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Treatment for NASH and T2DM burns up liver fat

(Credit: Image courtesy of KTH The Royal Institute of Technology)
ased on the results from the study, an improved intervention using a portfolio of substances has been designed

Researchers in Sweden are planning the clinical trial of a treatment for non-alcoholic steatohepatitis (NASH) and type 2 diabetes which harnesses liver cells' own ability to burn accumulated fats. In a study involving 86 people with varying degrees of fatty liver disease, researchers from KTH Royal Institute of Technology's Science for Life Laboratory (SciLifeLab) research centre and Gothenburg University found that the liver has the ability to burn up accumulated fats. The researchers propose a mixture of substances that will set this process in motion.

The researchers mapped the metabolic changes caused by accumulated fat in 86 patients' liver cells, and combined this data with an analysis of a genome-scale model of liver tissue. Doing so enabled them to identify the precise metabolic changes individual patients' liver cells undergo due to fat.

The results of the study, ‘Personal model‐assisted identification of NAD+ and glutathione metabolism as intervention target in NAFLD’, were published in journalMolecular Systems Biology.

Lead author, Adil Mardinoglu, a systems biologist at KTH and SciLifeLab fellow, is one of the researchers who had earlier established a connection between NAFLD and low levels of the antioxidant, glutathione (GSH). A proof of concept test showed that accumulated liver was burned off by treating human subjects with a "cocktail" that increases oxidation of fat and synthesis of the antioxidants.

Adil Mardinoglu

Mardinoglu said the team's metabolic modelling approach, which relied on data from Swedish-based Human Protein Atlas effort, can be used for a number of chronic liver diseases.

Based on the results from the study, an improved intervention using a portfolio of substances has been designed.

"This mixture can potentially decrease the amount of the fat accumulated in the liver," said Mardinoglu. "There is no such drug available at present and we are planning for further clinical trials later this year."

The approach combines systems biology and clinical medicine in a manner not previously done.

"The results are exciting, and we have now designed a mixture of substances that will boost the oxidation of fat and generate antioxidants in the liver tissue," said senior co-author, Jan Borén from the University of Gothenburg.

The researchers believe that the mixture of substances could also be used to treat accumulated liver fat due to alcoholic fatty liver disease and type 2 diabetes. "Considering NAFLD and diabetes are common conditions that regularly co-exist and can act synergistically to drive adverse outcomes, such a mixture of substances might also be used in the treatment of subjects with diabetes," says co-author, Ulf Smith of University of Gothenburg.

"I am extremely pleased that the resource created through the Human Protein Atlas effort has been used in the analysis of clinical data obtained from NAFLD patients and that this analysis has led to the design of a mixture of substances that can be used for treatment of this clinically important patient group,” said Mathias Uhlén, director of the Human Protein Atlas project and co-author of the paper."

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