at Google ScholarTitle data
Henkel, Janin ; Frede, Katja ; Schanze, Nancy ; Vogel, Heike ; Schürmann, Annette ; Spruss, Astrid ; Bergheim, Ina ; Püschel, Gerhard P.:
Stimulation of fat accumulation in hepatocytes by PGE₂-dependent repression of hepatic lipolysis, β-oxidation and VLDL-synthesis.
In: Laboratory Investigation.
Vol. 92
(2012)
Issue 11
.
- pp. 1597-1606.
ISSN 1530-0307
DOI: https://doi.org/10.1038/labinvest.2012.128
Abstract in another language
Hepatic steatosis is recognized as hepatic presentation of the metabolic syndrome. Hyperinsulinaemia, which shifts fatty acid oxidation to de novo lipogenesis and lipid storage in the liver, appears to be a principal elicitor particularly in the early stages of disease development. The impact of PGE₂, which has previously been shown to attenuate insulin signaling and hence might reduce insulin-dependent lipid accumulation, on insulin-induced steatosis of hepatocytes was studied. The PGE₂-generating capacity was enhanced in various obese mouse models by the induction of cyclooxygenase 2 and microsomal prostaglandin E-synthases (mPGES1, mPGES2). PGE₂ attenuated the insulin-dependent induction of SREBP-1c and its target genes glucokinase and fatty acid synthase. Nevertheless, PGE₂ enhanced incorporation of glucose into hepatic triglycerides synergistically with insulin. This was most likely due to a combination of a PGE₂-dependent repression of (1) the key lipolytic enzyme adipose triglyceride lipase, (2) carnitine-palmitoyltransferase 1, a key regulator of mitochondrial β-oxidation, and (3) microsomal transfer protein, as well as (4) apolipoprotein B, key components of the VLDL synthesis. Repression of PGC1α, a common upstream regulator of these genes, was identified as a possible cause. In support of this hypothesis, overexpression of PGC1α completely blunted the PGE₂-dependent fat accumulation. PGE₂ enhanced lipid accumulation synergistically with insulin, despite attenuating insulin signaling and might thus contribute to the development of hepatic steatosis. Induction of enzymes involved in PGE₂ synthesis in in vivo models of obesity imply a potential role of prostanoids in the development of NAFLD and NASH.
Further data
| Item Type: | Article in a journal |
|---|---|
| Refereed: | Yes |
| Institutions of the University: | Faculties > Faculty of Life Sciences: Food, Nutrition and Health Faculties Faculties > Faculty of Life Sciences: Food, Nutrition and Health > Lehrstuhl Biochemie der Ernährung > Lehrstuhl Biochemie der Ernährung - Univ.-Prof. Dr. Janin Henkel-Oberländer Faculties > Faculty of Life Sciences: Food, Nutrition and Health > Lehrstuhl Biochemie der Ernährung |
| Result of work at the UBT: | No |
| DDC Subjects: | 500 Science 500 Science > 570 Life sciences, biology |
| Date Deposited: | 26 Apr 2021 11:47 |
| Last Modified: | 19 Oct 2022 12:51 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/64434 |