TY - JOUR
T1 - Transcriptomic signature of fasting in human adipose tissue
AU - Defour, Merel
AU - Michielsen, Charlotte C.J.R.
AU - O’donovan, Shauna D.
AU - Afman, Lydia A.
AU - Kersten, Sander
PY - 2020/9/29
Y1 - 2020/9/29
N2 - Little is known about gene regulation by fasting in human adipose tissue. Accordingly, the objec-tive 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 libi-tum-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 Affy-metrix microarrays. We found that, 1) fasting downregulated numerous metabolic pathways in human adipose tissue, including triglyceride and fatty acid synthesis, glycolysis and glycogen syn-thesis, TCA cycle, oxidative phosphorylation, mitochondrial trans-lation, 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 transcrip-tome 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.
AB - Little is known about gene regulation by fasting in human adipose tissue. Accordingly, the objec-tive 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 libi-tum-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 Affy-metrix microarrays. We found that, 1) fasting downregulated numerous metabolic pathways in human adipose tissue, including triglyceride and fatty acid synthesis, glycolysis and glycogen syn-thesis, TCA cycle, oxidative phosphorylation, mitochondrial trans-lation, 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 transcrip-tome 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.
KW - Adipose tissue
KW - Fasting
KW - Human
KW - Lipolysis
KW - Starvation
U2 - 10.1152/physiolgenomics.00083.2020
DO - 10.1152/physiolgenomics.00083.2020
M3 - Article
C2 - 32866087
AN - SCOPUS:85092332313
SN - 1094-8341
VL - 52
SP - 451
EP - 467
JO - Physiological genomics
JF - Physiological genomics
IS - 10
ER -