Cheserek Maureen Jepkorir, Wu Guirong, Li Longnan, Li Lirong, Karangwa Eric, Shi Yonghui, Le Guowei
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province, China; Department of Human Nutrition, Faculty of Health Science, Egerton University, Egerton, Rift Valley, Kenya.
State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province, China.
J Nutr Biochem. 2016 Jul;33:36-44. doi: 10.1016/j.jnutbio.2016.02.008. Epub 2016 Mar 21.
This study investigated possible mechanisms for cardioprotective effects of lipoic acid (LA), quercetin (Q) and resveratrol (R) on oxidative stress related to thyroid hormone alterations in long-term obesity. Female C57BL/6 mice were fed on high-fat diet (HFD), HFD+LA, HFD+R, HFD+Q and normal diet for 26weeks. Body weight, blood pressure, thyroid hormones, oxidative stress markers, angiotensin converting enzyme (ACE), nitric oxide synthase (NOS) and ion pump activities were measured, and expression of cardiac genes was analyzed by real-time polymerase chain reaction. HFD induced marked increase (P<.05) in body weight, blood pressure and oxidative stress, while plasma triidothyronine levels reduced. ACE activity increased (P<.05) in HFD mice (0.69±0.225U/mg protein) compared with controls (0.28±0.114U/mg protein), HFD+LA (0.231±0.02U/mg protein) and HFD+Q (0.182±0.096U/mg protein) at 26weeks. Moreover, Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities increased in HFD mice whereas NOS reduced. A 1.5-fold increase in TRα1 and reduction in expression of the deiodinase iodothyronine DIO1, threonine protein kinase and NOS3 as well as up-regulation of AT1α, ACE, ATP1B1, GSK3β and Cja1 genes also occurred in HFD mice. Conversely, LA, Q and R inhibited weight gain; reduced TRα1 expression as well as increased DIO1; reduced ACE activity and AT1α, ATP1B1 and Cja1 gene expression as well as inhibited GSK3β; increased total antioxidant capacity, GSH and catalase activity; and reduced blood pressure. In conclusion, LA, resveratrol and quercetin supplementation reduces obesity thereby restoring plasma thyroid hormone levels and attenuating oxidative stress in the heart and thus may have therapeutic potential in heart diseases.
本研究调查了硫辛酸（LA）、槲皮素（Q）和白藜芦醇（R）对长期肥胖中与甲状腺激素改变相关的氧化应激的心脏保护作用的可能机制。将雌性C57BL/6小鼠分别用高脂饮食（HFD）、HFD+LA、HFD+R、HFD+Q和正常饮食喂养26周。测量体重、血压、甲状腺激素、氧化应激标志物、血管紧张素转换酶（ACE）、一氧化氮合酶（NOS）和离子泵活性，并通过实时聚合酶链反应分析心脏基因的表达。HFD导致体重、血压和氧化应激显著增加（P<0.05），而血浆三碘甲状腺原氨酸水平降低。与对照组（0.28±0.114U/mg蛋白质）、HFD+LA（0.231±0.02U/mg蛋白质）和HFD+Q（0.182±0.096U/mg蛋白质）相比，26周时HFD小鼠的ACE活性增加（P<0.05）（0.69±0.225U/mg蛋白质）。此外，HFD小鼠的Na(+)/K(+)-ATP酶和Ca(2+)-ATP酶活性增加，而NOS降低。HFD小鼠的TRα1增加了1.5倍，脱碘酶碘甲状腺原氨酸DIO1、苏氨酸蛋白激酶和NOS3的表达降低，以及AT1α、ACE、ATP1B1、GSK3β和Cja1基因上调。相反，LA、Q和R抑制体重增加；降低TRα1表达以及增加DIO1；降低ACE活性和AT1α、ATP1B1和Cja1基因表达以及抑制GSK3β；增加总抗氧化能力、谷胱甘肽和过氧化氢酶活性；并降低血压。总之，补充LA、白藜芦醇和槲皮素可减轻肥胖，从而恢复血浆甲状腺激素水平并减轻心脏中的氧化应激，因此可能对心脏病具有治疗潜力。
