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Elevation of Bile Acids After Bariatric Surgery May Attenuate Early Atherosclerosis
Raymond G. Lau*1, Louis Ragolia2, Randy Seeley3, Sunil Kumar2, Collin E. Brathwaite1, Drew Rideout4, Keneth Hall1, Christopher Hall2, Thomas Palaia2
1Department of Bariatric Surgery, Winthrop University Hospital, East Northport, NY; 2Department of Biomedical Research, Winthrop University Hospital, Mineola, NY; 3Department of Surgery, University Of Michigan at Ann Arbor, Ann Arbor, MI; 4Bay Pines Veteran Affairs Medical Center, Bay Pines, FL
Objective: Bariatric surgery is associated with a significant reduction in adverse cardiovascular events [1, 2]. We sought to evaluate the role of bile acid metabolism and its associated transport proteins on cardiovascular disease in response to bariatric surgery. We hypothesize that bile acids have a role in attenuating the improved atherosclerosis observed after bariatric surgery.
Methods: Roux-en-Y gastric bypass (RYGB) surgery was performed on Zucker diabetic fatty (ZDF) rodents (n=6) and compared with sham controls (n=4). Since, increased aortic wall thickness is associated with intravascular stress and early atherosclerosis, we measured aortic wall thickness as well as the levels of bile acids and a bile acid transport protein (lipocalin-type prostaglandin D2 synthase; L-PGDS) in obese ZDF rats that underwent RYGB and sham controls. In addition, sleeve gastrectomy (SG) was performed in a bile acid receptor knockout (KO) mouse model (Farnesyl-X-receptor, FXR) and aortic wall thickness was measured and compared to controls.
Results: RYGB surgery in ZDF rodents resulted in a significant 25% reduction in aortic wall thickness when compared to sham controls, 298.4 ± 78 versus 224.1 ± 26 (pixels2) respectively. In addition, bile acid levels were 3-fold higher after RYGB surgery (25.4 ± 6.7 versus 75.3 ± 24.8 µmol/l) when compared to sham animal controls. L-PGDS levels also increased nearly 2-fold following RYGB surgery (13.0 ± 2.4 versus 24.9 ± 3.2 ng/ml). Moreover, in wild type mice SG demonstrated an approximate 50% reduction in aortic wall thickness as compared to sham controls (219,923 versus 469,327 pixels2). Interestingly, SG in FXR KO mice demonstrated a lesser reduction in aortic wall thickness as compared to controls, although it was not statistically significant.
Study Limitations: The study was limited by sample size and the use of rodent animal models.
Conclusion: Bariatric surgery results in elevated bile acid levels and a substantial reduction of aortic wall thickness. Bile acid metabolism may be at least partially responsible for the cardiovascular improvement observed after bariatric surgery.
References:
1. Sjostrom, L., et al., Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med, 2004. 351(26): p. 2683-93.
2. Sjostrom, L., et al., Bariatric surgery and long-term cardiovascular events. JAMA, 2012. 307(1): p. 56-65.
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