Pluto Bioinformatics

GSE95640: Transcriptome profiling from adipose tissue during low-caloric diet reveals predictors of long-term weight and glycemic outcomes in obese, non-diabetic subjects

Bulk RNA sequencing

Background: Low-caloric diet (LCD) reduces fat mass excess, improves insulin sensitivity, and alters adipose tissue (AT) gene expression. Yet the relationship with long-term clinical outcomes remains unclear.; ; Objective: We evaluated transcriptome alterations in AT during LCD and association with weight and glycemic outcomes both at LCD termination and 6-month after the LCD.; ; Results: Upon LCD, we identified 1173 genes differentially expressed; with 350 and 33 genes associated respectively with changes in BMI and Matsuda. Twenty-nine genes were associated with both endpoints. Pathway analyses highlighted enrichment in lipid and glucose metabolism. Models were constructed to predict weight maintainers. A model based on clinical baseline parameters could not achieve any prediction (validations AUC= 0.50 [0.36, 0.64]), while a model based on clinical changes during LCD yielded to good performance (AUC=0.73 [0.60, 0.87]). Incorporating baseline expression from the 18 genes outperformed the best clinical model (AUC=0.87 [0.77, 0.96], Delongs p=0.012). Similar analyses were made to predict subjects with good glycemic improvements. Both baseline- and LCD-based clinical models yielded to similar performance (with best AUC=0.73 [0.60, 0.85]). Addition of expression changes during LCD improved substantially the performance (AUC=0.80 [0.69, 0.92], p=0.058). ; ; Conclusions: This study investigated AT transcriptome alterations following LCD in a large cohort of obese, non-diabetic patients. The identified genes enabled to significantly improve clinical models and predict long-term clinical outcomes. These biomarkers may help clinicians understanding the large inter-subject variability and better predict the success of dietary interventions. ; SOURCE: Gregory Lefebvre (gregory.lefebvre@rd.nestle.com) - Nestlé Institute of Health Science