Bi-directional regulation of liver/brain interaction via hepatic mitochondrial fission (A08)

• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 269925409

Liver mitochondria play a central role in metabolic adaptations to changing nutritional states. During the last funding period, we showed that sensory food perception rapidly induces mitochondrial fission in the liver via protein kinase B/AKT-dependent phosphorylation of the mitochondrial fission factor (MFFS131), a response mediated via activation of hypothalamic Pro-opiomelanocortin (POMC)-expressing neurons. We aim now to elucidate the molecular basis of how MFF-dependent mitochondrial fragmentation dynamically regulates gluconeogenesis in liver through detailed metabolomic flux analyses in cultured hepatocytes and mice in vivo. Further, we find that MFF deletion in liver impairs the locomotor stimulatory effect of POMC neuron stimulation. The proposed studies aim to define liver-derived signalling mediators as well as their neuronal targets.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1218: Mitochondrial regulation of cellular function
• Applicant Institution: Universität zu Köln
• Co-Applicant Institution: Max-Planck-Institut für Stoffwechselforschung
• Project Heads: Professor Dr. Jens Claus Brüning; Professor Dr. Tamas Horvath, until 6/2020