Effects of traffic noise exposure on susceptibility of mice for development of obesity and metabolic disease – from animal exposure models to mechanistic understanding and back to dietary interventions

• Applicants: Professor Dr. Andreas Daiber; Professor Dr. Tilman Grune
• Subject Area: Nutritional Sciences
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 537811220

The WHO estimated that noise accounts for 1.6 million lost healthy life years annually in Western Europe. In particular night-time noise exposure can shorten/disrupt sleep and thereby increase stress hormone levels and blood pressure, which in sum leads to a higher cardiovascular risk. Epidemiological studies have also shown that noise increases the risk of obesity and diabetes. The connection between noise exposure and adipose/diabetic metabolic disease was so far not investigated in sufficient detail. The project combines cardiovascular and redox-biochemical with nutrition-physiological expertise to study the pathomechanisms starting by neuronal stress responses, activation of (secondary) endocrinal systems of vasoconstriction, and progressing with inflammation and oxidative stress, all of which will lead to cardiovascular damage and dysregulation of metabolic pathways. We will apply our well-established mouse models of noise exposure and metabolic disease. Initially, we will investigate healthy mice regarding early phenotypic changes (especially pre-adipose/diabetic biomarkers such as insulin, leptin, adipokines). The nutrition-physiological project part will assess metabolic changes in exposed healthy versus obese/diabetic mice using the high fat diet, ob/ob and NZO model (Grune group). This project part will measure pre-adipose/diabetic biomarkers, adverse glycosylation reactions (AGE/RAGE), tissue changes, but also functional parameters such as macrophage differentiation as well as beta-cell and cardiomyocyte function. The cardiovascular project part will determine increases of stress hormones (e.g. adrenaline, cortisol and AT-II/diacylglycerol), oxidative stress and inflammatory markers in in tissues, blood pressure, endothelial and mitochondrial dysfunction and cardiac damage in the same noise-exposed mice (Daiber group). The role of monoamine oxidase (MAO) and of phagocytic NADPH oxidase (NOX-2) as central sources of noise-induced oxidative stress will be determined in isolated cells upon incubation with catecholamines (MAO substrates) and likewise AT-II/DAG (NOX-2 activators). The protective role of the transcription factor NRF2 will be tested by pharmacological stimulation of isolated cells from exposed versus non-exposed mice and validated using Nrf2-deficient mice. We anticipate an additive aggravation of metabolic and cardiovascular key parameters in Nrf2 knockout mice exposed to noise. In a last, from a nutrition-physiological point of view highly relevant approach we hope to prevent noise-induced damage in healthy versus obese/diabetic mice by treatment with an NRF2 activator, sulforaphane, which is also present in human diet. The expected results will help to improve diagnosis, treatment and prevention of adverse health effects caused by traffic noise thereby increasing the interest of policy makers and the general population in noise as an environmental risk factor.

• DFG Programme: Research Grants