What is the clinical evidence from this study?

Study design: Observational. Intervention: Fasting vs. Fed state. Primary outcome: Adipose tissue transcriptome.

What does this research mean for the field?

Fasting for 26 hours downregulates numerous metabolic pathways in human adipose tissue, but elicits distinct transcriptomic regulatory responses and less pronounced overall effects compared to mice. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

August 31, 2020Open Access

Transcriptomic signature of fasting in human adipose tissue

Key Result

Fasting for 26 hours downregulated numerous metabolic pathways in human adipose tissue, though many genes showed distinct regulatory responses compared to mice.

Study Design

Type

Observational (n=11)

Structured PICO

Population

11 human volunteers and C57Bl/6J mice

Intervention

Fasting (26 h in humans, 16 h in mice)

Comparator

Fed state (2 h after standardized meal in humans, ad libitum-fed in mice)

Outcome

Adipose tissue gene expression (transcriptome analysis using Affymetrix microarrays)surrogate

Fasting regulates numerous genes and pathways similarly in human and mouse adipose tissue, but many genes show distinct species-specific responses, highlighting differences in metabolic regulation.

Abstract

Little is known about gene regulation by fasting in human adipose tissue. Accordingly, the objective of this study was to investigate the effects of fasting on adipose tissue gene expression in humans. To that end, subcutaneous adipose tissue biopsies were collected from 11 volunteers 2 and 26 h after consumption of a standardized meal. For comparison, epididymal adipose tissue was collected from C57Bl/6J mice in the ab libitum-fed state and after a 16 h fast. The timing of sampling adipose tissue roughly corresponds with the near depletion of liver glycogen. Transcriptome analysis was carried out using Affymetrix microarrays. We found that, 1) fasting downregulated numerous metabolic pathways in human adipose tissue, including triglyceride and fatty acid synthesis, glycolysis and glycogen synthesis, TCA cycle, oxidative phosphorylation, mitochondrial translation, and insulin signaling; 2) fasting downregulated genes involved in proteasomal degradation in human adipose tissue; 3) fasting had much less pronounced effects on the adipose tissue transcriptome in humans than mice; 4) although major overlap in fasting-induced gene regulation was observed between human and mouse adipose tissue, many genes were differentially regulated in the two species, including genes involved in insulin signaling ( PRKAG2, PFKFB3), PPAR signaling ( PPARG, ACSL1, HMGCS2, SLC22A5, ACOT1), glycogen metabolism ( PCK1, PYGB), and lipid droplets ( PLIN1, PNPLA2, CIDEA, CIDEC). In conclusion, although numerous genes and pathways are regulated similarly by fasting in human and mouse adipose tissue, many genes show very distinct responses to fasting in humans and mice. Our data provide a useful resource to study adipose tissue function during fasting.