Apolipoprotein B: not just a biomarker but a causal factor in hepatic endoplasmic reticulum stress and insulin resistance

Insulin resistance is associated with dyslipidemia, which is initiated largely by the overproduction of VLDL particles. VLDL particles are produced in the liver via lipidation of nascent ApoB molecules in the endoplasmic reticulum (ER). In insulin-resistant states, excess flux of free fatty acids to the liver can lead to ApoB accumulation in the ER, causing ER stress. Recent studies reveal a critical role of hepatic ER stress and the unfolded protein response in the development of insulin resistance. This review summarizes the intersections between the three branches of unfolded protein response signaling and hepatic lipogenesis, presents recent findings regarding lipid-induced ER stress and the role of ApoB in the development of hepatic ER stress and insulin resistance, and briefly discusses the clinical utility of ApoB as a potential drug target.