Fig. 4: Hepatic MKP1 negatively regulates AMPKα-caspase 6 signaling in NASH diet fed mice.

a, b Immunoblots showing cytoplasmic and nuclear pp38 MAPK, pJNK and pERK1/2 and respective MAPK controls in livers from Mkp1^fl/fl and MKP1-LKO mice fed with CDAA diet for 22 weeks. c, d Densitometry of pMAPK/MAPK ratios in the cytosol and nucleus from (a) and (b), respectively. Data represent the mean ± SEM from 3 mice per genotype. p-values shown for cytoplasmic pp38 MAPK/p38 MAPK and pJNK/JNK were determined by a Mann–Whitney test, all other datasets were determined by two-sided student’s unpaired t-test. e Immunoblots showing phospho-AMPKα (Thr172), phospho-AMPKβ1 (Ser182) and phospho-ULK1 (Ser555) with corresponding total protein controls in livers. f–h Densitometry of pAMPKα/AMPKα, pAMPKβ1/AMPKβ1 and pULK1/ULK1 ratios from (e). Data represent the mean ± SEM from 6 mice. i Immunoblots for phospho-caspase 6 (Ser257), cleaved caspase 6 and caspase 6 in livers. j, k Quantitation of the ratio of phospho-caspase 6/caspase 6 and cleaved caspase 6/caspase 6 from (i). Data represent the mean ± SEM from 6 mice. l Staining of cleaved caspase 6 in liver sections from CSAA or CDAA diet fed Mkp1^fl/fl and MKP1-LKO mice. Scale bar = 25 μm. m Quantitation of percentage of cleaved caspase 6-positive cells for (l). Data represent the mean ± SEM from 5 mice. p-values shown in f–h, j, k and m were determined by two-way ANOVA. Key: fl/fl, Mkp1^fl/fl mice; LKO, MKP1-LKO mice.