The Role Of Adipocyte IRE1α In Regulation Of Hepatic Lipid Metabolism Under Fasting Condition

The endoplasmic reticulum（ER）is present in all eukaryotic cells.It is a key organelle responsible for the synthesis,processing,and quality control of membrane proteins and secreted proteins.It is also an important place for Ca²⁺storage and lipid synthesis.In mammals,three transmembrane proteins located in the ER,IRE1α,PERK and ATF6,can sense the accumulation of unfolded proteins or misfolded proteins in the ER lumen,and cooperatively mediate three classic UPR signaling pathways to restore the protein folding ability of the ER by promoting the expression of downstream target genes.Under various stress conditions,the UPR signaling pathways act to maintain cellular homeostasis and determine the life-and-death decision of the cell.Adipocytes serve as the body’s energy store,releasing free fatty acids and glycerin to supply energy for various tissues during fasting.IRE1α,the most conserved branch of the UPR signaling pathways,has been shown to play an important role in the differentiation and maturation of adipocytes and the chronic inflammation in adipose tissue.Nutritional deficiency during fasting is one of the factors that activate ER stress,and the physiological function of the ER stress-sensing protein IRE1αin adipose tissue under fasting conditions is unclear.Our study found that under fasting condition,IRE1αis activated in adipose tissue,but IRE1αdoes not affect the expression of lipolysis-related genes.Subsequently,we found that adipocyte IRE1αaffects liver lipid accumulation in fasted mice.Analysis of gene expression in the liver suggests that adipocyte IRE1αmay regulate liver lipid accumulation by affecting PDK4 gene expression.These results reveal that adipocyte IRE1αis involved in regulation of the communication between adipose tissue and the liver under fasting condition.Our findings provide new insights into the role of ER stress in the pathogenic progression of fatty liver diseases.