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DOI: 10.1055/s-0045-1807369
Nutrigenomic analysis in twins (NUGAT) study: Transcriptomic responses to switching from healthy low fat to unhealthy high fat Western diet indicates extensive transcriptional reprogramming of subcutaneous fat and heritable dietary responses
An unhealthy high saturated fat Western diet (HFD) increases the risk of cardio-metabolic disease. Apart from increases in LDL-cholesterol the mechanisms involved in healthy people are debated. We studied subcutaneous abdominal adipose tissue transcriptomic responses to the intake of 6 weeks HFD after 6 weeks of a healthy low-fat diet (LFD) in 92 twins
Methods: 92 twins (age: 31±14 years BMI: 22.8±2.7 kg/m2) consumed two 6-weeks diets with carefully monitored stable body weight to avoid interference of weight changes with nutrition: first a LFD (30%Energy (%E) fat, 15%E protein, 55%E carbohydrate) followed by an isocaloric HFD (45%E fat, 15%E protein, 40%E carbohydrate). Clinical investigation days were performed after 6 weeks of LFD, after 1 and 6 weeks of HFD. mRNA-gene expression profiles were determined with Agilent microarrays, and 20 cytokines and chemokines used R&D ELISA assays.
The HFD increased LDL- and HDL-cholesterol as expected indicating compliance. WGCNA (weighted gene coexpression network analysis) identified expression modules responding to the dietary change. The most significant module (p<7e-17), comprised genes which were enriched in Gene Ontology (GO) terms related to RNA polymerase II and DNA-templated transcription, chromatin remodeling and organization and DNA-damage response as well as cytoskeleton organization and signal transduction. Variance in the transcriptional responses was smaller within monozygotic twin pairs than between twin pairs indicating heritable individual responses to nutrition. Inflammatory changes were moderately pronounced after 1 week but returned mostly to baseline after 6 weeks indicating compensatory adaptation.
Conclusion: Nutrigenomic gene expression analysis shows extensive transcriptional reprogramming of adipose tissue including many chromatin remodeling factors by the dietary composition which show conservation within monozygotic twin pairs indicating genetically determined nutrigenomic responses.
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Publication History
Article published online:
28 May 2025
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