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  - Morales-Lozano, Maria I.
A1  - Viering, Oliver
A1  - Samnick, Samuel
A1  - Rodriguez-Otero, Paula
A1  - Buck, Andreas K.
A1  - Marcos-Jubilar, Maria
A1  - Rasche, Leo
A1  - Prieto, Elena
A1  - Kortüm, K. Martin
A1  - San-Miguel, Jesus
A1  - Garcia-Velloso, Maria J.
A1  - Lapa, Constantin
T1  - \(^{18}\)F-FDG and \(^{11}\)C-methionine PET/CT in newly diagnosed multiple myeloma patients: comparison of volume-based PET biomarkers
JF  - Cancers
N2  - \(^{11}\)C-methionine (\(^{11}\)C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of \(^{11}\)C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to \(^{18}\)F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone \(^{11}\)C-MET and \(^{18}\)F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion \(^{11}\)C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), \(^{11}\)C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in \(^{11}\)C-MET than in \(^{18}\)F-FDG (p < 0.05, respectively). \(^{11}\)C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that \(^{11}\)C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than \(^{18}\)F-FDG. Its implications for prognosis evaluation need further investigation.
KW  - multiple myeloma
KW  - methionine
KW  - total lesion glycolysis (TLG)
KW  - metabolic tumor volume (MTV)
KW  - total lesion methionine uptake (TLMU)
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203686
SN  - 2072-6694
VL  - 12
IS  - 4
ER  -