Kargl J

References (2)

Title : Tumor microenvironment-derived monoacylglycerol lipase provokes tumor-specific immune responses and lipid profiles - Gruden_2023_Prostaglandins.Leukot.Essent.Fatty.Acids_196_102585
Author(s) : Gruden E , Kienzl M , Hasenoehrl C , Sarsembayeva A , Ristic D , Schmid ST , Maitz K , Taschler U , Hahnefeld L , Gurke R , Thomas D , Kargl J , Schicho R
Ref : Prostaglandins Leukot Essent Fatty Acids , 196 :102585 , 2023
Abstract : We recently described that monoacylglycerol lipase (MGL) is present in the tumor microenvironment (TME), increasing tumor growth. In this study we compare the implications of MGL deficiency in the TME in different tumor types. We show that subcutaneous injection of KP (Kras(LSL-G12D)/p53(fl/fl), mouse lung adenocarcinoma) or B16-F10 cells (mouse melanoma) induced tumor growth in MGL wild type (WT) and knockout (KO) mice. MGL deficiency in the TME attenuated the growth of KP cell tumors whereas tumors from B16-F10 cells increased in size. Opposite immune cell profiles were detected between the two tumor types in MGL KO mice. In line with their anti-tumorigenic function, the number of CD8(+) effector T cells and eosinophils increased in KP cell tumors of MGL KO vs. WT mice whereas their presence was reduced in B16-F10 cell tumors of MGL KO mice. Differences were seen in lipid profiles between the investigated tumor types. 2-arachidonoylglycerol (2-AG) content significantly increased in KP, but not B16-F10 cell tumors of MGL KO vs. WT mice while other endocannabinoid-related lipids remained unchanged. However, profiles of phospho- and lysophospholipids, sphingomyelins and fatty acids in KP cell tumors were clearly distinct to those measured in B16-F10 cell tumors. Our data indicate that TME-localized MGL impacts tumor growth, as well as levels of 2-AG and other lipids in a tumor specific manner.
ESTHER : Gruden_2023_Prostaglandins.Leukot.Essent.Fatty.Acids_196_102585
PubMedSearch : Gruden_2023_Prostaglandins.Leukot.Essent.Fatty.Acids_196_102585
PubMedID: 37573716

Title : Dysregulation of Placental Lipid Hydrolysis by High-Fat\/High-Cholesterol Feeding and Gestational Diabetes Mellitus in Mice - Kuentzel_2022_Int.J.Mol.Sci_23_
Author(s) : Kuentzel KB , Bradic I , Mihalic ZN , Korbelius M , Rainer S , Pirchheim A , Kargl J , Kratky D
Ref : Int J Mol Sci , 23 : , 2022
Abstract : Advanced maternal age and obesity are the main risk factors to develop gestational diabetes mellitus (GDM). Obesity is a consequence of the increased storage of triacylglycerol (TG). Cytosolic and lysosomal lipid hydrolases break down TG and cholesteryl esters (CE) to release fatty acids (FA), free cholesterol, and glycerol. We have recently shown that intracellular lipases are present and active in the mouse placenta and that deficiency of lysosomal acid lipase alters placental and fetal lipid homeostasis. To date, intracellular lipid hydrolysis in GDM has been poorly studied despite the important role of FA in this condition. Therefore, we hypothesized that intracellular lipases are dysregulated in pregnancies complicated by maternal high-fat/high-cholesterol (HF/HCD) feeding with and without GDM. Placentae of HF/HCD-fed mice with and without GDM were more efficient, indicating increased nutrient transfer to the fetus. The increased activity of placental CE but not TG hydrolases in placentae of dams fed HF/HCD with or without GDM resulted in upregulated cholesterol export to the fetus and placental TG accumulation. Our results indicate that HF/HCD-induced dysregulation of placental lipid hydrolysis contributes to fetal hepatic lipid accumulation and possibly to fetal overgrowth, at least in mice.
ESTHER : Kuentzel_2022_Int.J.Mol.Sci_23_
PubMedSearch : Kuentzel_2022_Int.J.Mol.Sci_23_
PubMedID: 36293139