Effects of caspase-1 inhibition on hepatic fibrosis. LDLR−/−.Leiden mice were fed a high-fat diet for 21 weeks (HFD; n=15) or HFD+caspase-1 inhibitor Ac-YVAD-cmk (40 mg kg−1 daily) starting treatment after 9 weeks of HFD (HFD+YVAD; n=15). Low-fat diet (LFD)-fed mice (n=15) were included as a reference. (a) Representative photomicrographs of Picro-Sirius red-stained liver sections show hepatopericellular fibrosis in HFD animals, which is reduced in HFD+YVAD. (b) Quantification of positively stained area in Picro-Sirius red-stained liver sections show a clear induction of fibrosis in HFD, which is reduced in HFD+YVAD. (c) Col1a1 mRNA expression is reduced in HFD+YVAD. (d) mRNA expression of hepatic stellate cell activation marker Acta2 (α-SMA) tended to be induced in HFD and was reduced in HFD+YVAD. All data are from the t=21 weeks time point and are mean±s.e.m. *P<0.05, **P<0.01 compared with HFD.