TY - JOUR

T1 - Molecular Characterization of Microvesicular and Macrovesicular Steatosis Shows Widespread Differences in Metabolic Pathways

AU - Kristiansen, Maria

AU - Veidal, Sanne Skovgård

AU - Christoffersen, Christina

AU - Jelsing, Jacob

AU - Rigbolt, Kristoffer T G

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Gene expression

KW - Hepatic lipid metabolism

KW - Metabolic syndrome

KW - Molecular biology

KW - Nonalcoholic liver disease

U2 - 10.1002/lipd.12121

DO - 10.1002/lipd.12121

M3 - Journal article

C2 - 30723896

VL - 54

SP - 109

EP - 115

JO - Lipids

JF - Lipids

SN - 0024-4201

IS - 1

ER -