Effect of antibiotic treatment on fat absorption in mice with cystic fibrosis.

Effect of antibiotic treatment on fat absorption in mice with cystic fibrosis.
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DOI:
10.1038/pr.2011.4
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发表时间:
2012-01
期刊:
影响因子:
3.6
通讯作者:
Verkade, Henkjan J.
Verkade, Henkjan J.
中科院分区:
医学3区
文献类型:
--
作者:
Wouthuyzen-Bakker, Marjan;Bijvelds, Marcel J. C.;de Jonge, Hugo R.;De Lisle, Robert C.;Burgerhof, Johannes G. M.;Verkade, Henkjan J.

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改善脂肪吸收仍然是囊性纤维化(CF)的一个挑战。抗生素(AB)治疗已被证明可以改善CF小鼠的体重。其机制可能包括改善脂肪吸收。我们的目的是确定AB对两种CF小鼠模型脂肪吸收的影响。AB不能改善总脂肪吸收。有趣的是,AB加速了Δ/Δ和WT小鼠对同位素标记脂肪的吸收。观察到的变化与胆汁的溶解能力或小肠细菌的变化无关。在两种CF小鼠模型中,AB可使粪便胆酸排泄量减少约50% (P < 0.05),表明肠道胆盐吸收得到改善。综上所示,AB处理并不能改善CF小鼠的总脂肪吸收,但能减少粪便中胆盐的流失,加速长链脂肪酸(LCFA)的吸收。在3周的时间里,我们给纯合子ΔF508 (Δ/Δ)、囊性纤维化跨膜传导调节剂(CFTR)敲除(−/−)和野生型(WT)小鼠口服AB(环丙沙星/硝酸唑)或对照治疗,并通过72小时脂肪平衡测试定量脂肪吸收。在Δ/Δ小鼠中,我们通过给药3 -1- 13c -棕榈素和1- 13c -硬脂酸酯来评估脂肪吸收动力学,并测定血浆中稳定同位素标记脂肪的外观。我们定量测定了胆汁和粪胆盐(气相色谱法)和小肠细菌(定量pcr法)。
Improving fat absorption remains a challenge in cystic fibrosis (CF). Antibiotics (AB) treatment has been shown to improve body weight in CF mice. The mechanism may include improvement in fat absorption. We aimed to determine the effect of AB on fat absorption in two CF mouse models. AB did not improve total fat absorption. Interestingly, AB accelerated the absorption of isotope-labeled fats, in both Δ/Δ and WT mice. The changes observed were not related to the solubilization capacity of bile or to changes in the bacteria in the small intestine. AB reduced the fecal excretion of cholate by ∼50% (P < 0.05) in both CF mouse models, indicating improved intestinal bile salt absorption. In conclusion, AB treatment does not improve total fat absorption in CF mice but does decrease fecal loss of bile salts and accelerate long-chain fatty acid (LCFA) absorption. For 3 weeks, we administered oral AB (ciprofloxacin/metronidazole) or control treatment to homozygous ΔF508 (Δ/Δ), cystic fibrosis transmembrane conductance regulator (CFTR) knockout (−/−), and wild-type (WT) mice and quantified fat absorption using a 72-h fat balance test. In Δ/Δ mice, we assessed fat absorption kinetics by administering tri-1-13C-palmitin and 1-13C-stearate intragastrically and determining the appearance of stable isotope-labeled fats in plasma. We quantified biliary and fecal bile salts (gas chromatography) and small intestinal bacteria (quantitative-PCR).
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