Irbesartan ameliorates hyperlipidemia and liver steatosis in type 2 diabetic db/db mice via stimulating PPAR-γ, AMPK/Akt/mTOR signaling and autophagy

Zhong, Juan; Gong, Wangqiu; Lu, Lu; Chen, Jing; Lu, Zibin; Li, Hongyu; Liu, Wenting; Liu, Yangyang; Wang, Mingqing; Hu, Rong; Long, Haoyu; Wei, Lianbo

doi:10.1016/j.intimp.2016.11.015

Cited by 59 publications

(43 citation statements)

References 44 publications

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“…We identified 421 potential genes in the miRNA databases. On the basis of prior studies addressing mTOR and FOXO1 in regulating dyslipidemia (Houde et al, ; Sajan et al, ; Zhong et al, ), we hypothesized their major roles played downstream of miR‐96 (Data S6: miR‐96 predicted target score, mTOR: 98, FOXO1: 75, Atg16l1: 81, Atg9a: 55). Western blotting was performed to compare the protein levels of mTOR, p‐mTOR (ser2448), FOXO1, LC3A/B, P62, and Beclin‐1 in the liver (Figure ).…”

Section: Resultsmentioning

confidence: 99%

miR‐96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high‐fat‐diet‐induced dyslipidemia in mice

Shi

Jia

et al. 2019

Phytotherapy Research

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We aimed to investigate the possible signaling pathways underlying the regulation of grape seed proanthocyanidins extracts (GSPE) on lipid metabolism. One hundred male C57BL/6 mice were divided into four groups: control group (normal diet), GSPE group (normal diet + GSPE), high-fat diet group (HFD), and high-fat diet plus GSPE (200 mg/ kg/day) group (HFD + GSPE). Mice received the diets for 180 days. Body weight and serum lipid levels were measured. Autophagic flux characteristics, such as accumulation of lipids, mitochondria, and autophagosomes in the liver, were detected using transmission electron microscopy. Expression profile of microRNAs (miRNAs) in the liver was determined using RNA microarray and quantitative real time polymerase chain reaction (qRt-PCR). GSPE significantly decreased the weight gain, serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol but increased high-density lipoprotein cholesterol in the HFD mice. Autophagic flux was significantly increased by HFD but decreased by GSPE treatment. GSPE significantly attenuated HFD-induced miR-96 upregulation, which in turn reduced the expressions of miR-96 downstream molecules, FOXO1, mTOR, p-mTOR, and LC3A/B. These results suggested that the miR-96 is involved in the protective effect of GSPE against HFD-induced dyslipidemia. Possible mechanisms might be through mTOR and FOXO1, which facilitate autophagic flux for clearance of lipid accumulation. KEYWORDS autophagic flux, dyslipidemia, grape seed proanthocyanidins extracts (GSPE), high-fat diet (HFD), miR-96, mTOR

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Section: Resultsmentioning

confidence: 99%

miR‐96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high‐fat‐diet‐induced dyslipidemia in mice

Shi

Jia

et al. 2019

Phytotherapy Research

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“…PPARγ is the most extensively studied. Some ARBs can activate PPARs and have been widely recognized [173][174][175][176][177]. Current research shows PPARs and AMPK are also closely related.…”

Section: Pparsmentioning

confidence: 99%

AMPK: a balancer of the renin–angiotensin system

Liu

et al. 2019

Bioscience Reports

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The renin–angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves to draw attention to the cross-talk between RAS and AMPK, then summering the most recent literature which highlights AMPK as a point of balance between physiological and pathological functions of the RAS.

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“…Previous studies have shown that the activation of PPARγ has bene cial effects on the level of autophagy [27]. To further explore the role of PPARγ in O 3 -induced autophagy, chondrocytes were treated with the PPARγ inhibitor GW9662 before ozone treatment.…”

Section: Discussionmentioning

confidence: 99%

Ozone Induces Autophagy by Activating PPARγ/mTOR in Rat Chondrocytes Treated with IL-1β

Sun

Zhang

et al. 2020

Preprint

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Background: Osteoarthritis (OA) is the main cause of older pain and disability, its dysfunction due to discomfort as well as the quality of life of patients having adverse effects. Medical ozone (O3) has been found to have antioxidative and anti-inflammatory effects in the treatment of osteoarthritis. However, it is unclear whether O3 can induces autophagy through the PPARγ/mTOR autophagy pathway in chondrocytes treated with IL-1β. Methods: Primary chondrocytes were isolated from wistar rat cartilage within 3days. The OA chondrocyte model was induced via treatment with IL-1β to chondrocytes for 24 hours. Then the cells were treated with O3 and GW9662, the inhibitor of PPARγ. Cell viability was assessed by CCK-8. Further, the cells subjected to western blot analysis, qRT-PCR and immunofluorescence assay. The numbers of autophagosomes were observed via transmission electron microscopy. Results: 30μg/ml O3 improved the viability of chondrocytes. O3 significantly increased the level of autophagy proteins and the numbers of autophagosomes in chondrocytes treated with IL-1β via treated with O3. qRT-PCR results showed that O3 decreased the levels of IL-6,TNF-α and MMP-3,MMP-13 in chondrocytes treated with IL-1β. Conclusions: 30μg/ml O3 improved autophagy via activating PPARγ/mTOR signaling and suppressing inflammation in chondrocytes treated with IL-1β.

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Irbesartan ameliorates hyperlipidemia and liver steatosis in type 2 diabetic db/db mice via stimulating PPAR-γ, AMPK/Akt/mTOR signaling and autophagy

Cited by 59 publications

References 44 publications

miR‐96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high‐fat‐diet‐induced dyslipidemia in mice

miR‐96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high‐fat‐diet‐induced dyslipidemia in mice

AMPK: a balancer of the renin–angiotensin system

Ozone Induces Autophagy by Activating PPARγ/mTOR in Rat Chondrocytes Treated with IL-1β

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