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界面蛋白原纤维多态性调节脂肪扩张以控制肥胖。

Interfacial Protein Fibril Polymorphisms Regulate Adipose Expansion for Control of Obesity.

机构信息

College of Food Science and Technology, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu 210095, P. R. China.

Key Laboratory of Meat Processing and Quality Control, MOE, Key Laboratory of Meat Processing, MOA, Jiangsu Synergetic Innovation Center of Meat Processing and Quality Control, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P. R. China.

出版信息

ACS Nano. 2024 Jul 9;18(27):17969-17986. doi: 10.1021/acsnano.4c04758. Epub 2024 Jun 26.

DOI:10.1021/acsnano.4c04758
PMID:38920100
Abstract

Obesity is becoming a worldwide pandemic. Interfacial engineering of food lipid is expected to inhibit diet-induced obesity without damage to the eating enjoyment brought by high-fat diets. Unfortunately, this strategy has not been achieved yet. After screening different plant proteins, bromelain and papain were found to form wormlike and long-straight protein fibrils, respectively. The conversion of long-straight amyloid-like fibrils to wormlike fibrils was demonstrated in the fibrillation of bromelain. Using oil-in-water high internal phase emulsions (HIPEs) as a proof of concept, bromelain fibrils showed dramatically stronger interfacial stabilization capabilities than papain fibrils with high application potentials in the real-world formulation of high-fat food products such as mayonnaise. Compared with papain fibrils, oral administration of HIPEs stabilized by bromelain fibrils resulted in substantially higher fecal lipid contents and significantly decreased expression levels of the genes related to lipid absorption and transport in the intestine, including , , and , without a difference in intervening gut microbiota. Consequently, dramatically less lipid absorption in the small intestine, markedly smaller chylomicron particles in the plasma, lower serum triglycerides, and controlled energy and lipid metabolism, as well as the inhibition of adipose expansion and overweight, were observed in the group with gavage of HIPEs stabilized by the bromelain fibrils rather than the papain fibrils. Furthermore, with the same calorie, substitution of all the fat in the standard high-fat feed of mice with the HIPEs emulsified by the bromelain fibrils showed a significantly stronger effect than the ones prepared by the papain fibrils on preventing high-fat-diet (HFD)-induced obesity including alleviation of adipose expansion and inflammation as well as fatty liver, also via inhibiting the absorption and transport of lipid in the intestine. The effect is ascribed to the suppressed lipolysis caused by a more compact and elastic interfacial layer formed by the wormlike fibrils than that of the long-straight fibrils, which are resistant to gastric environments and replacement by bile acids in digestion. Therefore, we provide an appealing and general strategy for controlling obesity by reducing the supply of free fatty acids (FAs) for absorption in the enteric lumen through protein fibril polymorphisms at the interface.

摘要

肥胖正在成为一种全球性的流行疾病。人们期望通过对食物脂质进行界面工程处理来抑制饮食引起的肥胖,同时又不损害高脂肪饮食带来的进食享受。然而,这一策略尚未实现。在筛选了不同的植物蛋白后,发现菠萝蛋白酶和木瓜蛋白酶分别形成了蠕虫状和长直的蛋白纤维。菠萝蛋白酶的纤维化过程中证明了长直淀粉样纤维向蠕虫状纤维的转化。使用油包水高内相乳液(HIPE)作为概念验证,与木瓜蛋白酶纤维相比,菠萝蛋白酶纤维具有更强的界面稳定能力,在蛋黄酱等高脂肪食品的实际配方中有很高的应用潜力。与木瓜蛋白酶纤维相比,用菠萝蛋白酶纤维稳定的 HIPEs 灌胃后,粪便中的脂质含量明显升高,肠道中与脂质吸收和转运相关的基因表达水平显著降低,包括 、 、 和 ,而肠道微生物群没有差异。因此,在灌胃用菠萝蛋白酶纤维稳定的 HIPEs 的组中,小肠中脂质吸收明显减少,血浆中的乳糜微粒颗粒明显变小,血清甘油三酯降低,能量和脂质代谢得到控制,脂肪扩张和超重得到抑制。此外,用菠萝蛋白酶纤维乳化的 HIPEs 替代标准高脂肪饲料中的所有脂肪,与用木瓜蛋白酶纤维制备的 HIPEs 相比,对预防高脂肪饮食(HFD)引起的肥胖具有更强的效果,包括缓解脂肪扩张和炎症以及脂肪肝,这也是通过抑制脂质在肠道中的吸收和转运来实现的。这种效果归因于蠕虫状纤维形成的更紧凑和有弹性的界面层抑制了脂肪分解,而长直纤维则抵抗胃环境和消化过程中胆汁酸的替代。因此,我们通过在界面上的蛋白纤维多态性来减少肠腔中游离脂肪酸(FAs)的吸收供应,提供了一种控制肥胖的有吸引力和通用的策略。

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