Abstract
SID1 transmembrane family member 2 (Sidt2) is an integral lysosomal membrane protein. To investigate its explicit function, we generated a global Sidt2 knockout mouse model (Sidt2-/-). Compared with the littermate controls, Sidt2-/- mice exhibited a remarkable accumulation of lipid droplets in liver. First, it was observed that food consumption, hepatocyte fatty acid uptake and de novo lipogenesis, hepatocyte lipolysis, and TG secretion in the form of very low density lipoprotein were comparable between Sidt2-/- and WT mice. However, the hepatic β-oxidation of fatty acids decreased significantly as revealed by a low level of serum β-hydroxybutyrate in the Sidt2-/- mice along with normal mRNA expression of genes involved in fatty acid oxidation. In addition, the classical autophagy pathway marker proteins, p62 and LC3-II, increased in liver, along with compromised autophagic flux in primary hepatocytes, indicating a block of autophagosome maturation due to Sidt2 deficiency, which was also supported by electron microscopy image analysis both in livers and in primary hepatocytes from Sidt2-/- mice. It was concluded that Sidt2 plays an important role in mouse hepatic lipid homeostasis by regulating autophagy at the terminal stage.
Highlights
SID1 transmembrane family member 2 (Sidt2) is an integral lysosomal membrane protein
lipid droplet (LD) accumulate in the livers of Sidt2 / mice The volume of livers in Sidt2 / mice increased
The Sidt2 / mice weighed less than the WT mice at 6 weeks of age [21], there was no significant difference in body weight between the two groups after HF diet for 12 weeks (Fig. 1B)
Summary
SID1 transmembrane family member 2 (Sidt2) is an integral lysosomal membrane protein. Compared with the littermate controls, Sidt2 / mice exhibited a remarkable accumulation of lipid droplets in liver. It was observed that food consumption, hepatocyte fatty acid uptake and de novo lipogenesis, hepatocyte lipolysis, and TG secretion in the form of very low density lipoprotein were comparable between Sidt2 / and WT mice. The classical autophagy pathway marker proteins, p62 and LC3-II, increased in liver, along with compromised autophagic flux in primary hepatocytes, indicating a block of autophagosome maturation due to Sidt deficiency, which was supported by electron microscopy image analysis both in livers and in primary hepatocytes from Sidt2 / mice. It was concluded that Sidt plays an important role in mouse hepatic lipid homeostasis by regulating autophagy at the terminal stage.—Chen, X., X. Sidt regulates hepatocellular lipid metabolism through autophagy.
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.
