang C, Li C, Bournat JC, Romere C, Saha PK, Lee ME, Phillips KJ, Jain M, Jia P, Zhao Z, Farias M, Wu Q, Milewicz DM, Sutton VR, Moore DD, Butte NF, Krashes MJ, Xu Y, Chopra AR. (2017) Asprosin is a centrally acting orexigenic hormone.Nat Med. Dec;23(12):1444-1453. doi: https://doi.org/10.1038/nm.4432
- Helps treat fat metabolism at one of its key biological nodes—regulation of blood glucose release—without having to rely on appetite suppression or appetite increase as the main method of action.
- Highly targetable peptide hormone that would only need administration of small amounts of the drug to reduce asprosin levels and aid in weight loss.
- Natural human peptide with the ability to be easily produced synthetically for aiding patients with lipodystrophies.
- Only one drug exists to treat lipodystrophies—this new treatment will expand the market and give doctors and patients another option to help treat their condition.
- Potential to act as a drug to help regulate blood glucose in patients with diabetes.
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- Patent application submitted