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GPR120 agonist ameliorated insulin resistance and improved ovarian function

Published online by Cambridge University Press:  09 December 2021

Yang Liu
Affiliation:
Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, 226000, China
Jiayi Ding
Affiliation:
Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, 226000, China
Xiaofang Tan
Affiliation:
Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, 226000, China
Ya Shen
Affiliation:
Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, 226000, China
Li Xu
Affiliation:
Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, 226000, China
Tingting Li
Affiliation:
Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, 226000, China
Weiwei Ma
Affiliation:
Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, 226000, China
Jinting Wu*
Affiliation:
Department of Assisted Reproduction, Affiliated Maternity and Child Health Care Hospital of Nantong University, Jiangsu, 226000, China
*
Author for correspondence: Jinting Wu. 399 Shiji Dadao, Nantong, Jiangsu, 226000, China. Email: [email protected]

Summary

GPR120 is implicated in the regulation of glucose and lipid metabolism, and insulin resistance. In the current study, we aimed to investigate the role of GPR120 in polycystic ovary syndrome (PCOS). With the adoption of dehydroepiandrosterone, a rat model was established to simulate PCOS in vitro. mRNA and protein expression levels of GPR120 were measured using RT-qPCR and western blot, respectively. In addition, expression levels of testosterone, estradiol, luteinizing hormone and follicle-stimulating hormone, serum total cholesterol and triglyceride were assessed using the corresponding kits. Moreover, haematoxylin and eosin staining was used to detect pathological changes in ovary or liver and oil red staining was utilized to evaluate lipid accumulation. In the present study, GPR120 was downregulated in plasma, liver and ovary in the PCOS rat model. In addition, the GPR120 agonist regulated lipid metabolism in the liver and weight in the PCOS rat model. Furthermore, the GPR120 agonist decreased insulin resistance in the PCOS rat model but improved the ovarian function. It is suggested that GPR120 plays a vital role in suppressing insulin resistance, regulating ovary function and decreasing lipid accumulation in the liver, demonstrating that targeting GPR120 could be an effective method for the improvement of PCOS.

Type
Research Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Azziz, R (2018). Polycystic ovary syndrome. Obstet Gynecol 132, 321–36.CrossRefGoogle ScholarPubMed
Cox, JM, Chu, HD, Chelliah, MV, Debenham, JS, Eagen, K, Lan, P, Lombardo, M, London, C, Plotkin, MA, Shah, U, Sun, Z, Vaccaro, HM, Venkatraman, S, Suzuki, T, Wang, N, Ashley, ER, Crespo, A, Madeira, M, Leung, DH, et al. (2017). Design, synthesis, and evaluation of novel and selective G-protein coupled receptor 120 (GPR120) spirocyclic agonists. ACS Med Chem Lett 8, 4954.CrossRefGoogle ScholarPubMed
Cox, MJ, Edwards, MC, Rodriguez Paris, V, Aflatounian, A, Ledger, WL, Gilchrist, RB, Padmanabhan, V, Handelsman, DJ and Walters, KA (2020). Androgen action in adipose tissue and the brain are key mediators in the development of PCOS traits in a mouse model. Endocrinology 161, bqaa061.CrossRefGoogle ScholarPubMed
Fruzzetti, F, Perini, D, Russo, M, Bucci, F and Gadducci, A (2017). Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol 33, 3942.CrossRefGoogle Scholar
Goodarzi, MO and Korenman, SG (2003). The importance of insulin resistance in polycystic ovary syndrome. Fertil Steril 80, 255–8.CrossRefGoogle ScholarPubMed
Goodman, N. F., Cobin, R. H., Futterweit, W., Glueck, J. S., Legro, R. S., Carmina, E., American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE) and Androgen Excess and PCOS Society (2015). American Association of Clinical Endocrinologists, American College OF Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: Guide To The Best Practices in the Evaluation and Treatment of Polycystic Ovary Syndrome – Part 2. Endocr Pract 21, 1415–26.CrossRefGoogle Scholar
Katsuma, S, Hatae, N, Yano, T, Ruike, Y, Kimura, M, Hirasawa, A and Tsujimoto, G (2005). Free fatty acids inhibit serum deprivation-induced apoptosis through GPR120 in a murine enteroendocrine cell line STC-1. J Biol Chem 280, 19507–15.CrossRefGoogle Scholar
Kim, DS, Jeong, SK, Kim, HR, Kim, DS, Chae, SW and Chae, HJ (2010). Metformin regulates palmitate-induced apoptosis and ER stress response in HepG2 liver cells. Immunopharmacol Immunotoxicol 32, 251–7.CrossRefGoogle ScholarPubMed
Marzuillo, P, Grandone, A, Perrone, L and Miraglia Del Giudice, E (2015). Understanding the pathophysiological mechanisms in the pediatric non-alcoholic fatty liver disease: The role of genetics. World J Hepatol 7, 1439–43.CrossRefGoogle ScholarPubMed
Moghetti, P (2016). Insulin resistance and polycystic ovary syndrome. Curr Pharmaceut Design 22, 5526–34.CrossRefGoogle ScholarPubMed
Oh, DY, Walenta, E, Akiyama, TE, Lagakos, WS, Lackey, D, Pessentheiner, AR, Sasik, R, Hah, N, Chi, TJ, Cox, JM, Powels, MA, Di Salvo, J, Sinz, C, Watkins, SM, Armando, AM, Chung, H, Evans, RM, Quehenberger, O, Mcnelis, J, et al. (2014). A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nature Med 20, 942–7.CrossRefGoogle ScholarPubMed
Olefsky, JM and Glass, CK (2010). Macrophages, inflammation, and insulin resistance. Ann Rev Physiol 72, 219–46.CrossRefGoogle Scholar
Patel, S (2018). Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol 182, 2736.CrossRefGoogle Scholar
Petta, S, Ciresi, A, Bianco, J, Geraci, V, Boemi, R, Galvano, L, Magliozzo, F, Merlino, G, Craxì, A and Giordano, C (2017). Insulin resistance and hyperandrogenism drive steatosis and fibrosis risk in young females with PCOS. PLoS One 12, e0186136.CrossRefGoogle ScholarPubMed
Polak, K, Czyzyk, A, Simoncini, T and Meczekalski, B (2017). New markers of insulin resistance in polycystic ovary syndrome. J Endocrinol Invest 40, 18.CrossRefGoogle ScholarPubMed
Sawzdargo, M, George, SR, Nguyen, T, Xu, S, Kolakowski, LF and O’Dowd, BF (1997). A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1. Biochem Biophys Res Commun 239, 543–7.CrossRefGoogle Scholar
Song, T, Yang, Y, Zhou, Y, Wei, H and Peng, J (2017). GPR120: A critical role in adipogenesis, inflammation, and energy metabolism in adipose tissue. Cell Mol Life Sci 74, 2723–33.CrossRefGoogle ScholarPubMed
Winer, DA, Luck, H, Tsai, S and Winer, S (2016). The intestinal immune system in obesity and insulin resistance. Cell Metab 23, 413–26.CrossRefGoogle ScholarPubMed
Wiweko, B, Indra, I, Susanto, C, Natadisastra, M and Hestiantoro, A (2018). The correlation between serum AMH and HOMA-IR among PCOS phenotypes. BMC Res Notes 11, 114.CrossRefGoogle ScholarPubMed
Zhang, D and Leung, PS (2014). Potential roles of GPR120 and its agonists in the management of diabetes. Drug Design Dev Ther 8, 1013–27.Google ScholarPubMed
Zhang, X and Macielag, MJ (2020). GPR120 agonists for the treatment of diabetes: A patent review (2014 present). Expert Opin Ther Pat 30, 729–42.CrossRefGoogle Scholar