Asprosin

Last updated
Fibrillin 1
Identifiers
Symbol FBN1
NCBI gene 2200
HGNC 3603
OMIM 134797
RefSeq NP_000129
UniProt P35555
Other data
Locus Chr. 15 q21.1
Search for
Structures Swiss-model
Domains InterPro

Asprosin is a fasting-induced hormone encoded by the FBN1 gene and derived from the cleavage of the fibrillin-1 protein, a structural component of the extracellular matrix. It is primarily produced and secreted by white adipose tissue. 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] [2] Dysregulation of asprosin levels has been implicated in metabolic disorders such as obesity and diabetes, [3] [4] making it a promising target for therapeutic interventions.

Contents

Discovery

Asprosin was first identified by Dr. Atul Chopra and colleagues at Baylor College of Medicine during their study of Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as neonatal progeroid syndrome (NPS), a rare genetic disorder caused by mutations in the FBN1 gene. These mutations produce truncated profibrillin-1 protein, resulting in two key effects: the production of a mutant fibrillin-1 protein and significantly reduced plasma asprosin levels due to a dominant-negative mechanism. [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. [1] A subsequent study by Chopra and colleagues investigated the patients’ extreme thinness and abnormally low appetite, uncovering asprosin’s additional role as an orexigenic hormone that regulates appetite through hypothalamic neurons. [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. The findings not only provided insights into the pathophysiology of MPL but also underscored asprosin's therapeutic potential in obesity and diabetes.

Profibrillin cleavage and asprosin secretion

The asprosin mechanism begins with the cleavage of profibrillin-1. While the specific cellular location of profibrillin-1 cleavage is largely unknown, it is speculated to occur between the trans-Golgi network and the cell surface, or upon fibrillin-1 secretion. Furin cleaves asprosin at the R-C-K/R-R motif in the C-terminal domain. This cleavage event is important because it is required for the incorporation of fibrillin-1 into the extracellular matrix. 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.

Evidence suggests that asprosin is secreted from white adipose tissue, which accounts for 5–50% of human body weight and is already known to secrete adipokines such as leptin and adiponectin. While FBN1 is expressed in many tissues, its highest expression in both humans and mice is in white adipose. However, since FBN1 (and thus, asprosin) is widely expressed in many human tissues, it is likely that white adipose is not the only source of plasma asprosin. There has been evidence connecting asprosin secretion from wild-type human dermal fibroblasts suggesting that it may be secreted from skin. [5] It was also discovered that MIN6 pancreatic β-cells and human primary islets containing β-cells secrete asprosin and that secretion is induced by palmitate in a dose-dependent manner. [6] Asprosin has also been detected in saliva samples.

Function

Once in the circulation, asprosin targets the liver and the brain.

Hepatic Function

The liver stores excess glucose in the form of glycogen after a meal, in response to insulin. Between meals (or during fasting), the liver is stimulated to break down this glycogen to release glucose (glycogenolysis) and also synthesizes new glucose (gluconeogenesis); this glucose is released into the bloodstream to maintain normal function of the brain and other organs that burn glucose for energy. Glycogenolysis and gluconeogenesis are stimulated by hormones such as glucagon that activate the cyclic AMP pathway in liver hepatocytes, and this cAMP promotes activation of metabolic enzymes leading to glucose production and release; asprosin appears to utilize this same system of control. [7] [8] Asprosin was reported to stimulate glucose release from hepatocytes, and plasma levels of asprosin in obese high-fat-fed mice have been reported to nearly double. [5] However, in a study in 2019, a pharma replication group reported their inability to replicate these two key observations using recombinant asprosin, suggesting that issues with reagent purity may have been responsible for the effect observed in the initial asprosin study. [9] Nevertheless, a third group reported in 2019 that they had identified the liver receptor for asprosin, OR4M1, an olfactory receptor family GPCR, and showed that plasma asprosin levels increased with fasting and with diet-induced obesity, and confirmed asprosin's effect on stimulation of hepatic glucose production, replicating all facets of the original study. [10] Several studies have since confirmed asprosin's glucogenic function. [11] [12] [13] [14] [15] [16] [17]

Central Function

Asprosin can also exit the bloodstream and cross the blood–brain barrier to function in the brain. The first indication that asprosin was in fact a cerebrospinal fluid (CSF) protein, in addition to being a plasma protein, was the observation of asprosin in the CSF of rats at concentrations 5- to 10-fold lower than in the plasma. Additionally, intravenously introduced asprosin showed a dramatic ability to cross the blood–brain barrier and enter the CSF. [18] Asprosin induces appetite via activation of orexigenic AgRP neurons and deactivation of anorexigenic POMC neurons in the arcuate nucleus of the hypothalamus. [18] Asprosin’s orexigenic effects are mediated through binding to protein tyrosine phosphatase receptor delta (PTPRD). [19] Whole body deletion of Ptprd results in reduced appetite and extreme leanness (mirroring the effects of deficient asprosin) while selective loss of Ptprd in just AgRP neurons leads to reduced appetite and protection from diet-induced obesity.  Dr. Yanlin He and colleagues showed that the small-conductance calcium-activated potassium (SK) channel is required for the stimulatory effects of asprosin/Ptprd on AgRP neurons and appetite, and recorded asprosin-mediated activation of AgRP neurons in awake/behaving mice using fiber photometry. [20]

PTPRD is highly expressed throughout the brain, with particularly high levels in the cerebellum and cerebellar hemispheres, [21] leading to the discovery of the cerebellum's role in thirst regulation. Researchers demonstrated that asprosin directly activates cerebellar Purkinje neurons to modulate fluid intake in a Ptprd-dependent manner, notably without affecting the well-established role of Purkinje neurons in motor coordination. [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.

Classification

Asprosin is a protein hormone, but is unique in its generation as the C-terminal cleavage product of a large extracellular matrix protein. Therefore, it has been postulated to belong to a new protein hormone subclass: caudamins. It has been placed in this subclass along with the hormones: endostatin, endotrophin and placensin. [23] Members of this class are derived from a cleavage event that also generates a much larger, functionally unrelated, nonhormonal protein. The subclass was named caudamins, from the Latin word cauda meaning 'tail'.

Clinical significance

Asprosin

Obesity is characterized by an overall increase in adiposity and, given that asprosin is secreted by adipose tissue, it is not surprising that both obese humans and mice show pathologically elevated levels of asprosin compared with control subjects. Patients presenting with insulin resistance and obesity have elevated serum levels of asprosin, [24] [4] and female patients with polycystic ovary syndrome have particularly high serum levels. [25] Obese patients undergoing bariatric surgery for weight loss show decreased asprosin levels in serum after surgery. [26]

Asprosin-induced hyperphagia and hepatic glucose production could therefore be mechanisms that drive development of metabolic syndrome. [27]

Fibrillin-1

Fibrillin-1 is important for the formation of elastic fibers in connective tissues, and patients with mutations in FBN1 gene exhibit Marfan syndrome. [28] Individuals with Marfanoid–progeroid–lipodystrophy syndrome (MPL) are deficient in asprosin due to mutations affecting the carboxy terminus of the profibrillin-1 protein and its processing into fibrillin-1 and asprosin. [5] [29]

Therapeutic potential

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]

Monoclonal anti-asprosin antibody

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. These findings have led to an effort to optimize and develop clinical-grade anti-asprosin mAbs for use in humans. [32] Asprosin has also been reported to cross the blood–brain barrier to regulate neurons in the hypothalamus of the brain known to regulate hunger and satiety, and inhibiting asprosin in obese mice reduced feeding and led to decreased body weight. [18] [33]

Related Research Articles

<span class="mw-page-title-main">Insulin</span> Peptide hormone

Insulin is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats, and protein by promoting the absorption of glucose from the blood into cells of the liver, fat, and skeletal muscles. In these tissues the absorbed glucose is converted into either glycogen, via glycogenesis, or fats (triglycerides), via lipogenesis; in the liver, glucose is converted into both. Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules in the cells. Low insulin in the blood has the opposite effect, promoting widespread catabolism, especially of reserve body fat.

Insulin resistance (IR) is a pathological condition in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.

<span class="mw-page-title-main">Alpha cell</span> Glucagon secreting cell

Alpha cells (α-cells) are endocrine cells that are found in the Islets of Langerhans in the pancreas. Alpha cells secrete the peptide hormone glucagon in order to increase glucose levels in the blood stream.

<span class="mw-page-title-main">Adiponectin</span> Mammalian protein found in Homo sapiens

Adiponectin is a protein hormone and adipokine, which is involved in regulating glucose levels and fatty acid breakdown. In humans, it is encoded by the ADIPOQ gene and is produced primarily in adipose tissue, but also in muscle and even in the brain.

<span class="mw-page-title-main">Ghrelin</span> Peptide hormone involved in appetite regulation

Ghrelin is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid.

<span class="mw-page-title-main">Gastric inhibitory polypeptide</span> Mammalian protein found in Homo sapiens

Gastric inhibitory polypeptide(GIP), also known as glucose-dependent insulinotropic polypeptide, is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.

<span class="mw-page-title-main">Agouti-related peptide</span> Mammalian protein found in Homo sapiens

Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus. AgRP is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators. In humans, the agouti-related peptide is encoded by the AGRP gene.

<span class="mw-page-title-main">GLUT4</span> Protein

Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the SLC2A4 gene. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle. GLUT4 is distinctive because it is predominantly stored within intracellular vesicles, highlighting the importance of its trafficking and regulation as a central area of research. The first evidence for this glucose transport protein was provided by David James in 1988. The gene that encodes GLUT4 was cloned and mapped in 1989.

Nesfatin-1 is a neuropeptide produced in the hypothalamus of mammals. It participates in the regulation of hunger and fat storage. Increased nesfatin-1 in the hypothalamus contributes to diminished hunger, a 'sense of fullness', and a potential loss of body fat and weight.

<span class="mw-page-title-main">Blood sugar regulation</span> Hormones regulating blood sugar levels

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<span class="mw-page-title-main">Obesogen</span> Foreign chemical compound that disrupts lipid balance causing obesity

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<span class="mw-page-title-main">G protein-coupled bile acid receptor</span> Protein-coding gene in the species Homo sapiens

The G protein-coupled bile acid receptor 1 (GPBAR1) also known as G-protein coupled receptor 19 (GPCR19), membrane-type receptor for bile acids (M-BAR) or Takeda G protein-coupled receptor 5 (TGR5) is a protein that in humans is encoded by the GPBAR1 gene. Activated by bile acids, these receptors play a crucial role in metabolic regulation, including insulin secretion and energy balance, and are found in the gastrointestinal tract as well as other tissues throughout the body.

<span class="mw-page-title-main">Fibrillin-1</span> Protein found in humans

Fibrillin-1 is a protein that in humans is encoded by the FBN1 gene, located on chromosome 15. It is a large, extracellular matrix glycoprotein that serves as a structural component of 10–12 nm calcium-binding microfibrils. These microfibrils provide force bearing structural support in elastic and nonelastic connective tissue throughout the body. Mutations altering the protein can result in a variety of phenotypic effects differing widely in their severity, including fetal death, developmental problems, Marfan syndrome or in some cases Weill-Marchesani syndrome.

<span class="mw-page-title-main">Free fatty acid receptor 1</span> Protein-coding gene in the species Homo sapiens

Free fatty acid receptor 1 (FFAR1), also known as G-protein coupled receptor 40 (GPR40), is a rhodopsin-like G-protein coupled receptor that is coded by the FFAR1 gene. This gene is located on the short arm of chromosome 19 at position 13.12. G protein-coupled receptors reside on their parent cells' surface membranes, bind any one of the specific set of ligands that they recognize, and thereby are activated to trigger certain responses in their parent cells. FFAR1 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes at least three other FFARs viz., FFAR2, FFAR3, and FFAR4. FFARs bind and thereby are activated by certain fatty acids.

<span class="mw-page-title-main">PTPRD</span> Protein-coding gene in humans

Receptor-type tyrosine-protein phosphatase delta is an enzyme that, in humans, is encoded by the PTPRD gene.

The diet-induced obesity model is an animal model used to study obesity using animals that have obesity caused by being fed high-fat or high-density diets. It is intended to mimic the most common cause of obesity in humans. Typically mice, rats, dogs, or non-human primates are used in these models. These animals can then be used to study in vivo obesity, obesity's comorbidities, and other related diseases. Users of such models must take into account the duration and type of diet as well as the environmental conditions and age of the animals, as each may promote different bodyweights, fat percentages, or behaviors.

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<span class="mw-page-title-main">Marfanoid–progeroid–lipodystrophy syndrome</span> Medical condition

Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as Marfan lipodystrophy syndrome (MFLS) or progeroid fibrillinopathy, is an extremely rare medical condition which manifests as a variety of symptoms including those usually associated with Marfan syndrome, an appearance resembling that seen in neonatal progeroid syndrome, and severe partial lipodystrophy. It is a genetic condition that is caused by mutations in the FBN1 gene, which encodes profibrillin, and affects the cleavage products of profibrillin, fibrillin-1, a fibrous structural protein, and asprosin, a glucogenic protein hormone. As of 2016, fewer than 10 cases of the condition have been reported. Lizzie Velásquez and Abby Solomon have become known publicly through the media for having the condition.

Hepatokines are proteins produced by liver cells (hepatocytes) that are secreted into the circulation and function as hormones across the organism. Research is mostly focused on hepatokines that play a role in the regulation of metabolic diseases such as diabetes and fatty liver and include: Adropin, ANGPTL4, Fetuin-A, Fetuin-B, FGF-21, Hepassocin, LECT2, RBP4,Selenoprotein P, Sex hormone-binding globulin.

References

  1. 1 2 3 Romere, Chase; Duerrschmid, Clemens; Bournat, Juan; Constable, Petra; Jain, Mahim; Xia, Fan; Saha, Pradip K.; Del Solar, Maria; Zhu, Bokai; York, Brian; Sarkar, Poonam; Rendon, David A.; Gaber, M. Waleed; LeMaire, Scott A.; Coselli, Joseph S. (2016-04-21). "Asprosin, a Fasting-Induced Glucogenic Protein Hormone". Cell. 165 (3): 566–579. doi:10.1016/j.cell.2016.02.063. ISSN   1097-4172. PMC   4852710 . PMID   27087445.
  2. 1 2 3 Duerrschmid, Clemens; He, Yanlin; Wang, Chunmei; Li, Chia; Bournat, Juan C.; Romere, Chase; Saha, Pradip K.; Lee, Mark E.; Phillips, Kevin J.; Jain, Mahim; Jia, Peilin; Zhao, Zhongming; Farias, Monica; Wu, Qi; Milewicz, Dianna M. (December 2017). "Asprosin is a centrally acting orexigenic hormone". Nature Medicine. 23 (12): 1444–1453. doi:10.1038/nm.4432. ISSN   1546-170X. PMC   5720914 . PMID   29106398.
  3. Mahat, Roshan Kumar; Jantikar, Ashwini Manish; Rathore, Vedika; Panda, Suchismita (January 2024). "Circulating asprosin levels in type 2 diabetes mellitus: A systematic review and meta-analysis". Clinical Epidemiology and Global Health. 25: 101502. doi:10.1016/j.cegh.2023.101502. ISSN   2213-3984. Archived from the original on 2024-01-25.
  4. 1 2 Zhang, Y.; Yang, P.; Zhang, X.; Liu, S.; Lou, K. (August 2024). "Asprosin: its function as a novel endocrine factor in metabolic-related diseases". Journal of Endocrinological Investigation. 47 (8): 1839–1850. doi:10.1007/s40618-024-02360-z. ISSN   1720-8386. PMID   38568373.
  5. 1 2 3 4 Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, et al. (April 2016). "Asprosin, a Fasting-Induced Glucogenic Protein Hormone". Cell. 165 (3): 566–579. doi:10.1016/j.cell.2016.02.063. PMC   4852710 . PMID   27087445.
  6. Lee T, Yun S, Jeong JH, Jung TW (April 2019). "Asprosin impairs insulin secretion in response to glucose and viability through TLR4/JNK-mediated inflammation". Molecular and Cellular Endocrinology. 486: 96–104. doi:10.1016/j.mce.2019.03.001. PMID   30853600. S2CID   72334358.
  7. Levine R (1986). "Monosaccharides in health and disease". Annual Review of Nutrition. 6: 211–224. doi:10.1146/annurev.nu.06.070186.001235. PMID   3524617.
  8. Röder PV, Wu B, Liu Y, Han W (March 2016). "Pancreatic regulation of glucose homeostasis". Experimental & Molecular Medicine. 48 (3, March): e219. doi:10.1038/emm.2016.6. PMC   4892884 . PMID   26964835.
  9. von Herrath M, Pagni PP, Grove K, Christoffersson G, Tang-Christensen M, Karlsen AE, Petersen JS (April 2019). "Case Reports of Pre-clinical Replication Studies in Metabolism and Diabetes". Cell Metabolism. 29 (4): 795–802. doi: 10.1016/j.cmet.2019.02.004 . PMID   30879984.
  10. Li E, Shan H, Chen L, Long A, Zhang Y, Liu Y, et al. (August 2019). "OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin". Cell Metabolism. 30 (2): 319–328.e8. doi: 10.1016/j.cmet.2019.05.022 . PMID   31230984.
  11. Wei, Xuejing; Ao, Qingqing; Meng, Ling; Xu, Yilu; Lu, Cailing; Tang, Shen; Wang, Xinhang; Li, Xiyi (2020-01-30). "[Expression, purification and functional assessment of asprosin inclusion body]". Nan Fang Yi Ke da Xue Xue Bao = Journal of Southern Medical University. 40 (1): 67–72. doi:10.12122/j.issn.1673-4254.2020.01.11. ISSN   1673-4254. PMC   7040760 . PMID   32376560.
  12. Zhang, Yunhua; Zhu, Ziming; Zhai, Wenbo; Bi, Yanghui; Yin, Yue; Zhang, Weizhen (March 2021). "Expression and purification of asprosin in Pichia pastoris and investigation of its increase glucose uptake activity in skeletal muscle through activation of AMPK". Enzyme and Microbial Technology. 144: 109737. doi:10.1016/j.enzmictec.2020.109737. ISSN   1879-0909. PMID   33541572.
  13. Wei, Fangchao; Long, Aijun; Wang, Yiguo (2019). "The Asprosin-OLFR734 hormonal signaling axis modulates male fertility". Cell Discovery. 5: 55. doi:10.1038/s41421-019-0122-x. ISSN   2056-5968. PMC   6868220 . PMID   31798959.
  14. Yu, Yiping; He, Jia-Huan; Hu, Lin-Li; Jiang, Lin-Lin; Fang, Lanlan; Yao, Gui-Dong; Wang, Si-Jia; Yang, Qingling; Guo, Yanjie; Liu, Lin; Shang, Trisha; Sato, Yorino; Kawamura, Kazuhiro; Hsueh, Aaron Jw; Sun, Ying-Pu (2020-06-04). "Placensin is a glucogenic hormone secreted by human placenta". EMBO Reports. 21 (6): e49530. doi:10.15252/embr.201949530. ISSN   1469-3178. PMC   7271319 . PMID   32329225.
  15. Lu, Yanli; Yuan, Wanwan; Xiong, Xiaowei; Huang, Qianqian; Chen, Sheng; Yin, Tingting; Zhang, Yanan; Wang, Zhie; Zeng, Guohua; Huang, Qiren (March 2023). "Asprosin aggravates vascular endothelial dysfunction via disturbing mitochondrial dynamics in obesity models". Obesity (Silver Spring, Md.). 31 (3): 732–743. doi:10.1002/oby.23656. ISSN   1930-739X. PMID   36693798.
  16. Mishra, Ila; Duerrschmid, Clemens; Ku, Zhiqiang; He, Yang; Xie, Wei; Silva, Elizabeth Sabath; Hoffman, Jennifer; Xin, Wei; Zhang, Ningyan; Xu, Yong; An, Zhiqiang; Chopra, Atul R. (2021-04-27). "Asprosin-neutralizing antibodies as a treatment for metabolic syndrome". eLife. 10: e63784. doi: 10.7554/eLife.63784 . ISSN   2050-084X. PMC   8102062 . PMID   33904407.
  17. Mishra, Ila; Xie, Wei Rose; Bournat, Juan C.; He, Yang; Wang, Chunmei; Silva, Elizabeth Sabath; Liu, Hailan; Ku, Zhiqiang; Chen, Yinghua; Erokwu, Bernadette O.; Jia, Peilin; Zhao, Zhongming; An, Zhiqiang; Flask, Chris A.; He, Yanlin (2022-04-05). "Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor". Cell Metabolism. 34 (4): 549–563.e8. doi:10.1016/j.cmet.2022.02.012. ISSN   1932-7420. PMC   8986618 . PMID   35298903.
  18. 1 2 3 Duerrschmid C, He Y, Wang C, Li C, Bournat JC, Romere C, et al. (December 2017). "Asprosin is a centrally acting orexigenic hormone". Nature Medicine. 23 (12): 1444–1453. doi:10.1038/nm.4432. PMC   5720914 . PMID   29106398.
  19. Mishra I, Xie WR, Bournat JC, He Y, Wang C, Silva ES, et al. (April 2022). "Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor". Cell Metabolism. 34 (4): 549–563.e8. doi:10.1016/j.cmet.2022.02.012. PMC   8986618 . PMID   35298903.
  20. Feng, Bing; Liu, Hesong; Mishra, Ila; Duerrschmid, Clemens; Gao, Peiyu; Xu, Pingwen; Wang, Chunmei; He, Yanlin (2023-02-22). "Asprosin promotes feeding through SK channel-dependent activation of AgRP neurons". Science Advances. 9 (8): eabq6718. Bibcode:2023SciA....9.6718F. doi:10.1126/sciadv.abq6718. ISSN   2375-2548. PMC   9946352 . PMID   36812308.
  21. "GTEx Portal". www.gtexportal.org. Retrieved 2025-01-15.
  22. Mishra, Ila; Feng, Bing; Basu, Bijoya; Brown, Amanda M.; Kim, Linda H.; Lin, Tao; Raza, Mir Abbas; Moore, Amelia; Hahn, Abigayle; Bailey, Samantha; Sharp, Alaina; Bournat, Juan C.; Poulton, Claire; Kim, Brian; Langsner, Amos (September 2024). "The cerebellum modulates thirst". Nature Neuroscience. 27 (9): 1745–1757. doi:10.1038/s41593-024-01700-9. ISSN   1546-1726. PMID   38987435.
  23. Basu B, Jain M, Chopra AR (December 2021). "Caudamins, a new subclass of protein hormones". Trends in Endocrinology and Metabolism. 32 (12): 1007–1014. doi:10.1016/j.tem.2021.09.005. PMC   8585694 . PMID   34666940. S2CID   238996604.
  24. Mahat, Roshan Kumar; Jantikar, Ashwini Manish; Rathore, Vedika; Panda, Suchismita (2024-01-01). "Circulating asprosin levels in type 2 diabetes mellitus: A systematic review and meta-analysis". Clinical Epidemiology and Global Health. 25: 101502. doi:10.1016/j.cegh.2023.101502. ISSN   2213-3984.
  25. Alan M, Gurlek B, Yilmaz A, Aksit M, Aslanipour B, Gulhan I, et al. (March 2019). "Asprosin: a novel peptide hormone related to insulin resistance in women with polycystic ovary syndrome". Gynecological Endocrinology. 35 (3): 220–223. doi:10.1080/09513590.2018.1512967. PMID   30325247. S2CID   53290102.
  26. Wang CY, Lin TA, Liu KH, Liao CH, Liu YY, Wu VC, et al. (May 2019). "Serum asprosin levels and bariatric surgery outcomes in obese adults". International Journal of Obesity. 43 (5): 1019–1025. doi:10.1038/s41366-018-0248-1. PMID   30459402. S2CID   53872918.
  27. Yuan M, Li W, Zhu Y, Yu B, Wu J (2020). "Asprosin: A Novel Player in Metabolic Diseases". Frontiers in Endocrinology. 11: 64. doi: 10.3389/fendo.2020.00064 . PMC   7045041 . PMID   32153505.
  28. "What Is Marfan Syndrome?". NHLBI, NIH. October 1, 2010. Archived from the original on 6 May 2016. Retrieved 16 May 2016.
  29. Grens K (April 15, 2016). "Newly Discovered Hormone Explains Disease". The Scientist . Retrieved 18 April 2016.
  30. Greenhill C (June 2016). "Liver: Asprosin - new hormone involved in hepatic glucose release". Nature Reviews. Endocrinology. 12 (6): 312. doi:10.1038/nrendo.2016.66. PMID   27125501. S2CID   37629594.
  31. Pathak, Dipali (Apr 14, 2016). "Discovery of Asprosin, New Hormone Could Have Potential Implications in Treatment of Diabetes". Houston, TX: Baylor College of Medicine . Retrieved 18 April 2016.
  32. Mishra I, Duerrschmid C, Ku Z, He Y, Xie W, Silva ES, et al. (April 2021). Isales M, Zaidi C, Isales C (eds.). "Asprosin-neutralizing antibodies as a treatment for metabolic syndrome". eLife. 10: e63784. doi: 10.7554/eLife.63784 . PMC   8102062 . PMID   33904407.
  33. Beutler LR, Knight ZA (February 2018). "A Spotlight on Appetite". Neuron. 97 (4): 739–741. doi:10.1016/j.neuron.2018.01.050. PMC   5965268 . PMID   29470967.