Metformin treatment ameliorates endocrine-metabolic disturbances in letrozole-induced PCOS mice model by modulating adiponectin status

Shah, Mohd Zahoor ul Haq; Shrivastava, Vinoy K.; Mir, Manzoor Ahmad

doi:10.1016/j.obmed.2022.100392

Cited by 9 publications

(5 citation statements)

References 53 publications

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“…The PCOS mouse model indicated increased body weight and excess abdominal fat, but the deficiencies were corrected by oral DIC treatment. In a latest study, letrozole-induced PCOS in mice resulted in elevated body weights [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Diacerein mitigates endocrine and cardio-metabolic disruptions in experimental PCOS mice model by modulating AdipoR1/ PON 1

Shah,

Shrivastava,

Muzamil

et al. 2024

BMC Endocr Disord

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Background This study aimed to explore the impact of Diacerein (DIC) on endocrine and cardio-metabolic changes in polycystic ovarian syndrome (PCOS) mouse model. Methods A total of 18 adult female mice (Parkes strain), aged 4–5 weeks, were randomly assigned to three groups, each comprising 6 animals, as follows: Group I (control), received normal diet and normal saline as vehicle for 51 days; Group II received Letrozole (LET; 6 mg/kg bw) for 21 days to induce PCOS; Group III received LET, followed by daily oral gavage administration of DIC (35 mg/kg bw) for 30 days. Results This study indicates that treatment with LET resulted in PCOS with characteristics such as polycystic ovaries, elevated testosterone, weight gain, visceral adiposity, high levels of insulin as well as fasting blood glucose in addition to insulin resistance, improper handling of ovarian lipids, atherogenic dyslipidemia, impaired Na + /K + -ATPase activity and serum, cardiac, and ovarian oxidative stress. Serum/ovarian adiponectin levels were lowered in LET-treated mice. In mice treated with LET, we also discovered a reduction in cardiac and serum paraoxonase 1 (PON1). Interestingly, DIC restored ovarian andcardio-metabolic abnormalities in LET-induced PCOS mice. DIC prevented the endocrine and cardio-metabolic changes brought on by letrozole-induced PCOS in mice. Conclusion The ameliorative effects of DIC on letrozole-induced PCOS with concurrent oxidative stress, abdominal fat deposition, cardiac and ovarian substrate mishandling, glucometabolic dysfunction, and adiponectin/PON1 activation support the idea that DIC perhaps, restore compromised endocrine and cardio-metabolic regulators in PCOS.

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Section: Discussionmentioning

confidence: 99%

Diacerein mitigates endocrine and cardio-metabolic disruptions in experimental PCOS mice model by modulating AdipoR1/ PON 1

Shah,

Shrivastava,

Muzamil

et al. 2024

BMC Endocr Disord

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“…Patients with PCOS experience hyperandrogenism as well as hyperinsulinemia, which causes adipocytes to increase catecholamine-induced lipolysis, which then results in increased serum free fatty acid levels and dyslipidemia ( 24 ). Due to the increased production of free fatty acids by the liver, TG levels in the blood are increased ( 25 ). In this work, we discovered that letrozole-treated mice had higher TC and TG levels than the control group.…”

Section: Discussionmentioning

confidence: 99%

“…Ovarian dysfunction, cysts in ovaries, and hyperandrogenism are some of its diagnostic markers. Despite the lack of a clear aetiology, it appears an imbalance of hormones, particularly elevated testosterone level, as well as insulin resistance (IR), can be taken into account (1)(2)(3). Patients with PCOS who have infertility are frequently upset about their inability to get pregnant.…”

Section: Introductionmentioning

confidence: 99%

Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome

Shah,

Shrivastva,

Mir

et al. 2023

Front. Endocrinol.

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IntroductionPolycystic Ovary syndrome (PCOS) affects the health of many women around the world. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis.MethodsEighteen mature parkes strain mice (4-5 weeks old) weighing 18–21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kg bw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days.ResultsIn our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice.DiscussionQuercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn’t act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS.

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“…The lipid peroxidation assay was conducted as follows: The quantity of malonaldehyde (MDA) was measured to determine how much lipid peroxidation (LPO) occurred in the ovaries [ 23 ]. We dissected the ovaries in ice-cold normal saline using a glass homogenizer, and ten percent homogenate tissue was prepared.…”

Section: Methodsmentioning

confidence: 99%

Chlorogenic Acid Restores Ovarian Functions in Mice with Letrozole-Induced Polycystic Ovarian Syndrome Via Modulation of Adiponectin Receptor

et al. 2023

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Around the world, polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic condition that typically affects 6–20% of females. Our study’s major goal was to examine how chlorogenic acid (CGA) affected mice with endocrine and metabolic problems brought on by letrozole-induced PCOS. Group I served as the control for 81 days; Group II was given Letrozole (LETZ) orally at a dose of 6 mg/kg bw for 21 days to induce PCOS; Group III was given LETZ (6 mg/kg) for 21 days, followed by treatment with CGA (50 mg/kg bw daily) for 60 days. The study indicated that LETZ-treated mice displayed symptoms of PCOS, such as dyslipidemia, hyperinsulinemia, elevated testosterone, increases in inflammatory markers and malonaldehyde, and a decline in antioxidants (Ar, lhr, fshr, and esr2) in the ovaries. These alterations were affected when the mice were given CGA and were associated with reduced levels of adiponectin. Adiponectin showed interactions with hub genes, namely MLX interacting protein like (MLXIPL), peroxisome proliferator-activated receptor gamma Coactivator 1- alpha (PPARGC1), peroxisome proliferator-activated receptor gamma (Pparg), and adiponectin receptor 1 (Adipor1). Lastly, the gene ontology of adiponectin revealed that adiponectin was highly involved in biological processes. The findings from our research suggest that adiponectin has direct impacts on metabolic and endocrine facets of PCOS.

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Metformin treatment ameliorates endocrine-metabolic disturbances in letrozole-induced PCOS mice model by modulating adiponectin status

Cited by 9 publications

References 53 publications

Diacerein mitigates endocrine and cardio-metabolic disruptions in experimental PCOS mice model by modulating AdipoR1/ PON 1

Diacerein mitigates endocrine and cardio-metabolic disruptions in experimental PCOS mice model by modulating AdipoR1/ PON 1

Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome

Chlorogenic Acid Restores Ovarian Functions in Mice with Letrozole-Induced Polycystic Ovarian Syndrome Via Modulation of Adiponectin Receptor

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