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Biochemical mechanisms of development of non-alcoholic fatty liver disease under the influence of fructose

DOI 10.18127/j20700997-201804-02


Z.Sh. Pavlova – Ph.D. (Med.), Endocrinologist, Medical Scientific-Educational Center of Lomonosov Moscow State University
I.I. Golodnikov – Faculty of Fundamental Medicine, Lomonosov Moscow State University
A.A. Kamalov - Academician of RAS, Dr.Sc. (Med.), Professor, Director of Medical Scientific-Educational Center of Lomonosov Moscow State University; Head of the Department of Urology and Andrology, Faculty of Fundamental Medicine, Lomonosov Moscow State University

With many changes in the life of a modern person, negatively affecting his health, for example, a sedentary lifestyle, a nonphysiological diet, the excessive use of fructose and its pathological effect on the metabolism of carbohydrates in the liver comes to the top. It's no secret that fructose has been considered a harmless alternative to glucose for patients with type 2 diabetes mellitus for quite some time, and confectionery products were prepared on its basis, which doctors recommended to patients. We need to sort out - fructose - a wolf in sheep's clothing or an affordable and safe sweetness.
The ability of fructose to be both a substrate and an inducer of the synthesis of lipids de novo [DNL] in the liver is the main cause of the development of NAFLD [Non-alcoholic fatty liver disease], and oxidative stress, mitochondrial dysfunction and inflammation is a physic consequence of events developing in excessively formed fat tissues, including the progression of simple steatosis of the liver in NAFLD. This article presents key participants and mechanisms responsible for the development of fructose-induced non-alcoholic fatty liver disease, as well as a number of stages of fructose metabolism, understanding of which is necessary to represent the process as a whole.

  1. Bray G.A. Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people // Adv. Nutr. 2013. V. 4. № 2. Р. 220-225.
  2. DiBaise J.K., et al. Gut microbiota and its possible relationship with obesity // Mayo Clin. Proc. 2008. V. 83. № 4. Р. 460-469.
  3. Bugianesi E., et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms // Diabetologia. 2005. V. 48. № 4. Р. 634-642.
  4. de Moura Almeida A., et al. Fatty liver disease in severe obese patients: diagnostic value of abdominal ultrasound // World J. Gastroenterol. 2008. V. 14. № 9. Р. 1415-1418.
  5. Douard V., Ferraris R.P. The role of fructose transporters in diseases linked to excessive fructose intake // J. Physiol. 2013. V. 591. № 2. Р. 401-414.
  6. Karim S., Adams D.H., Lalor P.F. Hepatic expression and cellular distribution of the glucose transporter family // World J. Gastroenterol. 2012. V. 18. № 46. Р. 6771-6781.
  7. Vos M.B., Lavine J.E. Dietary fructose in nonalcoholic fatty liver disease // Hepatology. 2013. V. 57. № 6. Р. 2525-2531.
  8. Iizuka K. The Role of Carbohydrate Response Element Binding Protein in Intestinal and Hepatic Fructose Metabolism // Nutrients. 2017. V. 9. № 2.
  9. Sun S.Z., Empie M.W. Fructose metabolism in humans – what isotopic tracer studies tell us // Nutr. Metab. (Lond.). 2012. № 9. Р. 89.
  10. Black P.N. et al. Targeting the fatty acid transport proteins (FATP) to understand the mechanisms linking fatty acid transport to metabolism // Immunol. Endocr. Metab. Agents Med. Chem. 2009. V. 9. № 1. Р. 11-17.
  11. Shvarc V. Vospalenie zhirovoj tkani // Problemy ehndokrinologii. 2009. V. 55. № 4–6. S. 44–49, 43–48, 40–45.Seki E., Brenner D.A. Toll-like receptors and adaptor molecules in liver disease: update. Hepatology. 2008. V. 48. № 1. Р. 322-335.
  12. Bae J.S. et al. Hepatic Elovl6 gene expression is regulated by the synergistic action of ChREBP and SREBP-1c // Biochem. Biophys. Res. Commun. 2016. V. 478. № 3. Р. 1060-1066.
  13. Sirek A.S. et al. Insulin stimulates the expression of carbohydrate response element binding protein (ChREBP) by attenuating the repressive effect of Pit-1, Oct-1/Oct-2, and Unc-86 homeodomain protein octamer transcription factor-1 // Endocrinology. 2009. V. 150. № 8. Р. 3483-3492.
  14. Wong R.H., Sul H.S. Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective // Curr. Opin. Pharmacol. 2010. V. 10. № 6. Р. 684-691.
  15. Alam S. et al. Insulin resistance in development and progression of nonalcoholic fatty liver disease // World J. Gastrointest. Pathophysiol. 2016. V. 7. № 2. Р. 211-217.
  16. Dentin R., Girard J., Postic C. Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver // Biochimie. 2005. V. 87. № 1. Р. 81-86.
  17. Herman M.A. et al. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism // Nature. 2012. V. 484. № 7394. Р. 333-338.
  18. Ferre P., Foufelle F. Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c // Diabetes Obes. Metab. 2010. № 12 Suppl. 2. Р. 83-92.
  19. Chen Q. et al. Effects of Natural Products on Fructose-Induced Nonalcoholic Fatty Liver Disease (NAFLD) // Nutrients. 2017. V. 9. № 2.
  20. Madlala H.P., Maarman G.J., Ojuka E. Uric acid and transforming growth factor in fructose-induced production of reactive oxygen species in skeletal muscle // Nutr. Rev. 2016. V. 74. № 4. Р. 259-266.
  21. Lim J.S. et al. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome // Nat. Rev. Gastroenterol. Hepatol. 2010. V. 7. № 5. Р. 251-264.
  22. Staels B. et al. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis // Hepatology. 2013. V. 58. № 6. Р. 1941-1952.
  23. van Harmelen V. et al. Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes // Diabetes, 2002. V. 51. № 7. Р 2029-2036.
  24. Thrasher J. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies // Am. J. Cardiol. 2017. № 120(1s). Р. S4-s16.
  25. Martinez F.O., Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment // F1000Prime Rep. 2014. № 6.
  26. Galvan-Pena S., O'Neill L.A. Metabolic reprograming in macrophage polarization // Front Immunol. 2014. № 5. Р. 420.
  27. Lebensztejn D.M. et al. Hepatokines and non-alcoholic fatty liver disease // Acta Biochim. Pol. 2016. V. 63. № 3. Р. 459-467.
  28. Tanaka T. et al. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome // Proc. Natl. Acad. Sci. USA. 2003. V. 100. № 26. Р. 15924-15929.
  29. Capellino S. et al. Effects of estrogen peripheral metabolism in rheumatoid arthritis // Reumatismo. 2005. V. 57. № 2. Р. 78-82.
  30. Teff K.L. et al. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses // J. Clin. Endocrinol. Metab. 2009. V. 94. № 5. Р. 1562-1569.
  31. Graves D.T., Jiang Y. Chemokines, a family of chemotactic cytokines // Crit. Rev. Oral. Biol. Med. 1995. V. 6. № 2. Р. 109-118.
  32. Clement K. et al. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects // Faseb. J. 2004. V. 18. № 14. Р. 1657-1669.
  33. Cancello R. et al. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity // Diabetes. 2006. V. 55. № 6. Р. 1554-1561.
  34. Cancello R., Clement K. Is obesity an inflammatory illness? Role of low-grade inflammation and macrophage infiltration in human white adipose tissue // Bjog. 2006. V. 113. № 10. Р. 1141-1147.
  35. Suganami T., Nishida J., Ogawa Y. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha // Arterioscler. Thromb. Vasc. Biol. 2005. V. 25. № 10. Р. 2062-2068.
  36. Lumeng C.N., Bodzin J.L., Saltiel A.R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization // J. Clin. Invest. 2007. V. 117. № 1. Р. 175-184.
  37. Cinti S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans // J. Lipid. Res. 2005. V. 46. № 11. Р. 2347-2355.
  38. Rui L. et al. Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways // J. Clin. Invest. 2001. V. 107. № 2. Р. 181-189.
  39. Yuan M. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta // Science. 2001. V. 293. № 5535. Р. 1673-1677.
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