Аннотация
Сердечно-сосудистые заболевания являются важной глобальной проблемой в области медицины, социологии и экономики.
Одним из факторов, способствующих развитию этих заболеваний, являются нарушения метаболизма углеводов. В настоя-
щее время ведётся активный поиск новых биологических маркёров и терапевтических мишеней с целью разработки эффек-
тивных подходов к стратификации риска и вторичной профилактике сердечно-сосудистой патологии. Интерес исследо-
вателей привлекает Metrn (также известный как Metrnl, Meteorin-β, Subfatin, Cometin), являющийся секреторным белком с
высокой экспрессией в адипоцитах, эндотелиальных клетках, активированных моноцитах и миоцитах. Metrn представля-
ет собой новый секретируемый белок, оказывающий плейотропное воздействие на воспаление, иммунологию и метаболизм
Цель: анализ исследований, посвящённых изучению Metrnl в роли биомаркёра при атеросклерозе и нарушениях углеводного
обмена. Согласно имеющимся данным, Metrnl является перспективной молекулой, обладающей диагностическим и прогно-
стическим потенциалом при атеросклерозе и нарушениях углеводного обмена. Учитывая результат проведённых исследова-
ний, можно предположить, что определение уровня Metrnl окажется полезным при сахарном диабете 2 типа, ишемической
болезни сердца, при оценке риска атеросклероза и дисфункции эндотелия. Metrnl, по всей видимости, следует определять, в
качестве прогностического маркёра у пациентов с инфарктом миокарда, сердечной недостаточностью, острым наруше-
нием мозгового кровообращения. Особый интерес представляют данные по изменению уровню Metrnl на фоне физических
тренировок: динамическое отслеживание концентрации этого маркёра, возможно, позволит следить за эффективностью
таких упражнений. Необходимы дальнейшие исследования, посвящённые изучению Metrnl в качестве дополнительного ла-
бораторного показателя. Регуляция концентрации и экспрессии Metrnl, возможно, окажется многообещающей стратегией
для лечения людей с нарушениями липидного и углеводного обмена.
Annotation
Cardiovascular diseases are an important global problem in medicine, sociology and economics. One of the factors contributing to the
development of these diseases is carbohydrate metabolism disorders. Currently, there is an active search for new biological markers
and therapeutic targets in order to develop effective approaches to risk stratification and secondary prevention of cardiovascular
pathology. Of particular interest to researchers is Metrn (also known as Metrnl, Meteorin-β, Subfatin and Cometin), a secretory
protein with high expression in adipocytes, endothelial cells, activated monocytes and myocytes. Metrn is a new secreted protein that
has a pleiotropic effect on inflammation, immunology and metabolism. The purpose of this article is to analyze studies devoted to the
study of Metrnl as a biomarker in atherosclerosis and carbohydrate metabolism disorders. According to the available data, Metrnl
is a promising molecule with diagnostic and prognostic potential in atherosclerosis and carbohydrate metabolism disorders. Given
the results of the studies, it can be assumed that Metrnl level determination will be useful in type 2 diabetes mellitus, coronary heart
disease, in assessing the risk of atherosclerosis and endothelial dysfunction. Metrnl should apparently be determined as a prognostic
marker in patients with myocardial infarction, heart failure, and acute cerebrovascular accident. Of particular interest are the data
on changes in Metrnl level during physical training: dynamic monitoring of the concentration of this marker may allow monitoring
the effectiveness of such exercises. Further studies are needed to study Metrnl as an additional laboratory indicator. Regulation of
Metrnl concentration and expression may prove to be a promising strategy for the treatment of people with lipid and carbohydrate
metabolism disorders.
Key words: cardiovascular diseases; atherosclerosis; coronary heart disease; diabetes mellitus; biological marker; Metrnl
Список литературы
R E F E R E NC E S
1. Deng P., Fu Y., Chen M., Wang D., Si L. Temporal trends in inequalities
of the burden of cardiovascular disease across 186 countries and
territories. Int. J. Equity Health. 2023; 22 (1): 164. DOI: 10.1186/
s12939-023-01988-2.
2. Silva S., Fatumo S., Nitsch D. Mendelian randomization studies on
coronary artery disease: a systematic review and meta-analysis. Syst.
Rev. 2024; 13 (1): 29. DOI: 10.1186/s13643-023-02442-8.
3. Wong N.D., Sattar N. Cardiovascular risk in diabetes mellitus:
epidemiology, assessment and prevention. Nat. Rev. Cardiol. 2023;
20 (10): 685-95. DOI: 10.1038/s41569-023-00877-z.
4. Alieva A.M., Teplova N.V., Batov M.A., Voronkova K.V., Valiev
R.K., Shnakhova L.M. et al. Pentraxin-3 – a promising biological
marker in heart failure: literature review. Consilium Medicum. 2022;
24 (1):53-9. DOI: 10.26442/20751753.2022.1.201382. (in Russian)
5. Alieva A.M., Reznik E.V., Pinchuk T.V., Arakelyan R.A., Valiev R.K.,
Rakhaev A.M. et al. Growth differentiation factor-15 (GDF-15) is a
biological marker in heart failure. Arkhiv` vnutrenney meditsiny. 2023;
13 (1): 14-23. DOI: 10.20514/2226-6704-2023-13-1-14-23. (in Russian)
6. Alieva A.M., Teplova N.V., Kislyakov V.A., Voronkova K.V.,
Shnahova L.M., Valiev R.K. et al. Biomarkers in cardiology:
microRNA and heart failure. Terapiya. 2022; 1: 60-70. DOI: 10.18565/
therapy.2022.1.60-70. (in Russian)
7. Li Z., Gao Z., Sun T., Zhang S., Yang S., Zheng M. et al. Meteorin-
like/Metrnl, a novel secreted protein implicated in inflammation,
immunology, and metabolism: A comprehensive review of preclinical
and clinical studies. Front. Immunol. 2023; 14: 1098570. DOI:
10.3389/fimmu.2023.1098570.
8. Dong W.S., Hu C., Hu M., Gao Y.P., Hu Y.X., Li K. et al. Metrnl:
a promising biomarker and therapeutic target for cardiovascular and
metabolic diseases. Cell Commun. Signal. 2024; 22 (1): 389. DOI:
10.1186/s12964-024-01767-8.
9. Miao Z.W., Hu W.J., Li Z.Y., Miao C.Y. Involvement of the secreted
protein Metrnl in human diseases. Acta Pharmacol. Sin. 2020; 41
(12): 1525-30. DOI: 10.1038/s41401-020-00529-9.
10. Du Y.N., Teng J.M., Zhou T.H., Du B.Y., Cai W. Meteorin-like protein
overexpression ameliorates fulminant hepatitis in mice by inhibiting
chemokine-dependent immune cell infiltration. Acta Pharmacol. Sin.
2023; 44 (7): 1404-15. DOI: 10.1038/s41401-022-01049-4.
11. Huang D., Liu X., Gao X., Choi C.K., Giglio G., Farah L. et al.
Meteorin-like protein/METRNL/Interleukin-41 ameliorates atopic
dermatitis-like inflammation. Allergy. 2024. DOI: 10.1111/all.16150.
12. Zhang L., Li Y., Wu Z., Shen Q., Zeng C., Liu H. et al. Metrnl inhibits
choroidal neovascularization by attenuating the choroidal inflammation
via inactivating the UCHL-1/NF-κB signaling pathway. Front.
Immunol. 2024; 15: 1379586. DOI: 10.3389/fimmu.2024.1379586.
13. Lu Q.B., Ding Y., Liu Y., Wang Z.C., Wu Y.J., Niu K.M. et al. Metrnl
ameliorates diabetic cardiomyopathy via inactivation of cGAS/STING
signaling dependent on LKB1/AMPK/ULK1-mediated autophagy. J.
Adv. Res. 2023; 51: 161-79. DOI: 10.1016/j.jare.2022.10.014.
14. Qiu Y., Nguyen K.D., Odegaard J.I., Cui X., Tian X., Locksley R.M. et
al. Eosinophils and type 2 cytokine signaling in macrophages orchestrate
development of functional beige fat. Cell. 2014;157(6):1292-
308. DOI: 10.1016/j.cell.2014.03.066.
15. Li Z.Y., Song J., Zheng S.L., Fan M.B., Guan Y.F., Qu Y. et al. Adipocyte
Metrnl antagonizes insulin resistance through PPARγ signaling.
Diabetes. 2015; 64 (12): 4011-22. DOI: 10.2337/db15-0274.
16. Rao R.R., Long J.Z., White J.P., Svensson K.J., Lou J., Lokurkar I. et
al. Meteorin-like is a hormone that regulates immune-adipose interactions
to increase beige fat thermogenesis. Cell. 2014; 157 (6): 1279-
91. DOI: 10.1016/j.cell.2014.03.065.
17. Amano Y., Nonaka Y., Takeda R., Kano Y., Hoshino D. Effects of
electrical stimulation-induced resistance exercise training on white
and brown adipose tissues and plasma meteorin-like concentration in
rats. Physiol. Rep. 2020; 8 (16): e14540. DOI: 10.14814/phy2.14540.
18. Hu W., Wang R., Sun B. Meteorin-Like Ameliorates β Cell Function
by Inhibiting β Cell Apoptosis of and Promoting β Cell Proliferation
via Activating the WNT/β-Catenin Pathway. Front. Pharmacol. 2021;
12: 627147. DOI: 10.3389/fphar.2021.627147.
19. Jung T.W., Lee S.H., Kim H.C., Bang J.S., Abd El-Aty A.M.,
Hacımüftüoğlu A. et al. METRNL attenuates lipid-induced inflammation
and insulin resistance via AMPK or PPARδ-dependent pathways
in skeletal muscle of mice. Exp. Mol. Med. 2018; 50 (9): 1-11. DOI:
10.1038/s12276-018-0147-5.
20. Lee J.O., Byun W.S., Kang M.J., Han J.A., Moon J., Shin M.J. et al.
The myokine meteorin-like (metrnl) improves glucose tolerance in
both skeletal muscle cells and mice by targeting AMPKα2. FEBS J.
2020; 287 (10): 2087-3104. DOI: 10.1111/febs.15301.
21. Lin L., Huang S., Lin X., Liu X., Xu X., Li C. et al. Upregulation of
Metrnl improves diabetic kidney disease by inhibiting the TGF-β1/
Smads signaling pathway: A potential therapeutic target. PLoS One.
2024; 19 (8): e0309338. DOI: 10.1371/journal.pone.0309338.
22. Tayebi S.M., Motaghinasab S., Eslami R., Ahmadabadi S., Basereh
A., Jamhiri I. Impact of 8-week cold-and warm water swimming
training combined with cinnamon consumption on serum METRNL,
HDAC5, and insulin resistance levels in diabetic male rats. Heliyon.
2024; 10 (8): e29742. DOI: 10.1016/j.heliyon. 2024.e29742.
23. Yao Z., Lin P., Wang C., Wang K., Sun Y. Administration of metrnl
delays the onset of diabetes in non-obese diabetic mice. Endocr. J.
2021; 68 (2): 179-88. DOI: 10.1507/endocrj.EJ20-0351.
24. Zheng S., Li Z., Song J., Wang P., Xu J., Hu W. et al. Endothelial
METRNL determines circulating METRNL level and maintains endothelial
function against atherosclerosis. Acta Pharm. Sin. B. 2023;
13 (4): 1568-87. DOI: 10.1016/j.apsb.2022.12.008.
25. Jung T.W., Pyun D.H., Kim T.J., Lee H.J., Park E.S., Abd El-Aty A.M.
et al. Meteorin-like protein (METRNL)/IL-41 improves LPS-induced
inflammatory responses via AMPK or PPARδ-mediated signaling
pathways. Adv. Med. Sci. 2021; 66 (1): 155-61. DOI: 10.1016/j.advms.
2021.01.007.
26. Reboll M.R., Klede S., Taft M.H., Cai C.L., Field L.J., Lavine K.J.
et al. Meteorin-like promotes heart repair through endothelial KIT
receptor tyrosine kinase. Science. 2022; 376 (6599): 1343-7. DOI:
10.1126/science. abn3027.
27. Xu L., Cai Y., Wang Y., Xu C. Meteorin-Like (METRNL) Attenuates
Myocardial Ischemia/Reperfusion Injury-Induced Cardiomyocytes
Apoptosis by Alleviating Endoplasmic Reticulum Stress via Activation
of AMPK-PAK2 Signaling in H9C2 Cells. Med. Sci. Monit. 2020;
26: e924564. DOI: 10.12659/MSM.924564.
28. Alkhairi I., Cherian P., Abu-Farha M., Madhoun A.A., Nizam R., Melhem
M. et al. Increased expression of Meteorin-Like hormone in type
2 Diabetes and Obesity and its Association with Irisin. Cells. 2019; 8
(10). DOI: 10.3390/cells8101283.
29. Wang K., Li F., Wang C., Deng Y., Cao Z., Cui Y. et al. Serum levels
of Meteorin-Like (Metrnl) are increased in patients with newly
diagnosed type 2 diabetes Mellitus and are Associated with insulin
resistance. Med. Sci. Monit. 2019; 25: 2337-43. DOI: 10.12659/
MSM.915331.
30. Ding X., Chang X., Wang J., Bian N., An Y., Wang G. et al. Serum
metrnl levels are decreased in subjects with overweight or obesity
and are independently associated with adverse lipid profile. Front.
Endocrinol. (Lausanne). 2022; 13: 938341. DOI: 10.3389/fendo.
2022.938341.
31. Pellitero S., Piquer-Garcia I., Ferrer-Curriu G., Puig R., Martínez E.,
Moreno P. et al. Opposite changes in meteorin-like and oncostatin m levels
are associated with metabolic improvements after bariatric surgery.
Int. J. Obes. (Lond). 2018; 42 (4): 919-22. DOI: 10.1038/ijo.2017.268.
32. Moradi N., Fadaei R., Roozbehkia M., Nourbakhsh M., Nourbakhsh
M., Razzaghy-Azar M. et al. Meteorin-like protein and Asprosin Levels
in children and adolescents with obesity and their relationship with
insulin resistance and metabolic syndrome. Lab. Med. 2023; 54 (5):
457-63. DOI: 10.1093/labmed/lmac152.
33. Du Y., Ye X., Lu A., Zhao D., Liu J., Cheng J. et al. Inverse relationship
between serum Metrnl levels and visceral fat obesity (VFO) in
patients with type 2 diabetes. Diabetes Res. Clin. Pract. 2020; 161:
108068. DOI: 10.1016/j.diabres.2020.108068.
34. Liu M., Gao X., Tian Y., Li H., Yin Z., Han L. et al. Serum Metrnl is
Decreased in Metabolic Dysfunction-Associated Fatty Liver Disease:
A Case-Control Study. Diabetes Metab. Syndr. Obes. 2024; 17: 533-
43. DOI: 10.2147/DMSO.S447127.
35. Chung H.S., Hwang S.Y., Choi J.H., Lee H.J., Kim N.H., Yoo H.J. et
al. Implications of circulating Meteorin-like (Metrnl) level in human
subjects with type 2 diabetes. Diabetes Res. Clin. Pract. 2018; 136:
100-7. DOI: 10.1016/j.diabres.2017.11.031.
36. Fouani F.Z., Fadaei R., Moradi N., Zandieh Z., Ansaripour S.,
Yekaninejad M.S. et al. Circulating levels of meteorin-like protein in
polycystic ovary syndrome: a case-control study. PLoS ONE. 2020;
15 (4): e0231943. DOI: 10.1371/journal.pone.0231943.
37. Garcia-Beltran C., Navarro-Gascon A., López-Bermejo A., Quesada-
López T., de Zegher F., Ibáñez L. et al. Meteorin-like levels are
associated with active brown adipose tissue in early infancy. Front.
Endocrinol. (Lausanne). 2023; 14: 1136245. DOI: 10.3389/fendo.
2023.1136245.
38. Saghebjoo M., Einaloo A., Mogharnasi M., Ahmadabadi F. The response
of meteorin-like hormone and interleukin-4 in overweight
women during exercise in temperate, warm and cold water. Horm. Mol.
Biol. Clin. Investig. 2018; 36 (3). DOI: 10.1515/hmbci-2018-0027.
39. Alizadeh A., Alizadeh H. Downhill running exercise increases circulating
level of myokine meteorin-like hormone in humans. J.
Sports Med. Phys. Fit. 2022; 62 (5): 700–4. DOI: 10.23736/S0022-
4707.21.12246-7.
40. Tayebi S.M., Golmohammadi M., Eslami R., Shakiba N., Costa P.B.
The effects of Eight Weeks of Circuit Resistance Training on serum
METRNL levels and Insulin Resistance in individuals with type 2 diabetes.
J. Diabetes Metab. Disord. 2023; 22 (2): 1151-8. DOI: 10.1007/
s40200-023-01225-1.
41. Yao C., Zhang H., Wang L., Li J. Correlation of serum Meteorin-like
(Metrnl) level with type 2 diabetic peripheral neuropathy. BMC Endocr.
Disord. 2024; 24 (1): 83. DOI: 10.1186/s12902-024-01616-2.
42. Fadaei R., Dadmanesh M., Moradi N., Ahmadi R., Shokoohi Nahrkhalaji
A., Aghajani H. et al. Serum levels of subfatin in patients with type
2 diabetes mellitus and its association with vascular adhesion molecules.
Arch. Physiol. Biochem. 2020; 126 (4): 335-40. DOI:10.1080/
13813455.2018.1538248.
43. Onalan E., Cavlı C., Dogan Y., Onalan E., Gozel N., Buran I. et al.
Low serum levels of meteorin-like/subfatin: an indicator of diabetes
mellitus and insulin resistance? Endocrinol. Pol. 2020; 71 (5): 397-
403. DOI: 10.5603/EP.a2020.0038.
44. El-Ashmawy H.M., Selim F.O., Hosny T.A.M., Almassry H.N. Association
of low serum Meteorin like (Metrnl) concentrations with
worsening of glucose tolerance, impaired endothelial function
and atherosclerosis. Diabetes Res. Clin. Pract. 2019; 150: 57-63.
DOI:10.1016/j.diabres.2019.02.026.
45. Chen J., Li Z.Y., Xu F., Wang C.Q., Li W.W., Lu J. et al. Low Levels
of Metrnl are Linked to the Deterioration of Diabetic Kidney Disease.
Diabetes Metab. Syndr. Obes. 2024; 17: 959-67. DOI: 10.2147/
DMSO.S452055.
46. Lappas M. Maternal obesity and gestational diabetes decrease Metrnl
concentrations in cord plasma. J. Matern. Fetal Neonatal. Med. 2021;
34 (18): 2991-5. DOI: 10.1080/14767058.2019.1676713.
47. Dadmanesh M., Aghajani H., Fadaei R., Ghorban K. Lower serum
levels of Meteorin-like/Subfatin in patients with coronary artery disease
and type 2 diabetes mellitus are negatively associated with insulin
resistance and inflammatory cytokines. PLoS One. 2018; 13 (9):
e0204180. DOI: 10.1371/journal.pone.0204180.
48. Miao Z.W., Wang N., Hu W.J., Zheng S.L., Wang D.S., Chang F.Q. et
al. Chronic vascular pathogenesis results in the reduced serum Metrnl
levels in ischemic stroke patients. Acta Pharmacol. Sin. 2024; 45 (5):
914-25. DOI: 10.1038/s41401-023-01204-5.
49. Giden R., Yasak I.H. Meteorin-like protein decreases in acute coronary
syndrome. Eur. Rev. Med. Pharmacol. Sci. 2023; 27 (1): 208-14.
DOI: 10.26355/eurrev_202301_30873.
50. Ferrer-Curriu G., Rueda F., Revuelta-López E., García-García C., Codina
P., Gálvez-Montón C. et al. Meteorin-like protein is associated
with a higher risk profile and predicts a worse outcome in patients
with STEMI. Rev. Esp. Cardiol. (Engl. Ed). 2023; 76 (11): 891-900.
DOI: 10.1016/j.rec.2023.03.015.
51. Liu Z.X., Ji H.H., Yao M.P., Wang L., Wang Y., Zhou P. et al. Serum
Metrnl is associated with the presence and severity of coronary artery
disease. J. Cell Mol. Med. 2019; 23 (1): 271-80. DOI: 10.1111/
jcmm.13915.
52. Yasak I.H., Yilmaz M., Goktekin M.C., Giden R., Koyuncu İ. Meteorin-
Like Protein Levels Decrease in Patients With Acute Ischaemic
Stroke. Cureus. 2022; 14 (11): e32042. DOI: 10.7759/cureus.32042.