Fat absorption in cystic fibrosis mice is impeded by defective lipolysis and post-lipolytic events
Fat absorption in cystic fibrosis mice is impeded by defective lipolysis and post-lipolytic events
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DOI：
10.1152/ajpgi.00295.2004
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发表时间：
2005-04-01
影响因子：
4.5
通讯作者：
Verkade, HJ
中科院分区：
文献类型：
--
作者：
Bijvelds, MJC;Bronsveld, I;Verkade, HJ
囊性纤维化通常与胰腺外分泌功能的进行性丧失有关，导致膳食脂肪的不完全消化和吸收。补充胰腺脂肪酶可减少脂肪排泄，但不能完全纠正脂肪吸收不良，这表明额外的病理过程会影响脂肪分解和/或脂肪分解产物的吸收。为了阐明这种(后)脂肪分解过程在CF相关脂肪吸收不良中的作用，我们通过测量粪便脂肪排泄量和油酸和三油酸酯衍生的脂质的摄取，评估了两种小鼠CF模型的脂肪吸收、脂肪分解和脂肪酸摄取。分别测定脂肪酶分泌量和胆汁盐(BS)分泌量来评价胰腺和胆道功能。在CFTR缺失的小鼠中观察到粪便脂肪排泄显著增加，但在纯合子Delta F508小鼠中没有观察到。在两种CF模型中，粪便BS丢失均增加，但胆汁BS分泌率相似。在两种CF模型中，游离脂肪酸的摄取都延迟了，但只有在缺失的小鼠中，脂解活性明显降低，其特征是甘油三酯吸收明显减少。脂肪分解受损不是由于胰腺脂肪酶分泌减少所致。抑制胃酸分泌部分恢复了脂解活性和脂肪摄取，表明胃酸的不完全中和阻碍了脂肪的吸收。我们的结论是，CFTR基因缺失小鼠的脂肪吸收不良是由脂解障碍引起的，这可能是由于十二指肠pH调节异常所致。
Cystic fibrosis (CF) is frequently associated with progressive loss of exocrine pancreas function, leading to incomplete digestion and absorption of dietary fat. Supplementing patients with pancreatic lipase reduces fat excretion, but it does not completely correct fat malabsorption, indicating that additional pathological processes affect lipolysis and/or uptake of lipolytic products. To delineate the role of such ( post) lipolytic processes in CF-related fat malabsorption, we assessed fat absorption, lipolysis, and fatty acid uptake in two murine CF models by measuring fecal fat excretion and uptake of oleate- and triolein-derived lipid. Pancreatic and biliary function was investigated by determining lipase secretion and biliary bile salt (BS) secretion, respectively. A marked increase in fecal fat excretion was observed in cftr null mice but not in homozygous Delta F508 mice. Fecal BS loss was enhanced in both CF models, but biliary BS secretion rates were similar. Uptake of free fatty acid was delayed in both CF models, but only in null mice was a specific reduction in lipolytic activity apparent, characterized by strongly reduced triglyceride absorption. Impaired lipolysis was not due to reduced pancreatic lipase secretion. Suppression of gastric acid secretion partially restored lipolytic activity and lipid uptake, indicating that incomplete neutralization of gastric acid impedes fat absorption. We conclude that fat malabsorption in cftr null mice is caused by impairment of lipolysis, which may result from aberrant duodenal pH regulation.