Overexpression of the Lias gene attenuates hepatic steatosis in Leprdb/db mice

in Journal of Endocrinology
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  • 1 G Xu, Public Health, Xinxiang Medical College, Xinxiang, China
  • 2 T Yan, Public Health, Xinxiang Medical University, Xinxiang, China
  • 3 Q Peng, Public Health, Xinxiang Medical College, Xinxiang, China
  • 4 H Li, Public Health, Xinxiang Medical College, Xinxiang, China
  • 5 W Wu, Public Health, Xinxiang Medical College, Xinxiang, China
  • 6 X Yi, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, United States
  • 7 Y Zhao, public health, Xinxiang Medical College, Xinxiang, China

Correspondence: Xianwen Yi, Email: xyi2000@med.unc.edu

Oxidative stress is proposed to be involved in non-alcoholic fatty liver disease (NAFLD). However, antioxidant therapy results in controversial outcomes. Therefore, we generated a new antioxidant/NAFLD mouse model, LiasHigh/HighLeprdb/db mice, by crossbreeding Leprdb/dbmice, an obesity mouse model, with LiasHigh/Highmice, generated by overexpression of lipoic acid synthase gene (Lias) and having increased endogenous antioxidant capacity, to investigate whether the new model could block the development of NAFLD. We have systemically characterized the novel model based on the main features of human NAFLD, determined the impact of enhanced endogenous antioxidant capacity on the retardation of NAFLD and elucidated the underlying mechanisms using various biological and pathological methods. We found that LiasHigh/HighLeprdb/db mice ameliorated many pathological changes of NAFLD compared with the control. In particular, LiasHigh/HighLeprdb/db mice displayed the improved liver mitochondrial function, reflecting the decline of mitochondrial microvesicular steatosis, and reduced oxidative stress, which mainly contribute to alleviation of pathologic alterations of the NAFLD progression. Our new model shows that mitochondrial dysfunction is a major pathogenesis for liver steatosis. Overexpression of Lias gene effectively reduces oxidative stress and protects mitochondria, and consequently attenuates NAFLD/NASH.


Society for Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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