Six-month Calorie Restriction in Overweight Individuals Elicits Transcriptomic Response in Subcutaneous Adipose Tissue That is Distinct From Effects of Energy Deficit.
Calorie restriction confers health benefits distinct from energy deficit by exercise. We characterized the adipose-transcriptome to investigate the molecular basis of the differential phenotypic responses. Abdominal subcutaneous fat was collected from 24 overweight participants randomized in three groups (N = 8/group): weight maintenance (control), 25% energy deficit by calorie restriction alone (CR), and 25% energy deficit by calorie restriction with structured exercise (CREX). Within each group, gene expression was compared between 6 months and baseline with cutoffs at nominal p ≤ .01 and absolute fold-change ≥ 1.5. Gene-set enrichment analysis (false discovery rate < 5%) was used to identify significantly regulated biological pathways. CR and CREX elicited similar overall clinical response to energy deficit and a comparable reduction in gene transcription specific to oxidative phosphorylation and proteasome function. CR vastly outweighed CREX in the number of differentially regulated genes (88 vs 39) and pathways (28 vs 6). CR specifically downregulated the chemokine signaling-related pathways. Among the CR-regulated genes, 27 functioned as transcription/translation regulators (eg, mRNA processing or transcription/translation initiation), whereas CREX regulated only one gene in this category. Our data suggest that CR has a broader effect on the transcriptome compared with CREX which may mediate its specific impact on delaying primary aging.
Pennington Biomedical Research Center, Baton Rouge, Louisiana. Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia. yan.lam@sydney.edu.au.
Yan Y
YY
Lam
Pennington Biomedical Research Center, Baton Rouge, Louisiana. Centre for Computational Biology & Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, Singapore.
Sujoy
S
Ghosh
Pennington Biomedical Research Center, Baton Rouge, Louisiana. Novo Nordisk Research Center, Seattle, Washington.
Anthony E
AE
Civitarese
Pennington Biomedical Research Center, Baton Rouge, Louisiana.
Eric
E
Ravussin
D015502:Absorptiometry, Photon; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001823:Body Composition / Q000235:genetics; D031204:Caloric Restriction; D004734:Energy Metabolism / Q000235:genetics*; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D050177:Overweight / Q000235:genetics*; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D050151:Subcutaneous Fat / Q000378:metabolism*; D046888:Tissue Array Analysis; D059467:Transcriptome / Q000235:genetics*
D015415:Biomarkers
Caloric Restriction; Transcriptional regulation