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A08 - Role of mitochondrial dynamics and substrate utilisation in anorexigenic POMC-neurons

Jens Brüning
Max Planck Institute for Metabolism Research

Phone: +49 221 / 4726 202       
E-mail: BrueningSpamProtectionsf.mpg.de
For more information and contact please visit the BRÜNING LAB

Tamas Horvath
Yale University, Department of Comparative Medicine
New Haven, CT 06510, U.S.A.

Phone: +1 203/ 785 2525
E-mail: Tamas.HorvathSpamProtectionyale.edu
For more information and contact please visit the HORVATH LAB.


POMC-expressing neurons in the hypothalamus represent critical determinants of systemic energy and glucose homeostasis. They rapidly adapt their action potential firing in response to altered fuel storage of the organism through the integration of numerous hormonal and nutritional fuel sensing signals, many of which converge on the regulation of mitochondrial function and dynamics in these neurons. The overarching aim of the current proposal is to define, how mitochondrial fuel utilisation interacts with mitochondrial dynamics during the control of POMC-neuron activity as required for tight control of systemic energy and glucose homeostasis.

Latest publications
Raichur, S., Brunner, B., Bielohuby, M., Hansen, G., Pfenninger, A., Wang, B., Brüning, J.C., Larsen, P.J., and Tennagels, N. (2019). The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach. Mol. Metab. 21, 36-50.

Turpin-Nolan, S.M., Hammerschmidt, P., Chen, W., Jais, A., Timper, K., Awazawa, M., Brodesser, S., and Brüning, J.C. (2019). CerS1-Derived C18:0 Ceramide in Skeletal Muscle Promotes Obesity-Induced Insulin Resistance. (2019) Cell Rep. 26, 1-10.

Timper, K., Paeger, L., Sánchez-Lasheras, C., Varela, L., Jais, A., Nolte, H., Vogt, M.C., Hausen, A.C., Heilinger, C., Evers, N., Pospisilik, J.A., Penninger, J.M., Taylor, E.B., Horvath, T.L., Kloppenburg, P., Brüning, J.C.. (2018). Mild impairment of mitochondrial OXPHOS promotes fatty acid utilization in POMC neurons and improves glucose homeostasis in obesity. Cell Rep. 25, 383-397.

Brandt, C., Nolte, H., Henschke, S., Engström, Ruud, L., Awazawa, M., Morgan, D.A., Gabel, P., Sprenger, H.G., Hess, M.E., Günther, S., Langer, T., Rahmouni, K., Fenselau, H., Krüger, M., and Brüning, J.C. (2018). Food Perception Primes Hepatic ER-Homeostasis via Melanocortin-Dependent Control of mTOR-Activation. (2018) Cell Nov 15;175(5):1321-1335.

Steculorum S.M., Paeger, L., Bremser, S., Evers, N., Hinze, Y., Idzko, M., Kloppenburg, P., and Brüning, J.C. (2015). Hypothalamic UDP increases in obesity and promotes feeding via P2Y6-dependent activation of AgRP-neurons. Cell 162, 1404-1417.

Dietrich, M.O., Zimmer, M.R., Bober, J., and Horvath, T.L. (2015). Hypothalamic Agrp neurons drive stereotypic behaviors beyond feeding. Cell 160, 1222-1232.