Liraglutide modulates adipokine expression during adipogenesis, ameliorating obesity, and polycystic ovary syndrome in mice

Singh, Anusha; Fernandes, Joseph R.D.; Chhabra, Gagan; Krishna, Amitabh; Banerjee, Arundhati

doi:10.1007/s12020-019-01891-3

Cited by 10 publications

(9 citation statements)

References 70 publications

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“…It also improved ovarian function and elevated the level of adiponectin by increasing the expression of Akt and PI3K. 63…”

Section: Evidence For the Therapeutic Potentials Of Glp-1 Ra In Pcosmentioning

confidence: 96%

“…It also improved ovarian function and elevated the level of adiponectin by increasing the expression of Akt and PI3K. 63 Clinical studies. In an observational trial in 84 overweight/obese women with PCOS, the women received liraglutide at an initial dose of 0.6 mg subcutaneously once a day and then this was increased to 1.8 mg a day for 4 weeks.…”

Section: Liraglutidementioning

confidence: 99%

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The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence

Abdalla

Deshmukh

Atkin

et al. 2021

Therapeutic Advances in Endocrinology

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Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Metabolic consequences associated with PCOS include, but are not limited to, insulin resistance (IR), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). This narrative review aims to provide a comprehensive overview of the potential therapeutic roles of the incretin-based therapies in the management of PCOS. Methods: We performed a systematic search of databases including PubMed, MEDLINE and EMBASE up to 1 October 2020. We developed a search string of medical subject headings (MeSH) including the terms PCOS, incretin mimetics, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-1 receptor antagonists (GLP-1 RAs), liraglutide, exenatide, semaglutide, dipeptidyl peptidase-4 (DPP-4) inhibitors, combined with IR, testosterone and sex hormone-binding globulin (SHBG). Results: We identified 854 relevant articles and, after the initial screening, eight interventional animal studies, one observational animal study, 14 interventional human studies, two case–control studies and one systematic review were included. These studies showed the potential significant roles of GLP-1 RAs and DPP-4 inhibitors in the management of PCOS, with significant improvements in the metabolic parameters, including substantial weight reduction and improved insulin sensitivity. These agents also improved the hormonal parameters through decreased free androgen and increased SHBG. Moreover, they improved menstrual regularity, increased fertility with enhanced ovulation and pregnancy in obese women with PCOS. Conclusion: GLP-1 RAs and DPP-4 inhibitors have a promising therapeutic role in PCOS; however, larger clinical trials are needed to establish the role of incretin-based therapies in the management of PCOS.

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“…It also improved ovarian function and elevated the level of adiponectin by increasing the expression of Akt and PI3K. 63…”

Section: Evidence For the Therapeutic Potentials Of Glp-1 Ra In Pcosmentioning

confidence: 96%

Section: Liraglutidementioning

confidence: 99%

The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence

Abdalla

Deshmukh

Atkin

et al. 2021

Therapeutic Advances in Endocrinology

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“…Few reports are available about the effect of LG on adipokines production from adipose tissue. Only recently, LG treatment resulted in up-regulation of adiponectin along with down-regulation of leptin in differentiated 3T3-L1 adipocytes, 46 and as well it increased the expression of adiponectin and reduced the body weight in polycystic ovary in mice. 46 Previously, LG causes upregulation of serum adiponectin in type 2 diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

“…Only recently, LG treatment resulted in up-regulation of adiponectin along with down-regulation of leptin in differentiated 3T3-L1 adipocytes, 46 and as well it increased the expression of adiponectin and reduced the body weight in polycystic ovary in mice. 46 Previously, LG causes upregulation of serum adiponectin in type 2 diabetic patients. 36 Moreover, it has been demonstrated that the activity of LG to reduce body weight is due to reducing leptin plasma level 35 and that, GLP-1 analogue, NN2211, induced weight loss and reduced adiposity as indicated by lowered plasma levels of leptin in both normal lean and obese rats.…”

Section: Discussionmentioning

confidence: 99%

Anti-Proliferative Activity of Glucagon-Like Peptide-1 Receptor Agonist on Obesity-Associated Breast Cancer: The Impact on Modulating Adipokines’ Expression in Adipocytes and Cancer Cells

et al. 2021

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Obesity is associated with high risk and poor prognosis of breast cancer (BC). Obesity promotes BC cells proliferation via modulating the production of adipokines, including adiponectin (anti-neoplastic adipokine), leptin (carcinogenic adipokine) and inflammatory mediators. In the present study we investigated the anti-proliferative effects of liraglutide (LG; anti-diabetic and weight reducing drug) on MCF-7 human BC cells cultured in obese adipose tissue-derived stem cells-conditioned medium (ADSCs-CM) and whether this effect is mediated via modulating the adipokines in ADSCs and cancer cells. Proliferation was investigated using AlamarBlue viability test, colony forming assay and cell cycle analysis. Levels and expression of adipokines and their receptors were assayed using ELISA and RT-PCR. LG caused 48% inhibition of MCF-7 proliferation in obese ADSCs-CM, reduced the colony formation and induced G0/G1 phase arrest. LG also decreased the levels of inflammatory mediators, suppressed the expression of leptin, while increased mRNA levels of adiponectin and their receptors in obese ADSCs and cancer cells cultured in obese ADCSs-CM. In conclusion, LG could mitigate BC cell growth in obese subjects; therefore it could be used for clinical prevention and/or treatment of BC in obese subjects. It may assist to improve treatment outcomes and, reduce the mortality rate in obese patients with BC.

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“…When LIRA was administered in preclinical PCOS models, it promoted significant reductions in body weight, abdominal fat deposition and IR markers. [31][32][33] Liraglutide may also suppress the overexpressed Notch signaling pathway, which causes neuroinflammation and can promote cognitive dysfunction. 34 Moreover, in ovariectomized mice, LIRA was found to modulate Kisspeptin 1 neuronal populations in the ARC, which control the secretion of GnRH in a pulsatile fashion.…”

Section: Preclinical Evidencementioning

confidence: 99%

GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons

Papaetis¹,

Kyriacou²

2022

Adv Clin Exp Med

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Polycystic ovary syndrome (PCOS) is a disorder that involves several organ systems and cellular pathways. It is strongly influenced by environmental and epigenetic factors. The principal goal of all therapeutic approaches to individuals with reproductive abnormalities is the treatment of subfertility or the regulation of menstruation when pregnancy is not desired. Obesity is closely related to insulin resistance (IR) and subsequent hyperinsulinemia, which aggravate hyperandrogenism and impair early follicle development. Weight loss is of vital importance for overweight/obese individuals with anovulatory infertility. The GLP-1R agonists have achieved remarkable weight reduction and abdominal fat loss in patients with type 2 diabetes (T2D), as well as in overweight/obese individuals and individuals with prediabetes. They have also been shown to promote lower fasting insulin levels and insulin resistance markers. These beneficial effects have been suggested to be particularly helpful in women with PCOS, while their possible role in the hypothalamic-pituitary-gonadal axis is under intense research. This review analyzes the current evidence for GLP-1R agonists, focusing on their effects on ovarian morphology, menstrual dysfunction and fertility outcomes. It also discusses their future role in achieving targeted therapeutic approaches.

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Liraglutide modulates adipokine expression during adipogenesis, ameliorating obesity, and polycystic ovary syndrome in mice

Cited by 10 publications

References 70 publications

The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence

The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence

Anti-Proliferative Activity of Glucagon-Like Peptide-1 Receptor Agonist on Obesity-Associated Breast Cancer: The Impact on Modulating Adipokines’ Expression in Adipocytes and Cancer Cells

GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons

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