Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
J Clin Endocrinol Metab. 2013 Apr;98(4):E708-12. doi: 10.1210/jc.2012-3736. Epub 2013 Mar 1.
It has been hypothesized that increased plasma bile acids (BAs) contribute to metabolic improvements after Roux-en-Y gastric bypass (RYGB) surgery by the G protein-coupled receptor TGR5-mediated effects on glucagon-like peptide-1 secretion and thyroid hormones.
The objective of this study was to evaluate the importance of bariatric surgery-induced alterations in BA physiology on factors that regulate glucose homeostasis (insulin secretion and sensitivity) and energy metabolism (resting energy expenditure and thyroid hormone axis). DESIGN, PARTICIPANTS, INTERVENTION, AND MAIN OUTCOME MEASURE: Eighteen extremely obese subjects were studied before and after 20% weight loss, induced by either laparoscopic adjustable gastric banding (LAGB) (n = 10) or RYGB surgery (n = 8).
Plasma BAs more than doubled after RYGB [fasting: 1.08 (0.26-1.42) to 2.28 (1.59-3.28) μmol/L, P = .03; postprandial: 2.46 ± 1.59 to 6.00 ± 2.75 μmol/L, P = .01] but were either lower or did not change after LAGB [fasting: 1.80 (1.49-2.19) to 0.92 (0.73-1.15) μmol/L, P = .02; postprandial: 3.71 ± 2.61 to 2.82 ± 1.75 μmol/L, P = .14]. Skeletal muscle expression of TGR5 targets, Kir6.2 and cyclooxygenase IV, increased after RYGB but not LAGB. Surgery-induced changes in BAs were associated with increased peak postprandial plasma glucagon-like peptide-1 (r(2) = 0.509, P = .001) and decreased serum TSH (r(2) = 0.562, P < .001) but did not correlate with the change in insulin response to a meal (r(2) = 0.013, P = .658), insulin sensitivity (assessed as insulin stimulated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure) (r(2) = 0.001, P = .995), or resting energy expenditure (r(2) = 0.004, P = .807).
Compared with LAGB, RYGB increases circulating BAs and TGR5 signaling, but this increase in BAs is not a significant predictor of changes in glucose homeostasis or energy metabolism.
据推测，增加血浆胆汁酸（BAs）通过 G 蛋白偶联受体 TGR5 介导的胰高血糖素样肽-1分泌和甲状腺激素的作用，有助于 Roux-en-Y 胃旁路（RYGB）手术后的代谢改善。
本研究旨在评估减重手术引起的 BA 生理学改变对调节葡萄糖稳态（胰岛素分泌和敏感性）和能量代谢（静息能量消耗和甲状腺激素轴）的因素的重要性。
设计、参与者、干预措施和主要观察结果：在腹腔镜可调胃带（LAGB）（n = 10）或 RYGB 手术后（n = 8），18 名极度肥胖的受试者在 20%体重减轻前后接受了研究。
RYGB 后血浆 BAs 增加了两倍以上[空腹：1.08（0.26-1.42）至 2.28（1.59-3.28）μmol/L，P =.03；餐后：2.46 ± 1.59 至 6.00 ± 2.75 μmol/L，P =.01]，但 LAGB 后要么更低或没有变化[空腹：1.80（1.49-2.19）至 0.92（0.73-1.15）μmol/L，P =.02；餐后：3.71 ± 2.61 至 2.82 ± 1.75 μmol/L，P =.14]。RYGB 后 TGR5 靶标 Kir6.2 和环氧化酶 IV 的骨骼肌表达增加，但 LAGB 后没有增加。BA 的手术诱导变化与餐后血浆胰高血糖素样肽-1峰值增加（r（2）= 0.509，P =.001）和血清 TSH 降低（r（2）= 0.562，P <.001）相关，但与餐后胰岛素反应无关（r（2）= 0.013，P =.658），胰岛素敏感性（评估为高胰岛素-正常血糖钳夹过程中胰岛素刺激的葡萄糖处置）（r（2）= 0.001，P =.995）或静息能量消耗（r（2）= 0.004，P =.807）。
与 LAGB 相比，RYGB 增加了循环 BAs 和 TGR5 信号，但这种 BAs 的增加并不是葡萄糖稳态或能量代谢变化的重要预测因素。
