Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

Choi, Youngseok; Lee, Kang-Yo; Jung, Sung Il; Kim, Hyung Sik; Shim, Gayong; Kim, Mi‐Gyeong; Oh, Yu‐Kyoung; Oh, Seon-Hee; Jun, Dae Won; Lee, Byunghoon

doi:10.1016/j.taap.2016.12.019

Cited by 49 publications

(32 citation statements)

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“…AMP-activated protein kinase (AMPK) is an energy sensor involved in a pathway that largely regulates energy storage and consumption in liver and white adipose tissue [9]. The cells accumulate excess energy, leading to enhanced AMPK phosphorylation and activity for induced acetyl CoA carboxylase (ACC) phosphorylation [10].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat dietâ€“induced obese mice

Wang¹,

Liou²,

Wu³

et al. 2018

Oncotarget

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Ginkgolide B is isolated from Ginkgo biloba leaves. It has multiple biological functions, including alleviating lung injury and ischemic stroke in mice and protecting pancreatic beta cells and improving endothelial dysfunction in diabetic mice. Here we sought to determine whether ginkgolide B ameliorates nonalcoholic fatty liver disease (NALFD) in high-fat diet (HFD)-induced obese mice. We also evaluated whether or not ginkgolide B reduces lipid accumulation of hepatocytes in vitro. C57BL/6 mice were fed with HFD and treated with ginkgolide B by intraperitoneal injection twice a week for last 10 weeks of the 14-week HFD feeding period. In addition, HepG2 cells were treated with oleic acid to establish a fatty liver cell model and exposed to various concentrations of ginkgolide B. Ginkgolide B significantly decreased hepatic lipid accumulation and alleviated steatosis in HFD-induced obese mice. It also reduced body weight and epididymal adipose tissue weight. Serum assay results showed that ginkgolide B inhibited leptin, alanine aminotransferase, and aspartate aminotransferase levels and increased HDL levels compared to obese mice. It also decreased fatty acid synthase expression and increased Sirt-1 and phosphorylation of AMP-activated protein kinase α in liver tissue. Furthermore, ginkgolide B significantly inhibited lipid accumulation and expression of adipogenesis-related proteins and increased adipolysis-associated protein expression in hepatocytes in vitro. These results suggest that ginkgolide B is an effective natural compound for alleviating hepatic lipid accumulation and reducing body weight in obese mice. It also ameliorated NALFD in HFD-induced obese mice. www.impactjournals.com/oncotarget/

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat dietâ€“induced obese mice

Wang¹,

Liou²,

Wu³

et al. 2018

Oncotarget

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“…In addition, activated PPARa can further enhance the transcription of ACOX1 and CPT1 (41). TP feeding decreased CD36 levels, which can be induced by AMPK and regulate fatty acid uptake (42). In addition, TP feeding reduced synthesis of triacylglycerol and inhibited the cancer cell growth by downregulating DGAT1 (43).…”

Section: Discussionmentioning

confidence: 99%

Dietary Tomato Powder Inhibits High-Fat Diet–Promoted Hepatocellular Carcinoma with Alteration of Gut Microbiota in Mice Lacking Carotenoid Cleavage Enzymes

Xia

et al. 2018

Cancer Prevention Research

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Both incidence and death rate due to liver cancer have increased in the United States. Higher consumption of lycopene-rich tomato and tomato products is associated with a decreased risk of cancers. b-Carotene-15, 15 0 -oxygenase (BCO1), and b-carotene-9 0 , 10 0 -oxygenase (BCO2) cleave lycopene to produce bioactive apo-lycopenoids. Although BCO1/BCO2 polymorphisms affect human and animal lycopene levels, whether dietary tomato consumption can inhibit high-fat diet (HFD)-promoted hepatocellular carcinoma (HCC) development and affect gut microbiota in the absence of BCO1/BCO2 is unclear. BCO1/BCO2 double knockout mice were initiated with a hepatic carcinogen (diethylnitrosamine) at 2 weeks of age. At 6 weeks of age, the mice were randomly assigned to an HFD (60% of energy as fat) with or without tomato powder (TP) feeding for 24 weeks. Results showed that TP feeding significantly decreased HCC development (67%, 83%, and 95% reduction in incidence, multiplicity, and tumor volume, respectively, P < 0.05). Protective effects of TP feeding were associated with (1) decreased hepatic inflammatory foci development and mRNA expression of proinflammatory biomarkers (IL1b, IL6, IL12a, monocyte chemoattractant protein-1, and inducible NO synthase); (2) increased mRNA expression of deacetylase sirtuin 1 and nicotinamide phosphoribosyltransferase involving NAD þ production; and (3) increased hepatic circadian clock genes (circadian locomotor output cycles kaput, period 2, and cryptochrome-2, Wee1). Furthermore, TP feeding increased gut microbial richness and diversity, and significantly decreased the relative abundance of the genus Clostridium and Mucispirillum, respectively. The present study demonstrates that dietary tomato feeding independent of carotenoid cleavage enzymes prevents HFD-induced inflammation with potential modulating gut microbiota and inhibits HFD-promoted HCC development. Cancer Prev Res; 11(12); 797-810. Ó2018 AACR. Effects of TP feeding on microbiota richness and distribution at phylum, genus, and species levels in DENþHFD-fed BCO1 À/À BCO2 À/À double KO mice. A, Observed OTUs, Chao1, and ACE, representing community richness. B, Shannon index, representing community evenness. C, Relative abundance of gram-positive bacteria or gram-negative bacteria. D, Relative abundance of major bacteria at phylum level. E and F, Relative abundance of major bacteria at genus, species levels. Ã Significantly different from the DENþHFD, P < 0.05. Xia et al. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): H. Xia, C. Liu, S. TakahashiAnalysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

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“…Rats in the AICAR treatment group received a daily intraperitoneal injection of AICAR (25 mg/kg/day) that was initially prepared in DMSO and then further diluted with sterile saline to the desired concentration. Those rats were also fed the high-fat diet [ 22 , 23 ]. After 12 weeks, all the rats were killed by cervical dislocation, and their blood and liver tissues were collected.…”

Section: Methodsmentioning

confidence: 99%

The Chinese medicine Chai Hu Li Zhong Tang protects against non-alcoholic fatty liver disease by activating AMPKα

et al. 2018

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An effective treatment for non-alcoholic fatty liver disease (NAFLD) is urgently needed. In the present study, we investigated whether the Chinese medicine Chai Hu Li Zhong Tang (CHLZT) could protect against the development of NAFLD. Rats in an animal model of NAFLD were treated with CHLZT, and their serum levels of cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were detected with an automatic biochemical analyzer. A cellular model of NAFLD was also established by culturing HepG2 cells in a medium that contained a long chain fat emulsion. Those cells were treated with CHLZT that contained serum from rats. After treatment, the levels of adenylate-activated protein kinase (AMPK) α (AMPKα), p-AMPKα, acetyl coenzyme A carboxylase (ACC) α (ACCα), pACCα, PPARγ, and SREBP-2 were detected. The AMPK agonist, acadesine (AICAR), was used as a positive control compound. Our results showed that CHLZT or AICAR significantly decreased the serum levels of TG, TC, LDL-C, AST, ALT, and insulin in NAFLD rats, and significantly increased their serum HDL-C levels. Treatments with CHLZT or AICAR significantly decreased the numbers of lipid droplets in NAFLD liver tissues and HepG2 cells. CHLZT and AICAR increased the levels of p-AMPKα and PPARγ in the NAFLD liver tissues and HepG2 cells, but decreased the levels of ACC-α, p-ACC-α, SREBP-2, and 3-hydroxyl-3-methylglutaryl-coenzyme A reductase (HMGR). CHLZT protects against NAFLD by activating AMPKα, and also by inhibiting ACC activity, down-regulating SREBP2 and HMGR, and up-regulating PPAR-γ. Our results suggest that CHLZT might be useful for treating NAFLD in the clinic.

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Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

Cited by 49 publications

References 47 publications

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat dietâ€“induced obese mice

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat dietâ€“induced obese mice

Dietary Tomato Powder Inhibits High-Fat Diet–Promoted Hepatocellular Carcinoma with Alteration of Gut Microbiota in Mice Lacking Carotenoid Cleavage Enzymes

The Chinese medicine Chai Hu Li Zhong Tang protects against non-alcoholic fatty liver disease by activating AMPKα

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