ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet12899ometendo-12899Research ArticleОБЗОРЫREVIEWSМетаболические свойства ирисина в норме и при сахарном диабетеMetabolic properties of irisin in health and in diabetes mellitushttps://orcid.org/0000-0003-3224-1573РадугинФ. М.RaduginF. M.

Радугин Федор Михайлович, аспирант  кафедры эндокринологии

194021, Санкт-Петербург, пр. Пархоменко, д. 15

eLibrary SPIN: 7043-3620

Fyodor M. Radugin, MD, postgraduate student

194021, Saint-Petersburg, 15 Parkhomenko Avenue

eLibrary SPIN: 7043-3620

radugin.f.m@gmail.comhttps://orcid.org/0000-0001-9836-5427ТимкинаН. В.TimkinaN. V.

Тимкина Наталья Владимировна,  младший научный сотрудник НИЛ клинической эндокринологии

Санкт-Петербург

eLibrary SPIN: 6259-7745

Natalia V. Timkina, MD

Saint-Petersburg

eLibrary SPIN: 6259-7745

n.timkina2014@yandex.ruhttps://orcid.org/0000-0002-1547-0123КароноваТ. Л.KaronovaT. L.

Каронова Татьяна Леонидовна, доктор медицинских наук, главный научный сотрудник НИЛ клинической эндокринологии Института эндокринологии, профессор кафедры эндокринологии

Санкт-Петербург

eLibrary SPIN: 3337-4071

Tatiana L. Karonova, MD, PhD

Saint-Petersburg

eLibrary SPIN: 3337-4071

karonova@mail.ruНациональный медицинский исследовательский центр им. В.А. Алмазова Минздрава РоссииРоссияAlmazov National Medical Research CentreRussian Federation202204082022193332339Copyright © Радугин Ф.М., Тимкина Н.В., Каронова Т.Л., 20232023Радугин Ф.М., Тимкина Н.В., Каронова Т.Л.Radugin F.M., Timkina N.V., Karonova T.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/12899

Ирисин (irisin) — это полипептидный гормон мышечной ткани (миокин), синтез и секреция которого увеличиваются на фоне физических нагрузок, играющий значимую роль в метаболизме жировой, мышечной и костной тканей. Известно, что ирисин способствует превращению белой жировой ткани в бурую. Экспериментально доказано, что введение ирисина способствует увеличению костной массы и может быть использовано в профилактике остеопороза и мышечной атрофии. Существуют работы, указывающие на позитивный эффект ирисина в функционировании костной, жировой и мышечной тканей у человека. Сахарный диабет (СД) является независимым фактором риска остеопоротических переломов и развития специфической диабетической миопатии, на клеточном уровне схожей со старением мышечной ткани. Дополнительно СД 2-го типа ассоциирован с ожирением, что представляет интерес в изучении влияния ирисина на состояние костной, мышечной и жировой тканей и гомеостаз глюкозы у больных СД. Данный литературный обзор освещает биологические функции ирисина у здоровых людей и больных СД.

Irisin is a polypeptide hormone of muscle tissue (myokine), the synthesis and secretion of which increase against the background of physical exertion, which plays a significant role in the metabolism of fat, muscle and bone tissues. It is known that irisin promotes the transformation of white adipose tissue into brown adipose tissue. It has also been experimentally proven that the introduction of irisin contributed to an increase in bone mass and the prevention of osteoporosis and muscular atrophy. There are works indicating a positive effect of irisin in the functioning of bone, fat and muscle tissues in humans. Diabetes mellitus (DM) is an independent risk factor for osteoporotic fractures and the development of specific diabetic myopathy, at the cellular level similar to the aging of muscle tissue, and type 2 diabetes is also associated with the presence of obesity. Thus, it is of particular interest to study the effect of irisin on the state of bone, muscle and adipose tissues and glucose homeostasis in patients with diabetes. This literature review highlights the biological functions of irisin in healthy people and patients with DM.

ирисинсахарный диабетмышечная тканькостная тканьжировая тканьirisindiabetes mellitusmuscle tissuebone tissueadipose tissueReferencesBoström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-468. doi: https://doi.org/10.1038/nature10777dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-468. doi: https://doi.org/10.1038/nature10777Maak S, Norheim F, Drevon CA, Erickson HP. Progress and Challenges in the Biology of FNDC5 and Irisin. Endocr Rev. 2021;42(4):436-456. doi: https://doi.org/10.1210/endrev/bnab003Maak S, Norheim F, Drevon CA, Erickson HP. Progress and Challenges in the Biology of FNDC5 and Irisin. Endocr Rev. 2021;42(4):436-456. doi: https://doi.org/10.1210/endrev/bnab003Roca-Rivada A, Castelao C, Senin LL, et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One. 2013;8(4):e60563. doi: https://doi.org/10.1371/journal.pone.0060563Roca-Rivada A, Castelao C, Senin LL, et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One. 2013;8(4):e60563. doi: https://doi.org/10.1371/journal.pone.0060563Tsuchiya Y, Ando D, Takamatsu K, Goto K. Resistance exercise induces a greater irisin response than endurance exercise. Metabolism. 2015;64(9):1042-1050. doi: https://doi.org/10.1016/j.metabol.2015.05.010Tsuchiya Y, Ando D, Takamatsu K, Goto K. Resistance exercise induces a greater irisin response than endurance exercise. Metabolism. 2015;64(9):1042-1050. doi: https://doi.org/10.1016/j.metabol.2015.05.010Abdullahi A, Jeschke MG. White Adipose Tissue Browning: A Doubleedged Sword. Trends Endocrinol Metab. 2016;27(8):542-552. doi: https://doi.org/10.1016/j.tem.2016.06.006Abdullahi A, Jeschke MG. White Adipose Tissue Browning: A Doubleedged Sword. Trends Endocrinol Metab. 2016;27(8):542-552. doi: https://doi.org/10.1016/j.tem.2016.06.006Li H, Wang F, Yang M, et al. The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity. Int J Endocrinol. 2021;2021(1):1-12. doi: https://doi.org/10.1155/2021/6572342Li H, Wang F, Yang M, et al. The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity. Int J Endocrinol. 2021;2021(1):1-12. doi: https://doi.org/10.1155/2021/6572342Zhang Y, Li R, Meng Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2014;63(2):514-525. doi: https://doi.org/10.2337/db13-1106Zhang Y, Li R, Meng Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2014;63(2):514-525. doi: https://doi.org/10.2337/db13-1106Elsen M, Raschke S, Eckel J. Browning of white fat: does irisin play a role in humans?. J Endocrinol. 2014;222(1):R25-R38. doi: https://doi.org/10.1530/JOE-14-0189Elsen M, Raschke S, Eckel J. Browning of white fat: does irisin play a role in humans?. J Endocrinol. 2014;222(1):R25-R38. doi: https://doi.org/10.1530/JOE-14-0189Huh JY, Dincer F, Mesfum E, Mantzoros CS. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. Int J Obes (Lond). 2014;38(12):1538-1544. doi: https://doi.org/10.1038/ijo.2014.42Huh JY, Dincer F, Mesfum E, Mantzoros CS. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. Int J Obes (Lond). 2014;38(12):1538-1544. doi: https://doi.org/10.1038/ijo.2014.42Otero-Díaz B, Rodríguez-Flores M, Sánchez-Muñoz V, et al. Exercise Induces White Adipose Tissue Browning Across the Weight Spectrum in Humans. Front Physiol. 2018;9(1):1-12. doi: https://doi.org/10.3389/fphys.2018.01781Otero-Díaz B, Rodríguez-Flores M, Sánchez-Muñoz V, et al. Exercise Induces White Adipose Tissue Browning Across the Weight Spectrum in Humans. Front Physiol. 2018;9(1):1-12. doi: https://doi.org/10.3389/fphys.2018.01781Bettini S, Favaretto F, Compagnin C, et al. Resting Energy Expenditure, Insulin Resistance and UCP1 Expression in Human Subcutaneous and Visceral Adipose Tissue of Patients With Obesity. Front Endocrinol (Lausanne). 2019;10(1):1-12. doi: https://doi.org/10.3389/fendo.2019.00548Bettini S, Favaretto F, Compagnin C, et al. Resting Energy Expenditure, Insulin Resistance and UCP1 Expression in Human Subcutaneous and Visceral Adipose Tissue of Patients With Obesity. Front Endocrinol (Lausanne). 2019;10(1):1-12. doi: https://doi.org/10.3389/fendo.2019.00548Lim J, Park HS, Kim J, et al. Depot-specific UCP1 expression in human white adipose tissue and its association with obesity-related markers. Int J Obes (Lond). 2020;44(3):697-706. doi: https://doi.org/10.1038/s41366-020-0528-4Lim J, Park HS, Kim J, et al. Depot-specific UCP1 expression in human white adipose tissue and its association with obesity-related markers. Int J Obes (Lond). 2020;44(3):697-706. doi: https://doi.org/10.1038/s41366-020-0528-4Zhang Y, Xie C, Wang H, et al. Irisin exerts dual effects on browning and adipogenesis of human white adipocytes. Am J Physiol Endocrinol Metab. 2016;311(2):E530-E541. doi: https://doi.org/10.1152/ajpendo.00094.2016Zhang Y, Xie C, Wang H, et al. Irisin exerts dual effects on browning and adipogenesis of human white adipocytes. Am J Physiol Endocrinol Metab. 2016;311(2):E530-E541. doi: https://doi.org/10.1152/ajpendo.00094.2016Norheim F, Langleite TM, Hjorth M, et al. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 2014;281(3):739-749. doi: https://doi.org/10.1111/febs.12619Norheim F, Langleite TM, Hjorth M, et al. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 2014;281(3):739-749. doi: https://doi.org/10.1111/febs.12619Tsiloulis T, Carey AL, Bayliss J, et al. No evidence of white adipocyte browning after endurance exercise training in obese men. Int J Obes (Lond). 2018;42(4):721-727. doi: https://doi.org/10.1038/ijo.2017.295Tsiloulis T, Carey AL, Bayliss J, et al. No evidence of white adipocyte browning after endurance exercise training in obese men. Int J Obes (Lond). 2018;42(4):721-727. doi: https://doi.org/10.1038/ijo.2017.295Colaianni G, Cuscito C, Mongelli T, et al. The myokine irisin increases cortical bone mass [published correction appears in Proc Natl Acad Sci U S A. 2015;112(42):E5763]. Proc Natl Acad Sci U S A. 2015;112(39):12157-12162. doi: https://doi.org/10.1073/pnas.1516622112Colaianni G, Cuscito C, Mongelli T, et al. The myokine irisin increases cortical bone mass [published correction appears in Proc Natl Acad Sci U S A. 2015;112(42):E5763]. Proc Natl Acad Sci U S A. 2015;112(39):12157-12162. doi: https://doi.org/10.1073/pnas.1516622112Vaughan RA, Gannon NP, Mermier CM, Conn CA. Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism. J Physiol Biochem. 2015;71(4):679-689. doi: https://doi.org/10.1007/s13105-015-0433-9Vaughan RA, Gannon NP, Mermier CM, Conn CA. Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism. J Physiol Biochem. 2015;71(4):679-689. doi: https://doi.org/10.1007/s13105-015-0433-9MacKenzie MG, Hamilton DL, Pepin M, et al. Inhibition of myostatin signaling through Notch activation following acute resistance exercise. PLoS One. 2013;8(7):e68743. doi: https://doi.org/10.1371/journal.pone.0068743MacKenzie MG, Hamilton DL, Pepin M, et al. Inhibition of myostatin signaling through Notch activation following acute resistance exercise. PLoS One. 2013;8(7):e68743. doi: https://doi.org/10.1371/journal.pone.0068743Elkasrawy MN, Hamrick MW. Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact. 2010;10(1):56-63.Elkasrawy MN, Hamrick MW. Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact. 2010;10(1):56-63.Wong TS, Booth FW. Skeletal muscle enlargement with weightlifting exercise by rats. J Appl Physiol. 1988;65(2):950-954. doi: https://doi.org/10.1152/jappl.1988.65.2.950Wong TS, Booth FW. Skeletal muscle enlargement with weightlifting exercise by rats. J Appl Physiol. 1988;65(2):950-954. doi: https://doi.org/10.1152/jappl.1988.65.2.950Colaianni G, Cinti S, Colucci S, Grano M. Irisin and musculoskeletal health. Ann N Y Acad Sci. 2017;1402(1):5-9. doi: https://doi.org/10.1111/nyas.13345Colaianni G, Cinti S, Colucci S, Grano M. Irisin and musculoskeletal health. Ann N Y Acad Sci. 2017;1402(1):5-9. doi: https://doi.org/10.1111/nyas.13345Белая Ж.Е., Белова К.Ю., Бирюкова Е.В., и др. Федеральные клинические рекомендации по диагностике, лечению и профилактике остеопороза // Остеопороз и остеопатии. — 2021. — Т. 24. — №2. — С. 4-47. doi: https://doi.org/10.14341/osteo12930Belaya ZE, Belova KYu, Biryukova EV, et al. Federal clinical guidelines for diagnosis, treatment and prevention of osteoporosis. Osteoporosis and Bone Diseases. 2021;24(2):4-47. (In Russ.). doi: https://doi.org/10.14341/osteo12930Storlino G, Colaianni G, Sanesi L, et al. Irisin Prevents DisuseInduced Osteocyte Apoptosis. J Bone Miner Res. 2020;35(4):766-775. doi: https://doi.org/10.1002/jbmr.3944Storlino G, Colaianni G, Sanesi L, et al. Irisin Prevents DisuseInduced Osteocyte Apoptosis. J Bone Miner Res. 2020;35(4):766-775. doi: https://doi.org/10.1002/jbmr.3944Kim J-H, Kim D-Y. Aquarobic exercises improve the serum blood irisin and brain-derived neurotrophic factor levels in elderly women. Exp Gerontol. 2018;104(2):60-65. doi: https://doi.org/10.1016/j.exger.2018.01.024Kim J-H, Kim D-Y. Aquarobic exercises improve the serum blood irisin and brain-derived neurotrophic factor levels in elderly women. Exp Gerontol. 2018;104(2):60-65. doi: https://doi.org/10.1016/j.exger.2018.01.024Tu X, Rhee Y, Condon KW, et al. Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone. 2012;50(1):209-217. doi: https://doi.org/10.1016/j.bone.2011.10.025Tu X, Rhee Y, Condon KW, et al. Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone. 2012;50(1):209-217. doi: https://doi.org/10.1016/j.bone.2011.10.025Ma EB, Sahar NE, Jeong M, Huh JY. Irisin Exerts Inhibitory Effect on Adipogenesis Through Regulation of Wnt Signaling. Front Physiol. 2019;10(2):60-65. doi: https://doi.org/10.3389/fphys.2019.01085Ma EB, Sahar NE, Jeong M, Huh JY. Irisin Exerts Inhibitory Effect on Adipogenesis Through Regulation of Wnt Signaling. Front Physiol. 2019;10(2):60-65. doi: https://doi.org/10.3389/fphys.2019.01085Zhang J, Valverde P, Zhu X, et al. Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism. Bone Res. 2017;5(1):16056. doi: https://doi.org/10.1038/boneres.2016.56Zhang J, Valverde P, Zhu X, et al. Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism. Bone Res. 2017;5(1):16056. doi: https://doi.org/10.1038/boneres.2016.56Qiao X, Nie Y, Ma Y, et al. Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways. Sci Rep. 2016;6(1):18732. doi: https://doi.org/10.1038/srep18732Qiao X, Nie Y, Ma Y, et al. Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways. Sci Rep. 2016;6(1):18732. doi: https://doi.org/10.1038/srep18732Ye W, Wang J, Lin D, Ding Z. The immunomodulatory role of irisin on osteogenesis via AMPK-mediated macrophage polarization. Int J Biol Macromol. 2020;146(1):25-35. doi: https://doi.org/10.1016/j.ijbiomac.2019.12.028Ye W, Wang J, Lin D, Ding Z. The immunomodulatory role of irisin on osteogenesis via AMPK-mediated macrophage polarization. Int J Biol Macromol. 2020;146(1):25-35. doi: https://doi.org/10.1016/j.ijbiomac.2019.12.028Zhang D, Bae C, Lee J, et al. The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis. Bone. 2018;114(1):150-160. doi: https://doi.org/10.1016/j.bone.2018.05.013Zhang D, Bae C, Lee J, et al. The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis. Bone. 2018;114(1):150-160. doi: https://doi.org/10.1016/j.bone.2018.05.013Xu L, Shen L, Yu X, et al. Effects of irisin on osteoblast apoptosis and osteoporosis in postmenopausal osteoporosis rats through upregulating Nrf2 and inhibiting NLRP3 inflammasome. Exp Ther Med. 2020;19(2):1084-1090. doi: https://doi.org/10.3892/etm.2019.8313Xu L, Shen L, Yu X, et al. Effects of irisin on osteoblast apoptosis and osteoporosis in postmenopausal osteoporosis rats through upregulating Nrf2 and inhibiting NLRP3 inflammasome. Exp Ther Med. 2020;19(2):1084-1090. doi: https://doi.org/10.3892/etm.2019.8313Colaianni G, Errede M, Sanesi L, et al. Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Marker p21 in Osteoblasts. J Bone Miner Res. 2021;36(2):305-314. doi: https://doi.org/10.1002/jbmr.4192Colaianni G, Errede M, Sanesi L, et al. Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Marker p21 in Osteoblasts. J Bone Miner Res. 2021;36(2):305-314. doi: https://doi.org/10.1002/jbmr.4192Kawao N, Moritake A, Tatsumi K, Kaji H. Roles of Irisin in the Linkage from Muscle to Bone During Mechanical Unloading in Mice. Calcif Tissue Int. 2018;103(1):24-34. doi: https://doi.org/10.1007/s00223-018-0387-3Kawao N, Moritake A, Tatsumi K, Kaji H. Roles of Irisin in the Linkage from Muscle to Bone During Mechanical Unloading in Mice. Calcif Tissue Int. 2018;103(1):24-34. doi: https://doi.org/10.1007/s00223-018-0387-3Luo Y, Qiao X, Ma Y, et al. Disordered metabolism in mice lacking irisin. Sci Rep. 2020;10(1):17368. doi: https://doi.org/10.1038/s41598-020-74588-7Luo Y, Qiao X, Ma Y, et al. Disordered metabolism in mice lacking irisin. Sci Rep. 2020;10(1):17368. doi: https://doi.org/10.1038/s41598-020-74588-7Estell EG, Le PT, Vegting Y, et al. Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo. Elife. 2020;9(1):17368. doi: https://doi.org/10.7554/eLife.58172Estell EG, Le PT, Vegting Y, et al. Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo. Elife. 2020;9(1):17368. doi: https://doi.org/10.7554/eLife.58172Klangjareonchai T, Nimitphong H, Saetung S, et al. Circulating Sclerostin and Irisin Are Related and Interact with Gender to Influence Adiposity in Adults with Prediabetes. Int J Endocrinol. 2014;2014(1):1-6. doi: https://doi.org/10.1155/2014/261545Klangjareonchai T, Nimitphong H, Saetung S, et al. Circulating Sclerostin and Irisin Are Related and Interact with Gender to Influence Adiposity in Adults with Prediabetes. Int J Endocrinol. 2014;2014(1):1-6. doi: https://doi.org/10.1155/2014/261545Palermo A, Strollo R, Maddaloni E, et al. Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin Endocrinol (Oxf ). 2015;82(4):615-619. doi: https://doi.org/10.1111/cen.12672Palermo A, Strollo R, Maddaloni E, et al. Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin Endocrinol (Oxf ). 2015;82(4):615-619. doi: https://doi.org/10.1111/cen.12672Anastasilakis AD, Polyzos SA, Makras P, et al. Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos Int. 2014;25(5):1633-1642. doi: https://doi.org/10.1007/s00198-014-2673-xAnastasilakis AD, Polyzos SA, Makras P, et al. Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos Int. 2014;25(5):1633-1642. doi: https://doi.org/10.1007/s00198-014-2673-xSinghal V, Lawson EA, Ackerman KE, et al. Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS One. 2014;9(6):e100218. doi: https://doi.org/10.1371/journal.pone.0100218Singhal V, Lawson EA, Ackerman KE, et al. Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS One. 2014;9(6):e100218. doi: https://doi.org/10.1371/journal.pone.0100218Colaianni G, Notarnicola A, Sanesi L, et al. Irisin levels correlate with bone mineral density in soccer players. J Biol Regul Homeost Agents. 2017;31(4):21-28.Colaianni G, Notarnicola A, Sanesi L, et al. Irisin levels correlate with bone mineral density in soccer players. J Biol Regul Homeost Agents. 2017;31(4):21-28.Colaianni G, Faienza MF, Sanesi L, et al. Irisin serum levels are positively correlated with bone mineral status in a population of healthy children. Pediatr Res. 2019;85(4):484-488. doi: https://doi.org/10.1038/s41390-019-0278-yColaianni G, Faienza MF, Sanesi L, et al. Irisin serum levels are positively correlated with bone mineral status in a population of healthy children. Pediatr Res. 2019;85(4):484-488. doi: https://doi.org/10.1038/s41390-019-0278-yJiang N, Xia W. Assessment of bone quality in patients with diabetes mellitus. Osteoporos Int. 2018;29(8):1721-1736. doi: https://doi.org/10.1007/s00198-018-4532-7Jiang N, Xia W. Assessment of bone quality in patients with diabetes mellitus. Osteoporos Int. 2018;29(8):1721-1736. doi: https://doi.org/10.1007/s00198-018-4532-7Sundararaghavan V, Mazur MM, Evans B, et al. Diabetes and bone health: latest evidence and clinical implications. Ther Adv Musculoskelet Dis. 2017;9(3):67-74. doi: https://doi.org/10.1177/1759720X16687480Sundararaghavan V, Mazur MM, Evans B, et al. Diabetes and bone health: latest evidence and clinical implications. Ther Adv Musculoskelet Dis. 2017;9(3):67-74. doi: https://doi.org/10.1177/1759720X16687480Monaco CMF, Gingrich MA, Hawke TJ. Considering Type 1 Diabetes as a Form of Accelerated Muscle Aging. Exerc Sport Sci Rev. 2019;47(2):98-107. doi: https://doi.org/10.1249/JES.0000000000000184Monaco CMF, Gingrich MA, Hawke TJ. Considering Type 1 Diabetes as a Form of Accelerated Muscle Aging. Exerc Sport Sci Rev. 2019;47(2):98-107. doi: https://doi.org/10.1249/JES.0000000000000184Maliszewska K, Adamska-Patruno E, Krętowski A. The interplay between muscle mass decline, obesity, and type 2 diabetes. Pol Arch Intern Med. 2019;129(11):809-816. doi: https://doi.org/10.20452/pamw.15025Maliszewska K, Adamska-Patruno E, Krętowski A. The interplay between muscle mass decline, obesity, and type 2 diabetes. Pol Arch Intern Med. 2019;129(11):809-816. doi: https://doi.org/10.20452/pamw.15025Faienza MF, Brunetti G, Sanesi L, et al. High irisin levels are associated with better glycemic control and bone health in children with Type 1 diabetes. Diabetes Res Clin Pract. 2018;141:10-17. doi: https://doi.org/10.1016/j.diabres.2018.03.046Faienza MF, Brunetti G, Sanesi L, et al. High irisin levels are associated with better glycemic control and bone health in children with Type 1 diabetes. Diabetes Res Clin Pract. 2018;141:10-17. doi: https://doi.org/10.1016/j.diabres.2018.03.046Perakakis N, Triantafyllou GA, Fernández-Real JM, et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol. 2017;13(6):324-337. doi: https://doi.org/10.1038/nrendo.2016.221Perakakis N, Triantafyllou GA, Fernández-Real JM, et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol. 2017;13(6):324-337. doi: https://doi.org/10.1038/nrendo.2016.221Kurdiova T, Balaz M, Mayer A, et al. Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes. Peptides. 2014;56:1-7. doi: https://doi.org/10.1016/j.peptides.2014.03.003Kurdiova T, Balaz M, Mayer A, et al. Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes. Peptides. 2014;56:1-7. doi: https://doi.org/10.1016/j.peptides.2014.03.003Espes D, Lau J, Carlsson PO. Increased levels of irisin in people with long-standing Type 1 diabetes. Diabet Med. 2015;32(9):1172-1176. doi: https://doi.org/10.1111/dme.12731Espes D, Lau J, Carlsson PO. Increased levels of irisin in people with long-standing Type 1 diabetes. Diabet Med. 2015;32(9):1172-1176. doi: https://doi.org/10.1111/dme.12731Ates I, Arikan MF, Erdogan K, et al. Factors associated with increased irisin levels in the type 1 diabetes mellitus. Endocr Regul. 2017;51(1):1-7. doi: https://doi.org/10.1515/enr-2017-0001Ates I, Arikan MF, Erdogan K, et al. Factors associated with increased irisin levels in the type 1 diabetes mellitus. Endocr Regul. 2017;51(1):1-7. doi: https://doi.org/10.1515/enr-2017-0001Du XL, Jiang WX, Lv ZT. Lower Circulating Irisin Level in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis. Horm Metab Res. 2016;48(10):644-652. doi: https://doi.org/10.1055/s-0042-108730Du XL, Jiang WX, Lv ZT. Lower Circulating Irisin Level in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis. Horm Metab Res. 2016;48(10):644-652. doi: https://doi.org/10.1055/s-0042-108730Zhang C, Ding Z, Lv G, et al. Lower irisin level in patients with type 2 diabetes mellitus: A case-control study and meta-analysis. J Diabetes. 2016;8(1):56-62. doi: https://doi.org/10.1111/1753-0407.12256Zhang C, Ding Z, Lv G, et al. Lower irisin level in patients with type 2 diabetes mellitus: A case-control study and meta-analysis. J Diabetes. 2016;8(1):56-62. doi: https://doi.org/10.1111/1753-0407.12256Cui L, Qiao T, Xu F, et al. Circulating irisin levels of prenatal and postnatal patients with gestational diabetes mellitus: A systematic review and meta-analysis. Cytokine. 2020;126:154924. doi: https://doi.org/10.1016/j.cyto.2019.154924Cui L, Qiao T, Xu F, et al. Circulating irisin levels of prenatal and postnatal patients with gestational diabetes mellitus: A systematic review and meta-analysis. Cytokine. 2020;126:154924. doi: https://doi.org/10.1016/j.cyto.2019.154924Kurdiova T, Balaz M, Vician M, et al. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J Physiol. 2014;592(5):1091-1107. doi: https://doi.org/10.1113/jphysiol.2013.264655Kurdiova T, Balaz M, Vician M, et al. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J Physiol. 2014;592(5):1091-1107. doi: https://doi.org/10.1113/jphysiol.2013.264655Moreno-Navarrete JM, Ortega F, Serrano M, et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab. 2013;98(4):E769-E778. doi: https://doi.org/10.1210/jc.2012-2749Moreno-Navarrete JM, Ortega F, Serrano M, et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab. 2013;98(4):E769-E778. doi: https://doi.org/10.1210/jc.2012-2749Wang X, Hu T, Ruan Y, et al. The Association of Serum Irisin with Bone Mineral Density and Turnover Markers in New-Onset Type 2 Diabetic Patients. Merlotti D, ed. Int J Endocrinol. 2022;2022:1-7. doi: https://doi.org/10.1155/2022/7808393Wang X, Hu T, Ruan Y, et al. The Association of Serum Irisin with Bone Mineral Density and Turnover Markers in New-Onset Type 2 Diabetic Patients. Merlotti D, ed. Int J Endocrinol. 2022;2022:1-7. doi: https://doi.org/10.1155/2022/7808393Yang L, Zhi S, Yang G, et al. Molecular identification of FNDC5 and effect of irisin on the glucose metabolism in common carp (Cyprinus carpio L.). Merlotti D, ed. Gen Comp Endocrinol. 2021;301:113647. doi: https://doi.org/10.1016/j.ygcen.2020.113647Yang L, Zhi S, Yang G, et al. Molecular identification of FNDC5 and effect of irisin on the glucose metabolism in common carp (Cyprinus carpio L.). Merlotti D, ed. Gen Comp Endocrinol. 2021;301:113647. doi: https://doi.org/10.1016/j.ygcen.2020.113647Amengual J, García-Carrizo FJ, Arreguín A, et al. Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo. Cell Physiol Biochem. 2018;46(1):187-202. doi: https://doi.org/10.1159/000488422Amengual J, García-Carrizo FJ, Arreguín A, et al. Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo. Cell Physiol Biochem. 2018;46(1):187-202. doi: https://doi.org/10.1159/000488422le Maire A, Alvarez S, Shankaranarayanan P, et al. Retinoid receptors and therapeutic applications of RAR/RXR modulators. Curr Top Med Chem. 2012;12(6):505-527. doi: https://doi.org/10.2174/156802612799436687le Maire A, Alvarez S, Shankaranarayanan P, et al. Retinoid receptors and therapeutic applications of RAR/RXR modulators. Curr Top Med Chem. 2012;12(6):505-527. doi: https://doi.org/10.2174/156802612799436687Richard D, Carpentier AC, Doré G, et al. Determinants of brown adipocyte development and thermogenesis. Int J Obes (Lond). 2010;34(S2):S59-S66. doi: https://doi.org/10.1038/ijo.2010.241Richard D, Carpentier AC, Doré G, et al. Determinants of brown adipocyte development and thermogenesis. Int J Obes (Lond). 2010;34(S2):S59-S66. doi: https://doi.org/10.1038/ijo.2010.241Zhang X, Zhang QX, Wang X, et al. Dietary luteolin activates browning and thermogenesis in mice through an AMPK/ PGC1α pathway-mediated mechanism. Int J Obes (Lond). 2016;40(12):1841-1849. doi: https://doi.org/10.1038/ijo.2016.108Zhang X, Zhang QX, Wang X, et al. Dietary luteolin activates browning and thermogenesis in mice through an AMPK/ PGC1α pathway-mediated mechanism. Int J Obes (Lond). 2016;40(12):1841-1849. doi: https://doi.org/10.1038/ijo.2016.108Joffin N, Jaubert AM, Bamba J, et al. Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats. Adipocyte. 2015;4(2):129-134. doi: https://doi.org/10.4161/21623945.2014.989748Joffin N, Jaubert AM, Bamba J, et al. Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats. Adipocyte. 2015;4(2):129-134. doi: https://doi.org/10.4161/21623945.2014.989748Wang S, Liang X, Yang Q, et al. Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1. Int J Obes (Lond). 2015;39(6):967-976. doi: https://doi.org/10.1038/ijo.2015.23Wang S, Liang X, Yang Q, et al. Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1. Int J Obes (Lond). 2015;39(6):967-976. doi: https://doi.org/10.1038/ijo.2015.23Christakos S, Li S, De La Cruz J, Bikle DD. New developments in our understanding of vitamin D metabolism, action and treatment. Metabolism. 2019;98:112-120. doi: https://doi.org/10.1016/j.metabol.2019.06.010Christakos S, Li S, De La Cruz J, Bikle DD. New developments in our understanding of vitamin D metabolism, action and treatment. Metabolism. 2019;98:112-120. doi: https://doi.org/10.1016/j.metabol.2019.06.010Ferland G. The discovery of vitamin K and its clinical applications. Ann Nutr Metab. 2012;61(3):213-218. doi: https://doi.org/10.1159/000343108Ferland G. The discovery of vitamin K and its clinical applications. Ann Nutr Metab. 2012;61(3):213-218. doi: https://doi.org/10.1159/000343108Громова О.А., Торшин И.Ю., Гарасько Е.В., и др. Системный анализ взаимосвязей между метаболизмом витаминов микробиотой и выживанием позитивной микрофлоры ЖКТ // Экспериментальная и клиническая гастроэнтерология. — 2013. — №2. — С. 28-36.Gromova OA, Torshin IYu, Garas’ko EV, et al. System analysis of the relationship between the metabolism of vitamins by micro-biota and the survival of the positive microflora of the digestive tract. Experimental and clinical gastroenterology. 2013;2:28-36 (In Russ.).Панкратова Ю.В., Пигарова Е.А., Дзеранова Л.К. Витамин К-зависимые белки: остеокальцин, матриксный Gla-белок и их внекостные эффекты // Ожирение и метаболизм. — 2013. — Т. 10. — №2. — С. 11-18. doi: https://doi.org/10.14341/2071-8713-4818Pankratova YuВ, Pigarova EA, Dzeranova LK. Vitamin K-dependent proteins: osteocalcin, matrix Gla-protein and extra osseous effects. Obesity and metabolism. 2013;10(2):11-18. (In Russ.). doi: https://doi.org/10.14341/2071-8713-4818Li J, Zhang H, Yang C, et al. An overview of osteocalcin progress. J Bone Miner Metab. 2016;34(4):367-379. doi: https://doi.org/10.1007/s00774-015-0734-7Li J, Zhang H, Yang C, et al. An overview of osteocalcin progress. J Bone Miner Metab. 2016;34(4):367-379. doi: https://doi.org/10.1007/s00774-015-0734-7Dawson-Hughes B. Vitamin D and muscle function. Merlotti D, ed. J Steroid Biochem Mol Biol. 2017;173:313-316. doi: https://doi.org/10.1016/j.jsbmb.2017.03.018Dawson-Hughes B. Vitamin D and muscle function. Merlotti D, ed. J Steroid Biochem Mol Biol. 2017;173:313-316. doi: https://doi.org/10.1016/j.jsbmb.2017.03.018De Toni L, Di Nisio A, Rocca MS, et al. Osteocalcin, a bone-derived hormone with important andrological implications. Andrology. 2017;5(4):664-670. doi: https://doi.org/10.1111/andr.12359De Toni L, Di Nisio A, Rocca MS, et al. Osteocalcin, a bone-derived hormone with important andrological implications. Andrology. 2017;5(4):664-670. doi: https://doi.org/10.1111/andr.12359Mizokami A, Kawakubo-Yasukochi T, Hirata M. Osteocalcin and its endocrine functions. Biochem Pharmacol. 2017;132:1-8. doi: https://doi.org/10.1016/j.bcp.2017.02.001Mizokami A, Kawakubo-Yasukochi T, Hirata M. Osteocalcin and its endocrine functions. Biochem Pharmacol. 2017;132:1-8. doi: https://doi.org/10.1016/j.bcp.2017.02.001Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008;454(7203):463-469. doi: https://doi.org/10.1038/nature07206Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008;454(7203):463-469. doi: https://doi.org/10.1038/nature07206

The authors declare that there are no conflicts of interest present.