Program in Biology, School of Sciences, University of Louisiana at Monroe, 700 University Avenue, Monroe, LA, 71209, USA.
J Comp Physiol B. 2019 Apr;189(2):179-198. doi: 10.1007/s00360-019-01209-9. Epub 2019 Feb 27.
Obesity predisposes humans to a range of life-threatening comorbidities, including type 2 diabetes and cardiovascular disease. Obesity also aggravates neural pathologies, such as Alzheimer's disease, but this class of comorbidity is less understood. When Drosophila melanogaster (flies) are exposed to high-fat diet (HFD) by supplementing a standard medium with coconut oil, they adopt an obese phenotype of decreased lifespan, increased triglyceride storage, and hindered climbing ability. The latter development has been previously regarded as a potential indicator of neurological decline in fly models of neurodegenerative disease. Our objective was to establish the obesity phenotype in Drosophila and identify a potential correlation, if any, between obesity and neurological decline through behavioral assays and gene expression microarray. We found that mated female w flies exposed to HFD maintained an obese phenotype throughout adult life starting at 7 days, evidenced by increased triglyceride stores, diminished life span, and impeded climbing ability. While climbing ability worsened cumulatively between 7 and 14 days of exposure to HFD, there was no corresponding alteration in triglyceride content. Microarray analysis of the mated female w fly head revealed HFD-induced changes in expression of genes with functions in memory, metabolism, olfaction, mitosis, cell signaling, and motor function. Meanwhile, an Aversive Phototaxis Suppression assay in mated female flies indicated reduced ability to recall an entrained memory 6 h after training. Overall, our results support the suitability of mated female flies for examining connections between diet-induced obesity and nervous or neurobehavioral pathology, and provide many directions for further investigation.
肥胖使人类易患一系列危及生命的合并症，包括 2 型糖尿病和心血管疾病。肥胖还会加重神经病理学，如阿尔茨海默病，但这类合并症的了解较少。当黑腹果蝇（苍蝇）通过在标准培养基中添加椰子油来补充高脂肪饮食（HFD）时，它们会表现出寿命缩短、甘油三酯储存增加和攀爬能力下降的肥胖表型。后者的发展以前被认为是神经退行性疾病果蝇模型中神经衰退的潜在指标。我们的目标是在果蝇中建立肥胖表型，并通过行为测定和基因表达微阵列来确定肥胖和神经衰退之间是否存在任何潜在相关性。我们发现，接受 HFD 处理的交配雌性 w 蝇从 7 天开始，在整个成年期都保持肥胖表型，表现为甘油三酯储存增加、寿命缩短和攀爬能力下降。虽然在暴露于 HFD 的 7 至 14 天期间，攀爬能力逐渐恶化，但甘油三酯含量没有相应变化。对交配雌性 w 蝇头部的基因表达微阵列分析显示，HFD 诱导了与记忆、代谢、嗅觉、有丝分裂、细胞信号和运动功能相关的基因表达变化。同时，在交配雌性蝇中进行的厌恶光回避抑制测定表明，在训练后 6 小时，它们回忆起已适应的记忆的能力降低。总体而言，我们的结果支持交配雌性蝇适合研究饮食诱导的肥胖与神经或神经行为病理学之间的联系，并为进一步研究提供了许多方向。
