RNA-seq analysis of subcutaneous white adipose tissue from wild-type mice subjected to six months of calorie restriction reveals altered NCOA2 splicing.

Caloric restriction (CR) is a well-established intervention that extends lifespan and delays the onset of age-related diseases in various species. While previous studies have demonstrated CR-induced transcriptional changes in white adipose tissue (WAT), the impact of CR on alternative splicing remains underexplored. In this study, we performed RNA sequencing (RNA-seq) to investigate gene expression and alternative splicing in subcutaneous white adipose tissue (sWAT) of wild-type mice subjected to CR for six months, from 3 to 9 months of age. RNA-seq analysis identified 6,058 differentially expressed genes (DEGs) (p < 0.05; absolute log2-fold change >1.0) between ad libitum (AL) and CR conditions, with key upregulated genes related to lipid metabolism, including Elovl6, Fasn, Acc, and Srebp1c. Additionally, we detected 400 significant alternative splicing events (FDR < 0.05), with exon skipping being the most prevalent. Among these, we focused on the metabolism-related transcription factor Ncoa2, which exhibited CR-induced exon 13 inclusion, shifting the balance toward the full-length isoform. Functional analyses suggest that this shift enhances Ncoa2 coactivator activity for nuclear receptors involved in lipid metabolism. This dataset provides raw and processed RNA-seq data, including gene expression and alternative splicing analyses, which can be utilized to further explore the molecular mechanisms underlying CR-induced metabolic adaptations in adipose tissue.