The adenosine derivative 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxylaniline) adenosine activates AMPK and regulates lipid metabolism in vitro and in vivo

Guo, Peng; Lian, Zeqin; Sheng, Lixia; Wu, Chongming; Gao, Jian; Li, Jin; Wang, Yao; Guo, Yuchen; Zhu, Haibo

doi:10.1016/j.lfs.2011.09.001

Cited by 22 publications

(17 citation statements)

References 31 publications

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“…Adiponectin (Ad) plays a crucial role in hepatic lipid metabolism, which has been shown to activate the AMPK signaling pathway and mediates lipid metabolism in bovine hepatocytes in vitro by promoting lipid oxidation, suppressing lipid synthesis and reducing hepatic lipid accumulation . The activation of AMPK in the regulation of Ad in lipid metabolism has also been confirmed in vivo in the hamster (Guo et al, 2012) SIRT1 is the most studied member of a family of evolutionarily conserved NAD + -dependent histone/protein deacetylases (Ruderman et al, 2010), which has been best known for mediating the increase in longevity (Sinclair and Guarente, 2006;Finkel et al, 2009). SIRT1 has been identified as a novel regulator of hepatocyte lipid metabolism, via SIRT1/LKB1/AMPK signaling (Hou et al, 2008).…”

Section: Discussionmentioning

confidence: 92%

“…AMPK also regulates mitochondrial biogenesis and function (Jäger et al, 2007) and increases the ability of a cell to generate ATP and diminish oxidative stress (Ruderman and Prentki, 2004). Recently, several studies have clearly confirmed that AMPK regulates the lipid metabolism in hepatocytes and even in an in vivo model Guo et al, 2012;Huang et al, 2013;Imai et al, 2006;Lian et al, 2011;Oh et al, 2011; All experiments were performed in triplicate. Statistical significance was set as * p < 0.05, **p < 0.01, or ***p < 0.001, ns: no significance.…”

Section: Discussionmentioning

confidence: 99%

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Aspirin regulates hepatocellular lipid metabolism by activating AMPK signaling pathway

Peng

Duan

et al. 2015

J. Toxicol. Sci.

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-Aspirin has been reported to regulate lipid metabolism. However, the mechanism underlying the regulation is not clear. We presently investigated aspirin's promotion of AMP-activated protein kinase (AMPK) pathway activation in human hepatoma HepG2 cells by examining AMPK expression, the promotion of AMPK activation. Then we investigated the influence of aspirin-promoted AMPK signaling on fatty acid oxidation in HepG2 cells. The results demonstrated that aspirin treatment did not regulate the expression of AMPK and its downstream target, Acetyl-Coenzyme A Carboxylase (ACC), but activated the AMPK signaling pathway by promoting the phosphorylation of AMPK and ACC. And, interestingly, the promotion by aspirin is dependent of cellular esterase, which catalyzes aspirin to salicylate. Moreover, the activated AMPK signaling promoted the fatty acid oxidation, by promoting expression of Carnitine palmitoyltransferase I (CPT1) and Medium-Chain Acyl-CoA Dehydrogenase (MCAD) in both mRNA and protein levels. Thus, we confirmed in this study that aspirin promoted lipid oxidation by upregulating the AMPK signaling pathway.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Aspirin regulates hepatocellular lipid metabolism by activating AMPK signaling pathway

Peng

Duan

et al. 2015

J. Toxicol. Sci.

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“…We previously found that cordycepin decreases LDL cholesterol levels in vivo ( 34 ), but its effi cacy is limited due to poor bioavailability . IMM-H007 was synthesized and observed to stimulate the phosphorylation of AMPK and to decrease lipid biosynthesis ( 35 ). AMPK activation by IMM-H007 may partially explain the observed declines in LDL cholesterol and triglycerides in plasma and liver because AMPK activation attenuates cholesterol synthesis, lipogenesis', and triglyceride synthesis ( 36 ).…”

Section: Imm-h007 Promotes Macrophage Rct In Vivomentioning

confidence: 99%

Inhibition of ABCA1 protein degradation promotes HDL cholesterol efflux capacity and RCT and reduces atherosclerosis in mice

Huang

Fan

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org Supplementary key words ATP binding cassette transporter A1 • high density lipoprotein • macrophage • reverse cholesterol transportClinical and epidemiological studies have shown an inverse relationship between plasma levels of HDL cholesterol or its major apolipoprotein, apoA-I, and cardiovascular disease risk. For example, in the Framingham Heart Study, for every 1% increase in circulating HDL, there was a 2% decrease in the global risk of developing coronary heart disease ( 1 ). The direct infusion of reconstituted apoA-I particles reduces atherosclerotic plaque size in humans ( 2 ), and the overexpression of apoA-I in mice results in elevated HDL levels and the prevention of plaque progression ( 3, 4 ). Therefore, raising HDL cholesterol appears to be an attractive therapeutic strategy for atherosclerosis risk reduction.However, it has been observed that therapies such as CETP inhibitors and niacin ( 5, 6 ) that increase HDL level are not suffi cient to elucidate HDL's atheroprotective properties. Alternatively, the cardioprotective potential of HDL may be primarily related to its function, namely to promote reverse cholesterol transport (RCT) from peripheral tissues and cells to the liver. Thus, the synergistic enhancement of HDL function, as well as quantity, may represent a more effective means to harness HDL biology for therapeutic gain ( 7 ). The ABCA1 has been identifi ed as the key and rate-limiting transporter facilitating the

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“…IMM-H007 (triacetyl-3-hydroxyphenyladenosine) is a derivative of cordycepin, which is an adenosine analog [9]. IMM-H007 was observed to stimulate the phosphorylation of AMPK and to decrease lipid biosynthesis [10]. It has been observed to increase the circulating HDL level, and the cholesterol efflux capacity of HDL, and it can also enhance in vivo reverse cholesterol transport (RCT) from macrophages to the plasma, liver, and feces.…”

Section: Introductionmentioning

confidence: 99%

Comparative transcriptomic analysis of mice liver treated with different AMPK activators in a mice model of atherosclerosis

Wang

et al. 2017

Oncotarget

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Atherosclerosis is known to be the primary underlying factor responsible for the development of cardiovascular diseases. Suppression of AMP-activated protein kinase stimulates arterial deposition of excess lipids, resulting in the development of atherosclerotic lesions. In this study we successfully developed the disease model of mice and mimicked the therapeutic effect, for that we chose three different AMP-activated protein kinase activators (IMM-H007, A-769662 and Metformin) to identify which one has a superior effect in the atherosclerosis model. We combined the transcriptomes of four groups of mice liver including high-fat diet group and the experimental groups treated with different AMP-activated protein kinase activators. We analyzed the increased genes to candidate metabolic and disease pathways. Compared to the high-fat diet group, a total of 799 differentially expressed genes were identified in treatment groups. There were 291, 473, and 323 differentially expressed genes in H007, Metformin, and A-769662 group respectively. And seven statistically significant pathways were observed in both H007 and Metformin groups. We expect that gene expression profiling in the mice model would extend our understanding of atherosclerosis in the molecular level. This study provides a fundamental framework for future clinical research on human atherosclerosis and new clues for developing novel drugs for the treatment of atherosclerosis.

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The adenosine derivative 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxylaniline) adenosine activates AMPK and regulates lipid metabolism in vitro and in vivo

Cited by 22 publications

References 31 publications

Aspirin regulates hepatocellular lipid metabolism by activating AMPK signaling pathway

Aspirin regulates hepatocellular lipid metabolism by activating AMPK signaling pathway

Inhibition of ABCA1 protein degradation promotes HDL cholesterol efflux capacity and RCT and reduces atherosclerosis in mice

Comparative transcriptomic analysis of mice liver treated with different AMPK activators in a mice model of atherosclerosis

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