Background. How low-level psychological stress and overnutrition interact in influencing cardiometabolic disease is unclear. Mechanistic overlaps suggest potential synergies, however findings are contradictory. We test whether low level stress and Western diet (WD) feeding synergistically influence homeostasis, mood and myocardial ischemic tolerance. Methods. Male C57Bl6/J mice were fed a control or WD (32%/57%/11% calories from fat/carbohydrates/protein) for 12 wks, with subgroups restrained for 30 min/day over the final 3 wks. Metabolism, behavior, tolerance of perfused hearts to ischemia/reperfusion (I/R), and cardiac 'death proteins' were assessed. Results. The WD resulted in insignificant trends to increased body weight (+5%), glucose (+40%), insulin (+40%), triglycerides (+15%) and cholesterol (+20%), and reduced leptin (-20%), while significantly reducing insulin sensitivity (100% rise in HOMA-IR, P<0.05). Restraint did not independently influence metabolism, while increasing HOMA-IR a further 50% (and resulting in significant elevations in insulin and glucose to 60-90% above control) in WD mice (P<0.05), despite blunting weight gain in control and WD mice. Anxiogenesis with restraint or WD was non-additive, whereas anhedonia (reduced sucrose consumption) only arose with their combination. Neuroinflammation markers (hippocampal TNF-a, Il-1b) were unchanged. Myocardial I/R tolerance was unaltered with stress or WD alone, while combination worsened dysfunction and oncosis (LDH efflux). Apoptosis (nucleosome accumulation) and death protein expression (BAK, BAX, BCL-2, RIP-1, TNF-α, cleaved caspase-3 and PARP) were unchanged. Conclusion. Mild, anxiogenic yet cardio-metabolically 'benign' stress interacts synergistically with a WD to disrupt homeostasis, promote anhedonia (independently of neuroinflammation), and impair myocardial ischemic tolerance (independently of apoptosis and death protein levels).

中文翻译：

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低水平压力和西式饮食对代谢稳态，情绪和心肌缺血耐受的协同作用。

背景。尚不清楚低水平的心理压力和营养过剩如何影响心脏代谢疾病。机械重叠表明潜在的协同作用，但是发现是矛盾的。我们测试低水平压力和西式饮食（WD）是否协同影响稳态，情绪和心肌缺血耐受性。方法。给雄性C57B16 / J小鼠喂食对照或WD（脂肪/碳水化合物/蛋白质的卡路里为32％/ 57％/ 11％卡路里），持续12周，在最后3周中，每天将亚组限制30分钟。评估了代谢，行为，灌注心脏对缺血/再灌注（I / R）的耐受性以及心脏“死亡蛋白”。结果。WD导致体重增加（+ 5％），葡萄糖（+ 40％），胰岛素（+ 40％），甘油三酸酯（+ 15％）和胆固醇（+ 20％）和瘦素减少（-20）的趋势不明显％），同时显着降低胰岛素敏感性（HOMA-IR升高100％，P <0.05）。拘束并没有独立影响代谢，尽管对照组和对照组的体重增加缓慢，但WD小鼠的HOMA-IR进一步增加了50％（并导致胰岛素和葡萄糖显着升高至对照组的60-90％以上）（P <0.05）。 WD小鼠。具有约束作用或WD的血管生成是非加性的，而只有它们的组合才引起快感缺乏症（减少蔗糖消耗）。神经炎症标记（海马TNF-a，II-1b）未改变。单独施加压力或WD可使心肌I / R耐受性保持不变，而合并使用会使功能障碍和肿瘤恶化（LDH外排）。细胞凋亡（核小体积累）和死亡蛋白表达（BAK，BAX，BCL-2，RIP-1，TNF-α，裂解的caspase-3和PARP）均未改变。结论。轻度，