The Roles Of ORMDL3 In White Adipose Tissue Browning

The prominently function of Brown adipose tissue(BAT)is to generate heat through uncoupled respiration which is mediated by UCP1.By this mechanism the body maintains a normal temperature.The previous studies suggest that there are two distinct types of brown fat:classical BAT and UCP1-positive cells which emerged in white adipose tissue under the cold environment or administrated with β-adrenergic receptors active drugs.The latter type is also named beige or brite(brown in white).This conversion process is named white adipose tissue(WAT)browning.Beige cells are performed like classical brown cells that burn lipid droplets to maintain energy metabolism balance.Thus,increasing the percentage of beige cells in WAT may expend extra energy to decrease lipid accumulation.The previous studies show that ORMDL3,an ER-anchored protein,plays an important role in asthma and other related disease.But it’s roles in lipid metabolism are largely unknown.Here we find that ORMDL3 is highly expressed in BAT.Under the cold environment or administrated with β-adrenergic receptors active drugs,the level of WAT browning is sigliflcantly lower in Ormdl3-/-mouse when compared with WT mouse.It shows that under the cold environment,the rectal temperature is lower in Ormdl3-/-mouse.The expression level of Ucp1 and the genes marking fatty acid oxidation in white adipose tissue in Ormdl3-/-mouse is also reduced.The percentage of UCP1 positive cells is also less in WAT of Ormdl3-/-mouse which indicated damaged WAT browning.When challenged with high fat diets,the fasting triglyceride concentrations is significantly higher in Ormdl3-/-mouse,that indicated its lower rates of metabolism.Taken together,ORMDL3 plays an important role in WAT browning.The global epidemic of obesity and its associated risks of chronic diseases pose formidable challenges to human health.Our results showed ORMDL3 may be a targeted protein in WAT browning.This provides a novel insight into lipid metabolism and obesity.