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高脂肪饮食对成年斑马鱼代谢和骨骼的影响。

Metabolic and bone effects of high-fat diet in adult zebrafish.

机构信息

Gruppo Ospedaliero San Donato Foundation, Milan, Italy.

Policlinico San Donato IRCCS, Milan, Italy.

出版信息

Endocrine. 2018 Aug;61(2):317-326. doi: 10.1007/s12020-017-1494-z. Epub 2017 Dec 22.

Abstract

An increase of visceral fat affects human bone health causing fragility, mechanical strength reduction, and increased propensity to fractures because of impaired bone matrix microstructure and aberrant bone cell function. Adult Danio rerio (zebrafish) represents a powerful model to study both metabolic diseases and bone metabolism. The aim of this study was to generate an obese adult zebrafish by high-fat diet and evaluate metabolic and bone tissue effects. Fish blood glucose and insulin levels were found to be altered in high-fat diet fish revealing a failure in β-cells insulin production. Blood analysis of adipokines revealed significant alterations in adiponectin and leptin levels that are common in human and other obesity animal models. Advanced glycation end products (AGEs), derived from hyperglycemia condition, were found to be altered too. All these alterations were associated with an impaired bone metabolism. The scales of high-fat diet fish shown bone resorption lacunae associated with an intense osteoclastic tartrate-resistant acid phosphatase (TRAP) activity, whereas alkaline phosphatase (ALP) decreased. These data suggest that an imbalance of fat metabolism alters energy metabolism generating an osteoporosis-like phenotype in adult zebrafish scales. The zebrafish obesity model can contribute to elucidate in vivo the molecular mechanisms of metabolic changes in human obese patients.

摘要

内脏脂肪的增加会影响人类骨骼健康,导致脆弱、机械强度降低,并增加骨折的倾向,因为骨骼基质微结构受损和骨细胞功能异常。成年斑马鱼(Danio rerio)是研究代谢疾病和骨骼代谢的强大模型。本研究的目的是通过高脂肪饮食生成肥胖的成年斑马鱼,并评估代谢和骨骼组织的影响。高脂肪饮食鱼类的血液葡萄糖和胰岛素水平发生改变,表明β细胞胰岛素产生失败。脂肪细胞因子的血液分析显示出脂联素和瘦素水平的显著改变,这在人类和其他肥胖动物模型中很常见。源自高血糖状态的晚期糖基化终产物(AGEs)也发生了改变。所有这些改变都与骨骼代谢受损有关。高脂肪饮食鱼类的鳞片显示出与强烈的破骨细胞抗酒石酸酸性磷酸酶(TRAP)活性相关的骨吸收陷窝,而碱性磷酸酶(ALP)降低。这些数据表明,脂肪代谢失衡会改变能量代谢,导致成年斑马鱼鳞片出现骨质疏松样表型。斑马鱼肥胖模型有助于阐明肥胖患者体内代谢变化的分子机制。

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