Energy sensors and reproductive hypothalamo-pituitary ovarian axis (HPO) in female mammals: Role of mTOR (mammalian target of rapamycin), AMPK (AMP-activated protein kinase) and SIRT1 (Sirtuin 1)

Estienne, Anthony; Bongrani, Alice; Ramé, Christelle; Kurowska, Patrycja; Blaszczyk, Klaudia; Rak, Agnieszka; Ducluzeau, Pierre-Henri; Froment, Pascal; Dupont, Joëlle

doi:10.1016/j.mce.2020.111113

Cited by 22 publications

(16 citation statements)

References 155 publications

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“…SIRT1 prolongs the body's lifespan indirectly regulates energy restriction, but it also acts on many cells biological processes such as energy metabolism and mitochondria, which consistent with AMPK 18 . Previous research shows that both AMPK and SIRT1 have been activated under calorie restriction and body stress 19 . When AMPK activated, it can upregulate the expression of NAMPT and decrease the content of nicotinamide to increase the content of NAD+ in the cell and enhance the activity of SIRT1 stresses such as calorie restriction and exercise, and they can be mutually regulated.…”

Section: Introductionsupporting

confidence: 62%

Resveratrol, novel application by preconditioning to attenuate myocardial ischemia/reperfusion injury in mice through regulate AMPK pathway and autophagy level

Zheng

Zhang

et al. 2022

J Cellular Molecular Medi

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Myocardial ischemia/reperfusion injury (MI/RI) is the main cause of deaths in the worldwide, leading to severe cardiac dysfunction. Resveratrol (RSV) is a polyphenol plant‐derived compound. Our study aimed to elucidate the underlying molecular mechanism of preconditioning RSV in protecting against MI/RI. Mice were ligated and re‐perfused by the left anterior descending branch with or without RSV (30 mg/kg·ip) for 7 days. Firstly, we found that RSV pretreatment significantly alleviated myocardial infarct size, improved cardiac function and decreased oxidative stress. Furthermore, RSV activated p‐AMPK and SIRT1, ameliorated inflammation including the level of TNF‐α and IL‐1β, and promoting autophagy level. Moreover, neonatal rat ventricular myocytes (NRVMs) and H9c2 cells with knockdown the expression of AMPK, SIRT1 or FOXO1 were used to uncover the underlying molecular mechanism for the cardio‐protection of RSV. In NRVMs, RSV increased cellular viability, decreased LDH release and reduced oxidative stress. Importantly, Compound C(CpC) and EX527 reversed the effect of RSV against MI/RI in vivo and in vitro and counteracted the autophagy level induced by RSV. Together, our study indicated that RSV could alleviate oxidative stress in cardiomyocytes through activating AMPK/SIRT1‐FOXO1 signallingpathway and enhanced autophagy level, thus presenting high potential protection on MI/RI.

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Section: Introductionsupporting

confidence: 62%

Resveratrol, novel application by preconditioning to attenuate myocardial ischemia/reperfusion injury in mice through regulate AMPK pathway and autophagy level

Zheng

Zhang

et al. 2022

J Cellular Molecular Medi

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“…Hyperactivation of AMPK in the testes and ovaries can lead to impaired production of steroid hormones [ 124 , 125 , 126 , 127 , 128 ]. It was shown that an increase in AMPK activity in granulosa cells of broiler chickens leads to a decrease in the expression of genes encoding StAR, cytochrome CYP11A1 and dehydrogenase 3beta-HSD, causing a decrease in progesterone synthesis [ 126 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis

Bakhtyukov

Derkach

Sorokoumov

et al. 2021

IJMS

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In men with type 2 diabetes mellitus (T2DM), steroidogenesis and spermatogenesis are impaired. Metformin and the agonists of luteinizing hormone/human chorionic gonadotropin(hCG)-receptor (LH/hCG-R) (hCG, low-molecular-weight allosteric LH/hCG-R-agonists) can be used to restore them. The aim was to study effectiveness of separate and combined administration of metformin, hCG and 5-amino-N-tert-butyl-2-(methylsulfanyl)-4-(3-(nicotinamido)phenyl)thieno[2,3-d]pyrimidine-6-carboxamide (TP3) on steroidogenesis and spermatogenesis in male rats with T2DM. hCG (15 IU/rat/day) and TP3 (15 mg/kg/day) were injected in the last five days of five-week metformin treatment (120 mg/kg/day). Metformin improved testicular steroidogenesis and spermatogenesis and restored LH/hCG-R-expression. Compared to control, in T2DM, hCG stimulated steroidogenesis and StAR-gene expression less effectively and, after five-day administration, reduced LH/hCG-R-expression, while TP3 effects changed weaker. In co-administration of metformin and LH/hCG-R-agonists, on the first day, stimulating effects of LH/hCG-R-agonists on testosterone levels and hCG-stimulated expression of StAR- and CYP17A1-genes were increased, but on the 3–5th day, they disappeared. This was due to reduced LH/hCG-R-gene expression and increased aromatase-catalyzed estradiol production. With co-administration, LH/hCG-R-agonists did not contribute to improving spermatogenesis, induced by metformin. Thus, in T2DM, metformin and LH/hCG-R-agonists restore steroidogenesis and spermatogenesis, with metformin being more effective in restoring spermatogenesis, and their co-administration improves LH/hCG-R-agonist-stimulating testicular steroidogenesis in acute but not chronic administration.

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“…In our study, the multiple database analyses and bioactivity analyses were applied together to reveal that AMPK, SIRT1, and Akt proteins play a crucial role in the SFI intervention into mitochondrial dysfunction. The essential roles of the two regulators SIRT1 and AMPK are demonstrated in several studies [26,27]. Due to the triggering of AMPK phosphorylation and the fatty acid oxidation of transcription substrates such as PGC1α and NRF1, AMPK activity stimulates mitochondrial biosynthesis to increase muscle oxidative capacity [28,29].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology/Metabolomics‐Based Validation of AMPK and PI3K/AKT Signaling Pathway as a Central Role of Shengqi Fuzheng Injection Regulation of Mitochondrial Dysfunction in Cancer‐Related Fatigue

Guo

Liu

Zheng

et al. 2021

Oxidative Medicine and Cellular Longevity

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Chinese herbal medicines have multiple targets and properties, and their use in multidisciplinary cancer therapies has consequently received increasing attention. Here, we have investigated the possible active ingredients associated with cancer-related fatigue (CRF) in the Shengqi Fuzheng Injection (SFI). In vitro cell models were used to measure the regulation effects of SFI on CRF. Metabolomic analysis was used to identify the potential genes and pathways in C2C12 mouse myoblasts treated with SFI, and the interaction of compounds and CRF targets was predicted using network pharmacology and molecular docking analyses. The putative pathways were further verified using immuno-blotting assays. The results showed that SFI significantly inhibited muscle cell apoptosis and increased the mitochondrial membrane potential of muscle cells. The network pharmacology analysis results identified 36 candidate compounds, and 244 potential targets were yielded by SFI, and they shared 10 key targets associated with cancer-related fatigue. According to the enrichment analysis and experimental validation, SFI might ameliorate muscle cell mitochondrial function by activating AMPK and inhibiting the PI3K/Akt signaling pathways, and the expression changes of mitochondrial metabolic enzymes MnSOD and apoptosis-associated proteins Bax and Bcl-2 were also triggered. The functions and mechanisms of SFI in anticancer-related fatigue were found here to be at least partly due to the targeting of the AMPK and PI3K/Akt signaling pathways, and this has highlighted new potential applications for network pharmacology when researching Chinese Medicines.

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Energy sensors and reproductive hypothalamo-pituitary ovarian axis (HPO) in female mammals: Role of mTOR (mammalian target of rapamycin), AMPK (AMP-activated protein kinase) and SIRT1 (Sirtuin 1)

Cited by 22 publications

References 155 publications

Resveratrol, novel application by preconditioning to attenuate myocardial ischemia/reperfusion injury in mice through regulate AMPK pathway and autophagy level

Resveratrol, novel application by preconditioning to attenuate myocardial ischemia/reperfusion injury in mice through regulate AMPK pathway and autophagy level

The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis

Network Pharmacology/Metabolomics‐Based Validation of AMPK and PI3K/AKT Signaling Pathway as a Central Role of Shengqi Fuzheng Injection Regulation of Mitochondrial Dysfunction in Cancer‐Related Fatigue

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