探討有氧運動、阻力運動、間歇性高強度運動對於 高脂誘導肥胖小鼠產熱脂肪細胞與白脂褐化之影響

Abstract

背景 全球肥胖的盛行率持續上升，已對公共健康造成重大威脅。促進能量消耗的產熱脂肪細胞被視為具有潛力對抗肥胖的新興治療目標。本研究旨在探討有氧運動、阻力運動、及間歇性高強度訓練對於高脂誘導肥胖小鼠產熱脂肪細胞與白脂褐化之影響。此外，我們亦進一步探討有氧運動對於肥胖小鼠骨骼肌與副睪白色脂肪蛋白質體變化的影響。 方法 本研究首先將50隻6週齡的C57BL/6 雄性小鼠分為對照組和高脂飼料誘導肥胖組。經過8 週的肥胖誘導後，肥胖小鼠再被分為靜態、有氧運動、阻力運動和間歇性高強度訓練四組，分別進行為期8 週的運動訓練介入。接著使用液相層析串聯質譜儀分析小鼠骨骼肌和副睪白色脂肪之蛋白質體，並針對顯著表現差異的蛋白質以Gene Ontology和Ingenuity Pathway Analysis進行生物資訊分析。 結果 有氧運動、阻力運動和間歇性高強度運動均有助於顯著下降體重，並改善葡萄糖耐受性、總膽固醇和低密度脂蛋白膽固醇等代謝指標。然而，其中僅有氧運動顯著增加血中鳶尾素（Irisin）濃度、改善胰島素阻抗、及增加副睪白色脂肪產熱相關基因（如：Prdm16、Cidea和Pgc-1α）的表現。透過蛋白質體分析，我們進一步發現有氧運動透過調控骨骼肌及副睪白色脂肪之相關蛋白質，達到影響粒線體功能、改善胰島素敏感性，同時促進白脂褐化之機轉。 結論 我們的研究結果顯示，不同運動模式對於產熱脂肪細胞會有不同的影響。有氧運動可以顯著增加白色脂肪產熱基因的表現，並調節影響胰島素敏感性和白脂褐化的蛋白質。本研究提供了有關有氧運動誘導白脂褐化背後分子機轉的見解，冀盼有助於未來發展以產熱脂肪細胞為基礎之類運動治療模式。

Background Global prevalence of obesity has continued to rise and poses significant public health concerns. Thermogenic fat cells that increase energy expenditure may be a promising alternative target to combat obesity. Our study aims to investigate the effects of aerobic exercise (AE), resistance exercise (RE), and high-intensity interval training (HIIT) on thermogenic fat cells and browning of white adipose tissue (WAT). Furthermore, we sought to examine the proteomic alterations induced by AE in skeletal muscle and epididymal fat pad (EFP) of high fat diet induced obese mice. Methods Fifty 6-week-old male C57BL/6 mice were initially divided into control group and high-fat-diet obesity induction group. After 8 weeks of obesity induction, obese mice were further subdivided into sedentary, AE, RE, and HIIT groups. Trained obese mice were submitted to 8 weeks of exercise. Liquid chromatography-mass spectrometry was used to detect skeletal muscle and EFP proteins, and bioinformatic analyses were conducted on differentially regulated proteins using Gene Ontology enrichment analysis and Ingenuity Pathway Analysis. Results All three types of exercises significantly attenuated diet-induced obesity, and improved metabolic profiles including glucose tolerance, total cholesterol, and low-density lipoprotein cholesterol. Moreover, AE significantly increased serum irisin level, improved the homeostatic model assessment of insulin resistance, and increased thermogenic gene expressions such as Prdm16, Cidea, and Pgc-1α in EFP of obese mice. Furthermore, AE regulated skeletal muscle proteins that affect mitochondrial function and insulin sensitivity, while promoting proteins involved in the browning of WAT in EFP. Conclusion Our findings suggest that the modality of exercise should be considered when it comes to the adaptation of thermogenic fat cells. AE significantly increased thermogenic gene expression and regulated proteins that affect insulin resistance and browning of WAT. Our study provides insights into the molecular responses underlying the beneficial effects of AE and may contribute to the development of exercise-mimicking therapeutic targets.