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Fructose as a key player in the development of fatty liver disease.
World J Gastroenterol 2013; 19(8):1166-72WJ

Abstract

We aimed to investigate whether increased consumption of fructose is linked to the increased prevalence of fatty liver. The prevalence of nonalcoholic steatohepatitis (NASH) is 3% and 20% in nonobese and obese subjects, respectively. Obesity is a low-grade chronic inflammatory condition and obesity-related cytokines such as interleukin-6, adiponectin, leptin, and tumor necrosis factor-α may play important roles in the development of nonalcoholic fatty liver disease (NAFLD). Additionally, the prevalence of NASH associated with both cirrhosis and hepatocellular carcinoma was reported to be high among patients with type 2 diabetes with or without obesity. Our research group previously showed that consumption of fructose is associated with adverse alterations of plasma lipid profiles and metabolic changes in mice, the American Lifestyle-Induced Obesity Syndrome model, which included consumption of a high-fructose corn syrup in amounts relevant to that consumed by some Americans. The observation reinforces the concerns about the role of fructose in the obesity epidemic. Increased availability of fructose (e.g., high-fructose corn syrup) increases not only abnormal glucose flux but also fructose metabolism in the hepatocyte. Thus, the anatomic position of the liver places it in a strategic buffering position for absorbed carbohydrates and amino acids. Fructose was previously accepted as a beneficial dietary component because it does not stimulate insulin secretion. However, since insulin signaling plays an important role in central mechanisms of NAFLD, this property of fructose may be undesirable. Fructose has a selective hepatic metabolism, and provokes a hepatic stress response involving activation of c-Jun N-terminal kinases and subsequent reduced hepatic insulin signaling. As high fat diet alone produces obesity, insulin resistance, and some degree of fatty liver with minimal inflammation and no fibrosis, the fast food diet which includes fructose and fats produces a gene expression signature of increased hepatic fibrosis, inflammation, endoplasmic reticulum stress and lipoapoptosis. Hepatic de novo lipogenesis (fatty acid and triglyceride synthesis) is increased in patients with NAFLD. Stable-isotope studies showed that increased de novo lipogenesis (DNL) in patients with NAFLD contributed to fat accumulation in the liver and the development of NAFLD. Specifically, DNL was responsible for 26% of accumulated hepatic triglycerides and 15%-23% of secreted very low-density lipoprotein triglycerides in patients with NAFLD compared to an estimated less than 5% DNL in healthy subjects and 10% DNL in obese people with hyperinsulinemia. In conclusion, understanding the underlying causes of NAFLD forms the basis for rational preventive and treatment strategies of this major form of chronic liver disease.

Authors+Show Affiliations

Department of Gastroenterology and Hepatology, Bezmialem Vakif University, Istanbul 34400, Turkey. metin_basaranoglu@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23482247

Citation

Basaranoglu, Metin, et al. "Fructose as a Key Player in the Development of Fatty Liver Disease." World Journal of Gastroenterology, vol. 19, no. 8, 2013, pp. 1166-72.
Basaranoglu M, Basaranoglu G, Sabuncu T, et al. Fructose as a key player in the development of fatty liver disease. World J Gastroenterol. 2013;19(8):1166-72.
Basaranoglu, M., Basaranoglu, G., Sabuncu, T., & Sentürk, H. (2013). Fructose as a key player in the development of fatty liver disease. World Journal of Gastroenterology, 19(8), pp. 1166-72. doi:10.3748/wjg.v19.i8.1166.
Basaranoglu M, et al. Fructose as a Key Player in the Development of Fatty Liver Disease. World J Gastroenterol. 2013 Feb 28;19(8):1166-72. PubMed PMID: 23482247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fructose as a key player in the development of fatty liver disease. AU - Basaranoglu,Metin, AU - Basaranoglu,Gokcen, AU - Sabuncu,Tevfik, AU - Sentürk,Hakan, PY - 2012/07/20/received PY - 2012/09/20/revised PY - 2012/11/14/accepted PY - 2013/3/14/entrez PY - 2013/3/14/pubmed PY - 2013/12/16/medline KW - Cytokines KW - Diabetes KW - Fatty liver KW - Fructose KW - Insulin resistance KW - Nonalcoholic KW - Obesity SP - 1166 EP - 72 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 19 IS - 8 N2 - We aimed to investigate whether increased consumption of fructose is linked to the increased prevalence of fatty liver. The prevalence of nonalcoholic steatohepatitis (NASH) is 3% and 20% in nonobese and obese subjects, respectively. Obesity is a low-grade chronic inflammatory condition and obesity-related cytokines such as interleukin-6, adiponectin, leptin, and tumor necrosis factor-α may play important roles in the development of nonalcoholic fatty liver disease (NAFLD). Additionally, the prevalence of NASH associated with both cirrhosis and hepatocellular carcinoma was reported to be high among patients with type 2 diabetes with or without obesity. Our research group previously showed that consumption of fructose is associated with adverse alterations of plasma lipid profiles and metabolic changes in mice, the American Lifestyle-Induced Obesity Syndrome model, which included consumption of a high-fructose corn syrup in amounts relevant to that consumed by some Americans. The observation reinforces the concerns about the role of fructose in the obesity epidemic. Increased availability of fructose (e.g., high-fructose corn syrup) increases not only abnormal glucose flux but also fructose metabolism in the hepatocyte. Thus, the anatomic position of the liver places it in a strategic buffering position for absorbed carbohydrates and amino acids. Fructose was previously accepted as a beneficial dietary component because it does not stimulate insulin secretion. However, since insulin signaling plays an important role in central mechanisms of NAFLD, this property of fructose may be undesirable. Fructose has a selective hepatic metabolism, and provokes a hepatic stress response involving activation of c-Jun N-terminal kinases and subsequent reduced hepatic insulin signaling. As high fat diet alone produces obesity, insulin resistance, and some degree of fatty liver with minimal inflammation and no fibrosis, the fast food diet which includes fructose and fats produces a gene expression signature of increased hepatic fibrosis, inflammation, endoplasmic reticulum stress and lipoapoptosis. Hepatic de novo lipogenesis (fatty acid and triglyceride synthesis) is increased in patients with NAFLD. Stable-isotope studies showed that increased de novo lipogenesis (DNL) in patients with NAFLD contributed to fat accumulation in the liver and the development of NAFLD. Specifically, DNL was responsible for 26% of accumulated hepatic triglycerides and 15%-23% of secreted very low-density lipoprotein triglycerides in patients with NAFLD compared to an estimated less than 5% DNL in healthy subjects and 10% DNL in obese people with hyperinsulinemia. In conclusion, understanding the underlying causes of NAFLD forms the basis for rational preventive and treatment strategies of this major form of chronic liver disease. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/23482247/Fructose_as_a_key_player_in_the_development_of_fatty_liver_disease_ L2 - http://www.wjgnet.com/1007-9327/full/v19/i8/1166.htm DB - PRIME DP - Unbound Medicine ER -