TY  - JOUR
A1  - Werno, Martin Witold
A1  - Wilhelmi, Ilka
A1  - Kuropka, Benno
A1  - Ebert, Franziska
A1  - Freund, Christian
A1  - Schürmann, Annette
T1  - The GTPase ARFRP1 affects lipid droplet protein composition and triglyceride release from intracellular storage of intestinal Caco-2 cells
JF  - Biochemical and biophysical research communications
N2  - Intestinal release of dietary triglycerides via chylomicrons is the major contributor to elevated postprandial triglyceride levels. Dietary lipids can be transiently stored in cytosolic lipid droplets (LDs) located in intestinal enterocytes for later release. ADP ribosylation factor-related protein 1 (ARFRP1) participates in processes of LD growth in adipocytes and in lipidation of lipoproteins in liver and intestine. This study aims to explore the impact of ARFRP1 on LD organization and its interplay with chylomicron-mediated triglyceride release in intestinal-like Caco-2 cells. Suppression of Arfrp1 reduced release of intracellularly derived triglycerides (0.69-fold) and increased the abundance of transitional endoplasmic reticulum ATPase TERA/VCP, fatty acid synthase-associated factor 2 (FAF2) and perilipin 2 (Plin2) at the LD surface. Furthermore, TERA/VCP and FAF2 co-occurred more frequently with ATGL at LDs, suggesting a reduced adipocyte triglyceride lipase (ATGL)-mediated lipolysis. Accordingly, inhibition of lipolysis reduced lipid release from intracellular storage pools by the same magnitude as Arfrp1 depletion. Thus, the lack of Arfrp1 increases the abundance of lipolysis-modulating enzymes TERA/VCP, FAF2 and Plin2 at LDs, which might decrease lipolysis and reduce availability of fatty acids for triglyceride synthesis and their release via chylomicrons. (C) 2018 The Authors. Published by Elsevier Inc.
KW  - Chylomicron
KW  - Lipid droplet proteome
KW  - Triglyceride secretion
KW  - Lipolysis
Y1  - 2018
U6  - https://doi.org/10.1016/j.bbrc.2018.10.092
SN  - 0006-291X
SN  - 1090-2104
VL  - 506
IS  - 1
SP  - 259
EP  - 265
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Rödel, Claudia Jasmin
A1  - Otten, Cecile
A1  - Donat, Stefan
A1  - Lourenço, Marta Sofia Rocha
A1  - Fischer, Dorothea
A1  - Kuropka, Benno
A1  - Paolini, Alessio
A1  - Freund, Christian
A1  - Abdelilah-Seyfried, Salim
T1  - Blood Flow Suppresses Vascular Anomalies in a Zebrafish Model of Cerebral Cavernous Malformations
JF  - Circulation Research
N2  - RATIONALE: Pathological biomechanical signaling induces vascular anomalies including cerebral cavernous malformations (CCM), which are caused by a clonal loss of CCM1/KRIT1 (Krev interaction trapped protein 1), CCM2/MGC4607, or CCM3/PDCD10. Why patients typically experience lesions only in lowly perfused venous capillaries of the cerebrovasculature is completely unknown. OBJECTIVE: In contrast, animal models with a complete loss of CCM proteins lack a functional heart and blood flow and exhibit vascular anomalies within major blood vessels as well. This finding raises the possibility that hemodynamics may play a role in the context of this vascular pathology. METHODS AND RESULTS: Here, we used a genetic approach to restore cardiac function and blood flow in a zebrafish model of CCM1. We find that blood flow prevents cardiovascular anomalies including a hyperplastic expansion within a large Ccm1-deficient vascular bed, the lateral dorsal aorta. CONCLUSIONS: This study identifies blood flow as an important physiological factor that is protective in the cause of this devastating vascular pathology.
KW  - animal models
KW  - cerebral cavernous malformations
KW  - endothelial cell
KW  - hemodynamics
KW  - zebrafish
Y1  - 2019
U6  - https://doi.org/10.1161/CIRCRESAHA.119.315076
SN  - 0009-7330
SN  - 1524-4571
VL  - 125
IS  - 10
SP  - E43
EP  - E54
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  -