Niwa, H.; Iizuka, K.; Kato, T.; Wu, W.; Tsuchida, H.; Takao, K.; Horikawa, Y.; Takeda, J. ChREBP Rather than SHP Regulates Hepatic VLDL Secretion. Preprints2018, 2018020073. https://doi.org/10.20944/preprints201802.0073.v1
APA Style
Niwa, H., Iizuka, K., Kato, T., Wu, W., Tsuchida, H., Takao, K., Horikawa, Y., & Takeda, J. (2018). ChREBP Rather than SHP Regulates Hepatic VLDL Secretion. Preprints. https://doi.org/10.20944/preprints201802.0073.v1
Chicago/Turabian Style
Niwa, H., Yukio Horikawa and Jun Takeda. 2018 "ChREBP Rather than SHP Regulates Hepatic VLDL Secretion" Preprints. https://doi.org/10.20944/preprints201802.0073.v1
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 transactivity of each other. Mttp mRNA and protein levels of Shp/– mice were similar to those of wild-type; however, those of Chrebp–/–Shp–/– and Chrebp–/– mice were much lower. Consistent with this, the VLDL particle number and VLDL secretion rates in Shp–/–- mice were similar to wild-type, but were much lower in Chrebp–/– and Chrebp–/–Shp–/–- mice. These findings suggested that ChREBP rather than SHP regulates VLDL secretion and that ChREBP and SHP do not affect the transactivities of each other.
Keywords
carbohydrate response element binding protein; small heterodimer partner; microsomal triglyceride transfer protein; very-low-density lipoprotein
Subject
Medicine and Pharmacology, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.