Feldman Francis, Koudoufio Mireille, Sané Alain Théophile, Marcil Valérie, Sauvé Mathilde Foisy, Butcher James, Patey Natalie, Martel Catherine, Spahis Schohraya, Duan Haonan, Figeys Daniel, Desjardins Yves, Stintzi Alain, Levy Emile
Azraeli Research Centre, Sainte-Justine University Health Centre, Montreal, QC H3T 1C5, Canada.
Department of Nutrition, Université de Montréal, Montreal, QC H3T 1A8, Canada.
Antioxidants (Basel). 2025 Feb 26;14(3):268. doi: 10.3390/antiox14030268.
Metabolic syndrome (MetS) constitutes a spectrum of interconnected conditions comprising obesity, dyslipidemia, hypertension, and insulin resistance (IR). While a singular, all-encompassing treatment for MetS remains elusive, an integrative approach involving tailored lifestyle modifications and emerging functional food therapies holds promise in preventing its multifaceted manifestations. Our main objective was to scrutinize the efficacy of cranberry proanthocyanidins (PAC, 200 mg/kg/day for 12 weeks) in mitigating MetS pathophysiology in male mice subjected to standard Chow or high-fat/high-fructose (HFHF) diets while unravelling intricate mechanisms. The administration of PAC, in conjunction with an HFHF diet, significantly averted obesity, evidenced by reductions in body weight, adiposity across various fat depots, and adipocyte hypertrophy. Similarly, PAC prevented HFHF-induced hyperglycemia and hyperinsulinemia while also lessening IR. Furthermore, PAC proved effective in alleviating key risk factors associated with cardiovascular diseases by diminishing plasma saturated fatty acids, as well as levels of triglycerides, cholesterol, and non-HDL-C levels. The rise in adiponectin and drop in circulating levels of inflammatory markers showcased PAC's protective role against inflammation. To better clarify the mechanisms behind PAC actions, gut-liver axis parameters were examined, showing significant enhancements in gut microbiota composition, microbiota-derived metabolites, and marked reductions in intestinal and hepatic inflammation, liver steatosis, and key biomarkers associated with endoplasmic reticulum (ER) stress and lipid metabolism. This study enhances our understanding of the complex mechanisms underlying the development of MetS and provides valuable insights into how PAC may alleviate cardiometabolic dysfunction in HFHF mice.
代谢综合征（MetS）是一系列相互关联的病症，包括肥胖、血脂异常、高血压和胰岛素抵抗（IR）。虽然尚未找到针对代谢综合征的单一、全面的治疗方法，但一种综合方法，即量身定制的生活方式改变和新兴的功能性食品疗法，有望预防其多方面的表现。我们的主要目标是研究蔓越莓原花青素（PAC，200毫克/千克/天，持续12周）在减轻食用标准饲料或高脂/高果糖（HFHF）饮食的雄性小鼠代谢综合征病理生理学方面的功效，并揭示其复杂机制。与HFHF饮食相结合，给予PAC可显著预防肥胖，表现为体重减轻、各脂肪库的脂肪量减少以及脂肪细胞肥大。同样，PAC可预防HFHF诱导的高血糖和高胰岛素血症，同时也减轻胰岛素抵抗。此外，PAC通过降低血浆饱和脂肪酸以及甘油三酯、胆固醇和非高密度脂蛋白胆固醇水平，有效减轻了与心血管疾病相关的关键危险因素。脂联素升高和循环炎症标志物水平下降表明PAC对炎症具有保护作用。为了更好地阐明PAC作用背后的机制，我们检测了肠-肝轴参数，结果显示肠道微生物群组成、微生物群衍生代谢物显著改善，肠道和肝脏炎症、肝脂肪变性以及与内质网（ER）应激和脂质代谢相关的关键生物标志物显著减少。这项研究增进了我们对代谢综合征发展背后复杂机制的理解，并为PAC如何减轻HFHF小鼠的心脏代谢功能障碍提供了有价值的见解。
