KLF9 regulates hepatic lipid metabolism via inducing CD36 expression.
- Author:
Shi-Shi ZHOU
1
;
Yin-Liang ZHANG
1
;
Yong-Sheng CHANG
2
Author Information
1. Department of Physiology and Pathophysiology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China.
2. Department of Physiology and Pathophysiology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China. changys@tmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
CD36 Antigens/metabolism*;
Diet, High-Fat;
Kruppel-Like Transcription Factors/metabolism*;
Lipid Metabolism;
Liver;
Mice;
Mice, Inbred C57BL;
Mice, Knockout;
Non-alcoholic Fatty Liver Disease/metabolism*;
Oleic Acid/metabolism*
- From:
Acta Physiologica Sinica
2021;73(5):772-780
- CountryChina
- Language:Chinese
-
Abstract:
The development of nonalcoholic fatty liver disease (NAFLD) is closely related to the fatty acid (FA) uptake. This study aimed to investigate the effect of Krüppel-like factor 9 (KLF9) on CD36 (typical fatty acid translocase), hepatocellular lipid metabolism as well as the development and progression of nonalcoholic fatty liver. High-fat diet-induced obese C57BL/6J mice and db/db mice were used to test the expression levels of Klf9 and Cd36 in the livers. The primary hepatocytes were isolated from C57BL/6J mice, treated with Ad-GFP, Ad-Klf9, Ad-shCtrl or Ad-shKlf9, and then incubated with oleic acid and palmitic acid for 24 h. Liver-specific knockout of Klf9 mice were established. The protein levels and relative mRNA levels were examined by Western blot and real-time PCR, respectively. Triglyceride content was determined by using an assay kit. Lipid content was determined by Oil Red O staining. The results showed that: (1) Klf9 expression levels were increased in the livers of high-fat diet-induced obese mice and db/db mice, compared to their respective control mice. (2) Adenovirus-mediated overexpression of Klf9 in primary hepatocytes increased Cd36 expression and cellular triglyceride contents. (3) In contrast, adenovirus-mediated knockdown of Klf9 expression in primary hepatocytes by Ad-shKlf9 decreased Cd36 expression and cellular triglyceride contents. (4) Finally, Klf9 deficiency decreased liver Cd36 expression and alleviated fatty liver phenotype of high-fat diet-induced obese mice. These results suggest that KLF9 can regulate hepatic lipid metabolism and development of NAFLD by promoting the expression of CD36.
