The effect of sitagliptin combined with rosiglitazone on autophagy and inflammation in polycystic ovary syndrome by regulating PI3K/AKT/mTOR and TLR4/NF-κB pathway

Ren, Yixin; Ye, Yongju; Xuan, Feilan; Chen, Aixue; Jin, Ruiying; Zhou, Weimei; Lü, Jian

doi:10.1016/j.repbio.2023.100763

Cited by 6 publications

(2 citation statements)

References 36 publications

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“…A recent study on acute pancreatitis-related acute lung injury found that ST alleviated oxidative stress and excessive autophagy [62]. In polycystic ovary syndrome (PCOS) rat models, ST inhibited autophagy and inflammation by inhibiting the PI3K/AKT/mTOR and TLR4/NF-κB pathways, respectively [63]. Furthermore, the in vivo reports showed that ST downregulated the expression of mTOR protein in rat testes, thus modulating autophagy [64].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms

Alqahtani,

Alshehri,

Alhusaini

et al. 2023

Diseases

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Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms

Alqahtani,

Alshehri,

Alhusaini

et al. 2023

Diseases

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“…Hu et al [45] found that PCOS patients have greater TLR4 and NF-κB protein concentrations than controls. Ren et al [46] revealed that TLR4 signaling pathway expression was enhanced in PCOS-like rats, indicating that the TLR4 signaling pathway could be implicated in PCOS. TLR4 was also involved in alterations to the gut microbiota of rats with letrozoleinduced PCOS, as was discovered by Wang et al [47].…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Alleviates Inflammation, Insulin Resistance, and Reproductive Abnormalities in Mice with Polycystic Ovary Syndrome via the TLR4-NF-κB Signaling Pathway

Liu,

Wang,

Zhao

et al. 2024

Discovery Medicine

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Background: Polycystic ovary syndrome (PCOS) commonly impacts fertile females with potentially severe effects on fertility and metabolism. Blood ghrelin levels are lower in PCOS patients, and exogenous supplements have been proposed for their potential to trigger anti-inflammatory effects at the cellular level. This study aimed to investigate whether pretreatment with ghrelin reduced inflammation, insulin resistance, and reproductive abnormalities in PCOS and the underlying mechanism of this disorder. Methods: Ghrelin supplementation was first tested in an inflammation model using human ovarian granulosa cells (KGN cells) that were built by treated with Lipolyaccharide. KGN cells were pretreated with ghrelin and exposed to lipopolysaccharide (LPS). Inflammatory gene expression and cytokine production were analyzed by Enzyme-linked immunosorbent assay (ELISA). Based on these results, the PCOS mice model was built with Dehydroepiandrosterone (DHEA) and a high-fat diet. The mRNA and protein expressions of inflammatory factors including Toll-like receptor 4 (TLR4), nuclear factor kappa-B-p65 (NF-κB-p65), Phospho-NF-κB-p65 (p-NF-κB-p65) and myeloid differentiation factor 88 (MYD88) related to the TLR4/NF-κB signaling pathway were evaluated in KGN cells and mouse ovarian tissues using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and western blot, respectively. Lipid metabolism was quantified via an automated biochemical analyzer. Results: The mRNA and protein expressions of interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in ghrelin pretreated KGN cells were lower than the LPS group (p < 0.05). Protein expression was reduced for TLR4, NF-κB-p65, and MYD88 within KGN cells of ghrelin groups compared to the LPS group (p < 0.05). Ghrelin treatment restored the estrous cycle and slowed weight gain and abdominal fat weight of PCOS mice (p < 0.05). Ghrelin treatment decreased the serum concentrations of testosterone, luteinizing hormone, insulin, IL-6, IL-1β, and TNF-α compared to the PCOS group (p < 0.05). Estradiol concentrations of mice treated with ghrelin were higher than the PCOS group (p < 0.05). The concentrations of low and high-density lipoprotein, triglyceride, and cholesterol in mice treated with ghrelin were lower than in the PCOS mice (p < 0.05). Inflammatory gene expression for IL-6, IL-1β, TNF-α, TLR4, NF-κB-p65, and MYD88 decreased in the ovarian tissues of ghrelin-treated mice compared to the PCOS group (p < 0.05), along with reduced protein expression of TLR4, p-NF-κB-p65, and MYD88 (p < 0.05). Conclusions: In the present study, ghrelin treatment effectively reduced inflammation in vitro, and attenuated insulin resistance and reproductive abnormalities in PCOS mice through the TLR4/NF-κB signaling pathway, highlighting potential therapeutic avenues for future PCOS treatments and research directions.

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The impacts of dipeptidyl- peptidase 4 (DPP-4) inhibitors on common female malignancies: A systematic review

Niazmand,

Nedaeinia,

Vatandoost

et al. 2024

Gene

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The effect of sitagliptin combined with rosiglitazone on autophagy and inflammation in polycystic ovary syndrome by regulating PI3K/AKT/mTOR and TLR4/NF-κB pathway

Cited by 6 publications

References 36 publications

Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms

Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms

Ghrelin Alleviates Inflammation, Insulin Resistance, and Reproductive Abnormalities in Mice with Polycystic Ovary Syndrome via the TLR4-NF-κB Signaling Pathway

The impacts of dipeptidyl- peptidase 4 (DPP-4) inhibitors on common female malignancies: A systematic review

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