Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Hypertens Res. 2018 Aug;41(8):589-597. doi: 10.1038/s41440-018-0058-9. Epub 2018 Jun 12.
Activating transcription factor 3 (ATF3) has been implicated in cardiovascular disease and inflammation. This study examined the effects of ATF3 knockout (KO) on blood pressure, glucose intolerance, dyslipidemia, inflammation, and visceral adiposity in mice fed who did and did not consume a high-fructose diet. Male mice were divided into four groups (N = 15 for each group): the Con (control) group (wild-type mice fed a standard chow diet), Fru group (wild-type mice fed a high-fructose [60% fructose] diet), ATF3KO-Con group (ATF3 KO mice fed a standard chow diet), and ATF3KO-Fru group (ATF3 KO mice fed a high-fructose [60% fructose] diet). Experiments were conducted for 8 weeks. Our data demonstrated that ATF3 KO mice have lower systolic blood pressure (SBP) levels than do wild-type mice, and that high-fructose diets increase SBP levels in both wild-type and ATF3 KO mice. ATF3 KO in mice increased the serum levels of glucose, insulin, triglycerides, tumor necrosis factor-alpha, and intercellular adhesion molecule-1, impaired endothelium-dependent aortic relaxation, increased aorta wall thickness and lipid peroxide, and expanded visceral adiposity. These symptoms resembled those exhibited by the wild-type mice fed a high-fructose diet, which caused hyperglycemia, insulin resistance, dyslipidemia, endothelium-dependent aortic dysfunction, inflammation, aorta remodeling, and visceral adiposity. A high-fructose diet among ATF3 KO mice deteriorated metabolic parameters and inflammatory cytokines. The present results therefore suggest that ATF3 deficiency is involved in the pathogenesis of metabolic syndrome and ATF3 might have a therapeutic role in fructose-induced impairment of endothelium-dependent aortic relaxation, a rising of inflammatory cytokines, and metabolic syndrome.
激活转录因子 3（ATF3）已被牵连到心血管疾病和炎症中。本研究检测了 ATF3 敲除（KO）对喂食高果糖饮食和不喂食高果糖饮食的小鼠的血压、葡萄糖不耐受、血脂异常、炎症和内脏肥胖的影响。雄性小鼠被分为四组（每组 15 只）：对照组（喂食标准饮食的野生型小鼠）、Fru 组（喂食高果糖[60%果糖]饮食的野生型小鼠）、ATF3KO-Con 组（喂食标准饮食的 ATF3 KO 小鼠）和 ATF3KO-Fru 组（喂食高果糖[60%果糖]饮食的 ATF3 KO 小鼠）。实验进行了 8 周。我们的数据表明，ATF3 KO 小鼠的收缩压（SBP）水平低于野生型小鼠，而高果糖饮食会增加野生型和 ATF3 KO 小鼠的 SBP 水平。小鼠的 ATF3 KO 增加了血清中葡萄糖、胰岛素、甘油三酯、肿瘤坏死因子-α和细胞间黏附分子-1 的水平，损害了主动脉内皮依赖性松弛，增加了主动脉壁厚度和脂质过氧化物，并扩大了内脏肥胖。这些症状类似于喂食高果糖饮食的野生型小鼠所表现出的症状，高果糖饮食会导致高血糖、胰岛素抵抗、血脂异常、内皮依赖性主动脉功能障碍、炎症、主动脉重塑和内脏肥胖。ATF3 KO 小鼠的高果糖饮食恶化了代谢参数和炎症细胞因子。因此，本研究结果表明，ATF3 缺乏参与代谢综合征的发病机制，ATF3 可能在果糖诱导的内皮依赖性主动脉松弛受损、炎症细胞因子升高和代谢综合征中具有治疗作用。
