Under our experimental conditions, fatty liver damage in wild-type mice probably Leuprolide Acetate develops in the absence of insulin resistance. In summary, the present study demonstrates that a deficiency of IVA-PLA2 protected mice against the HF diet-induced development of fatty liver damage with adipose accumulation. The alleviation of fatty liver damage is probably associated with the decreased generation of IVA-PLA2 metabolites including PGs. To our knowledge, this is the first report to suggest the possible involvement of IVA-PLA2 in hepatic fat deposition progressing to NAFLD under HF dietary conditions. The development and function of B lymphocytes requires activation of the inositol-requiring enzyme 1 alpha signaling branch of the unfolded protein response. IRE1a is localized in the endoplasmic reticulum membrane and activated when the ER chaperone BiP is recruited away from the luminal domain of IRE1a to unfolded/misfolded substrates. The endoribonuclease activity of IRE1a splices an intron from the mRNA of X-box-protein 1 resulting in translation of a transcription factor that upregulates genes associated with ER biogenesis, protein folding and ER-associated degradation. During early B cell development, IRE1a is required at the proB cell stage for immunoglobulin heavy chain gene rearrangement. Consistent with these findings, spliced XBP1 is upregulated in pro-B cells. XBP1 splicing also occurs in transitional and mature B cells in the spleen following stimulation of the B cell receptor. During plasma cell differentiation, XBP1 is upregulated to promote ER expansion and increase protein folding, glycosylation and trafficking. Although B cells deficient in XBP1 generate normal numbers of plasma cells, their ability to secrete antibodies is impaired. Thus, IRE1a/ XBP1 is not required for plasma cell differentiation, but rather, to increase the secretory apparatus necessary for immunoglobulin synthesis. ER-localized DnaJ 4 is a downstream effector of the IRE1a/XBP1 pathway. ERdj4 belongs to the HSP40 family of cochaperones, which function to stimulate the ATPase activity of BiP, leading to a Hydrochlorothiazide conformational change that stabilizes client interaction.