Effect of quercetin on nonshivering thermogenesis of brown adipose tissue in high-fat diet-induced obese mice.
Effect of quercetin on nonshivering thermogenesis of brown adipose tissue in high-fat diet-induced obese mice.
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DOI：
10.1016/j.jnutbio.2020.108532
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发表时间：
2020-10
期刊：
影响因子：
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通讯作者：
Ya Pei;Dammah Otieno;I. Gu;Sun-Ok Lee;J. Parks;K. Schimmel;H. Kang
中科院分区：
文献类型：
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作者：
Ya Pei;Dammah Otieno;I. Gu;Sun-Ok Lee;J. Parks;K. Schimmel;H. Kang
激活棕色脂肪组织（BAT）中的非颤抖产热是预防肥胖的一种有前景的策略。这项研究调查了补充槲皮素是否可以通过增加 BAT 中的非颤抖产热和白色脂肪组织 (WAT) 褐变来改善小鼠的肥胖。与高脂饮食 (HFD) 喂养的小鼠相比，饲喂补充有 1% 槲皮素 (HFDQ) 的 HFD 的小鼠体重和血浆总胆固醇降低。在 HFDQ 喂养的小鼠中，腹膜后 WAT (RWAT) 重量下降，褐变效应和脂肪分解增加。 HFDQ 喂养的小鼠 BAT 中非颤抖生热基因的表达增加，包括解偶联蛋白 1 (UCP1)、过氧化物酶体增殖物激活受体-γ 共激活子 1α (PGC1α)、诱导细胞死亡的 DFFA 样效应子 A (CIDEA) 和线粒体转录因子 A (mtTFA)。补充槲皮素可增加 HFD 喂养小鼠的 β3 肾上腺素受体 (ADRB3)、p38 丝裂原激活蛋白激酶 (MAPK) 和 AMP 激活蛋白激酶 (AMPK) 通路中的基因和蛋白，而 AMPK 抑制剂或 ADRB3 拮抗剂可抑制这些通路。槲皮素不会改变能量消耗和核心体温，但在室温和低温的黑暗时期，HFDQ 小鼠的体力活动增加。槲皮素还降低了厚壁菌门与拟杆菌门的比例，并增加了 HFD 喂养小鼠粪便中短链脂肪酸的产生。总之，给高脂饮食喂养的小鼠补充槲皮素可能会减轻肥胖。尽管该研究没有显示 BAT 功能和肥胖之间的分子和病理生理学数据的一致性，但它也显示了槲皮素对健康的良好影响，同时还可以改善体力活动和肠道微生物群失调。
Activating nonshivering thermogenesis in brown adipose tissue (BAT) is a promising strategy to prevent obesity. This study investigated whether quercetin supplementation improves obesity in mice by increasing nonshivering thermogenesis in BAT and white adipose tissue (WAT) browning. Compared to high-fat diet (HFD)-fed mice, mice fed a HFD supplemented with 1% quercetin (HFDQ) had reduced body weight and total plasma cholesterol. In HFDQ-fed mice, retroperitoneal WAT (RWAT) weight was decreased, and browning effect and lipolysis were increased. HFDQ-fed mice had increased expression of nonshivering thermogenesis genes in BAT, including uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α), cell death-inducing DFFA-like effector A (CIDEA), and mitochondrial transcriptional factor A (mtTFA). Quercetin supplementation increased genes and proteins in β3-adrenergic receptor (ADRB3), p38 mitogen-activated protein kinase (MAPK), and AMP-activated protein kinase (AMPK) pathways in HFD-fed mice, which were suppressed by an AMPK inhibitor or an ADRB3 antagonist. Energy expenditure and core body temperature were not changed by quercetin, but physical activity was increased in HFDQ mice during dark periods at room and cold temperatures. Quercetin also decreased the Firmicutes to Bacteroidetes ratio and increased short-chain fatty acid production in the feces of HFD-fed mice. In summary, quercetin supplementation in HFD-fed mice may attenuate obesity. Although the study did not show consistency in data at molecular and pathophysiological levels between BAT function and obesity, it also shows promising health effects of quercetin, accompanied by improved physical activity and gut microbiota dysbiosis.