@unpublished{LoefflerMayerTrujilloVieraetal.2018,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}
}
@phdthesis{Slotta2019,
  author    = {Slotta, Anja Maria},
  title     = {The Role of Protein Kinase D 1 in the regulation of murine adipose tissue function under physiological and pathophysiological conditions},
  doi       = {10.25972/OPUS-17911},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179112},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Adipocytes are specialized cells found in vertebrates to ensure survival in terms of adaption to food deficit and abundance. However, their dysfunction accounts for the pathophysiology of metabolic diseases such as T2DM. Preliminary data generated by Mona L{\"o}ffler suggested that PKD1 is involved in adipocyte function. Here, I show that PKD1 expression and activity is linked to lipid metabolism of murine adipocytes. PKD1 gene expression and activity was reduced in murine white adipose tissue upon fasting, a physiological condition which induces lipolysis. Isoproterenol-stimulated lipolysis in adipose tissue and 3T3-L1 adipocytes reduced PKD1 gene expression. Silencing ATGL in adipocytes inhibited isoproterenol-stimulated lipolysis, however, the β-adrenergic stimulation of ATGL-silenced adipocytes lowered PKD1 expression levels as well. Adipose tissue of obese mice exhibited high PKD1 RNA levels but paradoxically lower protein levels of phosphorylated PKD1-Ser916. However, HFD generated a second PKD1 protein product of low molecular weight in mouse adipose tissue. Furthermore, constitutively active PKD1 predominantly displayed nuclear localization in 3T3-L1 adipocytes containing many fat vacuoles. However, adipocytes overexpressing non-functional PKD1 contained fewer lipid droplets and PKD1-KD was distributed in cytoplasm. Most importantly, deficiency of PKD1 in mouse adipose tissue caused expression of genes involved in adaptive thermogenesis such as UCP-1 and thus generated brown-like phenotype adipocytes. Thus, PKD1 is implicated in adipose tissue function and presents an interesting target for therapeutic approaches in the prevention of obesity and associated diseases.},
  subject      = {adipocyte},
  language  = {en}
}