Efficacy of Dietary Lipid Control in Healing High-Fat and High-Cholesterol Diet-Induced Fibrotic Steatohepatitis in Rats

PLoS One. 2016 Jan 4;11(1):e0145939. doi: 10.1371/journal.pone.0145939. eCollection 2016.

Abstract

Nonalcoholic steatohepatitis is related to lifestyle, particularly to dietary habits. We developed diet-induced fibrotic steatohepatitis model stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats showing steatosis, hepatic inflammation, and severe fibrosis induced by high-fat and -cholesterol (HFC) diet feeding. We aimed to clarify the efficacy of dietary intervention on the disease before and after the appearance of fibrosis. Male SHRSP5/Dmcr rats were divided into 9 groups; of these, 6 groups were fed control or HFC diet for several weeks and the remaining 3 groups represented the dietary intervention groups, which were fed the control diet after HFC diet feeding for 2 (before the appearance of fibrosis) or 8 (after the appearance of fibrosis) weeks. Dietary intervention before the appearance of fibrosis significantly improved the steatosis and reset the increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum total cholesterol (TC) levels. However, dietary intervention after the appearance of fibrosis was unable to reset the levels of hepatic TC, serum ALT, and fibrogenesis-related markers and had only a minor influence on hepatic fibrosis, although it reset the increased expression of transforming growth factor (TGF)-β1 and α-smooth muscle actin (SMA). It was noted that dietary intervention improved the increased AST levels; however, aggregated CD68-positive cells were still observed around the fibrosis area, which may be related to the findings of inflammatory cytokine mRNAs. Taken together, dietary intervention for fibrotic steatohepatitis improved steatosis, although it could not completely improve fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / biosynthesis
  • Animals
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Body Weight
  • Cholesterol, Dietary / adverse effects*
  • Cytokines / genetics
  • Dietary Fats / administration & dosage*
  • Dietary Fats / adverse effects
  • Inflammation Mediators / blood
  • Lipids / blood
  • Male
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Non-alcoholic Fatty Liver Disease / therapy*
  • Organ Size
  • RNA, Messenger / genetics
  • Rats

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD68 protein, rat
  • Cholesterol, Dietary
  • Cytokines
  • Dietary Fats
  • Inflammation Mediators
  • Lipids
  • RNA, Messenger
  • Aspartate Aminotransferases
  • Alanine Transaminase

Grants and funding

This study was supported by a Grant-in-Aid for Scientific Research (B. 15H04788) and a Grant-in-Aid for Young Scientists (B. 25870865) from the Japan Society for the Promotion of Science (https://www.jsps.go.jp/).