797-P: Composition of Morning and Afternoon Meals Affects Metabolism and Inflammation in Human Adipose Tissue

Abstract

Meal timing is an important factor for metabolic regulation. We recently showed that a diet where fat is mainly eaten in the morning and carbohydrates mainly in the evening worsens glycaemic control in subjects with prediabetes. Here, we investigated the effects of the day time of carbohydrate and fat intake on the subcutaneous adipose tissue (SAT) transcriptome in humans. In a cross-over study 34 non-obese men without diabetes (age 47.4 ± 2.4 years, BMI 27.4 ± 0.7 kg/m2) consumed two 4-week isocaloric diets - (1) HC/HF diet consisted of a high-carb breakfast and lunch (65 EN% carbohydrates, 20 EN% fat, 15 EN% protein) and a high-fat snack and dinner (35 EN% carbohydrates, 50 EN% fat, 15 EN% protein) or (2) inverse sequence of meals (HF/HC). After both dietary interventions, SAT samples were collected at 8.40, 12.20 and 19.00 hr. Gene expression was analyzed by microarrays and validated by PCR. Sinus model was fitted to expression levels of each transcript to predict the 24h rhythm. Out of 1345 SAT transcripts with a significant cosine rhythm, 37.8% transcripts were rhythmic on both diets, whereas 27.3% and 34.9% transcripts were rhythmic only on the HC/HF and HF/HC diet, respectively. Diets neither affected the oscillations of clock genes in SAT nor the salivary cortisol rhythm used as a central clock marker. However, dietary effects on a large set of oscillating and non-oscillating genes involved in glucose (e.g., IRS1, IRS2, PCK1, PDK4) and lipid metabolism (e.g., ACACA, ACAT1, ACOX2, PPARA) were found. Consumption of a HC/HF diet increased the expression of numerous inflammatory genes (e.g., CCL5, IL1B, ITGAX, CD3E) in SAT. Mechanisms underlying this remodeling included the change of activity of the insulin signaling, I-kappa B kinase/NF-kappa B and MAPK pathways. Collectively, our study revealed that the composition of the morning and afternoon meals strongly affect adipose tissue transcriptome in humans including the alteration of glucose and lipid metabolism and inflammatory pathways. Disclosure K. Kessler: None. K. Jürchott: None. N.N. Rudovich: None. A.F. Pfeiffer: Advisory Panel; Self; Abbott, Berlin-Chemie AG, Novo Nordisk A/S. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG, Sanofi-Aventis Deutschland GmbH. O. Ramich: None. Funding German Science Foundation (KFO218 PF164/16-1 to O.R., A.F.P.); German Diabetic Association (to O.R.); German Center for Diabetes Research (82DZD0019G to O.R.)