Central pharmacological antagonism and down‐regulation of κOR in the LHA alleviates MCD diet–induced NASH. Effect of a 7‐day PF04455242 ICV infusion (3.4 nmol/day) in rats fed the MCD diet on food intake and body weight (A), serum levels of AST and ALT (B), and TG liver content and oil red O and hematoxylin and eosin liver section staining represented in the microphotographs (C). Representative photomicrograph of brain section showing the injection of a lentivirus that encodes GFP precisely placed in the LHA (A) (×1.25 magnification). Food intake and body weight (D); TG liver content and representative photomicrograph of liver sections with oil red O, hematoxylin and eosin, and Massońs trichrome staining (E); liver messenger RNA levels of the inflammation markers TNFα, IL6, CD36, and CD68 (E); and liver protein levels of LPL, pJNK, JNK, pIRE1α, IRE1α, pPERK, peIF2α, eIF2α, XBP1S, and CHOP (F) of rats fed the MCD diet for 3 weeks after κOR inhibition in the LHA using an AAV vector. Protein β‐actin levels were used to normalize protein levels. Dividing lines indicate splicings within the same gel. Values are mean ± standard error of the mean of seven or eight animals per group. *
P < 0.05, **
P < 0.01, ***
P < 0.001 versus controls. Abbreviations: H&E, hematoxylin and eosin; 3v, third ventricle.