Browsing by Author "Kao, Hao-Han"

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    Exercise training upregulates SIRT1 to attenuate inflammation and metabolic dysfunction in kidney and liver of diabetic db/db mice
    (2019-04-02) Liu, Hung-Wen; Kao, Hao-Han; Wu, Chi-Hang
    Abstract Background Chronic inflammation and metabolic dysregulation may eventually cause tissue damage in obesity-related diseases such as type 2 diabetes. The effects of SIRT1 on integration of metabolism and inflammation may provide a therapeutic target for treatment of obesity-related diseases. We examined the underlying mechanism of moderate intensity aerobic exercise on kidney and liver in obese diabetic db/db mice, mainly focusing on inflammation and metabolic dysfunction. Methods Functional and morphological alterations and metabolic and inflammatory signaling were examined in type 2 diabetic db/db mice with or without exercise training (5.2 m/min, 1 h/day, and 5 days/week for a total of 8 weeks). Results Exercise training prevented weight gain in db/db + Ex mice, but it did not reduce glucose and insulin levels. Exercise lowered serum creatinine, urea, and triglyceride levels and hepatic AST and ALT activity in db/db + Ex mice. Reduced kidney size and morphological alterations including decreased glomerular cross-sectional area and hepatic macrovesicles were observed in db/db + Ex mice compared with untrained db/db mice. Mechanistically, preventing loss of SIRT1 through exercise was linked to reduced acetylation of NF-κB in kidney and liver of db/db + Ex mice. Exercise increased citrate synthase and mitochondrial complex I activity, subunits of mitochondrial complexes (I, II, and V) and PGC1α at protein level in kidney of db/db + Ex mice compared with non-exercise db/db mice. Changes in enzyme activity and subunits of mitochondrial complexes were not observed in liver among three groups. Conclusion Exercise-induced upregulation of SIRT1 attenuates inflammation and metabolic dysfunction, thereby alleviating the progression of diabetic nephropathy and hepatic steatosis in type 2 diabetes mellitus.
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    有氧運動訓練調控能量代謝路徑對糖尿病db/db小鼠腎功能之影響
    (2019) 高浩瀚; Kao, Hao-Han
    Sirtuin 1（SIRT1）、AMP-activated protein kinase （AMPK）及peroxisome proliferator-activated receptor gamma coactivator 1-α （PGC1-α）為細胞內調節能量代謝的關鍵樞紐，AMPKα/SIRT1/PGC1α路經的受損伴隨粒線體失能是導致糖尿病腎臟病的機轉之一。長期規律有氧運動可以改善早期糖尿病腎臟病變，避免病症繼續惡化。然而，運動訓練經由AMPKα/SIRT1/PGC1α路徑改善糖尿病腎病變的機制，目前仍尚未釐清。本研究假設為有氧運動訓練能上調腎臟中代謝路徑以及同時抑制發炎路徑的活化，達到改善早期糖尿病腎病變的效果。方法：本研究使用糖尿病動物模式，5週齡 BKS.CgDock7m +/+ Leprdb/J（db/db）小鼠購至國家實驗動物中心，實驗動物在適應一周後，隨機分配控制組（n=8）及運動組（n=8）。運動處方：跑步速度為5.2m/min，每天運動1小時，每週訓練 5 天，共進行 8 週。運動訓練結束後將小鼠犧牲，以PAS染色法觀察腎臟組織型態，西方墨點法（Western blot analyses）分析能量代謝（AMPKα/SIRT1/PGC1-α）及發炎路徑（IκB-α/NF-κB）。結果：八週有氧運動訓練後可以改善db/db小鼠腎絲球基質膜擴張，並增加 SIRT1蛋白表現及AMPKα活性，同時抑制NF-κB磷酸化。IκB-α、PGC1-α在運動組及控制組間無顯差異。結論：本研究證實有氧運動訓練是透過活化能量代謝路徑和抑制發炎路徑來延緩糖尿病腎病變惡化。