NAFLD (non-alcoholic fatty liver disease) is a multifactorial liver disease related to multiple causes or unhealthy conditions, including obesity and chronic inflammation. The accumulation of excess triglycerides, called steatosis, is known as a hallmark of an imbalance between the rates of hepatic fatty acid uptake/synthesis and oxidation/export. Furthermore, occurrence of NAFLD may lead to a cocktail of disease consequences caused by the altered metabolism of glucose, lipids, and lipoproteins, for instance, insulin resistance, type II diabetes, nonalcoholic steatohepatitis (NASH), liver fibrosis, and even hepatocarcinogenesis. Due to the complexity of the occurrence of NAFLD, a multi-targeting strategy is highly recommended to effectively address the issue and combat the causal loop. Ethanol extracts of legumes are popular supplements due to their richness and diversity in phytochemicals, especially isoflavones and anthocyanins. Although many of them have been reported to have efficacy in the treatment of different metabolic syndromes and obesity, there have not been many studies on them as a supplemental mixture. In this study, the alleviative effects of selected legume ethanol extracts (CrE) on high-fat-diet- and fructose-induced obesity, liver steatosis, and hyperglycemia are discussed. As revealed by the findings, CrE not only ameliorated obesity in terms of weight gained and enlargement of adipose tissue, but also significantly reduced the incidence of steatosis via phosphorylation of AMPK, resulting in inhibition of the downstream SREBP-1c/FAS pathway and an increase in an indicator of β-oxidation (carnitine palmitoyl transferase 1a, CPT1A). Furthermore, CrE dramatically alleviated inflammatory responses, including both plasma and hepatic TNF-α, IL-6, and MCP-1 levels. CrE also had attenuating effects on hyperglycemia and insulin resistance and significantly reduced the fasting glucose level, fasting insulin level, and plasma leptin, and it exhibited positive effects in the Oral glucose tolerance test (OGTT) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). At the molecular level, CrE could activate the PI3K/Akt/Glut2 pathway, which indicated an increase in insulin sensitivity and glucose uptake. Taken together, these results suggest that ethanol extracts of legumes could be potential supplements for metabolic syndromes, and their efficacy and effectiveness might facilitate the multi-targeting strategy required to mitigate NAFLD.

中文翻译：

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补充豆类乙醇提取物混合物的多目标策略，可改善高脂饮食和果糖诱导的（西方饮食诱导的）非酒精性脂肪肝疾病（NAFLD）。

NAFLD（非酒精性脂肪肝）是一种与多种原因或不健康状况（包括肥胖症和慢性炎症）相关的多因素肝病。多余的甘油三酸酯的积累（称为脂肪变性）被称为肝脏脂肪酸摄取/合成速率与氧化/输出速率之间不平衡的标志。此外，NAFLD的出现可能导致由葡萄糖，脂质和脂蛋白的代谢改变引起的疾病后果，例如胰岛素抵抗，II型糖尿病，非酒精性脂肪性肝炎（NASH），肝纤维化甚至肝癌的发生。由于NAFLD发生的复杂性，强烈建议采用多目标策略来有效解决该问题并消除因果关系。豆类的乙醇提取物因其丰富的植物化学物质（尤其是异黄酮和花青素）而丰富，是广受欢迎的补品。尽管已经报道其中许多在治疗不同的代谢综合症和肥胖症方面具有功效，但是关于它们作为补充混合物的研究还很少。在这项研究中，讨论了所选豆类乙醇提取物（CrE）对高脂饮食和果糖诱发的肥胖，肝脂肪变性和高血糖症的缓解作用。结果表明，CrE不仅减轻肥胖，增加体重，增加脂肪组织，而且显着降低脂肪变性的发生率。尽管已经报道其中许多在治疗不同的代谢综合症和肥胖症方面具有功效，但是关于它们作为补充混合物的研究还很少。在这项研究中，讨论了所选豆类乙醇提取物（CrE）对高脂饮食和果糖诱发的肥胖，肝脂肪变性和高血糖症的缓解作用。结果表明，CrE不仅减轻肥胖，增加体重，增加脂肪组织，而且显着降低脂肪变性的发生率。尽管已经报道其中许多在治疗不同的代谢综合症和肥胖症方面具有功效，但是关于它们作为补充混合物的研究还很少。在这项研究中，讨论了所选豆类乙醇提取物（CrE）对高脂饮食和果糖诱发的肥胖，肝脂肪变性和高血糖症的缓解作用。结果表明，CrE不仅减轻肥胖，增加体重，增加脂肪组织，而且显着降低脂肪变性的发生率。通过磷酸化AMPK，导致下游SREBP-1c / FAS途径受到抑制，β-氧化指标（肉碱棕榈酰转移酶1a，CPT1A）增加。此外，CrE大大减轻了炎症反应，包括血浆和肝TNF-α，IL-6和MCP-1的水平。CrE还对高血糖症和胰岛素抵抗具有减弱作用，并显着降低了空腹血糖水平，空腹胰岛素水平和血浆瘦素，并且在口服葡萄糖耐量试验（OGTT）和胰岛素抵抗稳态模型评估（HOMA- IR）。在分子水平上，CrE可以激活PI3K / Akt / Glut2途径，这表明胰岛素敏感性和葡萄糖摄取增加。在一起