Match!

The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome

Published on May 1, 2010in Nature Reviews Gastroenterology & Hepatology23.57
· DOI :10.1038/nrgastro.2010.41
Jung Sub Lim1
Estimated H-index: 1
,
Michele Mietus-Snyder22
Estimated H-index: 22
(UCSF: University of California, San Francisco)
+ 2 AuthorsRobert H. Lustig57
Estimated H-index: 57
(UCSF: University of California, San Francisco)
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide, and is commonly associated with the metabolic syndrome. Secular trends in the prevalence of these diseases may be associated with the increased fructose consumption observed in the Western diet. NAFLD is characterized by two steps of liver injury: intrahepatic lipid accumulation (hepatic steatosis), and inflammatory progression to nonalcoholic steatohepatitis (NASH) (the 'two-hit' theory). In the first 'hit', hepatic metabolism of fructose promotes de novo lipogenesis and intrahepatic lipid, inhibition of mitochondrial β -oxidation of long-chain fatty acids, triglyceride formation and steatosis, hepatic and skeletal muscle insulin resistance, and hyperglycemia. In the second 'hit', owing to the molecular instability of its five-membered furanose ring, fructose promotes protein fructosylation and formation of reactive oxygen species (ROS), which require quenching by hepatic antioxidants. Many patients with NASH also have micronutrient deficiencies and do not have enough antioxidant capacity to prevent synthesis of ROS, resulting in necroinflammation. We postulate that excessive dietary fructose consumption may underlie the development of NAFLD and the metabolic syndrome. Furthermore, we postulate that NAFLD and alcoholic fatty liver disease share the same pathogenesis.
  • References (192)
  • Citations (371)
References192
Newest
#2Blair U. BradfordH-Index: 47
Last.Ivan RusynH-Index: 55
view all 12 authors...
23 CitationsSource
#1M. SchreursH-Index: 1
#2Folkert Kuipers (UMCG: University Medical Center Groningen)H-Index: 72
Last.F. R. van der LeijH-Index: 1
view all 3 authors...
129 CitationsSource
#1Roger H UngerH-Index: 114
#2Gregory O. ClarkH-Index: 4
Last.Lelio Orci (University of Geneva)H-Index: 121
view all 4 authors...
348 CitationsSource
#2Jesse D. Schold (UF: University of Florida)H-Index: 43
Last.J López LilloH-Index: 1
view all 6 authors...
193 CitationsSource
#1Blanca Eugenia Farfán Labonne (UAM: Universidad Autónoma Metropolitana)H-Index: 2
#2Mario Gutiérrez (UAM: Universidad Autónoma Metropolitana)H-Index: 2
Last.María Concepción Gutiérrez-Ruiz (UAM: Universidad Autónoma Metropolitana)H-Index: 19
view all 11 authors...
46 CitationsSource
#1M A Bethel (Duke University)H-Index: 1
#2Prakash C. Deedwania (UCSF: University of California, San Francisco)H-Index: 67
Last.Peter Diem (University of Bern)H-Index: 34
view all 8 authors...
10 CitationsSource
96 CitationsSource
#1Wing-Kin Syn (University of Birmingham)H-Index: 25
#2Steve S. Choi (Durham University)H-Index: 38
Last.Anna Mae Diehl (Durham University)H-Index: 100
view all 3 authors...
80 CitationsSource
#1Ali Abid (Holy Family Hospital)H-Index: 1
#2Ola Taha (Holy Family Hospital)H-Index: 1
Last.Nimer Assy (Technion – Israel Institute of Technology)H-Index: 27
view all 6 authors...
149 CitationsSource
#2Andreas PeterH-Index: 29
Last.Norbert StefanH-Index: 64
view all 11 authors...
214 CitationsSource
Cited By371
Newest
#1Feryal Savari (Ahvaz Jundishapur University of Medical Sciences)H-Index: 1
#2Seyyed Ali Mard (Ahvaz Jundishapur University of Medical Sciences)H-Index: 9
Last.Mohammad Kazem Gharib-Naseri (Ahvaz Jundishapur University of Medical Sciences)H-Index: 5
view all 5 authors...
1 CitationsSource
#1Parvin Mirmiran (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 44
#2Zahra Gaeini (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 1
Last.Fereidoun Azizi (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 66
view all 4 authors...
Source
#1Diana M. Amaya-Cruz (Autonomous University of Queretaro)H-Index: 3
#2Iza F. Pérez-Ramírez (Autonomous University of Queretaro)H-Index: 6
Last.Rosalía Reynoso-Camacho (Autonomous University of Queretaro)H-Index: 21
view all 5 authors...
Source
#1Lu Li (Technology College)H-Index: 3
#2Jia-Xin Xu (Technology College)H-Index: 2
Last.Xu-Cong LvH-Index: 8
view all 12 authors...
Source
#1Wenxi He (HUST: Huazhong University of Science and Technology)H-Index: 4
#2Yanjiao Xu (HUST: Huazhong University of Science and Technology)H-Index: 6
Last.Dong Liu (HUST: Huazhong University of Science and Technology)H-Index: 10
view all 7 authors...
Source
#1Yanan Zhang (SDU: Shandong University)H-Index: 2
#2Abdur Rauf Khan (SDU: Shandong University)H-Index: 5
Last.Guangxi Zhai (SDU: Shandong University)H-Index: 2
view all 7 authors...
2 CitationsSource
view all 10 authors...
Source
#1R. Chris Skinner (WVU: West Virginia University)H-Index: 1
#2Derek C. Warren (WVU: West Virginia University)H-Index: 1
Last.Janet C. Tou (WVU: West Virginia University)H-Index: 20
view all 6 authors...
1 CitationsSource
#1Miss Nontobeko Gumede (University of the Witwatersrand)
#2Busisani W. Lembede (University of the Witwatersrand)H-Index: 2
Last.Eliton Chivandi (University of the Witwatersrand)H-Index: 7
view all 6 authors...
Source
1 CitationsSource
View next paperFructose consumption as a risk factor for non-alcoholic fatty liver disease