Weight loss following gastric bypass surgery was associated with changes in gene methylation that may affect insulin sensitivity, researchers said.

Whereas expression of 14 genes was abnormal prior to surgery because of different levels of DNA promoter methylation, compared with normal-weight patients, methylation status at 11 of the genes was normalized in the surgical patients when analyzed after weight loss had occurred, according to Juleen R. Zierath, PhD, of the Karolinska Institute in Stockholm.

"Dynamic changes in DNA methylation may be an early event that orchestrates metabolic gene transcription involved in the regulation of insulin sensitivity in human obesity," the researchers wrote.

Zierath and colleagues added that environmental factors may drive formation of what they called "the metabolic memory" of adult cells.

Previous studies had shown that DNA methylation is altered in obese individuals at genomic regions that regulate metabolic function, including some involved in insulin sensitivity.

It has also been noted that bariatric surgery can induce rapid and durable remission of type 2 diabetes. The mechanisms, however, have remained obscure. Zierath and colleagues sought to determine whether the surgery and resultant weight loss may lead to epigenetic changes relevant to metabolic activity.

They performed a series of analyses on 14 obese patients (eight women and six men) before undergoing Roux-en-Y bypass surgery and again 6 months later, as well as on 16 normal-weight, glucose-tolerant women age-matched to the obese women.

Global analysis of DNA methylation status in skeletal muscle biopsy specimens from the female patients indicated that methylation of so-called CpG and non-CpG sites did not differ between patients and controls, either before or after bariatric surgery.

But a separate genome-wide methylation analysis carried out in the six obese male patients undergoing bypass procedures, using a different chemistry and focusing on methylation of CpG sites, did reveal major changes between baseline and post-surgery follow-up.

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