Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD
Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD
复制标题
西式高脂饮食诱导的肥胖相关性非酒精性脂肪肝小鼠模型的代谢表型及脂肪和肝脏特征
DOI：
10.1152/ajpendo.00319.2015
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发表时间：
2016-03-15
影响因子：
5.1
通讯作者：
Greene, Michael W.
中科院分区：
文献类型：
--
作者：
Luo, Yuwen;Burrington, Christine M.;Greene, Michael W.
非酒精性脂肪性肝病（NAFLD）是一种肥胖和胰岛素抵抗相关的临床病症，其范围从单纯性脂肪变性到非酒精性脂肪性肝炎。为了模拟人类的状况，在小鼠中使用了包括液体糖消耗的高脂肪西方饮食。尽管肝脏病理生理学在模型中得到了很好的表征，但对代谢表型（例如，能量消耗、活动或食物摄入）。此外，在模型中，液态糖的消耗是否会加剧葡萄糖耐受不良、胰岛素抵抗和脂肪组织功能障碍的发展，目前还存在疑问。在我们的研究中，高脂西方饮食（HFWD）与液体糖[果糖和蔗糖（F/S）]诱导急性高摄食高于HFWD喂养小鼠中观察到的，但没有改变能量消耗。液体糖（F/S）加重HFWD诱导的葡萄糖耐受不良和胰岛素抵抗，并损害附睾白色脂肪组织（eWAT）的储存能力。肝TG，血浆丙氨酸氨基转移酶，和正常的肝脏重量显着增加，只有HFWD + F/S喂养的小鼠。HFWD + F/S还导致肝纤维化增加和胶原1a 2、胶原3a 1和TGF β基因表达升高。此外，HWFD + F/S喂养的小鼠发展出更严重的eWAT炎症，其特征在于脂肪细胞肥大、巨噬细胞浸润、冠状结构急剧增加和促炎基因表达上调。eWAT中的早期缺氧反应导致HFWD + F/S喂养小鼠中血管形成减少和纤维化基因表达增加。我们的研究结果表明，含糖水摄入会诱导急性食欲过盛，限制脂肪组织扩张，并加剧与NAFLD进展相关的葡萄糖不耐受和胰岛素抵抗。
nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition-ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD + F/S-fed mice. HFWD + F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGF beta gene expression. Furthermore, HWFD + F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD + F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression.