The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 1469 of 1547
Back to Result List

Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity

Please always quote using this URN: urn:nbn:de:bvb:20-opus-176093
  • 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 anNutrient 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.show moreshow less
Metadaten
Author: Mona C. LöfflerORCiD, Alexander E. Mayer, Jonathan Trujillo Viera, Angel Loza Valdes, Rabih El-Merahib, Carsten P. Ade, Till Karwen, Werner Schmitz, Anja Slotta, Manuela Erk, Sudha Janaki-Raman, Nuria Matesanz, Jorge L. Torres, Miguel Marcos, Guadalupe Sabio, Martin EilersORCiD, Almut Schulze, Grzegorz SumaraORCiD
URN:urn:nbn:de:bvb:20-opus-176093
Document Type:Preprint
Faculties:Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):The EMBO Journal
Year of Completion:2018
Source:The EMBO Journal (2018) 37, e99182. DOI 10.15252/embj.201899182
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 572 Biochemie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:AMP-activated protein kinase (AMPK); Beige adipocytes; C/EBP; Protein kinase D1 (PKD1); β3 adrenergic receptor (ADRB3)
Release Date:2019/02/21
Embargo Date:2019/05/15
EU-Project number / Contract (GA) number:260464
EU-Project number / Contract (GA) number:678119
OpenAIRE:OpenAIRE
Licence (German):License LogoDeutsches Urheberrecht