Gul Sarah S, Hamilton A Rebecca L, Munoz Alexander R, Phupitakphol Tanit, Liu Wei, Hyoju Sanjiv K, Economopoulos Konstantinos P, Morrison Sara, Hu Dong, Zhang Weifeng, Gharedaghi Mohammad Hadi, Huo Haizhong, Hamarneh Sulaiman R, Hodin Richard A
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.
Appl Physiol Nutr Metab. 2017 Jan;42(1):77-83. doi: 10.1139/apnm-2016-0346. Epub 2016 Nov 18.
Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP's protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.
饮用无糖汽水与实际体重减轻并无关联。阿斯巴甜（ASP）通常作为糖的替代品，其分解产物之一是苯丙氨酸（PHE），苯丙氨酸是一种已知的肠道碱性磷酸酶（IAP）抑制剂，IAP是一种肠道酶，已证实在小鼠中可预防代谢综合征。我们推测，基于苯丙氨酸对内源性IAP的抑制作用，饮用阿斯巴甜可能会导致代谢综合征的发生。本研究的设计如下：在体外模型中，将IAP添加到无糖汽水和普通汽水中，并测量IAP活性。在急性模型中，在小鼠体内创建一个封闭的肠袢。向其中注入阿斯巴甜或水，并测量IAP活性。在慢性模型中，给小鼠喂食普通饲料或高脂饮食（HFD），并在饮水中添加或不添加阿斯巴甜，持续18周。结果显示：在体外研究中，与对照组相比，含有阿斯巴甜的溶液中IAP活性较低（p < 0.05）。在急性模型中，与对照组相比，阿斯巴甜组的内源性IAP活性降低了50%（0.2±0.03对0.4±0.24）（p = 0.02）。在慢性模型中，高脂饮食+阿斯巴甜组的小鼠比高脂饮食+水组的小鼠体重增加更多（48.1±1.6对42.4±3.1，p = 0.0001）。高脂饮食±阿斯巴甜组之间的葡萄糖耐量存在显著差异（分别为53913±4000.58（mg·min）/dL对42003.75±5331.61（mg·min）/dL，p = 0.02）。高脂饮食+阿斯巴甜组的空腹血糖和血清肿瘤坏死因子-α水平显著更高（分别增加1.23倍和0.87倍，p = 0.006和p = 0.01）。总之，内源性IAP对代谢综合征的保护作用可能会被阿斯巴甜的代谢产物苯丙氨酸所抑制，这或许可以解释饮用无糖饮料为何未出现预期的体重减轻和代谢改善。
