Phenolic-rich grape pomace extract mitigates metabolic endotoxemia and hippocampal inflammation in obese mice

IF 0.3 Q4 NUTRITION & DIETETICS

CAHIERS DE NUTRITION ET DE DIETETIQUE Pub Date : 2026-08-01 Epub Date: 2026-09-24 DOI:10.1016/j.cnd.2026.08.031

Indira Martínez Jiménez, Victoria Muscia Saez, Fernanda Marra, Andrea N. Antoniolli, Diahann J. Perdicaro, Marcela A. Vazquez Prieto

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Metabolic parameters, circulating lipopolysaccharide (LPS) levels, and markers of hippocampal inflammation were evaluated.</div></div><div>Eight-week-old male C57BL/6 mice were fed either a standard diet (16%kcal from fat) or an HFD (60%kcal from fat), with or without GPE supplementation (300mg/kg/day), for 13 weeks (Protocol approval N<sup>o</sup> 240/2023, Institutional Animal Care and Use Committee of the School of Medical Science, University of Cuyo). Metabolic parameters, circulating lipopolysaccharide (LPS) levels, and markers of hippocampal inflammation were evaluated.</div><div><h3>Results</h3><div>HFD feeding induced obesity, increased visceral adiposity, insulin resistance, dyslipidemia, and metabolic endotoxemia, as evidenced by elevated plasma LPS concentrations. 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引用次数: 0

Abstract

Background

Obesity and high-fat diet (HFD) consumption are associated with increased intestinal permeability and enhanced translocation of endotoxins, which may contribute to neuroinflammation. We previously demonstrated that grape pomace extract (GPE), a phenolic-rich by product of winemaking, ameliorates HFD-induced obesity, intestinal permeability, and systemic inflammation.

Objective

The present study investigated whether dietary GPE could attenuate hippocampal inflammation in HFD-fed mice.

Methods

Eight-week-old male C57BL/6 mice were fed either a standard diet (16% kcal from fat) or an HFD (60% kcal from fat), with or without GPE supplementation (300 mg/kg/day), for 13 weeks (Protocol approval N^o 240/2023, Institutional Animal Care and Use Committee of the School of Medical Science, University of Cuyo). Metabolic parameters, circulating lipopolysaccharide (LPS) levels, and markers of hippocampal inflammation were evaluated.

Results

HFD feeding induced obesity, increased visceral adiposity, insulin resistance, dyslipidemia, and metabolic endotoxemia, as evidenced by elevated plasma LPS concentrations. These alterations were accompanied by increased hippocampal expression of inflammatory and microglial activation markers, including ionized calcium-binding adaptor molecule 1 (Iba-1), toll-like receptor 4 (TLR4), and NADPH oxidase 4 (NOX4). GPE supplementation significantly attenuated metabolic disturbances, reduced circulating LPS levels, and prevented the HFD-induced increase in hippocampal inflammatory markers.

Conclusion

Overall, these findings demonstrate that dietary GPE mitigates obesity-associated neuroinflammation and suggest that preservation of intestinal barrier function and reduction of metabolic endotoxemia may contribute to its protective effects within the gut–brain axis. Consumption of grape pomace-derived bioactive compounds could be a beneficial strategy to counteract obesity-related neuroinflammatory alterations.

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富酚葡萄渣提取物减轻肥胖小鼠代谢性内毒素血症和海马炎症

背景：肥胖和高脂肪饮食（HFD）消耗与肠道通透性增加和内毒素易位增强有关，这可能导致神经炎症。我们之前证明了葡萄渣提取物（GPE），一种富含酚的酿酒副产品，可以改善hfd诱导的肥胖，肠道通透性和全身性炎症。肥胖和高脂肪饮食（HFD）消耗与肠道通透性增加和内毒素易位增强有关，这可能导致神经炎症。我们之前证明了葡萄渣提取物（GPE），一种富含酚的酿酒副产品，可以改善hfd诱导的肥胖，肠道通透性和全身性炎症。目的观察膳食GPE是否能减轻hfd喂养小鼠海马炎症。本研究探讨了膳食GPE是否能减轻hfd喂养小鼠的海马炎症。方法8周龄雄性C57BL/6小鼠分别饲喂标准日粮（16%卡路里来自脂肪）和高热量日粮（60%卡路里来自脂肪），添加或不添加GPE （300 mg/kg/天），持续13周（方案批准号240/2023，凯约大学医学院动物保健与利用委员会）。评估代谢参数、循环脂多糖（LPS）水平和海马炎症标志物。8周龄雄性C57BL/6小鼠分别饲喂标准饮食（16%卡路里来自脂肪）或高热量饮食（60%卡路里来自脂肪），添加或不添加GPE （300 mg/kg/天），持续13周（方案批准号240/2023，库约大学医学院动物保健和使用委员会）。评估代谢参数、循环脂多糖（LPS）水平和海马炎症标志物。结果shfd喂养诱导肥胖，增加内脏脂肪，胰岛素抵抗，血脂异常和代谢性内毒素血症，血浆脂多糖浓度升高。这些改变伴随着炎症和小胶质细胞激活标志物的海马表达增加，包括离子钙结合接头分子1 （Iba-1）、toll样受体4 （TLR4）和NADPH氧化酶4 （NOX4）。GPE的补充显著减轻了代谢紊乱，降低了循环LPS水平，并阻止了hfd诱导的海马炎症标志物的增加。高脂饲料导致肥胖、内脏脂肪增加、胰岛素抵抗、血脂异常和代谢性内毒素血症，血浆脂多糖浓度升高就是证据。这些改变伴随着炎症和小胶质细胞激活标志物的海马表达增加，包括离子钙结合接头分子1 （Iba-1）、toll样受体4 （TLR4）和NADPH氧化酶4 （NOX4）。GPE的补充显著减轻了代谢紊乱，降低了循环LPS水平，并阻止了hfd诱导的海马炎症标志物的增加。综上所述，这些研究结果表明，膳食GPE减轻了肥胖相关的神经炎症，并表明维持肠道屏障功能和减少代谢性内毒素血症可能有助于其在肠-脑轴内的保护作用。食用葡萄渣衍生的生物活性化合物可能是对抗肥胖相关神经炎症改变的有益策略。总的来说，这些发现表明，膳食GPE减轻了肥胖相关的神经炎症，并表明保留肠道屏障功能和减少代谢性内毒素血症可能有助于其在肠-脑轴内的保护作用。食用葡萄渣衍生的生物活性化合物可能是对抗肥胖相关神经炎症改变的有益策略。

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来源期刊

CAHIERS DE NUTRITION ET DE DIETETIQUE NUTRITION & DIETETICS-

CiteScore

0.60

自引率

33.30%

发文量

审稿时长

65 days

期刊介绍： Les Cahiers de nutrition et de diététique sont le lieu de communication reconnu pour les médecins spécialistes de la nutrition, les diététiciens, les professionnels et les chercheurs de agro-alimentaire, les enseignants et les étudiants. Les Cahiers de nutrition et de diététique abordent les sujets se rapportant à la biologie générale, à la médecine et à la nutrition, aux aliments, aux comportements alimentaires, à la diététique pratique, ainsi que des thèmes variés : activité physique, apports nutritionnels conseillés, dénutrition, alcool, obésité de enfant, aliments à effet santé, plaisir alimentaire, restauration collective, goûters et collations, allergies alimentaires...