Faculté de médecine Faculté de médecine

Oxidative Stress in Obesity and Diabetes

Our research focuses on understanding the double roles of NADPH oxidases-derived oxygen radicals in the balance between healthy metabolic signalling and the onset of deleterious oxidative stress. Diverse NADPH oxidase isoforms have been discovered in critical metabolic organs: adipose tissues, liver, skeletal muscle and pancreatic islet cells. Our research interest is to uncover the physiological roles of these NADPH oxidases and to understand their implications in the development of obesity and diabetes.

Oxygen radicals are critical regulators of metabolic health in persons suffering from obesity and diabetes. Molecules, in particular, NADPH oxidases that produce oxygen radicals could provide novel therapeutic targets for improved treatment outcomes.

RESEARCH AIMS

NOX enzyme-mediated ROS production as a link between macrophage differentiation, adipose tissue inflammation and the regulation of lipid homeostasis
The main research topics of Dr. Szanto's lab are the molecular mechanisms governing the onset of metabolic diseases that are linked to the production of reactive oxygen species (ROS) and inflammation. Specifically, they focus on these processes in the regulation of fat accumulation between adipose tissue and ectopic sites of fat depot, e.g. the liver. The controlled production of ROS is increasingly acknowledged as a crucial mediator of healthy cellular metabolism. Inflammatory cell function is linked to the development of excess white adipose tissue storage and insulin resistance, while anti-inflammatory cells and cytokines exert a beneficial effect on glucose- and lipid homeostasis through the promotion of brown fat development. Their recent data indicate that a particular NOX enzyme isoform, NOX4, is a crucial mediator of anti-inflammatory (Th2-type) macrophage differentiation and thus, plays a critical role in the regulation of metabolic homeostasis. They generated mouse models lacking both NOX4 and STAT6, the major transcription factor of Th2-type macrophage differentiation, to have readily available models to evaluate the role of NOX4-derived ROS in the protection against metabolic diseases. They employ an unbiased proteomic approach to uncover novel targets of NOX4-derived ROS production with a specific emphasis on its effect on the interaction between STAT6 and the adipose-tissue differentiation factor PPARg. A coordinated interaction between these two redox-sensitive transcription factors is crucial for Th2 macrophage differentiation and, therefore, for the regulation of fat deposition and the maintenance of metabolic health. Isoform-specific modulation of NOX enzyme activity is among the emerging pharmacological targets for diverse pathological conditions; thus, their studies contribute to uncover a novel aspect of this therapeutic approach.  

CORE EXPERTISE

  • Rodent metabolic studies
  • Clinical study planning and data evaluation
  • Proteomics and metabolomics

SELECTED PUBLICATIONS

8 Jul 2025

Research