Researchers from the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) and the German Center for Diabetes Research (DZD) have revealed new molecular adaptations occurring in skeletal muscle following bariatric surgery, particularly in individuals with and without T2DM.
"Our study suggests that epigenetic mechanisms play a crucial role in mediating these responses and predicting the health outcome," explained Dr Ouni. "Our future research will investigate the molecular mechanisms underlying changes in DNA hydroxymethylation and its potential function in skeletal muscle post-surgery.”
It is known that during the development of type 2 diabetes (T2D), epigenetic alterations (DNA methylation and hydroxymethylation) occur in skeletal muscle, a key tissue taking up glucose in response to insulin. However, it is unclear to what extent these alterations are reversible through interventions such as bariatric surgery.
Therefore, an interdisciplinary DZD team including the researchers Leona Kovac, Annette Schürmann and Meriem Ouni from the DIfE as well as Drs Sabine Kahl and Michael Roden from the German Diabetes Center (DDZ) investigated the effects of surgically induced weight loss on metabolic, transcriptional and epigenetic adaptations in skeletal muscle of obese individuals with and without T2D, by using a comprehensive bioinformatic approach.
Additionally, multidimensional links between molecular and metabolic changes induced by bariatric surgery were explored. These links aimed at identifying novel prominent candidates associated with weight loss and improved muscle function.
The examined individuals were a subset of participants from the BARIA_DDZ cohort study, which closely monitors individuals through detailed metabolic characterization both before and over five years following bariatric surgery.
The study focused on the metabolic and molecular outcomes achieved during the first year. In total, 13 male participants with obesity and 13 participants with obesity and T2D underwent an extensive anthropometric and metabolic investigation, including a muscle biopsy and detection of tissue-specific insulin sensitivity before and one year after surgery.
DZD researchers found distinct molecular responses in skeletal muscle following bariatric surgery between obese individuals and those with additional T2D. Before surgery, T2D participants living with obesity exhibited higher fasting glucose and insulin levels alongside lower insulin sensitivity compared to patients living with obesity. Following surgery, improvements in metabolic health were more pronounced in in patients with obesity, reflected by differential gene expression patterns related to insulin signalling, intracellular signal transduction, and oxidative phosphorylation.
In contrast, T2D participants with obesity showed alterations only in genes associated with ribosome and spliceosome pathways, with less pronounced changes in DNA methylation, potentially linked to altered expression of one of the T2D risk genes involved in the demethylation processes.
These findings underscore the importance of understanding molecular adaptations in skeletal muscle post-bariatric surgery, particularly in individuals with type 2 diabetes.
“Furthermore, we aim to validate specific candidates identified by the bioinformatic approach as potential therapeutic targets in muscle," added Professor Dr. Schürmann, Head of the Department of Experimental Diabetology at DIfE. In this manner, approaches for individuals with different metabolic profiles could be tailored.
The findings were published in the paper, 'Different effects of bariatric surgery on epigenetic plasticity in skeletal muscle of individuals with and without type 2 diabetes', published in Diabetes & Metabolism.
To access this paper, please click here
Comments