Division of Life Science, Department of Pharmacy, Hokkaido University of Science, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido 006-8585, Japan.
Division of Life Science, Department of Pharmacy, Hokkaido University of Science, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido 006-8585, Japan.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Aug;1865(8):158726. doi: 10.1016/j.bbalip.2020.158726. Epub 2020 Apr 23.
Although obesity contributes to the onset and pathogenesis of metabolic diseases, it has been repeatedly demonstrated that being overweight or mildly obese carries a survival advantage compared with being thin or normal-weight. This relationship is called the obesity paradox. Hence, it is necessary to clarify the underlying mechanism of obesity onset for the prevention and treatment of these diseases. Catalase is distributed in peroxisomes under normal redox conditions and catalase activity is increased during the differentiation of 3T3-L1 preadipocytes to adipocytes. Although peroxisomes are responsible for lipid metabolism, the role of peroxisomal catalase in the process of lipid accumulation remains unclear. The present study aimed to investigate the relationships among catalase activity, peroxisome content, and lipid accumulation during the differentiation of 3T3-L1 preadipocytes to adipocytes. Increased catalase activity and lipid accumulation were observed during the differentiation of preadipocytes. Silencing of catalase by small interfering RNA or treatment with 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor, resulted in reduced lipid accumulation. Inhibition of catalase activity in peroxisomes increases hydrogen peroxide (HO) levels, which results in a reduction of peroxisome content. Extracellular HO had no influence on lipid accumulation during differentiation. The occurrence of autophagy was clearly enhanced in cells treated with 3-AT. Spautin-1, an inhibitor of autophagy flux, protected against a reduction in lipid accumulation by treatment with 3-AT. Our data provide evidence that catalase protects against the degradation of peroxisomes via the occurrence of autophagy triggered by the generation of HO in peroxisomes. These results suggest that catalase in peroxisomes is crucial to adipogenesis.
虽然肥胖会导致代谢性疾病的发生和发病机制，但反复的研究表明，与消瘦或体重正常相比，超重或轻度肥胖具有生存优势。这种关系被称为肥胖悖论。因此，有必要阐明肥胖发生的潜在机制，以预防和治疗这些疾病。
过氧化氢酶在正常氧化还原条件下分布于过氧化物酶体中，并且在 3T3-L1 前脂肪细胞分化为脂肪细胞的过程中过氧化氢酶活性增加。虽然过氧化物体负责脂质代谢，但过氧化物体过氧化氢酶在脂质积累过程中的作用尚不清楚。本研究旨在探讨 3T3-L1 前脂肪细胞分化为脂肪细胞过程中过氧化氢酶活性、过氧化物体含量和脂质积累之间的关系。
在前脂肪细胞的分化过程中观察到过氧化氢酶活性和脂质积累增加。用小干扰 RNA 沉默过氧化氢酶或用过氧化氢酶抑制剂 3-氨基-1,2,4-三唑（3-AT）处理会导致脂质积累减少。过氧化物体中过氧化氢酶活性的抑制会增加过氧化氢（HO）水平，从而导致过氧化物体含量减少。细胞外 HO 对分化过程中的脂质积累没有影响。在用 3-AT 处理的细胞中，自噬的发生明显增强。自噬通量抑制剂 Spautin-1 可防止 3-AT 处理导致的脂质积累减少。
我们的数据提供了证据表明，过氧化氢酶通过过氧化物体中 HO 的产生触发的自噬来防止过氧化物体的降解，从而保护过氧化物体。这些结果表明，过氧化物体中的过氧化氢酶对于脂肪生成至关重要。
