HARNESSING THE POWER OF G-PROTEIN COUPLED RECEPTOR-120 IN REDEFINING INSULIN RESISTANCE AND INFLAMMATION MANAGEMENT IN POLYCYSTIC OVARY SYNDROME

Authors

  • NEETI PATEL Department of Biochemistry, Parul Institute of Medical Sciences and Research, Parul University, Waghodiya, Gujarat, India https://orcid.org/0000-0002-6428-1927
  • IVVALA ANAND SHAKER
  • KANDARP PATEL

DOI:

https://doi.org/10.22159/ajpcr.2025v18i6.54774

Keywords:

GPR120, IL-10, Inflammation, Insulin Resistance, Polycystic Ovary Syndrome (PCOS)

Abstract

Objectives: This study aims to evaluate serum G-Protein Coupled Receptor 120 (GPR120) levels and its association with anti-inflammatory cytokine Interleukin-10 (IL-10), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and female reproductive hormones in PCOS subjects as it is disorder of affecting reproductive women with complex combination of symptoms like excess androgens, polycystic ovaries, ovulatory dysfunction, Insulin resistance and chronic low-grade inflammation.

Methods: In a cross-sectional study carried out at the tertiary care hospital of the South Gujarat district between March 2023 to December 2024. Using a convenience sampling technique, a total 248 women (124 PCOS and 124 age-matched healthy controls) were assessed for markers like Serum GPR120, IL-10, insulin, adiponectin, LH, FSH, testosterone, and anthropometric parameters. Student’s t-test (p-value) was applied for significance and Pearson’s correlation (r-value) for finding the association between parameters as a part of statistical analysis.

Results: Elevated serum LH:FSH, Testosterone, Insulin, HOMA-IR, and significantly decreased levels of GPR120, IL-10, and adiponectin were reported in PCOS subjects as compared to the non-PCOS group. GPR120 showed a strong positive correlation with Adiponectin (r = 0.925), IL-10 (r=0.681) and a negative correlation with BMI (r=-0.325), WHR (r=-0.516), Testosterone (r=-0.539), Insulin (r=-0.085) and HOMA-IR (r=-0.087) in women with PCOS disorder.

Conclusion: Lower levels of GPR120, and its strong correlation with HOMA-IR and inflammatory markers, suggest its key role in the pathophysiology of PCOS. GPR120 may serve as a novel therapeutic approach for alleviating metabolic and inflammatory disturbances in PCOS.

Downloads

Download data is not yet available.

References

Singh S, Pal N, Shubham S, Sarma DK, Verma V, Marotta F, et al. Polycystic ovary syndrome: Etiology, current management, and future therapeutics. J Clin Med. 2023 Feb 11;12(4):1454. doi: 10.3390/ jcm12041454, PMID 36835989, PMCID PMC9964744

Livadas S, Anagnostis P, Bosdou JK, Bantouna D, Paparodis R. Polycystic ovary syndrome and type 2 diabetes mellitus: A state-of-the-art review. World J Diabetes. 2022 Jan 15;13(1):5-26. doi: 10.4239/wjd. v13.i1.5, PMID 35070056, PMCID PMC8771268

Stuttgen GM, Sahoo D. FFAR4: A new player in cardiometabolic disease? Endocrinology. 2021 Aug 1;162(8):bqab111. doi: 10.1210/ endocr/bqab111, PMID 34043793, PMCID PMC8218936

Paschoal VA, Walenta E, Talukdar S, Pessentheiner AR, Osborn O, Hah N, et al. Positive reinforcing mechanisms between GPR120 and PPARγ modulate insulin sensitivity. Cell Metab. 2020 Jun 2;31(6):1173- 1188.e5. doi: 10.1016/j.cmet.2020.04.020, PMID 32413335, PMCID PMC7337476

Szukiewicz D. Potential therapeutic exploitation of G protein-coupled receptor 120 (GPR120/FFAR4) signaling in obesity-related metabolic disorders. Int J Mol Sci. 2025 Mar 11;26(6):2501. doi: 10.3390/ ijms26062501, PMID 40141148, PMCID PMC11941992

Rudnicka E, Suchta K, Grymowicz M, Calik-Ksepka A, Smolarczyk K, Duszewska AM, et al. Chronic low grade inflammation in pathogenesis of PCOS. Int J Mol Sci. 2021 Apr 6;22(7):3789. doi: 10.3390/ ijms22073789, PMID 33917519, PMCID PMC8038770

Vasyukova E, Zaikova E, Kalinina O, Gorelova I, Pyanova I, Bogatyreva E, et al. Inflammatory and anti-inflammatory parameters in PCOS patients depending on body mass index: A case-control study. Biomedicines. 2023 Oct 14;11(10):2791. doi: 10.3390/ biomedicines11102791, PMID 37893164, PMCID PMC10604137

Wang J, Huang Z, Cao Z, Luo Y, Liu Y, Cao H, et al. Loureirin B reduces insulin resistance and chronic inflammation in a rat model of polycystic ovary syndrome by upregulating GPR120 and activating the LKB1/ AMPK signaling pathway. Int J Mol Sci. 2024 Oct 17;25(20):11146. doi: 10.3390/ijms252011146, PMID 39456928, PMCID PMC11508921

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. doi: 10.1093/humrep/deh098, PMID 14688154

Sudjaroen Y, Thongkao K, Thongmuang P. A physiochemical study on drug delivery of metformin HCl-loaded CS-PLGA nanoparticles. Int J Appl Pharm. 2023;15(1):66-71. doi: 10.22159/ijap.2023v15i1.45842

Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010 Sep 3;142(5):687-98. doi: 10.1016/j.cell.2010.07.041, PMID 20813258, PMCID PMC2956412

Liu Y, Guo M, Li Y, Wang T, Ren Y, Wang R, et al. α-linolenic acid regulates macrophages via GPR120-NLRP3 inflammasome pathway to ameliorate diabetic rats. J Funct Foods. 2022 Dec 1;99:105348. doi: 10.1016/j.jff.2022.105348

Ichimura A, Hirasawa A, Poulain-Godefroy O, Bonnefond A, Hara T, Yengo L, et al. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature. 2012 Feb 19;483(7389):350-4. doi: 10.1038/nature10798, PMID 22343897

Liu Y, Ding J, Tan X, Shen Y, Xu L, Li T, et al. GPR120 agonist ameliorated insulin resistance and improved ovarian function. Zygote. 2022 Jun;30(3):380-5. doi: 10.1017/S0967199421000873, PMID 34879886

Chugh RM, Park HS, El Andaloussi A, Elsharoud A, Esfandyari S, Ulin M, et al. Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10. Stem Cell Res Ther. 2021 Jul 7;12(1):388. doi: 10.1186/ s13287-021-02472-w, PMID 34233746, PMCID PMC8261924

Shamsi M, Ghazavi A, Saeedifar AM, Mosayebi G, Pour SK, Ganji A. The immune system’s role in PCOS. Mol Biol Rep. 2022 Nov;49(11):10689-702. doi: 10.1007/s11033-022-07695-5, PMID 35752698

Steen EH, Wang X, Balaji S, Butte MJ, Bollyky PL, Keswani SG. The role of the anti-inflammatory cytokine interleukin-10 in tissue fibrosis. Adv Wound Care (New Rochelle). 2020 Apr 1;9(4):184- 98. doi: 10.1089/wound.2019.1032, PMID 32117582, PMCID PMC7047112

Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: Insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther. 2022;7(1):216. doi: 10.1038/s41392-022- 01073-0, PMID 35794109

Patil S, Veerabhadra Goud GK, Shivashankar RN, Anusuya SK, Ganesh V. Association of adiponectin levels with polycystic ovary syndrome among Indian women. Bioinformation. 2022 Oct 31;18(10):864-9. doi: 10.6026/97320630018864, PMID 37654825, PMCID PMC10465762

Shorakae S, Abell SK, Hiam DS, Lambert EA, Eikelis N, Jona E, et al. High-molecular-weight adiponectin is inversely associated with sympathetic activity in polycystic ovary syndrome. Fertil Steril. 2018 Mar;109(3):532-9. doi: 10.1016/j.fertnstert.2017.11.020, PMID 29428305

Groth SW. Adiponectin and polycystic ovary syndrome. Biol Res Nurs. 2010 Jul;12(1):62-72. doi: 10.1177/1099800410371824, PMID 20498127, PMCID PMC3646519

Suryapani A, Uniyal SM. Correlation of leptin and adiponectin levels with metabolic and hormonal profiles in PCOS patients: A comparative study with normal controls. Int J Curr Pharm Res. 2024;16(6):62-5. doi: 10.22159/ijcpr.2024v16i6.6009

Quesada-López T, Cereijo R, Turatsinze JV, Planavila A, Cairó M, Gavaldà-Navarro A, et al. The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes. Nat Commun. 2016 Nov 17;7:13479. doi: 10.1038/ncomms13479, PMID: 27853148, PMCID: PMC5118546

Yan H, Wang L, Zhang G, Li N, Zhao Y, Liu J, et al. Oxidative stress and energy metabolism abnormalities in polycystic ovary syndrome: From mechanisms to therapeutic strategies. Reprod Biol Endocrinol. 2024 Dec 26;22(1):159. doi: 10.1186/s12958-024-01337-0, PMID 39722030, PMCID PMC11670460

Khani B, Mardanian F, Fesharaki SJ. Omega-3 supplementation effects on polycystic ovary syndrome symptoms and metabolic syndrome. J Res Med Sci. 2017 May 30;22:64. doi: 10.4103/jrms.JRMS_644_16, PMID 28616051, PMCID PMC5461594

Mohammadi E, Rafraf M, Farzadi L, Asghari-Jafarabadi M, Sabour S. Effects of omega-3 fatty acids supplementation on serum adiponectin levels and some metabolic risk factors in women with polycystic ovary syndrome. Asia Pac J Clin Nutr. 2012;21(4):511-8. PMID 23017309

Oner G, Muderris II. Efficacy of omega-3 in the treatment of polycystic ovary syndrome. J Obstet Gynaecol. 2013;33(3):289-91. doi: 10.3109/01443615.2012.751365, PMID 23550861

Nadjarzadeh A, Dehghani-Firouzabadi R, Daneshbodi H, Lotfi MH, Vaziri N, Mozaffari-Khosravi H. Effect of Omega-3 supplementation on visfatin, adiponectin, and anthropometric indices in women with polycystic ovarian syndrome. J Reprod Infertil. 2015;16(4):212-20. PMID 27110520

Taha M. Therapeutic use of alpha - lipoic acid supplementation: A review on current use and future prospective. Int J Appl Pharm. 2024;16(6):21-7. doi: 10.22159/ijap.2024v16i6.51319

Published

07-06-2025

How to Cite

NEETI PATEL, et al. “HARNESSING THE POWER OF G-PROTEIN COUPLED RECEPTOR-120 IN REDEFINING INSULIN RESISTANCE AND INFLAMMATION MANAGEMENT IN POLYCYSTIC OVARY SYNDROME”. Asian Journal of Pharmaceutical and Clinical Research, vol. 18, no. 6, June 2025, pp. 143-6, doi:10.22159/ajpcr.2025v18i6.54774.

Issue

Section

Original Article(s)