Xiang Minghui, Tian Xiaoli, Wang Hui, Gan Ping, Zhang Qian
National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
School of Public Health, Xinjiang Medical College, Ürümqi 830000, China.
Nutrients. 2024 Dec 5;16(23):4208. doi: 10.3390/nu16234208.
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a refined categorization of non-alcoholic fatty liver disease (NAFLD), highlighting the intricate relationship between hepatic steatosis and metabolic dysfunction. Abdominal obesity (AO), a key diagnostic criterion for metabolic dysfunction, predominantly results from inappropriate diet and unhealthy dietary habits. To comprehensively investigate which dietary factors contribute to MASLD through AO and to understand the underlying biological mechanisms, we initially conducted a systematic review of meta-analysis articles in the PubMed database from the past decade, summarizing dietary factors that affect AO. Subsequently, we conducted targeted searches in the PubMed database for these dietary factors and provided a narrative review of the mechanisms of how these dietary factors lead to AO and how AO exacerbates MASLD. A diet characterized by excessive intake of energy, carbohydrates, fructose, or ultra-processed foods (UPFs) is considered inappropriate. Inappropriate diet leads to the formation of MASLD and AO by enhancing pathways such as de novo lipid synthesis (DNL) in the liver, insulin resistance (IR), gut-liver dysfunction, and inflammation. Dietary interventions for inappropriate diets can effectively intervene in and improve MASLD and AO. The mechanism of inappropriate diet on abdominal fat deposition is through excessive energy or the activation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) to increase endocortisol secretion. Then, the excessive accumulation of visceral fat facilitates a rapid and augmented flux of free fatty acids (FFAs) to the liver and initiates a series of deleterious effects, including oxidative stress (OS), endoplasmic reticulum stress (ERS), activation of protein kinase C (PKC) pathways, and inflammation. Additionally, FFAs may mediate excessive lipid deposition and hepatocellular damage through the action of hormones. These pathways to liver damage exacerbate MASLD and progression to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Furthermore, investigating other potential mechanisms by which AO may influence MASLD could offer new recommendations for the treatment guidelines of MASLD.
代谢功能障碍相关脂肪性肝病（MASLD）是对非酒精性脂肪性肝病（NAFLD）的一种细化分类，突出了肝脂肪变性与代谢功能障碍之间的复杂关系。腹部肥胖（AO）是代谢功能障碍的一项关键诊断标准，主要源于不当饮食和不健康的饮食习惯。为全面探究哪些饮食因素通过AO导致MASLD，并了解其潜在生物学机制，我们首先对过去十年PubMed数据库中关于荟萃分析文章进行了系统综述，总结影响AO的饮食因素。随后，我们在PubMed数据库中针对这些饮食因素进行了定向检索，并对这些饮食因素导致AO以及AO如何加剧MASLD的机制进行了叙述性综述。以能量、碳水化合物、果糖或超加工食品（UPF）摄入过多为特征的饮食被认为是不当的。不当饮食通过增强肝脏从头合成脂质（DNL）、胰岛素抵抗（IR）、肠-肝功能障碍和炎症等途径导致MASLD和AO的形成。针对不当饮食的饮食干预可有效干预并改善MASLD和AO。不当饮食导致腹部脂肪沉积的机制是通过能量过剩或激活11β-羟基类固醇脱氢酶1型（11β-HSD-1）来增加内源性皮质醇分泌。然后，内脏脂肪的过度积累促使游离脂肪酸（FFA）快速大量流入肝脏，并引发一系列有害影响，包括氧化应激（OS）、内质网应激（ERS）、蛋白激酶C（PKC）途径激活和炎症。此外，FFA可能通过激素作用介导过多的脂质沉积和肝细胞损伤。这些肝损伤途径会加剧MASLD，并进展为代谢功能障碍相关脂肪性肝炎（MASH）和肝纤维化。此外，研究AO可能影响MASLD的其他潜在机制可为MASLD的治疗指南提供新的建议。
