PPARγ regulates lipid metabolism and viability of sheep trophoblast cells

Hao, Kexing; Liu, Xiuxia; Chen, Yan; Zeng, Weibin; Chen, Lei; Wang, Jing; Hu, Guangdong

doi:10.1111/rda.14471

Cited by 2 publications

(2 citation statements)

References 59 publications

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“…Exogenous drug treatment of STCs involved groups treated with rosiglitazone (RSG) (5 μM), GW9662 (GW) (20 μM) [28], rapamycin (RAPA) (100 nM), 3methyladenine (3-MA) (5 mM) [29], GW9662 and rapamycin, and 3-MA and rosiglitazone (all reagents from MCE, Monmouth Junction, NJ, USA). For groups treated with pairs of drugs, cells were pretreated with GW9662 or 3-MA for 2 h followed by addition of rapamycin or rosiglitazone, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Metabolism in STCs. The roles of PPARγ and the mTOR signaling pathway in lipid metabolism in STCs were examined by exogenous treatment with the PPARγ activator rosiglitazone (RSG) and inhibitor GW9662 (GW) [28]. Phosphorylation of the p70S6K protein is a hallmark of activation by mTOR [31].…”

Section: Induction and Inhibition Of Pparγ Impacts Expression Of Auto...mentioning

confidence: 99%

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Peroxisome Proliferator-Activated Receptor γ Regulates Lipid Metabolism in Sheep Trophoblast Cells through mTOR Pathway-Mediated Autophagy

Hao,

Wang,

et al. 2023

PPAR Research

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Peroxisome proliferator-activated receptor gamma (PPARγ) is a key nuclear receptor transcription factor that is highly expressed in trophoblastic cells during embryonic attachment and is accompanied by rapid cell proliferation and increased lipid accumulation. We previously showed that the autophagy pathway is activated in cells after activation of PPARγ, accompanied by increased lipid accumulation. In this study, we used PPARγ agonist rosiglitazone and inhibitor GW9662, as well as autophagy activator rapamycin and inhibitor 3-methyladenine, to unravel the probable mechanism of PPARγ engaged in lipid metabolism in sheep trophoblast cells (STCs). After 12 h, 24 h, and 48 h of drug treatment, the levels of autophagy-related proteins were detected by Western blot, the triglyceride content and MDA level of cells were detected by colorimetry, and the lipid droplets and lysosomes were localized by immunofluorescence. We found that PPARγ inhibited the activity of mammalian target of rapamycin (mTOR) pathway in STCs for a certain period of time, promoted the increase of autophagy and lysosome formation, and enhanced the accumulation of lipid droplets and triglycerides. Compared with cells whose PPARγ function is activated, blocking autophagy before activating PPARγ will hinder lipid accumulation in STCs. Pretreatment of cells with rapamycin promoted autophagy with results similar to rosiglitazone treatment, while inhibition of autophagy with 3-methyladenine reduced lysosome and lipid accumulation. Based on these observations, we conclude that PPARγ can induce autophagy by blocking the mTOR pathway, thereby promoting the accumulation of lipid droplets and lysosomal degradation, providing an energy basis for the rapid proliferation of trophoblast cells during embryo implantation. In brief, this study partially revealed the molecular regulatory mechanism of PPARγ, mTOR pathway, and autophagy on trophoblast cell lipid metabolism, which provides a theoretical basis for further exploring the functional regulatory network of trophoblast cells during the attachment of sheep embryos.

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Section: Methodsmentioning

confidence: 99%

Section: Induction and Inhibition Of Pparγ Impacts Expression Of Auto...mentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor γ Regulates Lipid Metabolism in Sheep Trophoblast Cells through mTOR Pathway-Mediated Autophagy

Hao,

Wang,

et al. 2023

PPAR Research

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Effect of Rab18 on liver injury and lipid accumulation by regulating perilipin 2 and peroxisome proliferator‐activated receptor gamma in non‐alcoholic fatty liver disease

Zhang,

Xu,

Rong

et al. 2024

J of Gastro and Hepatol

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Background and AimNonalcoholic fatty liver disease (NAFLD) is currently one of the most common chronic liver diseases worldwide, characterized by the presence of lipid droplets. Rab18 is an important lipid droplet protein; however, its effects and mechanisms of action on NAFLD remain unclear.MethodsFree fatty acid‐stimulated AML‐12 cells and high‐fat diet (HFD)‐fed mice were used as NAFLD models. Lentiviruses overexpressing Rab18 (Rab18‐OE) or knockdown (Rab18‐KD) were used to generate stable cell lines for genetic analysis. Blood serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, glucose, and leptin were measured using a biochemical autoanalyzer. Hematoxylin and eosin staining was performed to detect pathological damage to the liver. Lipid accumulation in the cells was assessed by Oil Red O staining. Target expression was measured using qPCR, western blotting, and immunocytochemistry.ResultsRab18 mRNA and protein expression levels increased in free fatty acid‐stimulated AML‐12 cells and the livers of HFD‐fed mice. Rab18‐OE increased lipid accumulation in vitro, which was attenuated by Rab18‐KD. In vivo, Rab18‐OE augmented liver pathological damage, serum alanine aminotransferase/aspartate aminotransferase activity, and triglyceride, total cholesterol, and low‐density lipoprotein levels, whereas Rab18‐KD decreased these indicators. Rab18‐KD also downregulated blood glucose levels in HFD‐fed mice. Mechanistically, Rab18‐OE and Rab18‐KD regulated the mRNA and protein expression levels of perilipin 2 (PLIN2) and peroxisome proliferator‐activated receptor gamma (PPARγ) in vitro and in vivo, respectively. Immunocytochemistry revealed that Rab18 colocalized with PLIN2 and PPARγ in AML‐12 cells.ConclusionRab18 expression was elevated in vitro and in vivo in the NAFLD mouse model. Rab18 regulates PLIN2 and PPARγ expression to exaggerate liver injury and lipid accumulation in patients with NAFLD. Thus, Rab18 may be a crucial protein in this disease and a potential therapeutic target.

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PPARγ regulates lipid metabolism and viability of sheep trophoblast cells

Cited by 2 publications

References 59 publications

Peroxisome Proliferator-Activated Receptor γ Regulates Lipid Metabolism in Sheep Trophoblast Cells through mTOR Pathway-Mediated Autophagy

Peroxisome Proliferator-Activated Receptor γ Regulates Lipid Metabolism in Sheep Trophoblast Cells through mTOR Pathway-Mediated Autophagy

Effect of Rab18 on liver injury and lipid accumulation by regulating perilipin 2 and peroxisome proliferator‐activated receptor gamma in non‐alcoholic fatty liver disease

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