Dynamic transcriptome and methylome changes in adipose tissue and skeletal muscle after bariatric surgery

Introduction: Bariatric surgery is the most effective treatment for obesity, resulting in weight loss and an improvement of insulin sensitivity. Skeletal muscle (SM) and adipose tissue (AT) both play an important role in the regulation of whole-body insulin sensitivity. However, their epigenetic and transcriptional alterations following bariatric surgery have not yet been examined in a time-dependent manner.

Methods: Clinical phenotypes were collected from eight obese participants for RNA sequencing and six for DNA methylation profiling from the BARIA cohort study. Skeletal muscle and adipose tissue biopsies were taken before (w0), 12 (w12) and 52 weeks (w52) after bariatric surgery to investigate transcriptional and epigenetic changes.

Results: Weight loss and improvement of peripheral insulin sensitivity were accompanied by distinct molecular changes in skeletal muscle and adipose tissue. At 12 weeks, 509 genes were differentially expressed in AT and 1038 in SM, increasing to 1110 and 2013, respectively, at 52 weeks. Transcriptomic changes in metabolic pathways (e.g., MAPK and insulin signaling) appeared at 12 weeks in SM and at 52 weeks in AT (e.g., AMPK and insulin signaling). Furthermore, the surgery also induced changes in mRNA levels of transcription factors in both tissues. A higher number of differentially expressed transcription factors were detected at 52 weeks, of which several candidates are known to play a role in insulin signaling (e.g. PPARG) in AT and mitochondrial biogenesis (e.g. GABPA, RFX7) in SM. The overlap of transcriptome and methylome data revealed that approximately 80% of differentially expressed genes are potentially regulated by epigenetic modifications. Alterations in DNA methylation profiles were found in 413 differentially expressed genes in AT and 844 in SM at w12, as well as in 951 and 1582 in w52, respectively. DNA methylation changes in genes involved in metabolic pathways like vascular smooth muscle contraction and insulin signaling occurred in SM at 12 weeks and AMPK signaling in AT at 52 weeks.

Conclusion Remarkable changes in epigenetic and transcriptional programs were found in both tissues, SM and AT with stronger effects at week 52. Even though both tissues are involved the whole-body insulin sensitivity, their epigenetic and transcriptional alterations after surgery occur in a time-dependent manner. In response to surgically induced weight loss, SM showed faster molecular changes than AT.

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Artikel online veröffentlicht:
28. Mai 2025