Prohibitin-induced, obesity-associated insulin resistance and accompanying low-grade inflammation causes NASH and HCC

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Ande, Sudharsana R ^a   Nguyen, K Hoa ^a   Gregoire Nyomba B L ^a   Mishra, Suresh ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

PROHIBITIN; REPRESSOR PROTEIN; STAT3 PROTEIN; STAT3 PROTEIN, MOUSE;

ANIMAL; CARCINOMA, HEPATOCELLULAR; DEFICIENCY; DISEASE MODEL; FEMALE; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; INSULIN RESISTANCE; LIVER NEOPLASMS; MALE; METABOLISM; MOUSE; MOUSE MUTANT; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; SEXUAL DEVELOPMENT; SIGNAL TRANSDUCTION;

ANIMALS; CARCINOMA, HEPATOCELLULAR; DISEASE MODELS, ANIMAL; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; INSULIN RESISTANCE; LIVER NEOPLASMS; MALE; MAP KINASE SIGNALING SYSTEM; MICE; MICE, OBESE; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; REPRESSOR PROTEINS; SEX CHARACTERISTICS; STAT3 TRANSCRIPTION FACTOR;

EID: 84962288021     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep23608     Document Type: Article

References (54)

1. Nakagawa, H. et al. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell. 26, 331-343 (2014).
2. El-Serag, H. B. Hepatocellular carcinoma. N Engl J Med. 365, 118-127 (2011).
3. Turati, F. et al. Metabolic syndrome and hepatocellular carcinoma risk. Br J Cancer. 108, 222-228 (2013).
4. Tilg, H. & Moschen, A. R. Mechanisms behind the link between obesity and gastrointestinal cancers. Best Pract Res Clin Gastroenterol. 28, 599-610 (2014).
5. Calle, E. E. et al. Overweight, obesity and mortality from cancer in a prospective studied cohort of U.S. adults. N Engl J Med 348, 1625-1638 (2003).
6. Samanic, C. et al. Relation of body mass index to cancer risk in 362,552 Swedish men. Cancer Causes Control. 17, 901-909 (2006).
7. Wolk, A. et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 12, 13-21 (2001).
8. Borena, W. et al. Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults. Int J Cancer. 131, 193-200 (2012).
9. Schlesinger, S. et al. Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort. Int J Cancer. 132, 645-657 (2013).
10. Calle, E. F. & Kaaks, R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 4, 579-591 (2004).
11. Chen, C. L. et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: A follow-up study in Taiwan. Gastroenterology 135, 111-121 (2008).
12. Carmichael, A. R. Obesity as a risk factor for development and poor prognosis of breast cancer. BJOG. 113, 1160-1166 (2006).
13. Murphy, T. K. et al. Body mass index and colon cancer mortality in a large prospective study. Am J Epidemiol. 152, 847-854 (2000).
14. Marchesini, G. et al. Association of non-alcoholic fatty liver disease with insulin resistance. Am J Med. 107, 450-5 (1999).
15. Yin, X. et al. Glucose fluctuation increased hepatocyte apoptosis under lipotoxicity and the involvement of mitochondrial permeability transition opening. J Mol Endocrinol. 55, 169-81 (2015).
16. Bellanti, F. et al. Oxysterols induce mitochondrial impairment and hepatocellular toxicity in non-alcoholic fatty liver disease. Free Radic Biol Med. 75 Suppl 1, S16-7 (2014).
17. Kim, C. S. et al. Quercetin reduces obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1. Nutr Metab (Lond). 6, 12-33 (2015).
18. Ekstedt, M. et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 44, 865-873 (2006).
19. Rafiq, N. et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol. 7, 234-238 (2009).
20. Guzman, G. et al. Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Arch Pathol Lab Med. 132, 1761-1766 (2008).
21. Paradis, V. et al. Hepatocellular carcinoma in patients with metabolic syndrome often develop without significant liver fibrosis: A pathological analysis. Hepatology. 42, 851-859 (2009).
22. Ertle, J. et al. Nonalcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer. 128, 2436-2443 (2010).
23. Rahman, R. N. & Ibdah, J. A. Nonalcoholic fatty liver disease without cirrhosis is an emergent and independent risk factor of hepatocellular carcinoma: A population based study. Hepatology. 56, 241A (2012).
24. Marrero, J. A. et al. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 36, 1349-1354 (2002).
25. Karagozian, R., Derdak, Z. & Baffy, G. Obesity-associated mechanisms of hepatocarcinognesis. Metabolism. 63, 607-617 (2014).
26. Umemura, A. et al. Liver damage, inflammation, and enhanced tumorigenesis after persistent mTORC1 inhibition. Cell Metab. 20, 133-144 (2014).
27. Duan, X. Y. et al. High-saturate-fat diet delays initiation of diethylnitrosamine-induced hepatocellular carcinoma. BMC Gastroenterol. 14, 195 (2014).
28. Tajima, K. et al. Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice. Am J Physiol Endocrinol Metab. 305, E987-998 (2013).
29. Nishida, T. et al. Spontaneous onset of nonalcoholic steatohepatitis and hepatocellular carcinoma in a mouse model of metabolic syndrome. Lab Invest. 93, 230-241 (2013).
30. Miyata, S., Yamada N. & Kwada T. Possible involvement of hypothalamic nucleobindin-2 in hyperphagic feeding in Tsumara Suzuki Obese Diabetes mice. Biol. Pharm. Bull. 35, 1784-1793 (2012).
31. Horie, Y. et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest. 113, 1774-1783 (2004).
32. Wolfe, A. et al. Increased activation of the Wnt/?-catenin pathway in spontaneous hepatocellular carcinoma observed in farnesoid X receptor knockout mice. JPET 338, 12-21 (2011).
33. Wunderlich, F. T. et al. Hepatic NF-kB essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis. Proc Natl Sci Acad USA 105, 1297-1302 (2008).
34. Tsai, W.-C. et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Inves. 122, 2884-2897 (2012).
35. Ande, S. R. et al. Prohibitin overexpression in adipocytes induces mitochondrial biogenesis, leads to obesity development, and affects glucose homeostasis in a sex-specific manner. Diabetes. 63, 3734-3741 (2014).
36. Huh, J. Y., Park, Y. J., Ham, M. & Kim, J. B. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells. 37, 365-371 (2014).
37. Ande, S. R., Nguyen, K. H., Padilla-Meier, G. P., Nyomba, B. L. & Mishra, S. Expression of a mutant prohibitin from the aP2 gene promoter leads to obesity-linked tumor development in insulin resistance-dependent manner. Oncogene. Jan 11 doi: 10.1038/onc.2015.501 (2016). [Epub ahead of print]
38. Maeda, T. et al. Role of tissue trace elements in liver cancers and non-cancerous liver parenchyma. Hepatogastroenterology. 52, 187-190 (2005).
39. Rossignol, D. A. & Frye, R. E. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol. 5, 150 (2014).
40. Koliaki, C. et al. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab. 21, 739-746 (2015).
41. Chen, C. L., Tsukamoto, H. & Machida, K. Oncogenic signaling pathways and origins of tumor-initiating stem-like cells of hepatocellular carcinomas induced by hepatitis C virus, alcohol and/or obesity. Hepatol Int. 8, 330-338 (2014).
42. Mishra, S., Ande, S. R. & Nyomba, B. L. The role of prohibitin in cell signaling. FEBS J. 77, 3937-3946 (2010).
43. Baatar, D., Patel, K. & Taub, D. D. The effects of ghrelin on inflammation and the immune system. Mol Cell Endocrinol. 340, 44-58 (2011).
44. Kizaki, T. et al. Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages. Biochem Biophys Res Commun 413, 454-459 (2011).
45. Barazzoni, R., Semolic, A., Cattin, M. R., Zanetti, M. & Guamieri, G. Acylated ghrelin limits fat accumulation and improves redox state and inflammation markers in the liver of high-fat-fed rats. Obesity. 22, 170-177 (2014).
46. Li, Y. et al. Administration of ghrelin improves inflammation, oxidative stress, and apoptosis during and after non-alcoholic fatty liver disease development. Endocrine. 43, 376-386 (2013).
47. Fu, Y., Luo, L., Luo, N. & Garvey, W. T. Lipid metabolism mediated by adipocyte lipid binding protein (ALBP/aP2) gene expression in human THP-1 macrophages. Atherosclerosis. 188, 102-111 (2006).
48. Han, J., Yu, C., Souza, R. F. & Theiss, A. L. Prohibitin 1 modulates mitochondrial function of Stat3. Cell Signal. 26, 2086-2095 (2014).
49. Ko, K. S. et al. Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis, and hepatocellular carcinoma in mice. Hepatology. 52, 2096-2108 (2010).
50. Rajalingam, K. et al. Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration. Nat Cell Biol. 7, 837-843 (2005).
51. Wang, S., Fusaro, G., Padmanabhan, J. & Chellappan, S. P. Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression. Oncogene. 21, 8388-8396 (2002).
52. Nguyen, K. H., Yao, X. H., Moulik, S., Mishra, S. & Nyomba, B. L. G. Human IGF binding protein-3 overexpression impairs glucose regulation in mice via an inhibition of insulin secretion. Endocrinology. 152, 2184-2196 (2011).
53. Nguyen, K. H., Yao, X. H., Erickson, A. G., Mishra, S. & Nyomba, B. L. G. Glucose intolerance in aging male IGFBP-3 transgenic mice: Differential effects of human IGFBP-3 and its mutant IGFBP-3 devoid of IGF binding ability. Endocrinology. 156, 462-474 (2015).
54. Kelly, R. D. W., Mahmud, A., McKenzie, M., Trouche, I. A. & St John, J. C. Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A. Nucleic Acid Res. 40, 10124-10138 (2012).