Adropin

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

Adropin is a peptide encoded by the energy homeostasis-associated gene ENHO, [1] which is highly conserved across mammals. [2]

Contents

Adropin's biological role was first described in mice by a group led by Andrew Butler, as a protein hormone, secreted from the liver (hepatokine), in the context of obesity and energy homeostasis. They derived the name "Adropin" from the Latin "aduro" - to set fire to, and "pinguis" - fat. [3] The hormone adropin is produced in places like the liver and brain, as well as peripheral tissues in the heart and gastrointestinal tract. [4]

In animals, adropin has been shown to have a regulatory role in carbohydrate/lipid metabolism, [5] as well as in endothelial function. [6] [7] Adropin expression in the liver is regulated by feeding status and macronutrient content, [5] as well as by the biological clock. [8] Liver adropin is upregulated by estrogen [9] via ERa. [10]

In humans, lower levels of circulating adropin are associated with several medical conditions including metabolic syndrome, obesity [11] and inflammatory bowel disease. [12]

The brain is the organ with the highest levels of adropin expression. [13] In the brain, adropin has been shown to have a potential protective role role against neurological disease, [14] including in the context of brain aging and cognitive function, [15] [16] as well as following acute ischemia. [17]

The orphan G protein-coupled receptor GPR19, has been proposed as a receptor for adropin. [18] [19]

In the mouse ovary, adropin and GPR19 are strongly detected in the granulosa cells of large antral follicles and corpus luteum. [20] An additional study suggests a role for adropin in the acceleration of pubertal development. [21]

Structure and Synthesis

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. [1]

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. [22]

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. [23]

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. [24]

Cardiovascular effects

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. [25]

Brain function

Adropin is produced in the brain, particularly in the hypothalamus. [4] 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. [26] Circadian rhythms play a vital role in regulating various physiological processes, including sleep-wake cycles, hormone secretion, and metabolism.

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. [27]

Clinical Implications

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.

Related Research Articles

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References

  1. 1 2 "ENHO Gene - GeneCards | ENHO Protein | ENHO Antibody". www.genecards.org.
  2. ↑ "ortholog_gene_375704[group] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-08-21.
  3. ↑ 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.
  4. 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.
  5. 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ "Tissue expression of ENHO - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2022-08-21.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ Yang C, Liu L, Lavayen BP, Larochelle J, Gunraj RE, Butler AA, Candelario-Jalil E (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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  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. ↑ 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.
  24. ↑ 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.
  25. ↑ Bozic J, Kumric M, Ticinovic Kurir T, Males I, Borovac JA, Martinovic D, Vilovic M (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.
  26. ↑ 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.
  27. ↑ Liang, Minrui; Dickel, Nicholas; Györfi, Andrea-Hermina; SafakTümerdem, Bilgesu; Li, Yi-Nan; Rigau, Aleix Rius; Liang, Chunguang; Hong, Xuezhi; Shen, Lichong; Matei, Alexandru-Emil; Trinh-Minh, Thuong; Tran-Manh, Cuong; Zhou, Xiang; Zehender, Ariella; Kreuter, Alexander (2024-03-27). "Attenuation of fibroblast activation and fibrosis by adropin in systemic sclerosis". Science Translational Medicine. 16 (740). doi:10.1126/scitranslmed.add6570. ISSN   1946-6234.
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