About us

CNS control of metabolism

Diabetes type 2 and its comorbid sequelæ represent public health burdens of the first order, yet efficacious and personalized prevention and treatment strategies remain elusive for a large proportion of patients. Our research focuses on the role of the central nervous system (CNS) as potential common denominator for obesity and diabetes type 2. The CNS, especially homeostatic networks within the hypothalamus, have long been known to play a major role in appetite, energy expenditure, and body weight control. Today, we know that CNS circuitry that regulates energy homeostasis is often identical to circuitry that governs glucose control. Impairment of such CNS circuitry by a lipid-and calorie-rich environment drives the development of obesity and diabetes type 2. However, how exactly gene-environment interactions determine the propensity to develop obesity and diabetes type 2 remains poorly understood. Hypothalamic inflammation that leads to the so-called “leptin resistance” may be a key denominator for metabolic dysfunction, but exact molecular underpinnings remain elusive. Similar inflammatory signatures in metabolic disease and neurodegenerative diseases such as Parkinson or Alzheimer nevertheless suggest common if not identical principles in disease etiology. Understanding these common central principles is a scientific challenge of the highest priority that will help enabling the development of new and tailored strategies for a personalized prevention and therapy of common diseases.

Research at the interface between a fixed genome and dynamic environment:

We aim to address three major questions that limit our understanding of CNS-driven metabolic dysfunction:

  1. What are the hypothalamic, potentially epigenetic mechanisms that govern our adaptive physiological response to changes in the environment?
  2. What are the molecular origins of hypothalamic inflammation, and how do they impair systemic energy and glucose metabolism?
  3. What are the exact molecular underpinnings for leptin resistance and weight cycling?