Tissue-targeted circadian interventions for identifying genetic and molecular mechanisms regulating metabolic integrity in healthy and type 2 diabetic humans

Dr Jonathan Cedernaes
Akademiska sjukhuset Uppsala
200 000 SEK - 2019

Behavior and physiology such as circulating glucose levels, exhibit 24-h “circadian” rhythms that are driven by molecular tissue clocks, and light, food and sleep modulate these rhythms. Shift work and poor sleep disrupt blood glucose rhythms and increase the risk of obesity, insulin resistance and type 2 diabetes, but how circadian rhythms control metabolism at the tissue level - and their modulation by lifestyle factors such as diet - remain poorly understood in humans. We therefore had healthy participants eat both a “healthy” and an “unhealthy” diet for a week, followed by highly controlled repeated sampling of skeletal muscle, adipose tissue and blood.

This repeated sampling around the clock now enables us - for the first time - to establish true circadian rhythms in these metabolic tissues at the same time, in e.g. metabolites and proteins. This will determine circadian mechanisms by which an unhealthy diet can increase the risk of obesity and type 2 diabetes, through studies in key metabolic tissues that control overall and glucose metabolism.