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Adropin

From Wikipedia, the free encyclopedia

ENHO
Identifiers
AliasesENHO, C9orf165, UNQ470, energy homeostasis associated
External IDsMGI: 1916888; HomoloGene: 104312; GeneCards: ENHO; OMA:ENHO - orthologs
Orthologs
SpeciesHumanMouse
Entrez

375704

69638

Ensembl

ENSG00000168913

ENSMUSG00000028445

UniProt

Q6UWT2

Q8K1D8

RefSeq (mRNA)

NM_198573

NM_027147

RefSeq (protein)

NP_940975

NP_081423

Location (UCSC)Chr 9: 34.52 – 34.52 MbChr 4: 41.64 – 41.64 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Adropin is a protein encoded by the energy homeostasis-associated gene ENHO in humans[5] and is highly conserved across mammals.[6]

The biological role of adropin was first described in mice by Andrew Butler's team. They identified it as a protein hormone (hepatokine) secreted from the liver, playing a role in obesity and energy homeostasis. The name "Adropin" is derived from the Latin words "aduro" (to set fire to) and "pinguis" (fat).[7] Adropin is produced in various tissues, including the liver, brain, heart, and gastrointestinal tract.[8]

In animals, adropin regulates carbohydrate and lipid metabolism[9] and influences endothelial function.[10][11] Its expression in the liver is controlled by feeding status, macronutrient content,[9] as well as by the biological clock.[12] Liver adropin is upregulated by estrogen[13] via the estrogen receptor alpha (ERα).[14]

In humans, lower levels of circulating adropin are linked to several medical conditions, including the metabolic syndrome, obesity, and inflammatory bowel disease.[15] and inflammatory bowel disease.[16] The brain exhibits the highest levels of adropin expression,[17] In the brain, adropin has been shown to have a potential protective role against neurological disease,[18] where it may play a protective role against neurological diseases, brain aging, cognitive decline, and acute ischemia.[19][20] as well as following acute ischemia.[21]

The orphan G protein-coupled receptor GPR19 has been proposed as a receptor for adropin.[22][23]

Structure

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Predicted structure of Adropin (AlphaFold)

Adropin is a small protein composed of 76 amino acids, and it is produced primarily in the liver and the brain. The precursor of adropin is a larger protein called Energy Homeostasis-Associated (ENHO), and adropin is released through the cleavage of ENHO.[5]

Receptors and targets

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The specific receptors for adropin are not yet fully elucidated, and this is an area of active research. However, studies suggest that adropin might exert its effects by interacting with certain cell surface receptors.[24]

Function

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Metabolic

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One of the primary areas of interest regarding adropin is its role in metabolic regulation. Research indicates that adropin may play a crucial role in glucose and lipid metabolism. It has been associated with insulin sensitivity, suggesting a potential role in the regulation of blood sugar levels.[25]

In animal studies, alterations in adropin levels have been linked to changes in energy expenditure and body weight. For example, some studies have shown that mice with elevated adropin levels tend to be more resistant to diet-induced obesity.[26]

A study in humans demonstrated that changes in vascular insulin resistance following short-term adverse lifestyle changes were associated with a decrease in plasma adropin in men but not women,[27] perhaps related to adropin's regulation by estrogen.[13]

Cardiovascular

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Adropin also appears to have cardiovascular effects. It has been implicated in the regulation of endothelial function, which is essential for maintaining blood vessel health. Dysfunction in endothelial cells can contribute to conditions such as atherosclerosis and hypertension. Some studies suggest that adropin may have a protective role in cardiovascular health by promoting the dilation of blood vessels and reducing oxidative stress.[28]

In mice, adropin regulates cardiac energy metabolism and improves cardiac function and efficiency.[29] In rats, adropin treatment alleviated diabetes related myocardial fibrosis and diastolic dysfunction,[30] and enhanced the therapeutic potential of mesenchymal stem cells in myocardial infarction.[31]

Central nervous system

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Adropin is produced in the brain, particularly in the hypothalamus.[8] The hypothalamus is a crucial region for the regulation of various physiological processes, including metabolism and energy balance. The presence of adropin in the brain suggests that it may have additional roles in the central nervous system, although the specifics are still being explored.

Circadian rhythm

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There is evidence to suggest that adropin levels exhibit a circadian rhythm, meaning they follow a natural 24-hour cycle.[32] Circadian rhythms play a vital role in regulating various physiological processes, including sleep-wake cycles, hormone secretion, and metabolism.

Gonads and sexual development

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In mice, adropin treatment significantly increased sperm count and testicular testosterone by increasing expression of GPR19 and steroidogenic proteins via modulating redox potential.[33] In the mouse ovary, adropin and GPR19 are strongly detected in the granulosa cells of large antral follicles and corpus luteum.[34] An additional study suggests a role for adropin in the acceleration of pubertal development.[35]

Clinical significance

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Given its involvement in metabolic and cardiovascular processes, adropin has sparked interest as a potential biomarker and therapeutic target for conditions such as obesity, diabetes, and cardiovascular disease. However, much more research is needed to understand the precise mechanisms of adropin action and its potential applications in clinical settings.

Systemic sclerosis

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Adropin is a repressor of fibroblast activation and is dysregulated in patients with Systemic sclerosis. Adropin showed antifibrotic activity in mouse models of skin and lung fibrosis as well as in human skin biopsies. Thus, adropin is a potential therapeutic target in tissue fibrosis.[36]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000168913 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028445 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "ENHO Gene - GeneCards | ENHO Protein | ENHO Antibody". www.genecards.org.
  6. ^ "ortholog_gene_375704[group] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-08-21.
  7. ^ Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, et al. (December 2008). "Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism". Cell Metabolism. 8 (6): 468–481. doi:10.1016/j.cmet.2008.10.011. PMC 2746325. PMID 19041763.
  8. ^ a b Jasaszwili M, Billert M, Strowski MZ, Nowak KW, Skrzypski M (January 2020). "Adropin as A Fat-Burning Hormone with Multiple Functions-Review of a Decade of Research". Molecules. 25 (3): 549. doi:10.3390/molecules25030549. PMC 7036858. PMID 32012786.
  9. ^ a b Banerjee S, Ghoshal S, Stevens JR, McCommis KS, Gao S, Castro-Sepulveda M, et al. (October 2020). "Hepatocyte expression of the micropeptide adropin regulates the liver fasting response and is enhanced by caloric restriction". The Journal of Biological Chemistry. 295 (40): 13753–13768. doi:10.1074/jbc.RA120.014381. PMC 7535914. PMID 32727846.
  10. ^ Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, et al. (September 2010). "Adropin is a novel regulator of endothelial function". Circulation. 122 (11 Suppl): S185–S192. doi:10.1161/CIRCULATIONAHA.109.931782. PMID 20837912. S2CID 798093.
  11. ^ Jurrissen TJ, Ramirez-Perez FI, Cabral-Amador FJ, Soares RN, Pettit-Mee RJ, Betancourt-Cortes EE, et al. (November 2022). "Role of adropin in arterial stiffening associated with obesity and type 2 diabetes". American Journal of Physiology. Heart and Circulatory Physiology. 323 (5): H879–H891. doi:10.1152/ajpheart.00385.2022. hdl:10355/94230. PMC 9602697. PMID 36083795. S2CID 252160224.
  12. ^ Kolben Y, Weksler-Zangen S, Ilan Y (February 2021). "Adropin as a potential mediator of the metabolic system-autonomic nervous system-chronobiology axis: Implementing a personalized signature-based platform for chronotherapy". Obesity Reviews. 22 (2): e13108. doi:10.1111/obr.13108. PMID 32720402. S2CID 220841405.
  13. ^ a b Stokar J, Gurt I, Cohen-Kfir E, Yakubovsky O, Hallak N, Benyamini H, et al. (June 2022). "Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice". Molecular Metabolism. 60: 101482. doi:10.1016/j.molmet.2022.101482. PMC 9044006. PMID 35364299.
  14. ^ Meda C, Dolce A, Vegeto E, Maggi A, Della Torre S (August 2022). "ERα-Dependent Regulation of Adropin Predicts Sex Differences in Liver Homeostasis during High-Fat Diet". Nutrients. 14 (16): 3262. doi:10.3390/nu14163262. PMC 9416503. PMID 36014766.
  15. ^ Soltani S, Kolahdouz-Mohammadi R, Aydin S, Yosaee S, Clark CC, Abdollahi S (March 2022). "Circulating levels of adropin and overweight/obesity: a systematic review and meta-analysis of observational studies". Hormones. 21 (1): 15–22. doi:10.1007/s42000-021-00331-0. PMID 34897581. S2CID 245119139.
  16. ^ Brnić D, Martinovic D, Zivkovic PM, Tokic D, Tadin Hadjina I, Rusic D, et al. (June 2020). "Serum adropin levels are reduced in patients with inflammatory bowel diseases". Scientific Reports. 10 (1): 9264. Bibcode:2020NatSR..10.9264B. doi:10.1038/s41598-020-66254-9. PMC 7283308. PMID 32518265.
  17. ^ "Tissue expression of ENHO - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2022-08-21.
  18. ^ Gunraj RE, Yang C, Liu L, Larochelle J, Candelario-Jalil E (March 2023). "Protective roles of adropin in neurological disease". American Journal of Physiology. Cell Physiology. 324 (3): C674–C678. doi:10.1152/ajpcell.00318.2022. PMC 10027081. PMID 36717106.
  19. ^ Banerjee S, Ghoshal S, Girardet C, DeMars KM, Yang C, Niehoff ML, et al. (August 2021). "Adropin correlates with aging-related neuropathology in humans and improves cognitive function in aging mice". npj Aging and Mechanisms of Disease. 7 (1): 23. doi:10.1038/s41514-021-00076-5. PMC 8405681. PMID 34462439.
  20. ^ Aggarwal G, Morley JE, Vellas B, Nguyen AD, Butler AA (May 2023). "Low circulating adropin concentrations predict increased risk of cognitive decline in community-dwelling older adults". GeroScience. 46 (1): 897–911. doi:10.1007/s11357-023-00824-3. PMC 10828274. PMID 37233882.
  21. ^ Yang C, Liu L, Lavayen BP, Larochelle J, Gunraj RE, Butler AA, et al. (January 2023). "Therapeutic Benefits of Adropin in Aged Mice After Transient Ischemic Stroke via Reduction of Blood-Brain Barrier Damage". Stroke. 54 (1): 234–244. doi:10.1161/STROKEAHA.122.039628. PMC 9780180. PMID 36305313. S2CID 253184087.
  22. ^ Stein LM, Yosten GL, Samson WK (March 2016). "Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 310 (6): R476–R480. doi:10.1152/ajpregu.00511.2015. PMC 4867374. PMID 26739651.
  23. ^ Devine RN, Butler A, Chrivia J, Vagner J, Arnatt CK (June 2023). "Probing Adropin-Gpr19 Interactions and Signal Transduction". Journal of Pharmacology and Experimental Therapeutics. 385 (S3): 430. doi:10.1124/jpet.122.550630. ISSN 0022-3565.
  24. ^ Stein LM, Yosten GL, Samson WK (March 2016). "Adropin acts in brain to inhibit water drinking: potential interaction with the orphan G protein-coupled receptor, GPR19". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 310 (6): R476–R480. doi:10.1152/ajpregu.00511.2015. PMC 4867374. PMID 26739651.
  25. ^ Gao S, McMillan RP, Zhu Q, Lopaschuk GD, Hulver MW, Butler AA (April 2015). "Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance". Molecular Metabolism. 4 (4): 310–324. doi:10.1016/j.molmet.2015.01.005. PMC 4354928. PMID 25830094.
  26. ^ Ganesh Kumar K, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, et al. (July 2012). "Adropin deficiency is associated with increased adiposity and insulin resistance". Obesity. 20 (7): 1394–1402. doi:10.1038/oby.2012.31. PMC 3905465. PMID 22318315.
  27. ^ "Correction to: "Young Women are Protected Against Vascular Insulin Resistance Induced by Adoption of an Obesogenic Lifestyle"". Endocrinology. 164 (4). 2023-02-11. doi:10.1210/endocr/bqad037. ISSN 1945-7170. PMC 10413422. PMID 36869675.
  28. ^ Bozic J, Kumric M, Ticinovic Kurir T, Males I, Borovac JA, Martinovic D, et al. (October 2021). "Role of Adropin in Cardiometabolic Disorders: From Pathophysiological Mechanisms to Therapeutic Target". Biomedicines. 9 (10): 1407. doi:10.3390/biomedicines9101407. PMC 8533182. PMID 34680524.
  29. ^ Altamimi TR, Gao S, Karwi QG, Fukushima A, Rawat S, Wagg CS, et al. (September 2019). "Adropin regulates cardiac energy metabolism and improves cardiac function and efficiency". Metabolism. 98: 37–48. doi:10.1016/j.metabol.2019.06.005. PMID 31202835.
  30. ^ Liu M, Ai J, Shuai Z, Tang K, Li Z, Huang Y (2021-07-12). "Adropin Alleviates Myocardial Fibrosis in Diabetic Cardiomyopathy Rats: A Preliminary Study". Frontiers in Cardiovascular Medicine. 8: 688586. doi:10.3389/fcvm.2021.688586. PMC 8310998. PMID 34322528.
  31. ^ Li H, Hu D, Chen G, Zheng D, Li S, Lin Y, et al. (May 2021). "Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction". Cell Death & Disease. 12 (6): 505. doi:10.1038/s41419-021-03610-1. PMC 8131743. PMID 34006853.
  32. ^ Banerjee S, Ghoshal S, Stevens JR, McCommis KS, Gao S, Castro-Sepulveda M, et al. (October 2020). "Hepatocyte expression of the micropeptide adropin regulates the liver fasting response and is enhanced by caloric restriction". The Journal of Biological Chemistry. 295 (40): 13753–13768. doi:10.1074/jbc.ra120.014381. PMC 7535914. PMID 32727846.
  33. ^ Tripathi S, Maurya S, Singh A (June 2024). "Adropin promotes testicular functions by modulating redox homeostasis in adult mouse". Endocrine. doi:10.1007/s12020-024-03921-1. PMID 38878191.
  34. ^ Maurya S, Tripathi S, Arora T, Singh A (December 2023). "Adropin may regulate corpus luteum formation and its function in adult mouse ovary". Hormones. 22 (4): 725–739. doi:10.1007/s42000-023-00476-0. PMID 37597158. S2CID 261029605.
  35. ^ Maurya S, Tripathi S, Singh A (November 2023). "Ontogeny of adropin and its receptor expression during postnatal development and its pro-gonadal role in the ovary of pre-pubertal mouse". The Journal of Steroid Biochemistry and Molecular Biology. 234: 106404. doi:10.1016/j.jsbmb.2023.106404. PMID 37743028. S2CID 262133676.
  36. ^ Liang M, Dickel N, Györfi AH, SafakTümerdem B, Li YN, Rigau AR, et al. (March 2024). "Attenuation of fibroblast activation and fibrosis by adropin in systemic sclerosis". Science Translational Medicine. 16 (740): eadd6570. doi:10.1126/scitranslmed.add6570. PMID 38536934.

Further reading

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