Serum Bile Acids Are Higher in Humans With Prior Gastric Bypass: Potential Contribution to Improved Glucose and Lipid Metabolism

Abstract

The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 ± 4.84 µmol/l) than in both overweight (3.59 ± 1.95, P = 0.005, Ov) and severely obese (3.86 ± 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids were all significantly higher in GB compared to Ov (P < 0.05). Total bile acids were inversely correlated with 2-h post-meal glucose (r = −0.59, P < 0.003) and fasting triglycerides (r = −0.40, P = 0.05), and positively correlated with adiponectin (r = −0.48, P < 0.02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P < 0.003). Total bile acids strongly correlated inversely with thyrotropic hormone (TSH) (r = −0.57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB.

Surgical control of obesity and diabetes: The role of intestinal vs. gastric mechanisms in the regulation of body weight and glucose homeostasis

“…Bile acids have also been recognized as important modulators of whole-body metabolism, increasing energy expenditure and preventing obesity, insulin resistance, and hyperglycemia, during high-fat feeding in rodents (17,18). In humans, circulating bile acids levels correlate with measures of insulin sensitivity and it has been suggested that changes in bile acids metabolism could also contribute to improved metabolism post-RYGB (17,18).…”

“…Other plausible mechanisms for the improvement of glucose homeostasis after procedures that like DJB involve a bypass of the small intestine include: (1) alteration in gut microbiota (19,20); (2) bile acid perturbations (17,18); (3) changes in neuroendocrine signaling (21); and (4) alterations in putative gut factors regulated by the duodenum, that may be involved in the diabetic alterations of glucose homeostasis (''anti-incretin'' theory) (9,24). A recent study by Lam et al (7) demonstrates that duodenal-jejunal bypass surgery activates nutrient-sensing signals in the jejunum and rapidly lowers endogenous hepatic glucose production in nonobese rats with uncontrolled diabetes, suggesting a possible contribution of intestinal nutrient sensing to the glucose-lowering effects of bypass procedures.…”

“…In addition, the physiology of the digestive system and its role in glucose and energy homeostasis are complex and yet incompletely understood. Over the last decades the study of GI physiology has advanced at cellular and molecular levels revealing roles for several GI factors in the regulation of energy and glucose homeostasis including gut hormones (14)(15)(16) bile acids (17,18), miocrobiota (19,20), neural signals (21), and intestinal nutrient sensing (7). Paradoxically, however, the understanding of how anatomical segments of the GI tract contribute to metabolic regulation remains rudimentary.…”

Obesity diabetes and the role of bile acids in metabolism

“…The increase in bile acids strongly correlates with the improvement in glucose and lipid metabolism [28,29] . Interestingly, catheter-mediated bile diversion to the mid distal jejunum in rats induces weight loss, decreases adiposity, improves glucose tolerance, and increases circulating bile acids [30] .…”

Surgery in the treatment of type 2 diabetes mellitus

“…The studies with BA sequestrant colesevelam, a high-capacity BA-binding polymer, in humans with T2DM show significant reduction in LDL cholesterol, fpG, and HbA1c (69,70). patti et al (71) have found an increase in fasting total serum BA and individual BA concentrations of taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids levels 2-4 years after gastric bypass, as compared to nonoperated individuals matched for preoperative or current BMI. It was suggested that this increase in serum BA levels might contribute to observed improvement in insulin sensitivity, incretin secretion, and postprandial glycemia after gastric bypass.…”