title: Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis.
abstract: The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1) lipid inflow in the liver, (2) lipid outflow from the liver, (3) very-low-density lipoprotein (VLDL) synthesis in the liver, (4) triglyceride (TG) metabolites in the liver, and (5) lipid changes and oxidative DNA damage. Most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, VLDL synthesis and lipid outflow from the liver were impaired, and surplus TGs might have been produced as a result of lipid oxidation and oxidative DNA damage in the NASH group.
  
  
  CONCLUSIONS
  A growing body of literature suggests that a deterioration in fatty acid oxidation and VLDL secretion from the liver, caused by the impediment of VLDL synthesis, might induce serious lipid oxidation and DNA oxidative damage, impacting the degree of liver injury and thereby contributing to the progression of NASH. Therefore, dysfunctional VLDL synthesis and release may be a key factor in progression to NASH.
authors: Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Koji
authors: K
authors: Fujita
authors: Yuichi
authors: Y
authors: Nozaki
authors: Koichiro
authors: K
authors: Wada
authors: Masato
authors: M
authors: Yoneda
authors: Yoko
authors: Y
authors: Fujimoto
authors: Mihoyo
authors: M
authors: Fujitake
authors: Hiroki
authors: H
authors: Endo
authors: Hirokazu
authors: H
authors: Takahashi
authors: Masahiko
authors: M
authors: Inamori
authors: Noritoshi
authors: N
authors: Kobayashi
authors: Hiroyuki
authors: H
authors: Kirikoshi
authors: Kensuke
authors: K
authors: Kubota
authors: Satoru
authors: S
authors: Saito
authors: Atsushi
authors: A
authors: Nakajima
mesh_terms: D000328:Adult; D002352:Carrier Proteins; D004249:DNA Damage / Q000502:physiology; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D006801:Humans; D008079:Lipoproteins, VLDL / Q000096:biosynthesis* / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000096:biosynthesis; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000096:biosynthesis; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008079:Lipoproteins, VLDL; D047493:PPAR alpha; D000070778:Perilipin-1; D010750:Phosphoproteins; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride