Investigating a Potential Path to Medication for Nonalcoholic Steatohepatitis (NASH) in the Czech Lab
People with NASH are at increased risk of developing type 2 diabetes. No therapy is yet available.
Date Posted: Monday, August 22, 2022
A significant percentage of people living with type 2 diabetes also have too much fat accumulated in their liver that can develop into a condition called nonalcoholic steatohepatitis (NASH). It’s characterized by severe liver inflammation and fibrosis that can lead to cirrhosis and may require a liver transplantation. Currently, there is no medication for NASH.
To better understand how a medicine might be developed, the Czech lab studied fat production in the liver from carbohydrates by disrupting an enzyme that helps to convert blood glucose into fat in obese mice. Results of their research is published in the Journal of Biological Chemistry (August 2022).
“To our surprise, when we blocked this enzyme, we found higher fat synthesis not less,” said Michael P. Czech, PhD, the Isadore and Fannie Foxman Chair in Medical Research and professor of molecular medicine at UMass Chan Medical School. “We tracked this down to a way that the liver gets around this enzyme to produce fat, and now we see this new pathway as an opportunity to explore how a medication might be developed.”
Paradoxical activation of transcription factor SREBP1c and de novo lipogenesis by hepatocyte-selective ATP-citrate lyase depletion in obese mice
Batuhan Yenilmez 1, Mark Kelly 1, Guofang Zhang 2, Nicole Wetoska 1, Olga R Ilkayeva 2, Kyounghee Min 1, Leslie Rowland 1, Chloe DiMarzio 1, Wentao He 2, Naideline Raymond 1, Lawrence Lifshitz 1, Meixia Pan 3, Xianlin Han 3, Jun Xie 4, Randall H Friedline 1, Jason K Kim 1, Guangping Gao 4, Mark A Herman 2, Christopher B Newgard 5, Michael P Czech 6 PMID: 35988648 DOI: 10.1016/j.jbc.2022.102401
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