TY  - JOUR
A1  - Trujillo‐Viera, Jonathan
A1  - El‐Merahbi, Rabih
A1  - Schmidt, Vanessa
A1  - Karwen, Till
A1  - Loza‐Valdes, Angel
A1  - Strohmeyer, Akim
A1  - Reuter, Saskia
A1  - Noh, Minhee
A1  - Wit, Magdalena
A1  - Hawro, Izabela
A1  - Mocek, Sabine
A1  - Fey, Christina
A1  - Mayer, Alexander E.
A1  - Löffler, Mona C.
A1  - Wilhelmi, Ilka
A1  - Metzger, Marco
A1  - Ishikawa, Eri
A1  - Yamasaki, Sho
A1  - Rau, Monika
A1  - Geier, Andreas
A1  - Hankir, Mohammed
A1  - Seyfried, Florian
A1  - Klingenspor, Martin
A1  - Sumara, Grzegorz
T1  - Protein Kinase D2 drives chylomicron‐mediated lipid transport in the intestine and promotes obesity
JF  - EMBO Molecular Medicine
N2  - Lipids are the most energy‐dense components of the diet, and their overconsumption promotes obesity and diabetes. Dietary fat content has been linked to the lipid processing activity by the intestine and its overall capacity to absorb triglycerides (TG). However, the signaling cascades driving intestinal lipid absorption in response to elevated dietary fat are largely unknown. Here, we describe an unexpected role of the protein kinase D2 (PKD2) in lipid homeostasis. We demonstrate that PKD2 activity promotes chylomicron‐mediated TG transfer in enterocytes. PKD2 increases chylomicron size to enhance the TG secretion on the basolateral side of the mouse and human enterocytes, which is associated with decreased abundance of APOA4. PKD2 activation in intestine also correlates positively with circulating TG in obese human patients. Importantly, deletion, inactivation, or inhibition of PKD2 ameliorates high‐fat diet‐induced obesity and diabetes and improves gut microbiota profile in mice. Taken together, our findings suggest that PKD2 represents a key signaling node promoting dietary fat absorption and may serve as an attractive target for the treatment of obesity.
KW  - chylomicron
KW  - fat absorption
KW  - intestine
KW  - obesity
KW  - protein kinase D2/PKD2/PRKD2
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239018
VL  - 13
IS  - 5
ER  - 
TY  - JOUR
A1  - Kress, Sebastian
A1  - Baur, Johannes
A1  - Otto, Christoph
A1  - Burkard, Natalie
A1  - Braspenning, Joris
A1  - Walles, Heike
A1  - Nickel, Joachim
A1  - Metzger, Marco
T1  - Evaluation of a miniaturized biologically vascularized scaffold in vitro and in vivo
JF  - Scientific Reports
N2  - In tissue engineering, the generation and functional maintenance of dense voluminous tissues is mainly restricted due to insufficient nutrient supply. Larger three-dimensional constructs, which exceed the nutrient diffusion limit become necrotic and/or apoptotic in long-term culture if not provided with an appropriate vascularization. Here, we established protocols for the generation of a pre-vascularized biological scaffold with intact arterio-venous capillary loops from rat intestine, which is decellularized under preservation of the feeding and draining vascular tree. Vessel integrity was proven by marker expression, media/blood reflow and endothelial LDL uptake. In vitro maintenance persisted up to 7 weeks in a bioreactor system allowing a stepwise reconstruction of fully vascularized human tissues and successful in vivo implantation for up to 4 weeks, although with time-dependent decrease of cell viability. The vascularization of the construct lead to a 1.5× increase in cellular drug release compared to a conventional static culture in vitro. For the first time, we performed proof-of-concept studies demonstrating that 3D tissues can be maintained within a miniaturized vascularized scaffold in vitro and successfully implanted after re-anastomosis to the intrinsic blood circulation in vivo. We hypothesize that this technology could serve as a powerful platform technology in tissue engineering and regenerative medicine.
KW  - biological models
KW  - translational research
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176343
VL  - 8
IS  - 4719
ER  -