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Aberrant fatty acid metabolism plays important roles in the development of hepatic steatosis.Hepatic steatosis is increased in defective fatty acid metabolism, reflecting chronic increases in endoplasmic reticulum (ER) stress.However, whether the unfolded protein response (UPR), induced as an adaptive response by ER stress, also modulates fatty acid metabolism is unclear.This talk will discuss that the nuclear receptor PPAR α couples the UPR and hepatic fatty acid metabolism, and demonstrate 1) how cross-talk between the UPR and nuclear receptor coordinates at the transcriptional level, and contributes to hepatic lipid homeostasis;2) modulation of the UPR through ATF6 represents an alternative avenue to improve liver function and treat hepatic steatosis in obesity.