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  - 
TY  - JOUR
A1  - Yanku, Yifat
A1  - Bitman-Lotan, Eliya
A1  - Zohar, Yaniv
A1  - Kurant, Estee
A1  - Zilke, Norman
A1  - Eilers, Martin
A1  - Orian, Amir
T1  - Drosophila HUWE1 ubiquitin ligase regulates endoreplication and antagonizes JNK signaling during salivary gland development
JF  - Cells
N2  - The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster and Humans. Here, we report that the Drosophila ortholog, dHUWE1 (CG8184), is an essential gene whose loss results in embryonic lethality and whose tissue-specific disruption establishes its regulatory role in larval salivary gland development. dHUWE1 is essential for endoreplication of salivary gland cells and its knockdown results in the inability of these cells to replicate DNA. Remarkably, dHUWE1 is a survival factor that prevents premature activation of JNK signaling, thus preventing the disintegration of the salivary gland, which occurs physiologically during pupal stages. This function of dHUWE1 is general, as its inhibitory effect is observed also during eye development and at the organismal level. Epistatic studies revealed that the loss of dHUWE1 is compensated by dMyc proeitn expression or the loss of dmP53. dHUWE1 is therefore a conserved survival factor that regulates organ formation during Drosophila development.
KW  - HECT
KW  - HUWE1
KW  - ubiquitin
KW  - salivary gland
KW  - endoreplication
KW  - JNK
KW  - dMyc
KW  - dmP53
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197630
SN  - 2073-4409
VL  - 7
IS  - 10
ER  -