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Updated: Jun 10, 2026

Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
Down-regulation of SREBP-1c is associated with the development of burned-out NASH
Tadanobu Nagaya1, Naoki Tanaka, Takefumi Suzuki
1Department of Gastroenterology, Shinshu University School of Medicine, Japan. naopi@shinshu-u.ac.jp
Background & Aims:
It is well-known that hepatic triglycerides (TG) diminish with the progression of non-alcoholic steatohepatitis (NASH), which has been designated as burned-out NASH, but its mechanism remains unclear. We aimed to explore the changes in hepatic fatty acid (FA) and TG metabolism with disease progression.
Methods:
Hepatic expression of key genes in healthy individuals (n=6) and patients with simple steatosis (SS, n=10), mild NASH (fibrosis stage 1-2, n=20), and advanced NASH (fibrosis stage 3-4, n=20) were assessed by quantitative polymerase chain reaction.
Results:
Hepatic expression of genes related to FA uptake and oxidation and very-low-density lipoprotein synthesis/export did not differ among the groups. However, the mRNA levels of sterol regulatory element-binding protein (SREBP)-1c and its downstream genes FA synthase, acetyl-coenzyme A carboxylase 1, and diacylglycerol acyltransferase 1 were inversely correlated with fibrosis stage. Immunoblot analysis revealed a remarkable reduction in mature SREBP-1c levels in advanced NASH. Furthermore, hepatic expression of tumor necrosis factor-alpha increased in accordance with fibrosis progression, which was possibly related to the decrease in hepatic SREBP-1c expression.
Conclusions:
Down-regulation of SREBP-1c and lipogenic enzymes may be associated with the development of burned-out NASH.
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