Raghow Rajendra
Rajendra Raghow, Department of Veterans Affairs Medical Center, Memphis, TN 38104, United States.
World J Diabetes. 2015 Apr 15;6(3):367-70. doi: 10.4239/wjd.v6.i3.367.
Bariatric surgeries have emerged as highly effective treatments for obesity associated type-2 diabetes mellitus. Evidently, the desired therapeutic endpoints such as rates of weight loss, lower levels of glycated hemoglobin and remission of diabetes are achieved more rapidly and last longer following bariatric surgery, as opposed to drug therapies alone. In light of these findings, it has been suspected that in addition to causing weight loss dependent glucose intolerance, bariatric surgery induces other physiological changes that contribute to the alleviation of diabetes. However, the putative post-surgical neuro-hormonal pathways that underpin the therapeutic benefits of bariatric surgery remain undefined. In a recent report, Ryan and colleagues shed new light on the potential mechanisms that determine the salutary effects of bariatric surgery in mice. The authors demonstrated that the improved glucose tolerance and weight loss in mice after vertical sleeve gastrectomy (VSG) surgery were likely to be caused by post-surgical changes in circulating bile acids and farnesoid-X receptor (FXR) signaling, both of which were also mechanistically linked to changes in the microbial ecology of the gut. The authors arrived at this conclusion from a comparison of genome-wide, metabolic consequences of VSG surgery in obese wild type (WT) and FXR knockout mice. Gene expression in the distal small intestines of WT and FXR knockout mice revealed that the pathways regulating bile acid composition, nutrient metabolism and anti-oxidant defense were differentially altered by VSG surgery in WT and FXR(-/-) mice. Based on these data Ryan et al, hypothesized that bile acid homeostasis and FXR signaling were mechanistically linked to the gut microbiota that played a role in modulating post-surgical changes in total body mass and glucose tolerance. The authors' data provide a plausible explanation for putative weight loss-independent benefits of bariatric surgery and its relationship with metabolism of bile acids.
减肥手术已成为治疗肥胖相关2型糖尿病的高效疗法。显然，与单纯药物治疗相比，减肥手术后能更快实现体重减轻、糖化血红蛋白水平降低以及糖尿病缓解等预期治疗终点，且效果持续时间更长。鉴于这些发现，有人怀疑减肥手术除了导致与体重减轻相关的葡萄糖不耐受外，还会引发其他有助于缓解糖尿病的生理变化。然而，减肥手术治疗益处背后假定的术后神经激素途径仍不明确。在最近的一份报告中，瑞安及其同事对决定减肥手术对小鼠有益效果的潜在机制有了新的认识。作者表明，垂直袖状胃切除术（VSG）后小鼠葡萄糖耐量的改善和体重减轻可能是由循环胆汁酸和法尼醇X受体（FXR）信号的术后变化引起的，这两者在机制上也与肠道微生物生态的变化有关。作者通过比较肥胖野生型（WT）和FXR基因敲除小鼠VSG手术的全基因组代谢后果得出这一结论。WT和FXR基因敲除小鼠远端小肠的基因表达显示，调节胆汁酸组成、营养代谢和抗氧化防御的途径在WT和FXR（-/-）小鼠中因VSG手术而有不同改变。基于这些数据，瑞安等人推测胆汁酸稳态和FXR信号在机制上与肠道微生物群有关，肠道微生物群在调节全身质量和葡萄糖耐量的术后变化中发挥作用。作者的数据为减肥手术假定的与体重减轻无关的益处及其与胆汁酸代谢的关系提供了合理的解释。
