New treatment approach harnesses the abilty of liver cells to burn accumulated fats.
By harnessing the ability of liver cells to burn accumulated fats, investigators discovered a novel treatment option for non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D).
In a study published in Molecular Systems Biology, investigators enrolled 86 patients with varying degrees of fatty liver disease, and found that the liver can burn up accumulated fats.
The investigators have proposed a mixture of substances that would set this process in motion. Hepatic steatosis is one of the key characteristics of NAFLD, and has been linked to insulin resistance, obesity, T2D, and cardiovascular disease.
Up to 30% of patients with NAFLD develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and liver cancer.
For the study, the investigators mapped the metabolic changes caused by accumulated fat in the liver cells of 86 patients. The data were then combined with an analysis of genome-scale model of liver tissue. With this approach, the investigators identified the precise metabolic changes individual patients’ liver cells undergo due to fat.
Using a proof-of-concept test, the investigators showed that accumulated liver was burned off by treating individuals with a cocktail that increased oxidation of fat and synthesis of the antioxidants.
Lead author Adil Mardinoglu noted that this metabolic modeling approach could be used for several different chronic liver diseases. The approach relied on data from the Swedish-based Human Protein Atlas effort.
Based on the findings, the investigators designed an improved intervention using a portfolio of substances.
“This mixture can potentially decrease the amount of the fat accumulated in the liver,” Mardinoglu said. “There is no such drug available at present and we are planning for further clinical trials later this year.”
The novel approach combines systems biology and clinical medicine to create a mixture of substances.
“The results are exciting, and we have no 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.
The authors believe the mixture of substances could be used to treat accumulated liver fat due to alcoholic fatty liver disease and T2D.
“Considering NAFLD and diabetes are common conditions that regularly coexist and can act synergistically to drive adverse outcomes, such a mixture of substances might also be used in the treatment of subjects with diabetes,” said co-author Ulf Smith.
Co-author Mathias Uhlén added, “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.”