Fas activates lipolysis in a Ca2+-CaMKII-dependent manner in 3T3-L1 adipocytes.

Fas (CD95) is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a crucial role in the induction of apoptosis. However, like TNF, Fas can induce nonapoptotic signaling pathways. We previously demonstrated that mice lacking Fas specifically in adipocytes are partly protected from diet-induced insulin resistance, potentially via decreased delivery of FAs to the liver, as manifested by lower total liver ceramide content. In the present study, we aimed to delineate the signaling pathway involved in Fas-mediated adipocyte lipid mobilization. Treatment of differentiated 3T3-L1 adipocytes with membrane-bound Fas ligand (FasL) significantly increased lipolysis after 12 h without inducing apoptosis. In parallel, Fas activation increased phosphorylation of ERK1/2, and FasL-induced lipolysis was blunted in the presence of the ERK-inhibitor U0126 or in ERK1/2-depleted adipocytes. Furthermore, Fas activation increased phosphorylation of the Ca(2+)/calmodulin-dependent protein kinases II (CaMKII), and blocking of the CaMKII-pathway (either by the Ca(2+) chelator BAPTA or by the CaMKII inhibitor KN62) blunted FasL-induced ERK1/2 phosphorylation and glycerol release. In conclusion, we propose a novel role for CaMKII in promoting lipolysis in adipocytes.

The AdHOC (age, head injury, oxygenation, circulation) score: a simple assessment tool for early assessment of severely injured patients with major fractures.

PURPOSE: We sought to develop a simple, effective and accurate assessment tool using well-known prognostic parameters to predict mortality and morbidity in severely injured patients with major fractures at the stage of the trauma bay. METHODS: European Data from the TraumaRegister DGU® were queried for patients aged 16 or older and with an ISS of 9 and higher with major fractures. The development (2012-2015) and validation (2016) groups were separated. The four prognostic aspects Age, Head injury, Oxygenation and Circulation along with parameters were identified as having a relevant impact on the outcome of severely injured patients with major fractures. The performance of the score was analyzed with the area under the receiver operating characteristics curve and compared to other trauma scores. RESULTS: An increasing AdHOC (Age, Head injury, Oxygenation, Circulation) score value in the 17,827 included patients correlated with increasing mortality (0 points = 0.3%, 1 point = 5.3%, 2 points = 15.6%, 3 points = 42.5% and 4 points = 62.6%). With an AUROC of 0.858 for the development (n = 14,047) and 0.877 for the validation (n = 3780) group dataset, the score is superior in performance compared to the Injury Severity Score (0.806/0.815). CONCLUSION: The AdHOC score appears to be easy and accessible in every emergency room without the requirement of special diagnostic tools or knowledge of the exact injury pattern and can be useful for the planning of further surgical treatment.