Time-restricted feeding has a limited effect on hepatic lipid accumulation, inflammation and fibrosis in a choline-deficient high-fat diet-induced murine NASH model

PLoS One. 2024 Jan 29;19(1):e0296950. doi: 10.1371/journal.pone.0296950. eCollection 2024.

Abstract

Nonalcoholic steatohepatitis (NASH) occurs worldwide and is characterized by lipid accumulation in hepatocytes, hepatic inflammation, fibrosis, and an increased risk of cirrhosis. Although a major proportion of NASH patients exhibit obesity and insulin resistance, 20% lack a high body mass and are categorized as "non-obese NASH". Time-restricted feeding (TRF), limiting daily food intake within certain hours, improves obesity, lipid metabolism, and liver inflammation. Here, we determined whether TRF affects NASH pathology induced by a choline-deficient high-fat diet (CDAHFD), which does not involve obesity. TRF ameliorated the increase in epididymal white adipose tissue and plasma alanine transaminase and aspartate transaminase levels after 8 weeks of a CDAHFD. Although gene expression of TNF alpha in the liver was suppressed by TRF, it did not exhibit a suppressive effect on hepatic lipid accumulation, gene expression of cytokines and macrophage markers (Mcp1, IL1b, F4/80), or fibrosis, as evaluated by Sirius red staining and western blot analysis of alpha-smooth muscle actin. A CDAHFD-induced increase in gene expression related to fibrogenesis (Collagen 1a1 and TGFβ) was neither suppressed by TRF nor that of alpha-smooth muscle actin but was increased by TRF. Our results indicated that TRF has a limited suppressive effect on CDAHFD-induced NASH pathology.

MeSH terms

  • Actins / metabolism
  • Animals
  • Choline / metabolism
  • Choline Deficiency* / metabolism
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Fibrosis
  • Humans
  • Inflammation / pathology
  • Lipids / adverse effects
  • Liver / metabolism
  • Liver Cirrhosis / pathology
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Obesity / complications

Substances

  • Choline
  • Actins
  • Lipids

Grants and funding

Japan Society for the Promotion of Science KAKENHI, Grant Number JP21K21273 and JP22K17845 (both to Tomoyuki Sato).