The study will also evaluate the effect of PXL770 on its two main targeted metabolic pathways, which include hepatic de novo lipogenesis (DNL) and lipolysis.
There's only one other pathway that the body can use, and that's lipogenesis. The body can turn this very toxic substance [glucose] into safe storage [fat].
According to the company, TVB-2640 is an orally bioavailable, first-in-class inhibitor of FASN, which is a key enzyme in the de novo lipogenesis (DNL) pathway that is responsible for the synthesis of excess fat in the liver of patients with NASH.
The authors propose that curcumin may have multiple mechanisms of action that make it beneficial for treatment of NAFLD, including its ability to decrease expression of HMG-CoA reductase, and to decrease lipogenesis and adipogenesis.
About 20-30% of triglycerides are synthesized via de novo lipogenesis. Some studies showed that endoplasmic reticulum stress (ERS) is involved in this process, while others showed that a lipotoxic environment directly influences ER homeostasis.
Through this study, Karin and team also discovered that caspase-2 has a critical role in activating SREBP1 and 2 -- the master regulators of lipogenesis, a process that takes place in the liver where nutrients like carbohydrates are turned into fatty acids, triglycerides and cholesterol.
Pivotal in pathogenesis are the roles of hormones (insulin, insulinlike growth factor-1, androgens), Propionibacterium acnes, lipogenesis, and a proinflammatory lipid profile.
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