Tumor Necrosis Factor α-Converting Enzyme Inhibition Reverses Hepatic Steatosis and Improves Insulin Sensitivity Markers and Surgical Outcome in Mice
2011

Marimastat Reverses Liver Fat and Improves Insulin Sensitivity in Mice

Sample size: 25 publication 10 minutes Evidence: moderate

Author Information

Author(s): de Meijer Vincent E., Le Hau D., Meisel Jonathan A., Sharma Anisha K., Popov Yury, Puder Mark

Primary Institution: Children's Hospital Boston, Harvard Medical School

Hypothesis

Treatment with the pharmacologic tumor necrosis factor-α converting enzyme (TACE)-inhibitor Marimastat would reverse established steatosis, leading to improved outcome following hepatectomy.

Conclusion

Marimastat treatment improved insulin sensitivity and reversed liver fat in mouse models, reducing post-operative liver injury after surgery.

Supporting Evidence

  • Marimastat treatment led to a 66% decrease in hepatic steatosis.
  • Post-operative liver injury was significantly decreased by 57% and 44% for AST and ALT levels, respectively.
  • Insulin sensitivity markers improved significantly after Marimastat treatment.
  • Histological analysis showed nearly normal liver architecture in treated mice.

Takeaway

Researchers gave a medicine called Marimastat to mice with fatty livers to see if it would help them get better before surgery, and it worked!

Methodology

C57BL/6 male mice were fed a high fat diet and treated with Marimastat or vehicle, followed by surgical removal of two-thirds of the liver.

Potential Biases

Potential bias from the animal model and the controlled environment of the study.

Limitations

Results may not directly translate to humans, and long-term effects of TACE inhibition are uncertain.

Participant Demographics

C57BL/6 male mice and ob/ob mice were used in the study.

Statistical Information

P-Value

0.010

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0025587

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