Abstract
There are few long-term mechanistic studies in adipose tissue that investigate the metabolic effects of bariatric surgery. Changes in lipogenesis may be involved in long-term weight development. To investigate the long-term effect of bariatric surgery on lipogenesis in abdominal fat cells and whether surgical treatment could induce an epigenetic memory that would maintain improved lipogenesis in spite of body weight relapse. Karolinska University Hospital in Stockholm County, Sweden. A total of 22 women with obesity living in the Stockholm area were examined before, 2, 5, and 10 years after bariatric surgery. Abdominal adipose tissue biopsies were obtained. Fat cells were isolated and spontaneous and insulin stimulated glucose incorporation into lipids were assayed. CpG-methylation profiling was performed on adipocytes using the Infinium EPIC BeadChips. Bariatric surgery was associated with improvement in adipocyte spontaneous and insulin stimulated lipogenesis, which was maintained despite some later weight regain (29 % of initial weight loss). There was also an increase in fat cell size between 2- and 10-year follow-up, albeit not to presurgery levels. There were 7729 differentially methylated CpG sites (DMS) at 2 years that showed no sign of return to baseline at either 5 or 10 years. Merging results with expression profiles identified 1259 genes with DMS which showed early response or continual change in expression in one direction after surgery. Upregulated genes with DMS were enriched in gene sets linked to cellular response to insulin stimulus (e.g., IRS1, IRS2, PDE3B, and AKT2) and regulation of lipid metabolic processes. Bariatric surgery leads to long-term improvement of lipogenesis and insulin responsiveness in subcutaneous adipocytes in women in spite of some partial body weight regain postoperatively. This may to some extent be explained by epigenetic modifications of fat cell function.
Highlights
Impaired function of subcutaneous adipose tissue (SAT) is a key factor behind metabolic disturbances in obesity as reviewed[1]
This may to some extent be explained by epigenetic modifications of fat cell function
We recently demonstrated that the DNA methylation pattern in subcutaneous fat cells is linked to the expression of genes implicated in lipid metabolism in women with obesity[10]
Summary
Impaired function of subcutaneous adipose tissue (SAT) is a key factor behind metabolic disturbances in obesity as reviewed[1]. Despite bariatric surgery having become a prioritized treatment of severe obesity, the mechanisms behind the long-term beneficial metabolic effects of bariatric surgery are not entirely understood, which may be due to that most studies are performed during the early postoperative phase[4]. In the SoS study, irrespective of type of bariatric surgery, the dramatic weight loss during the first two post-operative years was followed by some weight relapse, albeit not to pre-operative weight. In spite of this partial weight regain most bariatric surgery patients are free from late relapse or protected from developing type 2 diabetes post-operatively[5 6]. We recently investigated SAT function in vitro before and two as well as five years after Roux-en-
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Schedule a callMore From: Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery
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