Alexander Jais

Group Leader "Diet-Induced Metabolic Alterations", HI-MAG

alexander.jais@helmholtz-munich.de

Leipzig

Dr. Alexander Jais group investigates how nutrient-derived signals act on brain circuits. He leads the Research Group on Diet-Induced Metabolic Alterations. He trained in Biomedicine at the University of Veterinary Medicine Vienna and completed his PhD in 2014 at the Medical University of Vienna under Harald Esterbauer, where his work focused on metabolic inflammation in adipose tissue during obesity. For his postdoctoral research with Jens Brüning at the Max Planck Institute for Metabolism Research in Cologne, he shifted his focus from adipose tissue to the brain, investigating how the blood-brain barrier adapts to dietary overload and identifying neuronal populations that drive diet-induced overeating. His group builds on this dual foundation, examining how hypothalamic circuits communicate with peripheral tissues to regulate energy balance and metabolic disease.

Our research investigates how the brain interprets nutritional and hormonal cues to regulate appetite, energy expenditure and glucose metabolism. Working at the intersection of neurobiology and metabolism, we aim to understand how defined neural circuits drive metabolic health and disease.

One central thread is the hypothalamic circuitry that governs feeding behavior. We focus on neuropeptide systems that shape the response to energy-rich, palatable foods. Beyond feeding, we investigate hypothalamic neurocircuits that control adipose tissue biology. The same brain regions that register nutritional state also send descending signals that influence lipid storage, lipolysis, thermogenesis and tissue inflammation. Here, we aim to understand how the brain governs not only what we eat but also how the body stores and spends the energy it takes in.

Obesity and diabetes are among the defining health challenges of our time. By understanding how the brain controls what we eat and how the body handles that energy, we hope to uncover new starting points for treatments that work with the body's own biology rather than against it.

Since 2021

Principal Investigator of the Research Group "Diet-Induced Metabolic Alterations" at the Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of Helmholtz Munich at Leipzig University and the University of Leipzig Medical Center.

2015 - 2021

Postdoctoral Fellow in the laboratory of Prof. Jens Brüning at the Max Planck Institute for Metabolism Research in Cologne, Germany, studying the neuronal control of metabolism.

2009 - 2014

Doctoral Researcher in the laboratory of Dr. Harald Esterbauer at the Department of Laboratory Medicine, Medical University of Vienna, studying the molecular mechanisms of metabolic inflammation.

EFSD / Novo Nordisk Foundation Future Leaders Program 2022
Award of Excellence, Austrian Federal Ministry of Science, Research and Economy 2014
Sanofi-Aventis Prize Sanofi-Aventis, Austria 2014

Stephanie C. Puente-Ruiz, Leona Ide, Julia Schuller, Adel Ben-Kraiem, Anne Hoffmann, Adhideb Ghosh, Falko Noé, Christian Wolfrum, Kerstin Krause, Martin Gericke, Nora Klöting, Jens C. Brüning, F. Thomas Wunderlich, Matthias Blüher, Alexander Jais

B cell-derived nociceptin/orphanin FQ contributes to impaired glucose tolerance and insulin resistance in obesity Immune-derived opioid peptides have been implicated in immune regulation and inflammatory processes. Here, we investigate the effects of nociceptin/orphanin FQ (N/OFQ) on metabolic function and inflammation in obesity. Selectively targeting N/OFQ, encoded by the Pnoc gene, in B cells mitigates the adverse metabolic effects of diet-induced obesity and enhances insulin sensitivity and glucose tolerance. Notably, B cell-specific Pnoc knockout mice display a marked reduction in markers of immune cell migration and diminished macrophage recruitment in adipose tissue and liver. Mechanistically, we identify that N/OFQ promotes macrophage recruitment and metabolic inflammation, exacerbating glucose intolerance and insulin resistance during obesity. Overall, the immunomodulatory properties exhibited by the N/OFQ-NOP system render it a promising therapeutic target for mitigating metabolic inflammation.

Yiyi Zhu, Oliver Mehlkop, Heiko Backes, Anna Lena Cremer, Marta Porniece, Paul Klemm, Lukas Steuernagel, Weiyi Chen, Ronja Johnen, F. Thomas Wunderlich, Alexander Jais*, Jens C. Brüning*

Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling Short-term transition to high-fat diet (HFD) feeding causes rapid changes in the molecular architecture of the blood-brain barrier (BBB), BBB permeability, and brain glucose uptake. However, the precise mechanisms responsible for these changes remain elusive. Here, we detect a rapid downregulation of Notch signaling after short-term HFD feeding. Conversely, Notch activation restores HFD-fed mouse serum-induced reduction of Glut1 expression and glycolysis in cultured brain microvascular endothelial cells (BMECs). Selective, inducible expression of the Notch intracellular domain (IC) in BMECs prevents HFD-induced reduction of Glut1 expression and hypothalamic glucose uptake. Caveolin (Cav)-1 expression in BMECs is increased upon short-term HFD feeding. However, NotchICBMECs mice display reduced caveola formation and BBB permeability. This ultimately translates into reduced hypothalamic insulin transport, action, and systemic insulin sensitivity. Collectively, we highlight a critical role of Notch signaling in the pleiotropic effects of short-term dietary transitions on BBB functionality.