Increased expression level of ANGPTL8 in White Adipose tissue under Chronic Cold Treatment

Abstract

Background It is well known that Angiopoietin like protein (ANGPTL) mainly 3, 4 and 8 play a major role in maintaining energy homeostasis by regulating lipoprotein lipase (LPL) activity, which is a key regulator of triglyceride (TG) metabolism. Our aim is to evaluate the level of ANGPTL3, 4 and 8 in mice maintained under cold conditions in the liver, brown adipose tissue (BAT), and white adipose tissue (WAT). Methods C57BL/6J mice were exposed to cold temperature at 4˚C over a period of ten days with food given ad libitum. Animal tissues were harvested at days 0, 1, 3, 5, and 10 (cold treatment groups, n = 10 in each group, control, n = 5). Liver, subcutaneous adipose tissue (SAT), and BAT were used to investigate the expression level of different genes. ANGPTL3, 4 and 8 genes expression were measured in liver. ANGPTL4, 8 and UCP1 were measured in SAT and BAT. Results ANGPTL 3 and 8 gene expression levels were significantly reduced in mice liver tissues after cold treatment (P-value < 0.05). However, the gene expression level of ANGPTL4 was not significantly changed. In BAT, ANGPTL8 expression was not changed after cold treatment while ANGPTL4 was significantly reduced (P-value < 0.05). ANGPTL4 level was also significantly reduced in SAT, whereas the gene expression level of ANGPTL8 showed over a 5-fold increase. Similarly, the UCP1 gene expression was also significantly increased in SAT. Additionally, protein overexpression of ANGPTL8 was further confirmed by immunohistochemistry after extended cold treatment. Conclusion Our data shows that ANGPTL proteins are inhibited in the liver and BAT under cold treatment. This agrees with other studies that showed that reduction in ANGPTL4 in BAT improved thermogenesis in response to acute cold exposure. However, in our study we also observed that ANGPTL8 is activated under these conditions in SAT. This suggests that it might be involved in the regulation of lipolysis as well as enhancing SAT browning.