Remodeling of human diurnal adipose tissue transcriptome by the composition of morning and afternoon meals

Circadian clocks orchestrate metabolic processes in the whole body and their response to food. Therefore, not only what and how much, but also when we eat has a significant impact on metabolism. In this context, daytime of carbohydrate and fat intake was recently shown to alter the metabolic state and potentially affect the disease risk. However, molecular mechanisms of this regulation in humans are poorly understood. In this crossover trial, we investigated the effects of two isocaloric 4-week dietary patterns – high carbohydrate in the morning and high fat in the afternoon (HC/HF) and the reverse (HF/HC) - on the subcutaneous adipose tissue (SAT) in overweight non-diabetic men. The SAT transcriptome was assessed using microarrays. Additionally, gene expression in peripheral blood monocytes (PBMCs) was analysed by qPCRs. Analysis of SAT samples collected across the day identified 1386 genes exhibiting diurnal oscillations. In SAT, both oscillatory and non-oscillatory genes related to lipid and glucose metabolism were modulated by the timing of macronutrient intake. Notably, expression of inflammatory response genes in SAT was elevated after HC/HF compared to HF/HC, suggesting that the HC/HF diet might promote an early proinflammatory state in SAT due to higher fat intake in the afternoon. Diet-induced remodelling of the SAT transcriptome was partly reflected in PBMCs. These findings demonstrate that diurnal macronutrient distribution significantly reshapes the SAT transcriptome, underscoring the relevance of eating timing-based (chrononutritional) strategies for prevention of metabolic dysfunction and systemic inflammation associated with obesity and type 2 diabetes. • Temporal macronutrient distribution reshapes the diurnal transcriptome of human SAT. • Carbs and fat timing reprograms rhythms of energy metabolism genes in SAT. • Parallel changes in peripheral blood monocyte genes by macronutrient distribution. • Concentrating fat in the afternoon elevated inflammatory gene expression in SAT.