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Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity
Author(s) -
Löffler Mona C,
Mayer Alexander E,
Trujillo Viera Jonathan,
Loza Valdes Angel,
ElMerahbi Rabih,
Ade Carsten P,
Karwen Till,
Schmitz Werner,
Slotta Anja,
Erk Manuela,
JanakiRaman Sudha,
Matesanz Nuria,
Torres Jorge L,
Marcos Miguel,
Sabio Guadalupe,
Eilers Martin,
Schulze Almut,
Sumara Grzegorz
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899182
Subject(s) - biomedicine , classics , library science , art history , biology , history , computer science , bioinformatics
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 ( PKD 1) is a DAG effector, which integrates multiple nutritional and hormonal inputs, but its physiological role in adipocytes is unknown. Here, we show that PKD 1 promotes lipogenesis and suppresses mitochondrial fragmentation, biogenesis, respiration, and energy dissipation in an AMP ‐activated protein kinase ( AMPK )‐dependent manner. Moreover, mice lacking PKD 1 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 PKD 1 promotes expression of the β3‐adrenergic receptor ( ADRB 3) in a CCAAT /enhancer binding 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 PKD 1 in adipocytes improves insulin sensitivity and ameliorates liver steatosis. Thus, depletion of PKD 1 in adipocytes increases energy dissipation by several complementary mechanisms and might represent an attractive strategy to treat obesity and its related complications.