Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis
Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis
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DOI：
10.1208/s12248-017-0053-0
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发表时间：
2017-05-01
期刊：
影响因子：
4.5
通讯作者：
Liu, Dexi
中科院分区：
文献类型：
--
作者：
Alsanea, Sary;Gao, Mingming;Liu, Dexi
作为代谢副产物产生的活性氧在肥胖和肥胖相关代谢并发症的发展中起着核心作用。本研究的目的是探索通过根皮素（一种从苹果树叶和东北杏中提取的天然抗氧化剂）阻断肥胖和改善代谢稳态的可能性。使用高脂饮食诱导的肥胖小鼠模型评估根皮素的预防和治疗活性。将根皮素每周两次腹腔注射到喂食高脂饮食的正常和肥胖小鼠中。监测根皮素处理对体重和组成、肝脏中的脂肪含量、葡萄糖和脂质代谢以及胰岛素抵抗的影响，并与对照动物进行比较。根皮素治疗显著阻断高脂饮食诱导的体重增加，但不诱导肥胖动物的体重减轻。根皮素改善葡萄糖稳态和胰岛素敏感性，减轻肝脏脂质积聚。RT-PCR分析显示根皮素处理抑制巨噬细胞标志物（F4/80和Cd 68）和促炎基因（Mcp-1和Ccr 2）的表达，并增强白色脂肪组织中脂联素基因的表达。此外，根皮素处理提高了脂肪酸氧化基因的表达，如肉毒碱棕榈酰转移酶1a和1b（Cpt 1a和Cpt 1b），并降低了单核细胞趋化蛋白-1（Mcp-1）、新生脂肪生成转录因子过氧化物酶体增殖物激活受体-γ 2（Ppar γ 2）及其靶向单酰基甘油O-酰基转移酶（Mgat-1）基因的表达。这些结果提供了直接的证据，支持根皮素可能用于减轻肥胖和维持代谢稳态。
Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-gamma 2 (Ppar gamma 2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.