A recent study published in Diabetes & Metabolism reveals significant differences in skeletal muscle molecular responses to bariatric surgery between patients with obesity alone and those with obesity and type 2 diabetes.
Researchers examined the differential impact of bariatric surgery on skeletal muscle gene expression and epigenetics in 26 patients, evenly divided into obesity and type 2 diabetes (T2D) groups. Each patient underwent comprehensive metabolic evaluations and skeletal muscle biopsies preoperatively and at one year postoperatively.
Patients with obesity experienced an average body weight reduction of 35.7%, whereas those with T2D saw a 28.5% reduction one year following surgery. After surgery, HbA1c levels dropped by 9.3% in the obesity group and by 20.0% in the T2D group. Whole-body insulin sensitivity, as indicated by M-value, increased by 110.3% in the obesity group and by 240% in the T2D group. Fasting glucose levels decreased by 13.1% in the obesity group and by 30.5% in the T2D group.
The study found that bariatric surgery led to 2,103 differentially expressed genes in skeletal muscle of patients with obesity, yet only 959 in those with T2D. In the obesity group, 62% of these genes were upregulated and 38% downregulated, while in the T2D group, 82% were upregulated and 18% downregulated.
Significant differences in DNA methylation patterns were observed. The obesity group showed 184,835 differentially methylated CpG sites post-surgery, with a tendency towards hypomethylation. In contrast, the T2D group had 76,308 differentially methylated sites, predominantly showing hypermethylation. The study identified 374 differentially methylated regions in the obesity group and 78 in the T2D group post-surgery.
Notably, the T2D group exhibited elevated global hydroxymethylation and reduced expression of the ten-eleven translocation enzyme 2 (TET2), which is crucial for DNA demethylation. This finding may explain the differences in epigenetic plasticity between the two groups and the distinct molecular adaptations observed.
The researchers used LASSO regression to identify genes strongly associated with improvements in metabolic parameters such as BMI, HbA1c, and insulin sensitivity. In the obesity group, changes in gene expression were particularly evident in pathways related to insulin signaling, oxidative phosphorylation, and lipid metabolism. The T2D group, however, showed changes predominantly in ribosomal and splicesomal pathways.
This study was supported by the German Ministry of Education and Research, the Brandenburg State, and the European Union's Horizon Europe Research and Innovation programme, with no conflicts of interest declared by the researchers.
