Alexander Jais

Head of the Junior Research Group on Diet-Induced Metabolic Alterations

alexander.jais@helmholtz-muenchen.de

Gebäude / Raum: HI-MAG Leipzig

Dr. Alexander Jais is a neuroscientist and metabolic researcher whose work explores how nutrient-derived signals interact with brain circuits to regulate energy balance, glucose metabolism, and immune-metabolic crosstalk. He is currently the head of the Junior Research Group Diet-Induced Metabolic Alterations at the Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG) in Leipzig, part of Helmholtz Munich.

Dr. Jais studied Biomedicine at the University of Veterinary Medicine in Vienna and earned his PhD in 2014 at the Medical University of Vienna under the mentorship of Harald Esterbauer. His doctoral research uncovered a key role for the enzyme heme oxygenase‑1 (HO‑1) in mediating metabolic inflammation during obesity (Cell, 2014). He continued his research as a postdoctoral fellow in the lab of Jens Brüning at the Max Planck Institute for Metabolism Research in Cologne. There, he demonstrated that high-fat diets suppress glucose transporter (GLUT1) expression at the blood–brain barrier, triggering a compensatory VEGF response from brain-associated macrophages to maintain cerebral glucose supply (Cell, 2016). This work uncovered a novel link between neurovascular regulation and metabolic disease.

In 2020, Dr. Jais identified a population of prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus that promote diet-induced overeating (Neuron, 2020). Building on this discovery, his group at HI-MAG continues to explore how specific hypothalamic circuits respond to dietary signals and shape metabolic outcomes, with a focus on the role of neuropeptides in regulating energy balance.

Our research focuses on how the brain processes nutritional and hormonal signals to regulate appetite, energy use, and glucose metabolism. We work at the intersection of neurobiology, metabolism, and immunometabolism, aiming to understand how specific neural circuits contribute to metabolic health and disease.

At HI-MAG, we use neuroscience tools to study how the brain responds to energy-rich, palatable foods. We are particularly interested in how chronic overnutrition alters these circuits over time, leading to lasting changes in behavior and metabolic function.

Since 2021

Principal Investigator of the Helmholtz Young Investigator Group "Diet-Induced Metabolic Alterations" at the Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, based at the University of Leipzig

2015 - 2021

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

2009 - 2014

Doctoral Researcher at the Medical University of Vienna under the supervision of Dr. Harald Esterbauer, Department of Laboratory Medicine, focusing on the molecular mechanisms of metabolic inflammation

Awards Alexander Jais; EFSD / Novo Nordisk Foundation Future Leaders Programm 2022; Award of Excellence Austrian Federal Ministry of Science Research and Economy 2014; Sanofi-Aventis Prize Sanovi-Aventis, Austria 2014

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

Variante: Gold Star Awards Luxury Background

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.