We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A novel small compound TOIDC suppresses lipogenesis via SREBP1-dependent signaling to curb MAFLD.
- Authors
Shao, Yaodi; Yao, Zhi; Zhou, Junyi; Yu, Miao; Chen, Suzhen; Yuan, Yanmei; Han, Liu; Jiang, Liqin; Liu, Junli
- Abstract
Background: Inhibition of hepatic lipogenesis is widely regarded as an effective treatment for metabolic-associated fatty liver disease (MAFLD), although numerous related drugs have failed to reach clinical application. The goal of this study is to identify a novel small compound that can effectively treat MAFLD. Methods: Primary hepatocytes were first exposed to palmitic acid and oleic acid, then treated with compounds prior to high through screening for cellular lipid content. The efficacy of these compounds was measured by Nile Red staining and triglyceride analysis. The potential cellular toxicity caused by these compounds was evaluated by CCK8 assay. qPCR and Western blot were used to determine expression of RNAs and proteins, respectively. The compound was intraperitoneally injected into diet-induced obese (DIO) mice to examine its efficacy in vivo. Results: We identified the dimethyl 1-methyl-2-thioxoindoline-3,3-dicarboxylate (TOIDC) as a powerful chemical to reduce cellular lipid with minimal cellular toxicity. When injected intraperitoneally, TOIDC effectively ameliorates MAFLD in DIO mice. Mechanically, TOIDC suppresses de novo lipogenesis through inhibiting sterol regulatory element-binding protein 1 (SREBP1). Conclusions: Our findings indicate that TOIDC could be a promising lead compound to develop new drugs to treat MAFLD.
- Subjects
LIPID metabolism; RNA analysis; ANALYSIS of triglycerides; LIPID analysis; OBESITY; INDOLE compounds; LIVER; ANIMAL experimentation; WESTERN immunoblotting; NON-alcoholic fatty liver disease; INTRAPERITONEAL injections; CELLULAR signal transduction; DNA-binding proteins; ACYCLIC acids; LIVER cells; POLYMERASE chain reaction; LIPIDS; MICE; CHEMICAL inhibitors
- Publication
Nutrition & Metabolism, 2022, Vol 19, Issue 1, p1
- ISSN
1743-7075
- Publication type
Article
- DOI
10.1186/s12986-022-00713-0