果蝇在肥胖及相关代谢性疾病研究中的应用与进展

doi:10.12300/j.issn.1674-5817.2025.104

摘要/Abstract

摘要：

肥胖是一种由能量摄入与消耗长期失衡引起的慢性代谢性疾病，该病可显著增加心血管疾病、2型糖尿病、多种癌症及早衰等风险。世界卫生组织最新统计结果显示，全球成年人超重与肥胖率持续攀升，肥胖已成为亟待精准防治的公共卫生难题。本综述系统总结了黑腹果蝇（Drosophila melangaster）作为模式生物在肥胖代谢研究中的独特价值与应用进展。果蝇因其生命周期短、饲养成本低、器官功能保守且与人类疾病相关基因高度同源，以及遗传工具完善，已成为解析肥胖与代谢紊乱的高效模式生物。通过给果蝇饲喂高糖/高脂饮食可稳定复制脂质蓄积、胰岛素抵抗、心脏代谢功能受损与寿命缩短等典型肥胖相关表型，并可与组织或细胞类型特异性遗传的操控结合，用于靶点发现与机制验证。在器官层面，果蝇脂肪体是储能、代谢感应和内分泌调节的中枢；绛色细胞参与脂质、固醇与超长链脂肪酸代谢及饥饿应答；中肠通过区域化吸收与肠内分泌的功能来整合来自营养物质与肠道微生物的信号；马氏管除排泄功能外，还通过调控能量感应信号通路的表达与葡萄糖转运体的膜定位，调控自身重吸收水平并影响代谢和生长发育；肌肉是果蝇主要的能量消耗器官，其中飞行肌的能量需求最旺盛，以血淋巴中的海藻糖和葡萄糖作为主要的能量供给，同时可动员糖原与脂肪酸参与能量代谢，并通过肌源性因子调节全身体内代谢稳态。此外，昼夜节律与进食时间可重塑外周时钟-代谢耦合，缓解饮食诱导的代谢紊乱。在跨器官内分泌调控网络中，脑部类胰岛素样肽生成细胞通过分泌胰岛素样肽降低血糖，从而促进代谢平衡；心侧体通过分泌脂动激素升高血糖并促进脂解，这两种内分泌系统相互拮抗，共同构成了果蝇体内关键的代谢稳态调控轴。脂肪体与肠道通过释放非配对蛋白2、限制素及类脂联素样因子，按营养状态调节胰岛素样肽的分泌，形成“肠-脂肪体-脑-外周器官”的多层次反馈环。综上所述，果蝇凭借其在器官功能与代谢通路的高度保守性，以及强大的遗传操作优势，为解析肥胖病因学机制、阐明跨组织信号网络、发掘潜在的转化靶点与评估营养/药物干预策略提供了高效、可拓展的实验平台。

关键词: 模式动物, 黑腹果蝇, 肥胖, 代谢紊乱, 糖脂代谢

Abstract:

Obesity is a chronic metabolic disease caused by long-term imbalance between energy intake and expenditure, which can significantly increase risks of cardiovascular diseases, type 2 diabetes, various cancers, and premature aging. The latest WHO statistics show that global overweight and obesity rates among adults continue to rise, making obesity a public health problem requiring urgent precise prevention and control. This review systematically summarizes the unique value and application advances of Drosophila melanogaster as a model organism in obesity and metabolic disease research. Due to its short life cycle, low rearing cost, high homology with human disease-related genes, conserved organ functions, and well-developed genetic tools, Drosophila has emerged as an efficient model organism for analyzing obesity and metabolic disorders. Feeding high-sugar/high-fat diets to Drosophila can stably replicate typical obesity-related phenotypes such as lipid accumulation, insulin resistance, impaired cardiometabolic function, and shortened lifespan, and can be combined with tissue- or cell type–specific genetic manipulations for target discovery and mechanism verification. At the organ level, the fat body functions as a central hub for energy storage, metabolic sensing, and endocrine regulation; oenocytes participate in lipid, sterol, and very-long-chain fatty acid metabolism and starvation response; the midgut integrates signals from nutrients and gut microbiota through regionalized absorption and enteroendocrine functions; the malpighian tubules, besides excretion, also regulate reabsorption and influence body size through energy sensing pathways and glucose transporter membrane localization. Muscles are the primary energy-consuming organs in Drosophila with flight muscles exhibiting the highest energy demand. They primarily utilize trehalose and glucose from the hemolymph for energy supply. Additionally, they can mobilize glycogen and fatty acids to participate in energy metabolism. Additionally, circadian rhythm and feeding time (such as time-restricted feeding) can reshape peripheral clock-metabolism coupling, alleviating diet-induced metabolic disorders. Moreover, they regulate systemic metabolic homeostasis through myogenic factors.In cross-organ endocrine regulatory network, brain insulin-like peptide producing cells secrete insulin-like peptides to lower blood sugar and promote metabolic balance, whereas the corpora cardiaca release adipokinetic hormone to increase blood sugar and stimulate lipolysis. These two endocrine systems functionally antagonize each other, together forming a key metabolic homeostasis regulatory axis in Drosophila. Fat body and intestine regulate insulin-like peptide secretion according to nutritional status by releasing Unpaired 2, Limostatin, and adiponectin-like factors, forming a multi-level "gut-fat body-brain-peripheral organ" feedback loop. In summary, Drosophila, with its highly conserved organ functions and metabolic pathways and its powerful genetic tools, provides an efficient and scalable experimental platform for analyzing obesity etiology, elucidating cross-tissue signaling networks, discovering potential translational targets, and evaluating nutritional/pharmacological intervention strategies.

Key words: Model animal, Drosophila melanogaster, Obesity, Metabolic disorder, Glucose and lipid metabolism

中图分类号:

Q964

陈浩田,刘竞男. 果蝇在肥胖及相关代谢性疾病研究中的应用与进展[J]. 实验动物与比较医学, 2025, 45(6): 688-704. DOI: 10.12300/j.issn.1674-5817.2025.104.

CHEN Haotian,LIU Jingnan. Applications and Advances of Drosophila in Research of Obesity and Its Related Metabolic Diseases[J]. Laboratory Animal and Comparative Medicine, 2025, 45(6): 688-704. DOI: 10.12300/j.issn.1674-5817.2025.104.

图/表 3

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