Asprosin is a centrally acting orexigenic hormone
Open accessAbstract
Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood-brain barrier and directly activates orexigenic AgRP+ neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin. Furthermore, we found that obese humans and mice had pathologically elevated concentrations of circulating asprosin, and neutralization of asprosin in the blood with a monoclonal antibody reduced appetite and body weight in obese mice, in addition to improving their glycemic profile. Thus, in addition to performing a glucogenic function, asprosin is a centrally acting orexigenic hormone that is a potential therapeutic target in the treatment of both obesity and diabetes.
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Asprosin can directly target the CNS to increase food intake.
“Additionally, asprosin can directly target the central nervous system (CNS) to increase food intake 60.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [60]
Circulating asprosin levels are higher in obese humans and mice.
“Circulating asprosin levels are higher in obese humans and mice 60.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [60]
High asprosin could contribute to the difficulties to obtain a voluntary reduction in food intake in obese patients due to its orexigenic effects.
“Due to the orexigenic effects of this hormone, this alteration could contribute to the difficulties to obtain a voluntary reduction in food intake in obese patients 60.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [60]
Asprosin can be targeted to modulate food intake and lower glycemia in obese subjects.
“More recently, a neutralizing antibody against asprosin was used in obese mice to reduce appetite, body weight, and blood glucose, suggesting that this orexigenic hormone can be targeted to modulate food intake and lower glycemia in obese subjects 60.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [60]
A neutralizing antibody against asprosin reduces appetite, body weight, and blood glucose in obese mice.
“More recently, a neutralizing antibody against asprosin was used in obese mice to reduce appetite, body weight, and blood glucose, suggesting that this orexigenic hormone can be targeted to modulate food intake and lower glycemia in obese subjects 60.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [60]
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- Authors
- Duerrschmid, C., He, Y., Wang, C., Li, C., Bournat, J. C., Romere, C., Saha, P. K., Lee, M. E., Phillips, K. J., Jain, M., Jia, P., Zhao, Z., Farias, M., Wu, Q., Milewicz, D. M., Sutton, V. R., Moore, D. D., Butte, N. F., Krashes, M. J., Xu, Y., & Chopra, A. R.
- Affiliations
- Baylor College of Medicine (US)
- National Institutes of Health (US)
- Kennedy Krieger Institute (US)
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Xu, Yong
- Chopra, Atul R
- ORCID
- Venue
- Nature Medicine
- Published
- 2017-11-06
- Volume
- 23
- Issue
- 12
- Pages
- 1444-1453
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC5720914
- OpenAlex
- W2767694961
- Cited by
- 357
- References
- 32
- Citations by year
- 2026: 45 · 2025: 37 · 2024: 45 · 2023: 44 · 2022: 55 · 2021: 48 · 2020: 38 · 2019: 27 · 2018: 16 · 2012: 1
- FWCI
- 13.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Diabetes Association (1-17-PDF-138, 16POST27260254)
- American Heart Association (16POST29630010)
- National Institutes of Health (5r01dk111631-04)
- National Human Genome Research Institute (UM1HG006542, UM1HG006348)
- National Cancer Institute (P30CA125123, P30CA016086)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK101379, K08DK102529, P30DK079638, R01 DK111631, R01DK093587, R56DK109194)
- U.S. National Library of Medicine (R01LM012806)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- asprosin, orexigenic hormones, food intake regulation, AgRP neurons, POMC neurons, GABA signaling, cAMP signaling, blood-brain barrier, hepatic glucose production, appetite, obesity, diabetes mellitus, adipose tissue, monoclonal antibodies, body weight
- MeSH terms
- Fibrillin-1, Adolescent, Adult, Animals, Appetite Depressants, Appetite Regulation, Female, Humans, Hypothalamus, Male, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Neurons, Peptide Fragments, Signal Transduction, Peptide Hormones, Mice, Rats, Adipokines, Young Adult
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