ESPEYB15 11 Obesity and Weight Regulation Hungry fat cells (1 abstracts)
11.12 Asprosin is a centrally acting orexigenic hormone
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
Departments of Molecular and Cellular Biology, Molecular and Human Genetics, Children’s Nutrition Research Center, and Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
To read the full abstract: Nat Med. 2017 Dec; 23(12): 1444–1453
This study highlights the importance of asprosin in the regulation of appetite. This peptide hormone was first described by Romere et al. in 2016 (1), who reported 2 patients with neonatal progeroid syndrome (NPS) due to truncating heterozygous mutations in the fibrillin-gene (FBN1). The FBN1 gene encodes profibrillin which is cleaved by the protease furin, yielding mature fibrillin and a C-terminal cleavage product, asprosin. The mutation led to a 50% reduced asprosin concentration in serum, associated with extreme leanness. Usually, partial or general lipodystrophy leads to insulin resistance, which is not the case in these patients (1, 2). Asprosin is highly expressed in adipose tissue and its secretion stimulates hepatic glucose release and acts as an orexigenic agent in the hypothalamus (1). Like leptin, asprosin concentration rises with fasting and decreases with refeeding.
The authors showed that a single subcutaneous injection of recombinant asprosin in mice was able to rescue the hypophagia in Fbn1NPS/+ mice, suggesting an interaction with AgRP+ neurons. Additionally, asprosin inhibited by 85% signaling of anorexigenic POMC+ neurons. However, it might also be possible that asprosin promotes appetite by interacting with other anorexigenic or orexigenic neurons. A pharmaceutical treatment option in obese and insulin resistant patients might be to decrease asprosin concentrations by neutralizing antibodies. In this mouse model, antibodies neutralized asprosin, thereby lowering the activity of AgRp+ neurons and resulting in a reduced daily food intake. In summary, this work is highly relevant to further understand the regulation of hunger and satiety. Effects of asprosin should also be considered when investigating the leptin-melanocortin pathway in other studies.
1. Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, et al. Asprosin, a Fasting-Induced Glucogenic Protein Hormone. Cell. 2016;165(3):566-79.
2. Bindlish S, Presswala LS, Schwartz F. Lipodystrophy: Syndrome of severe insulin resistance. Postgraduate medicine. 2015;127(5):511-6.
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ESPE Yearbook of Paediatric Endocrinology
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