@unpublished{LoefflerMayerTrujilloVieraetal.2018,
  author    = {L{\"o}ffler, Mona C. and Mayer, Alexander E. and Trujillo Viera, Jonathan and Loza Valdes, Angel and El-Merahib, Rabih and Ade, Carsten P. and Karwen, Till and Schmitz, Werner and Slotta, Anja and Erk, Manuela and Janaki-Raman, Sudha and Matesanz, Nuria and Torres, Jorge L. and Marcos, Miguel and Sabio, Guadalupe and Eilers, Martin and Schulze, Almut and Sumara, Grzegorz},
  title     = {Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity},
  series = {The EMBO Journal},
  journal   = {The EMBO Journal},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176093},
  year      = {2018},
  abstract  = {Nutrient overload in combination with decreased energy dissipation promotes obesity and diabetes. Obesity results in a hormonal imbalance, which among others, activates G-protein coupled receptors utilizing diacylglycerol (DAG) as secondary messenger. Protein kinase D1 (PKD1) is a DAG effector which integrates multiple nutritional and hormonal inputs, but its physiological role in adipocytes is unknown. Here, we show that PKD1 promotes lipogenesis and suppresses mitochondrial fragmentation, biogenesis, respiration, and energy dissipation in an AMP-activated protein kinase (AMPK)-dependent manner. Moreover, mice lacking PKD1 in adipocytes are resistant to diet-induced obesity due to elevated energy expenditure. Beiging of adipocytes promotes energy expenditure and counteracts obesity. Consistently, deletion of PKD1 promotes expression of the β3-adrenergic receptor (ADRB3) in a CCAAT/enhancerbinding protein (C/EBP)-α and δ-dependent manner, which leads to the elevated expression of beige markers in adipocytes and subcutaneous adipose tissue. Finally, deletion of PKD1 in adipocytes improves insulin sensitivity and ameliorates liver steatosis. Thus, loss of PKD1 in adipocytes increases energy dissipation by several complementary mechanisms and might represent an attractive strategy to treat obesity and its related complications.},
  language  = {en}
}
@article{Trujillo‐VieraEl‐MerahbiSchmidtetal.2021,
  author    = {Trujillo-Viera, Jonathan and El-Merahbi, Rabih and Schmidt, Vanessa and Karwen, Till and Loza-Valdes, Angel and Strohmeyer, Akim and Reuter, Saskia and Noh, Minhee and Wit, Magdalena and Hawro, Izabela and Mocek, Sabine and Fey, Christina and Mayer, Alexander E. and L{\"o}ffler, Mona C. and Wilhelmi, Ilka and Metzger, Marco and Ishikawa, Eri and Yamasaki, Sho and Rau, Monika and Geier, Andreas and Hankir, Mohammed and Seyfried, Florian and Klingenspor, Martin and Sumara, Grzegorz},
  title     = {Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity},
  series = {EMBO Molecular Medicine},
  volume    = {13},
  journal   = {EMBO Molecular Medicine},
  number    = {5},
  doi       = {10.15252/emmm.202013548},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239018},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@phdthesis{Karwen2024,
  author    = {Karwen, Till},
  title     = {Platelets promote insulin secretion of pancreatic β-cells},
  doi       = {10.25972/OPUS-31393},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313933},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The pancreas is the key organ for the maintenance of euglycemia. This is regulated in particular by α-cell-derived glucagon and β-cell-derived insulin, which are released in response to nutrient deficiency and elevated glucose levels, respectively. Although glucose is the main regulator of insulin secretion, it is significantly enhanced by various potentiators. Platelets are anucleate cell fragments in the bloodstream that are essential for hemostasis to prevent and stop bleeding events. Besides their classical role, platelets were implemented to be crucial for other physiological and pathophysiological processes, such as cancer progression, immune defense, and angiogenesis. Platelets from diabetic patients often present increased reactivity and basal activation. Interestingly, platelets store and release several substances that have been reported to potentiate insulin secretion by β-cells. For these reasons, the impact of platelets on β-cell functioning was investigated in this thesis. Here it was shown that both glucose and a β-cell-derived substance/s promote platelet activation and binding to collagen. Additionally, platelet adhesion specifically to the microvasculature of pancreatic islets was revealed, supporting the hypothesis of their influence on glucose homeostasis. Genetic or pharmacological ablation of platelet functioning and platelet depletion consistently resulted in reduced insulin secretion and associated glucose intolerance. Further, the platelet-derived lipid fraction was found to enhance glucose-stimulated insulin secretion, with 20-hydroxyeicosatetraenoic acid (20-HETE) and possibly also lyso-precursor of platelet-activating factor (lysoPAF) being identified as crucial factors. However, the acute platelet-stimulated insulin secretion was found to decline with age, as did the levels of platelet-derived 20-HETE. In addition to their direct stimulatory effect on insulin secretion, specific defects in platelet activation have also been shown to affect glucose homeostasis by potentially influencing islet vascular development. Taking together, the results of this thesis suggest a direct and indirect mechanism of platelets in the regulation of insulin secretion that ensures glucose homeostasis, especially in young individuals.},
  subject      = {Thrombozyt},
  language  = {en}
}