4.5 Article

Knockout of calpain-1 protects against high-fat diet-induced liver dysfunction in mouse through inhibiting oxidative stress and inflammation

Journal

FOOD SCIENCE & NUTRITION
Volume 9, Issue 1, Pages 367-374

Publisher

WILEY
DOI: 10.1002/fsn3.2002

Keywords

calpain-1 knockout; hyperlipidemia; inflammation; liver dysfunction; oxidative stress

Funding

  1. National Natural Science Foundation of China [81560391, 81870329, 81960673]
  2. Natural Science Foundation of Liaoning Province [20180530069]
  3. Cuiying Technological Innovation Foundation of Lanzhou University Second Hospital [CY2019-MS03]
  4. Industrial Support Program for Colleges and Universities in Gansu Province [2020C-04]
  5. Special Research Project of Lanzhou University Serving the Economic and Social Development of Gansu Province

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The study found that knockout of calpain-1 protects against high-fat diet-induced liver dysfunction by inhibiting oxidative stress and inflammation.
The present study was designed to investigate the significance of calpain-1 in the high-fat diet (HFD)-induced liver dysfunction and to explore the possible mechanism. C57 mice and calpain-1 knockout (KO) mice were fed with standard diet (SD) or HFD, respectively, for 16 weeks. The activities of calpain, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and superoxide dismutase (SOD) in serum and/or liver of mouse were measured. Lipid profiles in the serum and liver were examined. Contents of oxidized low-density lipoprotein (oxLDL), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha), and interleukin-6 (IL-6) in serum or/and liver were detected. The results showed that compared with C57 mice fed with SD, HFD-fed C57 mice showed the increased activities of AST and ALT in the serum, which was decreased in calpain-1 KO mice fed with HFD. In addition, knockout of calpain-1 decreased the contents of oxLDL, MDA, TNF-alpha, and IL-6, while increased SOD activity, in serum and/or liver. However, knockout of calpain-1 had no effects on lipid profiles in both serum and liver. When fed with SD, all these parameters of C57 and calpain-1 KO mice were comparable except for decreased calpain activity in the liver of calpain-1 KO mice. The results suggested that knockout of calpain-1 protects against HFD-induced liver dysfunction through inhibiting oxidative stress and inflammation.

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