Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):7003-8. doi: 10.1073/pnas.1220180110. Epub 2013 Apr 8.
Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.
代谢综合征包括一组相关的疾病，包括肥胖、葡萄糖耐量受损、胰岛素抵抗、血脂异常和脂肪肝。最近，肠道来源的慢性内毒素血症已被确定为触发导致代谢综合征发生的低度炎症的主要介质。在本研究中，我们研究了小肠刷状缘酶，肠碱性磷酸酶（IAP）在预防小鼠高脂肪饮食诱导的代谢综合征中的作用。我们发现，内源性和口服补充的 IAP 可抑制饮食脂肪引起的内毒素（脂多糖）的吸收，口服 IAP 补充不仅可预防，还可逆转代谢综合征。此外，IAP 补充可改善喂食标准低脂饲料的小鼠的脂质谱。这些结果表明，针对高危人群的代谢综合征的治疗具有潜在的独特性。
