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

Maria Baandrup Kristiansen; Sanne Skovgård Veidal; Christina Christoffersen; Jacob Jelsing; Kristoffer T G Rigbolt

doi:10.1002/lipd.12121

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

Maria Baandrup Kristiansen, Sanne Skovgård Veidal, Christina Christoffersen, Jacob Jelsing, Kristoffer T G Rigbolt^*

^*Corresponding author for this work

Department of Biomedical Sciences

3 Citations (Scopus)

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.

Original language	English
Journal	Lipids
Volume	54
Issue number	1
Pages (from-to)	109-115
ISSN	0024-4201
DOIs	https://doi.org/10.1002/lipd.12121
Publication status	Published - Jan 2019

Keywords

Gene expression
Hepatic lipid metabolism
Metabolic syndrome
Molecular biology
Nonalcoholic liver disease

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10.1002/lipd.12121

Cite this

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title = "Molecular Characterization of Microvesicular and Macrovesicular Steatosis Shows Widespread Differences in Metabolic Pathways",

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",

author = "Kristiansen, {Maria Baandrup} and Veidal, {Sanne Skovg{\aa}rd} and Christina Christoffersen and Jacob Jelsing and Rigbolt, {Kristoffer T G}",

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

AU - Kristiansen, Maria Baandrup

AU - Veidal, Sanne Skovgård

AU - Christoffersen, Christina

AU - Jelsing, Jacob

AU - Rigbolt, Kristoffer T G

PY - 2019/1

Y1 - 2019/1

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

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