Table 1 Caspase deficiency in mouse models of dietary-induced obesity, NAFLD and NASH
From: Caspases in metabolic disease and their therapeutic potential
Caspase | Mouse model | Dietary model | Duration | Phenotype/outcomes |
|---|---|---|---|---|
Caspase-1a | Casp1 and Casp11 knockout mice; (Casp1−/−Casp11129mt/129mt− C57BL/6) | HFD (42% kJ fat) | 12 weeks | Increased susceptibility to obesity but protected from NAFLD/NASH [50] |
HFD (45% kJ fat) or LFD (10% kJ fat) | 52 weeks | Increased susceptibility to obesity with sex-specific differences [49] | ||
HFD (45% kJ fat) | 16 weeks | Protected from DIO and insulin resistance [37] | ||
HFD (45% kJ fat) | 16 weeks | Protected from obesity, NAFLD and insulin resistance [38] | ||
HFD (60% kJ fat) | 8 weeks | Increased susceptibility to obesity, greater adiposity and inflammation and similar insulin sensitivity to WT control [48] | ||
HFD (45% kJ fat) | 16 weeks | Developed obesity and NAFLD similar to WT controls [45] | ||
HFD (60% kJ fat) | 12 weeks | Increased susceptibility to obesity but similar insulin sensitivity to WT control [47] | ||
MCD | 24 days | Increased NASH, increased NAFLD activity score, steatosis and inflammation and infiltration and liver injury (increased ALT) [52] | ||
Caspase-2 | Casp2 null mice; (Casp2−/−;B6.129SY-Casp2tm1Yuan/J) | MCD; HFD (20% kJ fat); HFD + MCD | 8 weeks | Protected from NAFLD on HFD; protected from development of NASH but not steatosis on MCD or HFD + MCD [28] |
Casp2 null mice (Casp2−/− C57BL/6J) | Western diet (45% kJ fat) | 16 weeks | Protected from DIO, NAFLD and insulin resistance [67] | |
HFD (60% kJ fat) | 12 weeks | Protected from DIO, NAFLD and insulin resistance [65] | ||
Caspase-3 | Casp3 null mice (Casp3−/− C57BL/6, exon3 deletion) | MCD | 6 weeks | Protected from development of NASH but not steatosis or liver injury [79] |
Caspase-8 | Hepatocyte-specific Casp8 null mice (Casp8Δhepa, C57BL/6) | MCD | 10 weeks | Protected from development of NASH and steatosis [80] |
Liver parenchymal (LPC;hepatocytes and cholangiocytes) specific Casp8 null mice—(Casp8LPC-KO,C57BL/6) | MCD | 8 weeks | Increased liver injury (AST, ALT and GLDH glutamate dehydrogenase), compensatory proliferation of parenchymal liver cells, inflammation and fibrosis [83] | |
LPC-specific Casp8 null mice and Rip3 null mice (Casp8LPC-KO/RIP3−/−; C57BL/6) | MCD | 8 weeks | Reduced liver injury (decreased AST, ALT and GLD), compensatory proliferation, inflammation and fibrosis compared to MCD-fed Casp8LPC-KO and WT controls; increased hepatic steatosis compared to all groups [83] | |
Casp8 and Rip3 null mice (Casp8/RIP3−/− C57BL/6) | CD-HFD | 16 weeks | Casp8 deletion rescued the phenotype of RIPK3−/− mice, resulting in development of obesity, WAT inflammation and insulin resistance similar to CD-HFD WT mice [86] | |
LPC-specific Casp8 null mice—(Casp8LPC-KO,C57BL/6) | CD-HFD | 16 weeks | Hepatocyte deletion of Casp8 did not rescue RIPK3−/− from glucose intolerance, insulin resistance or WAT inflammation [86] | |
Caspase-11 | Casp11 null mice (Casp11−/− C57BL/6 background) | HFD (45% kJ fat) | 16 weeks | Develop obesity similar to WT control [45] |
Caspase-12 | Casp12 null mice (Casp12−/−(b6) C57BL/6 and Casp12−/−(129) SV 129) | HFD (45% kJ fat) | 16 weeks | Increased obesity, NAFLD and insulin resistance in both strains [45] |
