Croft Amanda J, Kelly Conagh, Chen Dongqing, Haw Tatt Jhong, Sverdlov Aaron L, Ngo Doan T M
School of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, Australia.
Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
Antioxidants (Basel). 2023 May 22;12(5):1137. doi: 10.3390/antiox12051137.
Obesity is associated with significant metabolic co-morbidities, such as diabetes, hypertension, and dyslipidaemia, as well as a range of cardiovascular diseases, all of which lead to increased hospitalisations, morbidity, and mortality. Adipose tissue dysfunction caused by chronic nutrient stress can result in oxidative stress, mitochondrial dysfunction, inflammation, hypoxia, and insulin resistance. Thus, we hypothesised that reducing adipose tissue oxidative stress via adipose tissue-targeted overexpression of the antioxidant mitochondrial catalase (mCAT) may improve systemic metabolic function. We crossed mCAT (floxed) and Adipoq-Cre mice to generate mice overexpressing catalase with a mitochondrial targeting sequence predominantly in adipose tissue, designated AdipoQ-mCAT. Under normal diet conditions, the AdipoQ-mCAT transgenic mice demonstrated increased weight gain, adipocyte remodelling, and metabolic dysfunction compared to the wild-type mice. Under obesogenic dietary conditions (16 weeks of high fat/high sucrose feeding), the AdipoQ-mCAT mice did not result in incremental impairment of adipose structure and function but in fact, were protected from further metabolic impairment compared to the obese wild-type mice. While AdipoQ-mCAT overexpression was unable to improve systemic metabolic function per se, our results highlight the critical role of physiological HO signalling in metabolism and adipose tissue function.
肥胖与显著的代谢合并症相关，如糖尿病、高血压和血脂异常，以及一系列心血管疾病，所有这些都会导致住院率、发病率和死亡率增加。慢性营养应激引起的脂肪组织功能障碍可导致氧化应激、线粒体功能障碍、炎症、缺氧和胰岛素抵抗。因此，我们假设通过脂肪组织靶向过表达抗氧化线粒体过氧化氢酶（mCAT）来降低脂肪组织氧化应激，可能会改善全身代谢功能。我们将mCAT（floxed）小鼠与Adipoq-Cre小鼠杂交，以生成主要在脂肪组织中过表达带有线粒体靶向序列的过氧化氢酶的小鼠，命名为AdipoQ-mCAT。在正常饮食条件下，与野生型小鼠相比，AdipoQ-mCAT转基因小鼠表现出体重增加、脂肪细胞重塑和代谢功能障碍。在致肥胖饮食条件下（高脂/高蔗糖喂养16周），与肥胖野生型小鼠相比，AdipoQ-mCAT小鼠并未导致脂肪结构和功能进一步受损，事实上，它们受到保护，免受进一步的代谢损伤。虽然AdipoQ-mCAT过表达本身无法改善全身代谢功能，但我们的结果突出了生理性HO信号在代谢和脂肪组织功能中的关键作用。
