Dietary quercetin supplementation in mice increases skeletal muscle PGC1α expression, improves mitochondrial function and attenuates insulin resistance in a time-specific manner.
Dietary quercetin supplementation in mice increases skeletal muscle PGC1α expression, improves mitochondrial function and attenuates insulin resistance in a time-specific manner.
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DOI：
10.1371/journal.pone.0089365
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Stewart LK
中科院分区：
文献类型：
--
作者：
Henagan TM;Lenard NR;Gettys TW;Stewart LK
高脂肪饮食（HFD）诱导的胰岛素抵抗（IR）的部分特征是骨骼肌线粒体功能和过氧化物酶体增殖物激活受体γ辅助激活因子1α (PGC1α)表达的降低。我们之前的研究表明，高剂量的生物类黄酮槲皮素加重了hfd诱导的IR；然而，其他人已经证明槲皮素可以改善胰岛素敏感性。本研究的目的是研究不同剂量的槲皮素是否以时间依赖的方式减弱hfd诱导的IR，并改善骨骼肌线粒体功能和PGC1α表达。C57BL/6J小鼠分别饲喂低剂量（50 ug/天，HF+50Q）和高剂量（600 ug/天，HF+600Q）槲皮素3周或8周。评估全身和代谢表型以及胰岛素敏感性。采用qRT-PCR检测骨骼肌酰基肉碱代谢组学分析和PGC1α mRNA表达。50 ug/天的槲皮素处理8周后，可减弱hfd诱导的脂肪量、体重和IR的增加，并增加PGC1α的表达，而600 ug/天的槲皮素则会加剧脂肪量的积累，但不会改变体重、IR或PGC1α。HF和HF+600Q中PGC1α表达与酰基肉碱水平相关性相似；这些相关性在HF+50Q中不存在。在这两个时间点，HF+50Q时能量消耗增加，HF+600Q时能量消耗减少，与PGC1α和IR无关。低剂量而非高剂量的长期膳食补充槲皮素可以改善饮食诱导的IR的发展，同时增加肌肉中PGC1α的表达，这表明骨骼肌可能是低剂量槲皮素胰岛素增敏作用的重要靶点。
High fat diet (HFD)-induced insulin resistance (IR) is partially characterized by reduced skeletal muscle mitochondrial function and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) expression. Our previous study showed that a high dose of the bioflavonoid quercetin exacerbated HFD-induced IR; yet, others have demonstrated that quercetin improves insulin sensitivity. The aim of this study was to investigate whether differing doses of quercetin act in a time-dependent manner to attenuate HFD-induced IR in association with improved skeletal muscle mitochondrial function and PGC1α expression. C57BL/6J mice were fed HFD for 3 or 8 wks, with or without a low (50 ug/day; HF+50Q) or high (600 ug/day, HF+600Q) dose of quercetin. Whole body and metabolic phenotypes and insulin sensitivity were assessed. Skeletal muscle metabolomic analysis of acylcarnitines and PGC1α mRNA expression via qRT-PCR were measured. Quercetin at 50 ug/day for 8 wk attenuated HFD-induced increases in fat mass, body weight and IR and increased PGC1α expression, whereas 600 ug/day of quercetin exacerbated fat mass accumulation without altering body weight, IR or PGC1α. PGC1α expression correlated with acylcarnitine levels similarly in HF and HF+600Q; these correlations were not present in HF+50Q. At both time points, energy expenditure increased in HF+50Q and decreased in HF+600Q, independent of PGC1α and IR. Chronic dietary quercetin supplementation at low but not higher dose ameliorates the development of diet-induced IR while increasing PGC1α expression in muscle, suggesting that skeletal muscle may be an important target for the insulin-sensitizing effects of a low dose of quercetin.
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