Sweeney P, O'Hara K, Xu Z, Yang Y
Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY, USA.
Int J Obes (Lond). 2017 Aug;41(8):1237-1245. doi: 10.1038/ijo.2017.112. Epub 2017 May 3.
The association between the development of obesity and its metabolic comorbidities, and chronic consumption of high-fat diet (HFD) has been well-demonstrated. Interestingly, emerging evidence indicates that obesity is also associated with an increased risk for psychiatric disorders including anxiety and depression. Although HFD feeding is associated with anxiety-related behaviors, previous studies have reported inconsistent findings on the direction of this relationship. Therefore, in this study we sought to investigate the link between HFD feeding, body weight, energy states and anxiety levels in mice and specifically to determine if the duration of HFD exposure has distinct effects on anxiety-related behaviors.
To disentangle the temporal dynamic effects of HFD feeding on anxiety-related behaviors, mice were fed a HFD or regular chow (RC) diet and were assayed periodically for anxiety-related behaviors by using behavioral tests (open field test; OFT) and the elevated plus maze. To determine if obesity phenotypes correlate with anxiety-related behaviors, changes in anxiety-related behaviors in OFTs were correlated with changes in both body weight and glucose sensitivity following various levels of HFD and RC exposure.
Our results demonstrate a time-dependent biphasic effect of HFD feeding on anxiety-related behaviors. At 5 weeks, mice fed HFD show a reduction in anxiety-related behaviors when compared to pair-fed RC mice. At 8 weeks of HFD or RC feeding, anxiety levels were the same in both groups. Following 15 weeks of HFD and RC feeding, however, mice displaying metabolic symptoms of obesity showed increased anxiety-related behaviors relative to mice resilient to obesity phenotypes, independent of feeding conditions.
Taken together our findings suggest that HFD bi-directionally effects anxiety-related behaviors such that short-term exposure to a HFD reduces anxiety levels, while longer exposure to a HFD promotes anxiety levels selectively in mice that display metabolic symptoms of obesity. Regardless of diet (HFD or RC), heavier animals display increased anxiety-like behaviors. These findings indicate diverse overlapping roles for HFD and body weight in modulating anxiety-related behaviors, and may partly resolve previous inconsistencies in studies examining the relationship between HFD feeding and anxiety.
肥胖及其代谢合并症的发展与长期食用高脂饮食（HFD）之间的关联已得到充分证实。有趣的是，新出现的证据表明，肥胖还与包括焦虑和抑郁在内的精神疾病风险增加有关。尽管高脂饮食喂养与焦虑相关行为有关，但先前的研究报告了这种关系方向上不一致的结果。因此，在本研究中，我们试图探究高脂饮食喂养、体重、能量状态与小鼠焦虑水平之间的联系，特别是确定高脂饮食暴露的持续时间是否对焦虑相关行为有不同影响。
为了厘清高脂饮食喂养对焦虑相关行为的时间动态影响，给小鼠喂食高脂饮食或常规饲料（RC），并通过行为测试（旷场试验；OFT）和高架十字迷宫定期检测焦虑相关行为。为了确定肥胖表型是否与焦虑相关行为相关，在不同水平的高脂饮食和常规饲料暴露后，将旷场试验中焦虑相关行为的变化与体重和葡萄糖敏感性的变化进行关联。
我们的结果表明，高脂饮食喂养对焦虑相关行为具有时间依赖性的双相效应。在5周时，与配对喂养的常规饲料小鼠相比，喂食高脂饮食的小鼠焦虑相关行为减少。在高脂饮食或常规饲料喂养8周时，两组的焦虑水平相同。然而，在高脂饮食和常规饲料喂养15周后，表现出肥胖代谢症状的小鼠相对于对肥胖表型有抵抗力的小鼠，焦虑相关行为增加，与喂养条件无关。
综合我们的研究结果表明，高脂饮食对焦虑相关行为有双向影响，即短期暴露于高脂饮食可降低焦虑水平，而长期暴露于高脂饮食则选择性地促进表现出肥胖代谢症状的小鼠的焦虑水平。无论饮食（高脂饮食或常规饲料）如何，较重的动物表现出更多的焦虑样行为。这些发现表明高脂饮食和体重在调节焦虑相关行为中具有多种重叠作用，并且可能部分解决先前研究中关于高脂饮食喂养与焦虑之间关系的不一致之处。
