Effect of irisin on ovarian phosphatidylinositol-3-kinase/protein kinase B signaling pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways of rats with polycystic ovary syndrome.
MAPK/ERK pathway
PI3K/AKT pathway
insulin resistance
irisin
polycystic ovarian syndrome
Journal
The journal of obstetrics and gynaecology research
ISSN: 1447-0756
Titre abrégé: J Obstet Gynaecol Res
Pays: Australia
ID NLM: 9612761
Informations de publication
Date de publication:
03 Sep 2024
03 Sep 2024
Historique:
received:
01
05
2024
accepted:
23
08
2024
medline:
3
9
2024
pubmed:
3
9
2024
entrez:
3
9
2024
Statut:
aheadofprint
Résumé
To investigate the independent effects of irisin on insulin resistance (IR) in ovary of polycystic ovary syndrome (PCOS) and explore possible pathways. We established PCOS medel using Poretsky L's method, then PCOS rats were randomly divided into model group (M) and irisin group (I), and normal rats (N) were used as the control. Then rats in the group I were injected with recombinant irisin. Then the levels of circulating fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR) and PI3K/AKT and MAPK/ERK pathways in each group were observed, as well as the effects of irisin on the levels of circulating HOMA-IR and PI3K/AKT and MAPK/ERK pathways in ovary of PCOS rats were evaluated. Compared with normal group, levels of FBG, FINS, and HOMA-IR of model group were significantly increased (p < 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p-PI3K, PI3K, p-AKT, and AKT (p = 0.015, p = 0.010, p = 0.005, and p = 0.009, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.001, and p = 0.005, respectively) were decreased, while the levels of average optical density of p-ERK, ERK (p = 0.011, and p = 0.013, respectively) and level of mRNA concentration of ERK (p < 0.001) were increased in ovary. After irisin intervention, compared with model group, levels of FBG, FINS, and HOMA-IR of rats in irisin group were significantly decreased (p = 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p-PI3K, PI3K, p-AKT, and AKT (p = 0.030, p = 0.024, p = 0.012, and p = 0.025, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.002, and p = 0.003, respectively) were significantly increased, while the levels of average optical density of p-ERK, ERK (p = 0.004, and p = 0.026, respectively) and level of mRNA concentration of ERK (p = 0.001) were significantly decreased. Our study demonstrated that irisin could not only improve circulating insulin resistance, but may also improve ovarian IR through an increase in the activity of PI3K/AKT signaling and a decrease of MAPK/ERK signaling.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Project of Hebei Provincal Administration of Traditional Chinese Medicine
ID : 2024191
Organisme : Project of Postdoctoral Workstation at the First Affiliated Hospital of Xingtai Medical College
Informations de copyright
© 2024 Japan Society of Obstetrics and Gynecology.
Références
Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1‐a‐dependent myokine that drives brown‐fat‐like development of white fat and thermogenesis. Nature. 2012;481:463–468.
Lidia IA, Laura M, Mihai C. Irisin: a hope in understanding and managing obesity and metabolic syndrome. Front Endocrinol. 2019;10:524.
Nikolaos P, Georgios AT, José MF, Joo YH, Kyung HP, Jochen S, et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol. 2017;13:324–337.
Mo L, Shen J, Liu QH, Zhang Y, Kuang J, Pu S, et al. Irisin is regulated by CAR in liver and is a mediator of hepatic glucose and lipid metabolism. Mol Endocrinol. 2016;30:533–542.
Zheng YJ, He J, Yang DY, Yuan M, Liu S, Dai F, et al. Irisin reduces the abnormal reproductive and metabolic phenotypes of PCOS by regulating the activity of brown adipose tissue in mice. Biol Reprod. 2022;107:1046–1058.
Shi XL, Lin MZ, Liu CQ, Xiao F, Liu Y, Huang P, et al. Elevated circulating irisin is associated with lower risk of insulin resistance: association and path analyses of obese Chinese adults. BMC Endocr Disord. 2016;16:44.
Wang JG, Zhao YT, Zhang L, Dubielecka PM, Zhuang S, Qin G, et al. Irisin improves myocardial performance and attenuates insulin resistance in spontaneous mutation (Leprdb) mice. Front Pharmacol. 2020;11:769.
Mamo G, Pandi A, Tolessa D. A review on the role of irisin in insulin resistance and type 2 diabetes mellitus. J Pharmacopuncture. 2017;20:235–242.
Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98:2133–2223.
Lee SH, Park SY, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J. 2022;46:15–37.
Zhao H, Zhang JQ, Cheng XY, Nie X, He B. Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment. J Ovarian Res. 2023;16:9.
Valeria C, Elvira V, Hellas C, Vittoria CM, Carolina FT, Elisavietta T, et al. Polycystic ovary syndrome in insulin‐resistant adolescents with obesity: the role of nutrition therapy and food supplements as a strategy to protect fertility. Nutrients. 2021;13:1848.
Moghetti P, Tosi F. Insulin resistance and PCOS: chicken or egg? J Endocrinol Investig. 2021;44:233–244.
Tosi F, Bonora E, Moghetti P. Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic‐hyperinsulinaemic clamp and surrogate indexes. Hum Reprod. 2017;32:2515–2521.
Moghetti P. Insulin resistance and polycystic ovary syndrome. Curr Pharm Des. 2016;22:5526–5534.
Wu XK, Zhou SY, Liu JX, Pöllänen P, Sallinen K, Mäkinen M, et al. Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome. Fertil Steril. 2003;80:954–965.
Wu XK, Risto E. Ovarian insulin resistance and insulin sensitizer effect on polycystic ovary syndrome. Zhonghua Fu Chan Ke Za Zhi. 2004;39:804–808.
Rice S, Christoforidis N, Gadd C, Nikolaou D, Seyani L, Donaldson A, et al. Impaired insulin‐dependent glucose metabolism in granulosa‐lutein cells from anovulatory women with polycystic ovaries. Hum Reprod. 2005;20:373–381.
Yen HW, Jakimiuk AJ, Munir I, Magoffin DA. Selective alterations in insulin receptor substrates‐1, ‐2 and ‐4 in theca but not granulosa cells from polycystic ovaries. Mol Hum Reprod. 2004;10:473–479.
Evanthia DK, Antonios C, Efstathia P, Dimitrios K, Michael K. Advanced glycation end‐products and insulin signaling in granulosa cells. Exp Biol Med (Maywood). 2016;241:1438–1445.
Hao MH, Yuan F, Jin CC, Zhou Z, Cao Q, Xu L, et al. Overexpression of Lnk in the ovaries is involved in insulin resistance in women with polycystic ovary syndrome. Endocrinology. 2016;157:3709–3718.
Poretsky L, Clemons J, Bogovich K. Hyperinsulinemia and human chorionic gonadotropin synergistically promote the growth of ovarian follicular cysts in rats. Metab Clin Exp. 1992;41:903–910.
Dicky LT, Livy BP, Nissha AF, Cicilia M, Syahidatul W, Farid K, et al. Challenges in the diagnosis of insulin resistance: focusing on the role of HOMA‐IR and Tryglyceride/glucose index. Diabetes Metab Syndr. 2022;16:102581.
Li XX, Zhu QL, Wang WS, Qi J, He Y, Wang Y, et al. Elevated chemerin induces insulin resistance in human granulosa‐lutein cells from polycystic ovary syndrome patients. FASEB J. 2019;33:11303–11313.
Yoshiteru H, Seiji A, Ichiro Y, Shinji T, Rie MN, Hisaaki K, et al. Collagen‐induced p38 MAP kinase activation is a biomarker of platelet hyper‐aggregation in patients with diabetes mellitus. Life Sci. 2009;85:386–394.
Saskia MB, Kohjiro U, Jeffrey AE, Ronald CK, Lewis CC. Phosphoinositide 3‐kinase catalytic subunit deletion and regulatory subunit deletion have opposite effects on insulin sensitivity in mice. Mol Cell Biol. 2005;25:1596–1607.
Midori F, Yukiko G, Hideki K, Hideyuki S, Takehide O, Motonobu A, et al. Three mitogen‐activated protein kinases inhibit insulin signaling by different mechanisms in 3T3‐L1 adipocytes. Mol Endocrinol. 2003;17:487–497.
Tong C, Wu Y, Zhang LL, Yu Y. Insulin resistance, autophagy and apoptosis in patients with polycystic ovary syndrome: association with PI3K signaling pathway. Front Endocrinol (Lausanne). 2022;13:1091147.
Anne C, Zhao HY, Salida M, Fraser A, Andrea D. Enhanced mitogenic signaling in skeletal muscle of women with polycystic ovary syndrome. Diabetes. 2006;55:751–759.
Madhurima R, Sandra B, Daniel JC, Christopher L, Antonio JR, Giles ET, et al. Insulin resistance in polycystic ovary syndrome is associated with defective regulation of ERK1/2 by insulin in skeletal muscle in vivo. Biochemistry. 2009;418:665–671.
Kong LG, Wang Q, Jin JW, Xiang Z, Chen T, Shen S, et al. Insulin resistance enhances the mitogen‐activated protein kinase signaling pathway in ovarian granulosa cells. PLoS One. 2017;12:e0188029.
Su Y, Wu J, He JL, Liu X, Chen X, Ding Y, et al. High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process. Endocr J. 2017;64:613–621.
Zhang C, Wu J, He JL, Liu X, Chen X, Tong C, et al. The regulation of high insulin levels on ovary apoptosis in early pregnant mice. Biochem Biophys Res Commun. 2017;483:786–792.
Weng Y, Zhang Y, Wang D, Wang R, Xiang Z, Shen S, et al. Exercise‐induced irisin improves follicular dysfunction by inhibiting IRE1α‐TXNIP/ROS‐NLRP3 pathway in PCOS. J Ovarian Res. 2023;16:151.
Li CG, Zhou L, Xie Y, Guan C, Gao H. Effect of irisin on endometrial receptivity of rats with polycystic ovary syndrome. Gynecol Endocrinol. 2019;35:395–400.