Fig. 7

Angptl3 promotes blood TG clearance that is associated with SmarcAL1 activities. (A) Angptl3 protein has a long-term effect on reducing blood TG levels. Female (left) and male (right) WT mice (16 weeks) were fed with HFD for 4 weeks. Purified Fc and Fc-Angptl3 proteins as in sFig. 12 were injected into these mice. Blood samples were collected ten days after the first injection and analyzed for plasma TG levels (see Methods for experimental details). (B) Angptl3 promotes fat accumulation in the livers. Liver sections from the mice were stained with oil red staining and large lipid macrovesicles were quantified using ImageJ (right). Scale bar, 25 µM. (C) Ex vivo analysis of mouse primary hepatocytes. Primary hepatocytes harvested from the livers of the mice as in A (see Methods for details) were fixed and hybridized with anti-PMP70 (green) and -SmarcAL1 (red) plus fluorescence-labeled secondary antibodies. Images were collected from confocal microscopy. Quantification was conducted using CellProfiler. Scale bar, 10 µM. (D) Schematic representation of the role of Angptl3-SmarcAL1 interaction in TG storage and trafficking. Under increased Angptl3 expression, slow cell growth induces SmarcAL1 translocation from nucleus to cytoplasmic peroxisomes by interacting with Angptl3 favoring fat storage. Fast cell growth reverses the process, and SmarcAL1 moves back to nucleus for regulating the expression of key lipid genes responsible for lipid metabolism. P values shown in this figure were calculated from two-sided unpaired t-test.