Effects of thyroid hormone on adipocyte-brain-crosstalk

Project Description:

Thyroid hormone is an important mediator of body temperature, as seen in hyperthyroid patients that are heat sensitive and have higher body temperature. Our recent study has revealed that the hormone has direct effects in the thermogenic brown and beige fat, but also acts in the brain to elevate the body temperature setpoint. In this project, we aim to dissect the actions of the hormone on brown fat thermogenesis to understand when the tissue specific actions are important and under which conditions the brain actions prevail for the regulation of body temperature. We will employ combinations of pharmacological experiments, genetically modified mice, alteration of gene expression in the brain using adeno-associated virus in combination with cold exposure and finally studies with human volunteers to better understand the mechanisms that govern body temperature regulation.   

 

Experimental Methods:

• Working with genetically modified mice (knock-out mice), including breeding strategies
• Pharmacological induction of hypo- and hyperthyroidism in mice
• Stereotaxic delivery of adeno-associated virus carrying transgenes to modulate thyroid hormone signaling in the brain
• Phenotyping of mice including measurement of thermogenesis by e.g. infrared thermography, energy expenditure and body weight
• Brown fat tissue explants cell culture
• Studies with human volunteers and thyroid hormone administration (orally, intranasally) and recordings of sympathetic/parasympathetic activity, temperature measurements, energy expenditure, lipid profiling
• RNA extraction, cDNA synthesis, qPCR, Western Blot, Chromatin Immunoprecipitation, luciferase assays