Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Remodelling of whole-body lipid metabolism and a diabetic-like phenotype caused by loss of CDK1 and hepatocyte division

Ow, Jin Rong ; Cadez, Matias J ; Zafer, Gözde ; Foo, Juat Chin ; Li, Hong Yu ; Ghosh, Soumita ; Wollmann, Heike ; Cazenave-Gassiot, Amaury ; Ong, Chee Bing and Wenk, Markus R , et al. (2020) In eLife 9.
Abstract

Cell cycle progression and lipid metabolism are well-coordinated processes required for proper cell proliferation. In liver diseases that arise from dysregulated lipid metabolism, proliferation is diminished. To study the outcome of CDK1 loss and blocked hepatocyte proliferation on lipid metabolism and the consequent impact on whole-body physiology, we performed lipidomics, metabolomics, and RNA-seq analyses on a mouse model. We observed reduced triacylglycerides in liver of young mice, caused by oxidative stress that activated FOXO1 to promote expression of ATGL. Additionally, we discovered that hepatocytes displayed malfunctioning b-oxidation, reflected by increased acylcarnitines and reduced b-hydroxybutyrate. This led to elevated... (More)

Cell cycle progression and lipid metabolism are well-coordinated processes required for proper cell proliferation. In liver diseases that arise from dysregulated lipid metabolism, proliferation is diminished. To study the outcome of CDK1 loss and blocked hepatocyte proliferation on lipid metabolism and the consequent impact on whole-body physiology, we performed lipidomics, metabolomics, and RNA-seq analyses on a mouse model. We observed reduced triacylglycerides in liver of young mice, caused by oxidative stress that activated FOXO1 to promote expression of ATGL. Additionally, we discovered that hepatocytes displayed malfunctioning b-oxidation, reflected by increased acylcarnitines and reduced b-hydroxybutyrate. This led to elevated plasma free fatty acids, which were transported to the adipose tissue for storage and triggered greater insulin secretion. Upon aging, chronic hyperinsulinemia resulted in insulin resistance and hepatic steatosis through activation of LXR. Here we demonstrate that loss of hepatocyte proliferation is not only an outcome but possibly causative for liver pathology.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
eLife
volume
9
article number
e63835
publisher
eLife Sciences Publications
external identifiers
  • scopus:85099171720
  • pmid:33345777
ISSN
2050-084X
DOI
10.7554/eLife.63835
language
English
LU publication?
yes
additional info
© 2020, Ow et al.
id
023a7d33-db5c-4d03-98a9-41c34058e722
date added to LUP
2020-12-28 10:41:12
date last changed
2024-05-16 00:14:15
@article{023a7d33-db5c-4d03-98a9-41c34058e722,
  abstract     = {{<p>Cell cycle progression and lipid metabolism are well-coordinated processes required for proper cell proliferation. In liver diseases that arise from dysregulated lipid metabolism, proliferation is diminished. To study the outcome of CDK1 loss and blocked hepatocyte proliferation on lipid metabolism and the consequent impact on whole-body physiology, we performed lipidomics, metabolomics, and RNA-seq analyses on a mouse model. We observed reduced triacylglycerides in liver of young mice, caused by oxidative stress that activated FOXO1 to promote expression of ATGL. Additionally, we discovered that hepatocytes displayed malfunctioning b-oxidation, reflected by increased acylcarnitines and reduced b-hydroxybutyrate. This led to elevated plasma free fatty acids, which were transported to the adipose tissue for storage and triggered greater insulin secretion. Upon aging, chronic hyperinsulinemia resulted in insulin resistance and hepatic steatosis through activation of LXR. Here we demonstrate that loss of hepatocyte proliferation is not only an outcome but possibly causative for liver pathology.</p>}},
  author       = {{Ow, Jin Rong and Cadez, Matias J and Zafer, Gözde and Foo, Juat Chin and Li, Hong Yu and Ghosh, Soumita and Wollmann, Heike and Cazenave-Gassiot, Amaury and Ong, Chee Bing and Wenk, Markus R and Han, Weiping and Choi, Hyungwon and Kaldis, Philipp}},
  issn         = {{2050-084X}},
  language     = {{eng}},
  month        = {{12}},
  publisher    = {{eLife Sciences Publications}},
  series       = {{eLife}},
  title        = {{Remodelling of whole-body lipid metabolism and a diabetic-like phenotype caused by loss of CDK1 and hepatocyte division}},
  url          = {{http://dx.doi.org/10.7554/eLife.63835}},
  doi          = {{10.7554/eLife.63835}},
  volume       = {{9}},
  year         = {{2020}},
}