Time-restricted eating improves glycemic control and dampens energy-consuming pathways in human adipose tissue

•Under highly controlled conditions, time-restricting eating reduces fasting glucose and glycated hemoglobin and tended to improve 24-h glucose in men with obesity but impaired glucose response to a dinner meal.•Time-restricted eating alters the adipose tissue transcriptome, down-regulating genes involved in mitoribosome regulation and proteasome functioning, which may be an adaptive response to lowered energy availability and reduced mitochondrial oxidative stress.•Time-restricted eating could be a preventative or therapeutic strategy to assist glycemic management for people with prediabetes or type 2 diabetes. We sought to examine the effects of 8 wk of time-restricted eating (TRE) on glucose metabolism and the adipose tissue transcriptome during a metabolic ward stay in men with obesity. In a single-arm, pre-post trial, 15 men (ages 63 ± 4 y, body mass index = 30.5 ± 2.4 kg/m2, waist circumference = 113 ± 4 cm) with obesity but no history of diabetes were enrolled and underwent 2 wk of baseline monitoring before they were instructed to eat their regular diets within a contiguous 10-h time frame each day for 8 wk. Metabolic testing was performed at baseline and week 8 during a 35-h metabolic ward stay, during which all food intake was strictly timed and controlled. Identical meal-tolerance tests were performed at breakfast and dinner. Blood glucose, glucoregulatory hormones, and subjective appetite score were measured. Subcutaneous adipose tissue biopsies were performed and the transcriptome was assessed. The primary outcome, plasma glucose area under the curve, was altered by TRE, being unchanged at breakfast but increased at dinner. However, TRE reduced fasting glucose, glycated hemoglobin, body weight, and body fat, and increased glucose-dependent insulinotropic peptide area under the curve at dinner. In subcutaneous adipose tissue, 117 genes were up-regulated and 202 genes down-regulated by TRE. Pathway analysis revealed down-regulation of genes involved in proteasome function and mitochondrial regulation. TRE had a net effect of reducing glycemia and dampening energy-consuming pathways in adipose tissue.