The timing of carbohydrate and fat intake modulates the metabolic status, yet the underlying mechanisms in humans remain 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) transcriptome in non-diabetic men. Analysis of SAT samples collected across the day identified 1386 genes exhibiting diurnal oscillations. Both oscillatory and non-oscillatory genes related to lipid and glucose metabolism were modulated by the timing of macronutrient intake, in SAT as well as in peripheral blood monocytes. Notably, expression of inflammatory response genes in SAT was elevated after HC/HF compared to HF/HC. These findings demonstrate that diurnal macronutrient distribution significantly reshapes the SAT transcriptome, underscoring the relevance of chrononutrition as a potential strategy to prevent metabolic dysfunction and systemic inflammation associated with obesity and type 2 diabetes.

The authors have declared no competing interest.

NCT02487576

The study was supported by the German Research Foundation (DFG KFO218 PF164/16-1, project number 101434729 to AK, AFHP and DFG RA 3340/4-1, project number 530918029 to OPR), by the German Diabetes Association (Allgemeine Projektförderung, 2015, to OPR), by the German Center for Diabetes Research (DZD 82DZD0019G to OPR), and by an internal grant of the German Institute of Human Nutrition (2015, KK).

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The study protocol and informed consent form were approved by the Ethics Commission of Charité University Medicine.

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