The interaction of hepatic lipid and glucose metabolism in liver diseases

Bechmann, Lars P.; Hannivoort, Rebekka A.; Gerken, Guido; Hotamisligil, G S; Trauner, Michael; Canbay, Ali

doi:10.1016/j.jhep.2011.08.025

Cited by 752 publications

(583 citation statements)

References 130 publications

(182 reference statements)

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“…13,[28][29][30][31][32][33] In contrast, solely a mild hepatic inflammation and no evidence of enhanced cell death or the development of insulin resistance was found in our model. Neither glucose nor insulin levels were altered and no relevant differences indicating development of diabetes in our model was observed in the diabetes assay.…”

Section: Discussioncontrasting

confidence: 60%

Steatosis does not impair liver regeneration after partial hepatectomy

Sydor

Schlattjan

et al. 2013

Laboratory Investigation

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Hepatic steatosis is a key feature of non-alcoholic fatty liver disease (NAFLD). While storage of lipid droplet-bound triglycerides in simple steatosis is physiologically inert, non-alcoholic steatohepatitis (NASH) is associated with hepatocyte damage and apoptosis. Mitochondrial oxidation of free fatty acids (FFA), derived from lipid droplets and hepatocellular uptake, is a rapid and effective way of energy supply for proliferating cells and FFA esterification provides substrates for lipid synthesis and cell proliferation. Thus, we investigated whether simple steatosis induced by western diet (WD) improves liver regeneration after partial hepatectomy (PHx). WD feeding for 6 weeks caused simple steatosis with hepatic lipid droplet and triglyceride accumulation accompanied by induction of fatty acid transport proteins (FATP), death receptors (DR), pro-and anti-apoptotic genes, hepatocyte growth factor (Hgf ) as well as increased serum leptin levels in a mouse model. After PHx, liver cell proliferation was higher in WD-fed mice and associated with FATP and Hgf induction. In addition, Erk1/2 (extracellular-related MAP kinase 1/2) dephosphorylation observed in standard diet (SD) mice was reduced in WD animals. PHx in steatotic livers did not affect hepatocyte apoptosis, despite DR upregulation. WD-induced steatosis enhances liver cell proliferation, which is accompanied by increased Hgf and leptin signaling as well as Erk1/2 phosphorylation. Induction of mild steatosis may therefore be beneficial for surgical outcome of hepatectomies.

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Section: Discussioncontrasting

confidence: 60%

Steatosis does not impair liver regeneration after partial hepatectomy

Sydor

Schlattjan

et al. 2013

Laboratory Investigation

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“…PEPCK and G6Pase are ratelimiting gluconeogenic enzymes and their expressions are increased in NAFLD. 28) Our study comfirmed it and paeoniflorin did effectively restrain the gluconeogenesis for hyperglycemia lowing.…”

Section: Discussionsupporting

confidence: 59%

Paeoniflorin Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice

Zhang

Yang

2015

Biological & Pharmaceutical Bulletin

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Paeoniflorin, a natural product and active ingredient of Paeonia lactiflora, has been demonstrated to have many pharmacological effects including antiinflammatory and antihyperglycemic activity. We investigated the effects of paeoniflorin on NAFLD in mice and its underlying mechanisms. We examined this hypothesis using a well-established animal model of NAFLD. The effects of paeoniflorin on inflammation and glucolipid metabolism disorder were evaluated. The corresponding signaling pathways were measured using real-time polymerase chain reaction (PCR). We demonstrated that the mice developed obesity, dyslipidemia, and fatty liver, which formed the NAFLD model. Paeoniflorin attenuated NAFLD and exhibited potential cardiovascular protective effects in vivo by lowering body weight, hyperlipidemia, and insulin resistance; blocking inflammation; and inhibiting lipid ectopic deposition. Further investigation revealed that the antagonistic effect on hyperlipidemia and lipid ectopic deposition was related to lowering the lipid synthesis pathway (de novo pathway, 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoAR)), promoting fatty acid oxidation [peroxisome proliferator-activated receptor-alpha (PPARα), carnitine palmitoyltransferase-1, etc.] and increasing cholesterol output (PPARγ-liver X receptor-α-ATP-binding cassette transporter-1); the inhibitory effects on inflammation and hyperglycemia were mediated by blocking inflammatory genes activation and reducing gluconeogenic genes expression (phosphoenolpyruvate carboxykinase and G6Pase). These results suggest that paeoniflorin prevents the development of NAFLD and reduces the risks of atherosclerosis through multiple intracellular signaling pathways. It may therefore be a potential therapeutic compound for NAFLD.

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“…Additionally, the process of glucose metabolism and liver development were found to be involved in the toxicity of CCl 4 . The liver is a central organ in gluconeogenesis metabolism (Bechmann et al, 2012). Usually after liver injury, there would be glucose metabolic disorder (Bahr et al, 2006) and abnormal liver development (Yin et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of CCl<sub>4</sub>-induced liver fibrosis with combined transcriptomic and proteomic analysis

et al. 2016

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-The classic toxicity of carbon tetrachloride (CCl 4 ) is to induce liver lesion and liver fibrosis. Liver fibrosis is a consequence of chronic liver lesion, which can progress into liver cirrhosis even hepatocarcinoma. However, the toxicological mechanisms of CCl 4 -induced liver fibrosis remain not fully understood. We combined transcriptomic and proteomic analysis and biological network technology, predicted toxicological targets and regulatory networks of CCl 4 in liver fibrosis. Wistar rats were treated with CCl 4 for 9 weeks. Histopathological changes, hydroxyproline (Hyp) contents, serum ALT and AST in the CCl 4 -treated group were significantly higher than that of CCl 4 -untreated group. CCl 4 -treated and -untreated liver tissues were examined by microarray and iTRAQ. The results showed that 3535 genes (fold change ≥ 1.5, P < 0.05) and 1412 proteins (fold change ≥ 1.2, P < 0.05) were differentially expressed. Moreover, the integrative analysis of transcriptomics and proteomics data showed 523 overlapped proteins, enriched in 182 GO terms including oxidation reduction, response to oxidative stress, inflammatory response, extracellular matrix organization, etc. Furthermore, KEGG pathway analysis showed that 36 pathways including retinol metabolism, PPAR signaling pathway, glycolysis/gluconeogenesis, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabolism. Network of protein-protein interaction (PPI) and key function with their related targets were performed and the degree of network was calculated with Cytoscape. The expression of key targets such as CYP4A3, ALDH2 and ALDH7A1 decreased after CCl 4 treatment. Therefore, the toxicological mechanisms of CCl 4 -induced liver fibrosis may be related with multi biological process, pathway and targets which may provide potential protection reaction mechanism for CCl 4 detoxication in the liver.

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The interaction of hepatic lipid and glucose metabolism in liver diseases

Cited by 752 publications

References 130 publications

Steatosis does not impair liver regeneration after partial hepatectomy

Steatosis does not impair liver regeneration after partial hepatectomy

Paeoniflorin Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice

Mechanisms of CCl<sub>4</sub>-induced liver fibrosis with combined transcriptomic and proteomic analysis

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