ECE2009 Oral Communications Diabetes & Obesity (5 abstracts)
Mc2 receptor in adipocytes is significant for lipid composition and regular lipolysis
Nilay Hatiboglu 1 , Matthias J Betz 1 , Dirk Hadaschick 3 , Brigitte Mauracher 1 , Monika Rachl 2 , Johann Demmelmair 2 , Berthold Koletzko 2 , Marc Slawik 2 & Felix Beuschlein 1
1Endocrine Research Unit, Medizinische Klinik-Innenstadt, Ludwig-Maximilians-University, Munich, Germany; 2von Hauner Children’s Hospital, Ludwig-Maximilians-University, Munich, Germany; 3MRL, IMS, University of Cambridge, Cambridge, UK.
The melanocortin system is significant for energy homeostasis and receptors have distinct tissue specific expression. The melanocortin 2-receptor (Mc2r) transmits ACTH dependent signalling in the adrenal cortex. Increased expression in adipocytes during differentiation indicates relevance for lipid homeostasis. Mc2r activation in adipocytes results in increased lipolysis, however, implication compared to norepinephrine (NE) stimulated lipolysis is unknown. To further define functional significance of Mc2r dependent pathways for adipocyte physiology we used an in vitro system of stably expressing shRNA in order to knock down Mc2r expression in differentiated 3T3 L1 adipocytes. Using the pSiren retro-virus system 2 of 4 tested shRNA sequences reduced Mc2r expression in differentiated adipocytes by at least 75%. Knock-down (kd) cell lines showed less lipid accumulation. In parallel, ACTH and NE stimulated lipolysis were substantially reduced (Control versus Kd as compared to respective baseline: 1 nM ACTH, 174±22 vs 108±9%, P=0.028; 10 nM ACTH, 231±29 vs 147±8%, P=0.027; NE 1 μM, 560±100 vs 155±26%, P=0.007) demonstrating functional significance of Mc2r kd on the lipolysis pathway. The expression of differentiation markers like PPARγ2, aP2 and preadipocyte marker Pref1 was not significantly different between groups, as well as the expression of Elovl5 and Elovl6, fatty acid synthase, and fatty acid desaturase 1 and 2. Interestingly, the expression of stearoyl-Coenzyme A desaturase 1 and 2 was significantly reduced in kd cells (21±8 vs 100±13%, P=0.01 and 32±3 vs 100±15%, P=0.046). Gas chromatography was used to analyse lipid composition. Preliminary results indicate changed distribution of saturated vs. unsaturated fatty acids. In summary, Mc2r might play an important role in regular lipid accumulation. Moreover, changes in lipid composition indicate that Mc2r function has an impact on saturation of fatty acids.
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Endocrine Abstracts
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