缺氧对非酒精性脂肪性肝病发病的影响*

doi:10.3969/j.issn.1672-5069.2016.02.034

Abstract

Abstract: Systematic and local hypoxia in liver is common in patients with nonalcoholic fatty liver diseases （NAFLD）. Studies on the relationship between obstructive sleep apnea and NAFLD show that the extent of hypoxia is positively correlated with insulin resistance,liver steatosis,and hepatic inflammation and fibrosis. Experiments in animals and molecular researches demonstrate that hypoxia and the hypoxia-inducible factors could promote the occurrence and progression of hepatic steatosis,inflammation,fibrosis,and even induce carcinoma in liver.

Key words: Nonalcoholic fatty liver disease, Hypoxia, Hypoxia-induced factor

Guan Hongyu, Cai Xiaobo, Lu Lungen. Hypoxia in the pathogenesis of nonalcoholic fatty liver diseases[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(2): 237-240.

References

[1] Bhala N,Jouness RI,Bugianesi E.Epidemiology and natural history of patients with NAFLD. Curr Pharm Des,2013,19（29）:5169-5176.
[2] 范建高,曾民德.脂肪性肝病. 2版,北京：人民卫生出版社,2013:128-132.
[3] Savransky V,Nanayakkara A,Vivero A,et al. Chronic intermittent hypoxia predisposes to liver injury. Hepatology,2007,45（4）:1007-1013.
[4] Tanne F,Gagnadoux F,Chazouilleres O,et al. Chronic liver injury during obstructive sleep apnea. Hepatology,2005,41（6）:1290-1296.
[5] Lemoine M,Serfaty L.Chronic intermittent hypoxia:a breath of fresh air in the understanding of NAFLD pathogenesis. J Hepatol,2012,56（1）:20-22.
[6] Nath B,Szabo G. Hypoxia and hypoxia inducible factors: diverse roles in liver diseases. Hepatology,2012,55（2）:622-633.
[7] Broughan TA,Naukam R,Tan C,et al. Effects of hepatic zonaloxygen levels on hepatocyte stress responses. J Surg Res,2008,145:150-160.
[8] Mantena SK,Vaughn DP,Andringa KK,et al. High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo. Biochem J,2009,417（1）:183-193.
[9] Burgueo AL,Gianotti TF,Mansilla NG,et al. Cardiovascular disease is associated with high-fat-diet-induced liver damage and up-regulation of the hepatic expression of hypoxia-inducible factor 1α in a rat model.Clin Sci（Lond）,2013,124（1）:53-63.
[10] Polotsky VY,Patil SP,Savransky V,et al. Obstructive sleep apnea,insulin resistance,and steatohepatitis in severe obesity. Am J Respir Crit Care Med,2009,179（3）:228-234.
[11] Li J,Grigoryev DN,Ye SQ,et al. Chronicintermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol,2005,99（5）:1643-1648.
[12] Savransky V,Bevans S,Nanayakkara A,et al. Chronicintermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol,2007,293（4）:871-877.
[13] Aron-Wisnewsky J,Minville C,Tordjman J,et al. Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol,2012,56（1）:225-233.
[14] Sookoian S,Pirola CJ. Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes:a meta-analysis.Obes Surg,2013,23（11）:1815-1825.
[15] Bostrom P,Magnusson B,Svensson PA,et al. Hypoxia converts human macrophages into triglyceride-loaded foam cells. Arterioscler Thromb Vasc Biol,2006,26（8）:1871-1876.
[16] Wada T,Shimba S,Tezuka M. Transcriptional regulation of the hypoxia inducible factor-2alpha （HIF-2alpha） gene during adipose differentiation in 3T3-L1 cells. Biol Pharmaceut Bull, 2006,29（1）:49-54.
[17] Belanger A,Luo Z,Vincent K,et al. Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor alpha/retinoid X receptor. Biochem Biophy Res Commun,2007,364（3）:567-572.
[18] Nath B,Levin I,Csak T,et al. Hepatocyte-specific hypoxia-inducible factor-1α is a determinant of lipid accumulation and liver injury in alcohol-induced steatosis in mice.Hepatology, 2011,53（5）:1526-1537.
[19] Rankin EB,Rha J,Selak MA,et al. HIF-2 regulates hepatic lipid metabolism. Mol Cell Biol,2009,29（16）:4527-4538.
[20] Kucejova B,Sunny NE,Nguyen AD,et al. Uncoupling hypoxia signaling from oxygen sensing in the liver results in hypoketotic hypoglycemic death. Oncogene,2011,30（18）:2147-2160.
[21] Kim WY,Safran M,Buckley MR,et al. Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J,2006,25（19）:4650-4662.
[22] Nishiyama Y,Goda N,Kanai M,et al. HIF-1α induction suppresses excessive lipid accumulation in alcoholic fatty liver in mice. J Hepatol,2012,56（2）:441-447.
[23] Carabelli J,Burgueo AL,Rosselli MS,et al. High fat diet-induced liver steatosispromotes an increase in liver mitochondrial biogenesis in response to hypoxia. J Cell Mol Med,2011,15（6）:1329-1338.
[24] Koumenis C,Naczki C,Koritzinsky M,et al. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor HIF2alpha. Mol Cell Biol,2002,22（21）:7405-7416.
[25] Chalasani N,Gorski CJ,Asghar MS,et al. Hepatic cytochrome P450 2E1 activity in non-diabetic patients with nonalcoholic steatohepatitis. Hepatology,2003,37（3）:544-550.
[26] Peyssonnaux C,Cejudo-Martin P,Doedens A,et al. Cutting edge: Essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. J Immunol, 2007,178（12）:7516-7519.
[27] Scharte M,Han X,Uchiyama T,et al. LPS increases hepatic HIF-1alpha protein and expression of the HIF-1-dependent gene aldolase A in rats. J Surg Res,2006,135（2）:262-267.
[28] Blouin CC,Page EL,Soucy GM,et al. Hypoxic gene activation by lipopolysaccharide inmacrophages:implication of hypoxia-inducible factor 1alpha. Blood,2004,103（3）:1124-1130.
[29] Qu A,Taylor M,Xue X,et al. Hypoxia-inducible transcription factor 2α promotes steatohepatitis through augmenting lipid accumulation,inflammation,and fibrosis.Hepatology,2011,54（2）:472-483.
[30] Nakamura K,Zen Y,Sato Y,et al. Vascular endothelial growth factor,its receptor Flk-1,and hypoxia inducible factor-1alpha are involved in malignant transformation in dysplastic nodules of the liver. Hum Pathol,2007,38（10）:1532-1546.
[31] Moon J,Welch T,Gonzalez F,et al. Reduced liver fibrosis in hypoxia-induciblefactor-1{alpha}-deficient mice. Am J Physiol, 2009,296（3）:582-592.
[32] Corpechot C,Barbu V,Wendum D,et al. Hypoxiainduced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology,2002,35（5）:1010-1021.
[33] Shi YF,Fong CC,Zhang Q,et al. Hypoxia induces theactivation of human hepatic stellate cells LX-2 through TGF-beta signaling pathway. FEBS Lett,2007,581（2）:203-210.
[34] Desmet VJ. Ductal plates in hepatic ductular reactions. Hypothesis and implications. I. Types of ductular reaction reconsidered.Virch Arch,2011,458（3）:251-259.
[35] Corpechot C,Barbu V,Wendum D,et al. Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology, 2002,35（5）:1010-1021.
[36] Novo E,Cannito S,Zamara E,et al. Proangiogenic cytokines as hypoxiadependentfactors stimulating migration of human hepatic stellate cells. Am J Pathol,2007,170（6）:1942-1953.
[37] Rosmorduc O,Housset C.Hypoxia:a link between fibrogenesis, angiogenesis,and carcinogenesis in liver disease. Semin Liver Dis,2010,30（3）:258-270.
[38] Wong CC,Kai AK,Ng IO.The impact of hypoxia in hepatocellular carcinoma metastasis.Front Med,2014,8（1）:33-41.

Hypoxia in the pathogenesis of nonalcoholic fatty liver diseases

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