TY - INPR A1 - Löffler, Mona C. A1 - Mayer, Alexander E. A1 - Trujillo Viera, Jonathan A1 - Loza Valdes, Angel A1 - El-Merahib, Rabih A1 - Ade, Carsten P. A1 - Karwen, Till A1 - Schmitz, Werner A1 - Slotta, Anja A1 - Erk, Manuela A1 - Janaki-Raman, Sudha A1 - Matesanz, Nuria A1 - Torres, Jorge L. A1 - Marcos, Miguel A1 - Sabio, Guadalupe A1 - Eilers, Martin A1 - Schulze, Almut A1 - Sumara, Grzegorz T1 - Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity T2 - The EMBO Journal N2 - 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. KW - AMP-activated protein kinase (AMPK) KW - Beige adipocytes KW - β3 adrenergic receptor (ADRB3) KW - C/EBP KW - Protein kinase D1 (PKD1) Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176093 ER -