Landgraf Kathrin, Schuster Susanne, Meusel Andrej, Garten Antje, Riemer Thomas, Schleinitz Dorit, Kiess Wieland, Körner Antje
Center for Pediatric Research Leipzig (CPL), University Hospital for Children & Adolescents, University of Leipzig, Liebigstraße 21, 04103, Leipzig, Germany.
Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.
BMC Physiol. 2017 Mar 21;17(1):4. doi: 10.1186/s12899-017-0031-x.
Obese individuals differ in their risk of developing metabolic and cardiovascular complications depending on fat distribution (subcutaneous versus visceral) and adipose tissue (AT) phenotype (hyperplasic versus hypertrophic). However, the exact mechanisms which determine whether an obese individual is metabolically healthy or unhealthy are not clear, and analyses of the underlying pathomechanisms are limited by the lack of suitable in vivo models in which metabolically healthy versus metabolically unhealthy AT accumulation can be specifically induced. In the current study, we aimed to establish a protocol for the use of zebrafish as a model for obesity-related metabolically healthy versus metabolically unhealthy AT accumulation.
We overfed adult male zebrafish of the AB strain with normal fat diet (NFD) or high fat diet (HFD) for 8 weeks and compared parameters related to obesity, i.e. body weight, body mass index, condition index and body fat percentage, to control zebrafish fed under physiological conditions. In addition, we investigated the presence of early obesity-related metabolic alterations by quantifying blood glucose levels, plasma triglyceride and cholesterol levels, and by assessing ectopic lipid accumulation in the liver of zebrafish. Finally, we determined gene expression levels of marker genes related to lipid metabolism, inflammation and fibrosis in visceral AT and liver.
We show that 8-weeks overfeeding with either NFD or HFD leads to a significant increase in body weight and AT mass compared to controls. In contrast to NFD-overfed zebrafish, HFD-overfed zebrafish additionally present metabolic alterations, e.g. hyperglycemia and ectopic lipid accumulation in the liver, and a metabolically unhealthy AT phenotype with adipocyte hypertrophy especially in the visceral AT depot, which is accompanied by changes in the expression of marker genes for lipid metabolism, inflammation and fibrosis.
In summary, we have established a method for the specific induction of metabolically distinct obesity phenotypes in zebrafish. Our results indicate that zebrafish represents an attractive model to study regulatory mechanisms involved in the determination of AT phenotype during development of metabolically healthy versus metabolically unhealthy obesity.
肥胖个体发生代谢和心血管并发症的风险因脂肪分布（皮下与内脏）和脂肪组织（AT）表型（增生性与肥大性）而异。然而，决定肥胖个体代谢健康或不健康的具体机制尚不清楚，且由于缺乏合适的体内模型来特异性诱导代谢健康与代谢不健康的AT积累，对潜在病理机制的分析受到限制。在本研究中，我们旨在建立一种使用斑马鱼作为肥胖相关代谢健康与代谢不健康AT积累模型的方案。
我们用正常脂肪饮食（NFD）或高脂肪饮食（HFD）对成年雄性AB品系斑马鱼进行8周过度喂养，并将与肥胖相关的参数，即体重、体重指数、条件指数和体脂百分比，与在生理条件下喂养的对照斑马鱼进行比较。此外，我们通过量化血糖水平、血浆甘油三酯和胆固醇水平，并评估斑马鱼肝脏中的异位脂质积累，来研究早期肥胖相关代谢改变的存在情况。最后，我们测定了内脏AT和肝脏中与脂质代谢、炎症和纤维化相关的标记基因的表达水平。
我们发现，与对照组相比，用NFD或HFD进行8周过度喂养均导致体重和AT质量显著增加。与NFD过度喂养的斑马鱼不同，HFD过度喂养的斑马鱼还出现代谢改变，如高血糖和肝脏中的异位脂质积累，以及代谢不健康的AT表型，尤其是在内脏AT库中出现脂肪细胞肥大，这伴随着脂质代谢、炎症和纤维化标记基因表达的变化。
总之，我们建立了一种在斑马鱼中特异性诱导代谢不同的肥胖表型的方法。我们的结果表明，斑马鱼是研究代谢健康与代谢不健康肥胖发展过程中AT表型决定机制的有吸引力的模型。
