De Goede 2018 MiP2018
The prevalence of people with type 2 diabetes mellitus (T2DM) has increased markedly over the last decades. The current best strategy for prevention of T2DM is increasing physical exercise combined with reducing caloric intake. Both exercise and caloric intake affect mitochondrial capacity of skeletal muscle and muscle is the most important tissue for glucose uptake. Indeed, recent work suggests that targeting muscle mitochondrial functioning could prevent and treat T2DM. Furthermore, recently it has been suggested that mitochondrial functioning is under control of the biological clock. In this regard it is not unexpected that epidemiological studies found an increased risk of obesity and T2DM in night-shift workers.
To characterize the effects of night-shift work on (whole body) metabolism, rats were subjected to ad libitum (AL) feeding or time-restricted feeding (TRF) during the night- (nTRF) or daytime (dTRF) whilst body temperature was measured using temperature loggers. Additionally, in a total of 96 rats we measured mitochondrial metabolism in permeabilized skeletal muscle fibers (soleus muscle) ex vivo using high-resolution respirometry (Oroboros) at 4 different time-points along the light/dark cycle.
We show that dTRF phase-advances the daily rhythm of subcutaneous body temperature by 6 hours when compared to AL conditions (p=0.02). Interestingly, mean body temperature of dTRF animals was also lowered by 0.2°C (p=0.02). nTRF did not alter body temperature measures. Furthermore, we demonstrate that muscle mitochondrial metabolism shows both a time of day as well as a TRF effect for both maximal coupled and uncoupled mitochondrial respiration (i.e. state 3 and state 3U respiration). Highest levels in the AL and nTRF animals were found in the inactive phase, with the strongest rhythm found in nTRF animals. Finally, average daily mitochondrial respiration was lowest for dTRF animals and did not differ between nTRF and AL fed animals for either maximal coupled and uncoupled respiration.
Ongoing experiments should reveal whether these differences in mitochondrial respiration result from altered mitochondrial abundance, altered mitochondrial morphology or can be attributed to specific components of the respiratory system and whether these changes translate in functional changes (i.e. glucose tolerance).
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Diabetes
Organism: Rat Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: OXPHOS, ET
De Goede P(1), Ritsema W(1), Wuest RCI(1), Kalsbeek A(1,2)
- Academic Medical Center (AMC)
- Netherlands Inst Neurosciences (NIN), Amsterdam, The Netherlands. - [email protected]