Molecular Characterization of Microvesicular and Macrovesicular Steatosis Shows Widespread Differences in Metabolic Pathways

Lipids. 2019 Jan;54(1):109-115. doi: 10.1002/lipd.12121. Epub 2019 Feb 5.

Abstract

Simple steatosis is the hallmark of nonalcoholic fatty liver disease, with lipid accumulating as either microvesicular or macrovesicular lipid droplets within hepatocytes. The present study used a combination of laser capture microdissection and RNAseq to characterize murine gene expression in nonsteatotic, microsteatotic, and macrosteatotic compartments collected from the same liver. The data indicate that microvesicular steatosis is intermediate to macrovesicular steatosis, showing a widespread and pronounced metabolic gene regulation of lipid export, gluconeogenesis, and de novo lipogenesis. Key enzymes, such as fatty acid synthase and fructose 1,6-bisphosphatase as well as apolipoprotein C-III, were identified to show clear expression differences between the compartments. Furthermore, increased expression of lipid particle formation genes provided a molecular description of the fusion of microsteatotic lipid compartments to produce macrosteatotic cells with a single enlarged lipid droplet.

Keywords: Gene expression; Hepatic lipid metabolism; Metabolic syndrome; Molecular biology; Nonalcoholic liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gluconeogenesis / physiology
  • Hepatocytes / metabolism
  • Lipid Metabolism / physiology
  • Lipogenesis / physiology
  • Liver / metabolism
  • Male
  • Metabolic Networks and Pathways / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / metabolism*