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 (H2O2) levels, which results in a reduction of peroxisome content. Extracellular H2O2 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 H2O2 in peroxisomes. These results suggest that catalase in peroxisomes is crucial to adipogenesis.

中文翻译：

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过氧化氢酶是脂肪形成过程中过氧化物酶体维持所必需的。

尽管肥胖有助于代谢疾病的发作和发病机理，但已经反复证明，与瘦或正常体重相比，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，有必要弄清楚肥胖发作的潜在机制，以预防和治疗这些疾病。在正常氧化还原条件下，过氧化氢酶分布在过氧化物酶体中，并且在3T3-L1前脂肪细胞向脂肪细胞的分化过程中过氧化氢酶活性增加。尽管过氧化物酶体负责脂质代谢，但过氧化物酶体过氧化氢酶在脂质积累过程中的作用仍不清楚。本研究旨在调查过氧化氢酶活性，过氧化物酶体含量，和3T3-L1前脂肪细胞向脂肪细胞分化过程中脂质的积累。在前脂肪细胞分化过程中观察到过氧化氢酶活性和脂质积累增加。通过小的干扰RNA沉默过氧化氢酶或用3-氨基-1,2,4-三唑（3-AT）（一种过氧化氢酶抑制剂）进行处理，会导致脂质积聚减少。过氧化物酶体中过氧化氢酶活性的抑制会增加过氧化氢（H2O2）的水平，从而导致过氧化物酶体含量的减少。细胞外过氧化氢对分化过程中脂质的积累没有影响。用3-AT处理的细胞中自噬的发生明显增强。Spautin-1是自噬通量的抑制剂，通过用3-AT处理可防止脂质堆积减少。我们的数据提供了证据，过氧化氢酶通过过氧化物酶体中过氧化氢的生成触发自噬的发生，从而防止过氧化物酶体的降解。这些结果表明过氧化物酶体中的过氧化氢酶对脂肪形成至关重要。