Dutta Raghbendra Kumar, Lee Joon No, Maharjan Yunash, Park Channy, Choe Seong-Kyu, Ho Ye-Shih, Park Raekil
Department of Biomedical Science & Engineering, GRI, Gwangju Institute of Science & Technology, Gwangju, 61005, Republic of Korea.
Department of Microbiology and Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk, 54538, Republic of Korea.
Cell Biosci. 2021 Dec 7;11(1):201. doi: 10.1186/s13578-021-00710-5.
Fatty acids (FA) derived from adipose tissue and liver serve as the main fuel in thermogenesis of brown adipose tissue (BAT). Catalase, a peroxisomal enzyme, plays an important role in maintaining intracellular redox homeostasis by decomposing hydrogen peroxide to either water or oxygen that oxidize and provide fuel for cellular metabolism. Although the antioxidant enzymatic activity of catalase is well known, its role in the metabolism and maintenance of energy homeostasis has not yet been revealed. The present study investigated the role of catalase in lipid metabolism and thermogenesis during nutrient deprivation in catalase-knockout (KO) mice.
We found that hepatic triglyceride accumulation in KO mice decreased during sustained fasting due to lipolysis through reactive oxygen species (ROS) generation in adipocytes. Furthermore, the free FA released from lipolysis were shuttled to BAT through the activation of CD36 and catabolized by lipoprotein lipase in KO mice during sustained fasting. Although the exact mechanism for the activation of the FA receptor enzyme, CD36 in BAT is still unclear, we found that ROS generation in adipocytes mediated the shuttling of FA to BAT.
Taken together, our findings uncover the novel role of catalase in lipid metabolism and thermogenesis in BAT, which may be useful in understanding metabolic dysfunction.
源自脂肪组织和肝脏的脂肪酸（FA）是棕色脂肪组织（BAT）产热的主要燃料。过氧化氢酶是一种过氧化物酶体酶，通过将过氧化氢分解为水或氧气来维持细胞内氧化还原稳态，而水或氧气会氧化并为细胞代谢提供燃料，在这一过程中发挥重要作用。尽管过氧化氢酶的抗氧化酶活性已广为人知，但其在能量稳态的代谢和维持中的作用尚未明确。本研究调查了过氧化氢酶基因敲除（KO）小鼠在营养剥夺期间过氧化氢酶在脂质代谢和产热中的作用。
我们发现，在持续禁食期间，KO小鼠肝脏甘油三酯积累减少，这是由于脂肪细胞中通过产生活性氧（ROS）进行脂解所致。此外，在持续禁食期间，KO小鼠脂解产生的游离脂肪酸通过激活CD36转运至BAT，并由脂蛋白脂肪酶进行分解代谢。尽管BAT中FA受体酶CD36激活的确切机制仍不清楚，但我们发现脂肪细胞中的ROS生成介导了FA向BAT的转运。
综上所述，我们的研究结果揭示了过氧化氢酶在BAT脂质代谢和产热中的新作用，这可能有助于理解代谢功能障碍。
