Adropin

Last updated

ENHO
Identifiers
Aliases ENHO , C9orf165, UNQ470, energy homeostasis associated, Adropin, IPR034461
External IDs MGI: 1916888; HomoloGene: 104312; GeneCards: ENHO; OMA:ENHO - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_198573

NM_027147

RefSeq (protein)

NP_940975

NP_081423

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

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

Contents

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

Predicted structure of Adropin (AlphaFold) AF-Q6UWT2-F1.png
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

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

Metabolic

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

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

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

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

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

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

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

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000168913 Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. 1 2 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. 1 2 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.
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  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) bqad037. 2023-02-11. doi:10.1210/endocr/bqad037. ISSN   1945-7170. PMC   10413422 . PMID   36869675.
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  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. 86 (1): 428–440. 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.
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  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