1601-P: Regulation of Circadian Rhythmicity of Human Adipose Tissue in Obesity

Adipose tissue (AT) is highly responsive to nutrient delivery associated with conventional feed/fast cycles over 24 hr and also has a molecular circadian clock that regulates transcriptional rhythms. The joint contribution of these dual inputs to human AT function has not been studied, nor how this interplay changes in obesity. Ten lean (BMI 20-25 kg/m²) and 7 people with upper body obesity (UBO) (BMI 30-35 kg/m²) were within group randomized to either continuous feeding (“CONT”) or intermittent feeding (“INT”) of Ensure via nasogastric tube (NG). CONT was fed at rates to meet 24 hr caloric needs and INT fed 3 evenly spaced feedings (1/3 of daily caloric needs per meal) during daylight hours and fasted overnight. Each person received 4 abdominal AT biopsies across 24 hr. We performed RNA-Seq analysis on AT samples; dryR was used to assess circadian rhythmicity of genes differential between groups and GO and ClusterProfiler for pathway analysis. Most rhythmic genes were driven by feed/fast cycles, 538 transcripts were significantly rhythmic in INT groups and lost rhythmicity in CONT groups (adj. P <0.02)(BICW > 0.1). These genes were enriched for lipid metabolism pathways including biosynthesis and oxidation. Many genes (237) were significantly rhythmic in lean and not UBO individuals regardless of feeding regime (adj. P<0.05)(BICW > 0.1), these were enriched for pathways related to immune response. 399 genes were significantly rhythmic (adj. P<0.02)(BICW > 0.13) in lean CONT and INT and UBO INT, but lost rhythmicity only in UBO CONT. These were enriched for metabolic pathways related to glucose and carbohydrate homeostasis and molecular circadian system. Overall, the fast/feed cycle over 24 hr drives a significant portion of AT gene rhythmicity. Our data suggests lean individuals maintain AT clock system integrity independent of feeding time while patients with UBO require feed-fast cycles to sustain AT clock circadian rhythmicity, suggesting feeding time might be particularly relevant for patients with obesity.