Dietary Capsaicin Reduces Obesity-induced Insulin Resistance and Hepatic Steatosis in Obese Mice Fed a High-fat Diet
Dietary Capsaicin Reduces Obesity-induced Insulin Resistance and Hepatic Steatosis in Obese Mice Fed a High-fat Diet
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DOI：
10.1038/oby.2009.301
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发表时间：
2010-04-01
期刊：
影响因子：
6.9
通讯作者：
Yu, Rina
中科院分区：
文献类型：
--
作者：
Kang, Ji-Hye;Tsuyoshi, Goto;Yu, Rina
肥胖引起的炎症导致肥胖相关代谢紊乱的发展，如胰岛素抵抗、2型糖尿病、脂肪肝和心血管疾病。在这项研究中，我们调查了饮食辣椒素是否可以减少肥胖引起的炎症和代谢紊乱，如胰岛素抵抗和肝脏脂肪变性。雄性C57BL/6肥胖小鼠喂饲高脂饲料10周后，再补充0.015%辣椒素10周，并与未添加辣椒素的对照组进行比较。糖耐量试验评估糖耐量。用逆转录聚合酶链式反应和酶联免疫吸附试验检测脂肪细胞因子基因和相应蛋白的转录本，用流式细胞仪检测巨噬细胞数。RT-PCR检测瞬时受体电位香草样物质-1(TRPV-1)、过氧化物酶体增殖物激活受体(PPAR)-α和PPAR-1α(PGC-1α)mRNAs，PPARα荧光素酶活性测定。膳食辣椒素可降低肥胖小鼠的空腹血糖、胰岛素、瘦素水平，并显著减轻糖耐量受损。脂肪组织和肝脏中肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)和白介素6(IL-6)的mRNAs和蛋白水平显著降低，脂肪组织中巨噬细胞浸润、肝甘油三酯和TRPV-1的表达也显著降低。同时，脂肪组织中脂联素和肝脏中PPARα/PGC-1α的mRNA/蛋白表达增加。此外，荧光素酶分析表明辣椒素能够与PPARα结合。我们的数据表明，饮食中的辣椒素不仅可以抑制炎症反应，还可以促进脂肪组织和/或肝脏中的脂肪酸氧化，从而减少肥胖引起的葡萄糖耐量减少，而脂肪组织和/或肝脏是影响胰岛素抵抗的重要外围组织。辣椒素在脂肪组织和肝脏中的作用与其对PPARα和TRPV-1表达/激活的双重作用有关。
Obesity-induced inflammation contributes to the development of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether dietary capsaicin can reduce obesity-induced inflammation and metabolic disorders such as insulin resistance and hepatic steatosis. Male C57BL/6 obese mice fed a high-fat diet for 10 weeks received a supplement of 0.015% capsaicin for a further 10 weeks and were compared with unsupplemented controls. Glucose intolerance was estimated by glucose tolerance tests. Transcripts of adipocytokine genes and the corresponding proteins were measured by reverse transcription-PCR and enzyme-linked immunosorbent assay, and macrophage numbers were determined by flow cytometric analysis. Transient receptor potential vanilloid type-1 (TRPV-1), peroxisome proliferator-activated receptor (PPAR)-alpha, and PPAR gamma coactivator-1 alpha (PGC-1 alpha) mRNAs were also measured by RT-PCR, and PPAR alpha luciferase assays were performed. Dietary capsaicin lowered fasting glucose, insulin, leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Levels of tumor necrosis factor-alpha (TNF alpha), monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-6 mRNAs and proteins in adipose tissue and liver decreased markedly, as did macrophage infiltration, hepatic triglycerides, and TRPV-1 expression in adipose tissue. At the same time, the mRNA/protein of adiponectin in the adipose tissue and PPAR alpha/PGC-1 alpha mRNA in the liver increased. Moreover, luciferase assays revealed that capsaicin is capable of binding PPAR alpha. Our data suggest that dietary capsaicin may reduce obesity-induced glucose intolerance by not only suppressing inflammatory responses but also enhancing fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. The effects of capsaicin in adipose tissue and liver are related to its dual action on PPAR alpha and TRPV-1 expression/activation.