Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization

Cheng, Junrui; Liu, Chun; Hu, Kang‐Quan; Greenberg, Andrew S.; Wu, Dayong; Ausman, Lynne M.; McBurney, Michael W.; Wang, Xiangdong

doi:10.1016/j.bbadis.2017.08.004

Cited by 40 publications

(26 citation statements)

References 48 publications

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“…By deacetylating transcription factors and cofactors, SIRT1 plays a beneficial role in regulating hepatic lipid metabolism, liver steatosis, and tumorigenesis (33). We have reported that ablation of SIRT1 caused an overloaded accumulation of hepatic triglyceride with higher levels of SREBP-1 and SCD1 and lower levels of phosphorylation of LKB1 and AMPK in the liver, and higher mRNA expression of lipogenic genes in the mesenteric adipose tissue (34). In the present study, TP feeding increased the expression mRNA and protein levels of SIRT1 and decreased acetylation of FOXO1 significantly without changing the total FOXO1 level in DENþHFD and BCO1 À/À BCO2 À/À double KO mice, which indicated an increased deacetylase activity of SIRT1 and may explain the reduction of tumor incidence.…”

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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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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“…The liver Chol and TG measurements were performed as previously described [25]. In brief, frozen liver tissue (50 mg) was homogenized with 1 mL lysis buffer.…”

Section: Liver Chemistry Measurementmentioning

confidence: 99%

Low Expression of Sirtuin 1 in the Dairy Cows with Mild Fatty Liver Alters Hepatic Lipid Metabolism

Zou

Ding

et al. 2020

Animals

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Dairy cows usually experience negative energy balance coupled with an increased incidence of fatty liver during the periparturient period. The purpose of this study was to investigate the effect of hepatic steatosis on the expression of the sirtuin 1 (SIRT1), along with the target mRNA and protein expressions and activities related to lipid metabolism in liver tissue. Control cows (n = 6, parity 3.0 ± 2.0, milk production 28 ± 7 kg/d) and mild fatty liver cows (n = 6, parity 2.3 ± 1.5, milk production 20 ± 6 kg/d) were retrospectively selected based on liver triglycerides (TG) content (% wet liver). Compared with the control group, fatty liver cows had greater concentrations of cholesterol and TG along with the typically vacuolated appearance and greater lipid droplets in the liver. Furthermore, fatty liver cows had greater mRNA and protein abundance related to hepatic lipid synthesis proteins sterol regulatory element binding proteins (SREBP-1c), long-chain acyl-CoA synthetase (ACSL), acyl-CoA carbrolase (ACC) and fatty acid synthase (FAS) and lipid transport proteins Liver fatty acid binding protein (L-FABP), apolipoprotein E (ApoE), low density lipoprotein receptor (LDLR) and microsomal TG transfer protein (MTTP) (p < 0.05). However, they had lower mRNA and protein abundance associated with fatty acid β-oxidation proteins SIRT1, peroxisome proliferator-activated receptor co-activator-1 (PGC-1α), peroxisome proliferator–activated receptor-α (PPARα), retinoid X receptor (RXRα), acyl-CoA 1 (ACO), carnitine palmitoyltransferase 1 (CPT1), carnitine palmitoyltransferase 2 (CPT2) and long- and medium-chain 3-hydroxyacyl-CoA dehydrogenases (LCAD) (p < 0.05). Additionally, mRNA abundance and enzyme activity of enzymes copper/zinc superoxide dismutase (Cu/Zn SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and manganese superoxide dismutase (Mn SOD) decreased and mRNA and protein abundance of p45 nuclear factor-erythroid 2 (p45 NF-E2)-related factor 1 (Nrf1), mitochondrial transcription factor A (TFAM) decreased (p < 0.05). Lower enzyme activities of SIRT1, PGC-1α, Cu/Zn SOD, CAT, GSH-Px, SREBP-1c and Mn SOD (p < 0.05) and concentration of reactive oxygen species (ROS) were observed in dairy cows with fatty liver. These results demonstrate that decreased SIRT1 associated with hepatic steatosis promotes hepatic fatty acid synthesis and inhibits fatty acid β-oxidation. Hence, SIRT1 may represent a novel therapeutic target for the treatment of the fatty liver disease in dairy cows.

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“…It is reported that SIRT1 was targeted by miR‐181b to regulate steatosis and down‐regulated in NAFLD 27 . Another study further explored that ablated SIRT1 activity resulted in more severe NAFLD by affecting liver‐mesenteric adipose tissue fatty acid mobilization 28 . In addition, a prior study also noted that SIRT1 exacerbates liver fibrosis in mice 29 .…”

Section: Discussionmentioning

confidence: 97%

GRHL2 induces liver fibrosis and intestinal mucosal barrier dysfunction in non‐alcoholic fatty liver disease via microRNA‐200 and the MAPK pathway

Wang

Zeng

Lin

et al. 2020

J Cellular Molecular Medi

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Non‐alcoholic fatty liver disease (NAFLD) serves as the most common subtype of liver diseases and cause of liver dysfunction, which is closely related to obesity and insulin resistance. In our study, we sought to investigate effect of transcription factor grainyhead‐like 2 (GRHL2) on NAFLD and the relevant mechanism. NAFLD mouse model was established with a high‐fat feed. Then, serum was extracted from NAFLD patients and mice, followed by ectopic expression and depletion experiments in NAFLD mice and L02 cells. Next, the correlation between GRHL2 and microRNA (miR)‐200 and between miR‐200 and sirtuin‐1 (SIRT1) was evaluated. The observations demonstrated that miR‐200 and GRHL2 were overexpressed in the serum of NAFLD patients and mice, while SIRT1 was poorly expressed. GRHL2 positively regulated miR‐200 by binding to miR‐200 promoter region, which negatively targeted SIRT1. The inhibition of miR‐200 and GRHL2 or SIRT1 overexpression lowered HA and LN in mouse liver tissue, occludin and ZO‐1 in mouse small intestine tissue, TNF‐α and IL‐6 in mouse serum, glucose, total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mouse serum, and also inhibited liver fibrosis and intestinal mucosal barrier dysfunction. Meanwhile, GRHL2 induced activation of MAPK signalling pathway in NAFLD mice. Collectively, GRHL2 played a contributory role in NAFLD by exacerbating liver fibrosis and intestinal mucosal barrier dysfunction with the involvement of miR‐200‐dependent SIRT1 and the MAPK signalling pathway.

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Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization

Cited by 40 publications

References 48 publications

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

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

Low Expression of Sirtuin 1 in the Dairy Cows with Mild Fatty Liver Alters Hepatic Lipid Metabolism

GRHL2 induces liver fibrosis and intestinal mucosal barrier dysfunction in non‐alcoholic fatty liver disease via microRNA‐200 and the MAPK pathway

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