TY  - JOUR
A1  - Henkel, Janin
A1  - Coleman Mac Gregor of Inneregny, Charles Dominic
A1  - Schraplau, Anne
A1  - Jöhrens, Korinna
A1  - Weiss, Thomas Siegfried
A1  - Jonas, Wenke
A1  - Schürmann, Annette
A1  - Püschel, Gerhard Paul
T1  - Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model
JF  - Scientific Reports
N2  - In a subset of patients, non-alcoholic fatty liver disease (NAFLD) is complicated by cell death and inflammation resulting in non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and subsequent organ failure. Apart from cytokines, prostaglandins, in particular prostaglandin E-2 (PGE(2)), play a pivotal role during inflammatory processes. Expression of the key enzymes of PGE(2) synthesis, cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), was increased in human NASH livers in comparison to controls and correlated with the NASH activity score. Both enzymes were also induced in NASH-diet-fed wild-type mice, resulting in an increase in hepatic PGE(2) concentration that was completely abrogated in mPGES-1-deficient mice. PGE(2) is known to inhibit TNF-alpha synthesis in macrophages. A strong infiltration of monocyte-derived macrophages was observed in NASH-diet-fed mice, which was accompanied with an increase in hepatic TNF-alpha expression. Due to the impaired PGE(2) production, TNF-alpha expression increased much more in livers of mPGES-1-deficient mice or in the peritoneal macrophages of these mice. The increased levels of TNF-alpha resulted in an enhanced IL-1 beta production, primarily in hepatocytes, and augmented hepatocyte apoptosis. In conclusion, attenuation of PGE(2) production by mPGES-1 ablation enhanced the TNF-alpha-triggered inflammatory response and hepatocyte apoptosis in diet-induced NASH.
KW  - suppress VLDL secretion
KW  - mice lacking
KW  - nonalcoholic steatohepatthis
KW  - insulin-resistance
KW  - rat hepatocytes
KW  - kupffer cells
KW  - E-2
KW  - disease
KW  - expression
KW  - accumulation
Y1  - 2018
U6  - https://doi.org/10.1038/s41598-018-34633-y
SN  - 2045-2322
IS  - 8
SP  - 1
EP  - 11
PB  - Nature Research
CY  - London
ER  - 
TY  - JOUR
A1  - Hartwich, Melanie
A1  - Martin-Creuzburg, Dominik
A1  - Wacker, Alexander
T1  - Seasonal changes in the accumulation of polyunsaturated fatty acids in zooplankton
JF  - Journal of plankton research
N2  - In aquatic food webs, consumers, such as daphnids and copepods, differ regarding their accumulation of polyunsaturated fatty acids (PUFAs). We tested if the accumulation of PUFAs in a seston size fraction containing different consumers and in Daphnia as a separate consumer is subject to seasonal changes in a large deep lake due to changes in the dietary PUFA supply and specific demands of different consumers. We found that the accumulation of arachidonic acid (ARA) in Daphnia increased from early summer to late summer and autumn. However, ARA requirements of Daphnia appeared to be constant throughout the year, because the accumulation of ARA increased when the dietary ARA supply decreased. In the size fraction 140 m, we found an increased accumulation of docosahexaenoic acid (DHA) during late summer and autumn. These seasonal changes in DHA accumulation were linked to changes in the proportion of copepods in this size fraction, which may have increasingly accumulated DHA for active overwintering. We show that consumer-specific PUFA demands can result in seasonal changes in PUFA accumulation, which may influence the trophic transfer of PUFAs within the food web.
KW  - accumulation
KW  - Daphnia
KW  - copepods
KW  - ARA
KW  - DHA
Y1  - 2013
U6  - https://doi.org/10.1093/plankt/fbs078
SN  - 0142-7873
VL  - 35
IS  - 1
SP  - 121
EP  - 134
PB  - Oxford Univ. Press
CY  - Oxford
ER  -