Abstract
The regulation of hepatic very-low-density lipoprotein (VLDL) secretion plays an important role in the pathogenesis of dyslipidemia and fatty liver diseases. VLDL is controlled by hepatic microsomal triglyceride transfer protein (MTTP). Mttp is regulated by carbohydrate response element binding protein (ChREBP) and small heterodimer partner (SHP). However, it is unclear whether both coordinately regulate Mttp expression and VLDL secretion. Here, adenoviral overexpression of ChREBP and SHP in rat primary hepatocytes induced and suppressed Mttp mRNA, respectively. However, Mttp induction by ChREBP was much more potent than suppression by SHP. Promoter assays of Mttp and the liver type pyruvate kinase gene revealed that SHP and ChREBP did not affect the transcriptional activity of each other. Mttp mRNA and protein levels of Shp−/− mice were similar to those of wild-types; however, those of Chrebp−/−Shp−/− and Chrebp−/− mice were significantly much lower. Consistent with this, the VLDL particle number and VLDL secretion rates in Shp−/− mice were similar to wild-types but were much lower in Chrebp−/− and Chrebp−/−Shp−/− mice. These findings suggest that ChREBP, rather than SHP, regulates VLDL secretion under normal conditions and that ChREBP and SHP do not affect the transcriptional activities of each other.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world [1,2]
Adenoviral carbohydrate response element binding protein (ChREBP) caused an increase in Mttp and Pklr mRNA expression, while small heterodimer partner (SHP) suppressed only Mttp expression in primary rat hepatocytes (Figure 1A,B)
SHP overexpression failed to suppress ChREBP-mediated Pklr induction (Figure 1B). This suggested that ChREBP induced Mttp expression more potently than SHP suppressed it
Summary
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world [1,2]. High fat diets and high carbohydrate diets are responsible in the development of NAFLD [3,4,5]. High carbohydrate diets cause fatty liver by increasing hepatic de novo lipogenesis [3]. High fat diets increase hepatic fat content [4]. Lifestyle modifications, including hypocaloric diets, are critical for the prevention and treatment of NAFLD.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
