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口服离子液体治疗饮食诱导的肥胖。

Oral ionic liquid for the treatment of diet-induced obesity.

机构信息

School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Wyss Institute of Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138.

出版信息

Proc Natl Acad Sci U S A. 2019 Dec 10;116(50):25042-25047. doi: 10.1073/pnas.1914426116. Epub 2019 Nov 25.


DOI:10.1073/pnas.1914426116
PMID:31767747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6911186/
Abstract

More than 70% of American adults are overweight or obese, a precondition leading to chronic diseases, including diabetes and hypertension. Among other factors, diets with high fat and carbohydrate content have been implicated in obesity. In this study, we hypothesize that the choline and geranate (CAGE) ionic liquid can reduce body weight by decreasing fat absorption through the intestine. In vitro studies performed using docosahexaenoic acid (DHA), a model fat molecule, show that CAGE forms particles 2 to 4 μm in diameter in the presence of fat molecules. Ex vivo permeation studies in rat intestine showed that formation of such large particles reduces intestinal fat absorption. In vivo, CAGE reduces DHA absorption by 60% to 70% compared with controls. DHA administered with CAGE was retained in the intestine even after 6 h. Rats fed with a high-fat diet (HFD) and 10 μL of daily oral CAGE exhibited 12% less body weight gain compared with rats fed with an HFD without CAGE for 30 d. Rats that were given CAGE also ate less food than the control groups. Serum biochemistry and histology results indicated that CAGE was well tolerated by the rats. Collectively, our data support the hypothesis that CAGE interacts with fat molecules to prevent their absorption through intestinal tissue and potentially providing a feeling of satiety. We conclude that CAGE offers an effective means to control body weight and a promising tool to tackle the obesity epidemic.

摘要

超过 70%的美国成年人超重或肥胖,这是导致包括糖尿病和高血压在内的慢性疾病的前提条件。在其他因素中,高脂肪和高碳水化合物含量的饮食与肥胖有关。在这项研究中,我们假设胆碱和石榴酸(CAGE)离子液体可以通过减少肠道脂肪吸收来降低体重。使用二十二碳六烯酸(DHA)——一种模型脂肪分子——进行的体外研究表明,在脂肪分子存在的情况下,CAGE 形成直径为 2 到 4 微米的颗粒。在大鼠肠的离体渗透研究中,发现形成如此大的颗粒会减少肠道脂肪吸收。在体内,与对照组相比,CAGE 将 DHA 的吸收减少了 60%至 70%。与未用 CAGE 处理的 DHA 相比,用 CAGE 处理的 DHA 在肠道中保留时间更长,即使在 6 小时后也是如此。用高脂肪饮食(HFD)和每日口服 10 μL CAGE 喂养的大鼠与未用 CAGE 喂养的 HFD 大鼠相比,体重增加减少了 12%,持续 30 天。给予 CAGE 的大鼠比对照组吃得也更少。血清生化和组织学结果表明,CAGE 被大鼠很好地耐受。总的来说,我们的数据支持了 CAGE 与脂肪分子相互作用以防止其通过肠组织吸收的假设,并可能提供饱腹感。我们得出结论,CAGE 提供了一种有效控制体重的方法,是解决肥胖流行的有前途的工具。

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本文引用的文献

[1]
The Influence of Water on Choline-Based Ionic Liquids.

ACS Biomater Sci Eng. 2019-7-8

[2]
Nanotechnology-Mediated Drug Delivery for the Treatment of Obesity and Its Related Comorbidities.

Adv Healthc Mater. 2019-4-2

[3]
Long-term oral administration of Exendin-4 to control type 2 diabetes in a rat model.

J Control Release. 2018-12-18

[4]
Is "choline and geranate" an ionic liquid or deep eutectic solvent system?

Proc Natl Acad Sci U S A. 2018-11-20

[5]
Reply to Rogers and Gurau: Definitions of ionic liquids and deep eutectic solvents.

Proc Natl Acad Sci U S A. 2018-11-20

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A randomized controlled trial of lorcaserin and lifestyle counselling for weight loss maintenance: changes in emotion- and stress-related eating, food cravings and appetite.

Clin Obes. 2018-12

[7]
Ionic liquids for oral insulin delivery.

Proc Natl Acad Sci U S A. 2018-6-25

[8]
Oral delivery of a therapeutic gene encoding glucagon-like peptide 1 to treat high fat diet-induced diabetes.

J Control Release. 2017-8-30

[9]
Size-Dependent Translocation of Nanoemulsions via Oral Delivery.

ACS Appl Mater Interfaces. 2017-6-23

[10]
Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis.

Int J Obes (Lond). 2017-2

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