JNK Inhibition Mimics Roux-en-Y Gastric Bypass Surgery: Improves Endothelial Dysfunction

Roux-en-Y gastric bypass surgery (RYGB) has been found to decrease cardiovascular risk in obese patients.

In a poster presented Saturday, March 14, at the 2015 American College of Cardiology annual meeting, Elena Osto, MD, PhD, wrote, “RYGB improved endothelial vasorelaxation in diet-induced obese (DIO) rats 8 days following surgery.”

Osto noted this was independent from weight loss through decreased aortic JNK phosphorylation and increased endothelial Nitric Oxide Synthase (eNOS) activity.

Essentially, the researchers wanted to investigate whether in vivo inhibition of JNK activity keenly mirrored the vascular effects of RYGB.

The team administered either RYGB or sham surgery to DIO male Wistar rats for 8 days post-surgery. This produced cumulative concentration-relaxation curves in rings of thoracic aorta, which directly responded to Glucagon like Peptide-1 or insulin. They repeated the tests with an eNOS inhibitor and superoxide dismutase after pre-incubation.

Body weight was discovered not to have significantly differed between sham_SP and sham_AL rats, whereas RYGB rats’ weight loss was tremendous 8 days following surgery.

GLP-1- and insulin-induced vasorelaxation improved in RYGB compared to sham_AL rats. Also, the free radical scavenger SOD significantly improved the vasorelaxation only in sham_AL, supporting an important role of oxidative stress in these rats.

Findings indicated levels of aortic NADPH oxidase activity was similarly reduced upon administering RYGB and in sham_SP compared to sham_AL rats.

“Our study underlines a crucial role of JNK in obesity-induced endothelial dysfunction and oxidative stress, suggesting a novel mechanism for the endothelial protective effects of RYGB,” Osto concluded.