TABLE 3.
Chemically and genetically (hyperphagic) induced fibrosis1
| Chemical/genetic | Species (ref) | Fibrosis (time to development) | Comments/applicable to advanced NASH fibrosis? |
|---|---|---|---|
| CCL4 | Mice and rats (101, 102) | Centrilobular fibrosis (week 2), central-central bridging fibrosis (week 4–6); cirrhosis (week 9–16). | Disease etiology differs significantly from humans; weight loss; not applicable |
| TAA | Mice and rats (101) | Periportal fibrosis (week 6); portal-portal and portal-central bridging fibrosis (week 12); cirrhosis (week 16) | Disease etiology differs significantly from humans; fibrosis can have portal origin; weight loss; not applicable |
| CCl4 + Western diet | Mice (108) | Bridging fibrosis (week 12); cirrhosis in some animals (week 24) | Transciptomic pathways similar to humans; CCl4 decreases weight gain, insulin, and dyslipidemia; no role of CCl4 in human NASH; potential applicable for specific research questions, but other models may be more advantageous |
| DMN and DEN | Rats (110, 111) | Central fibrosis (week 3) and portal-central bridging fibrosis and cirrhosis (week 8–12) | Bridging necrosis, weight loss, and high mortality; weight loss; not applicable |
| Streptozotocin | Rats (112–114) | Central and portal fibrosis (week 20); bridging fibrosis in some animals if administered postnatally (week 20) | Disease etiology differs from humans; hypoinsulinemic; not applicable |
| Ob/ob | Mice (115, 116) | Absent on feed pellet diet; mild perisinusoidal fibrosis in portal areas on HFD (week 12); bridging fibrosis on AMLN diet (week 12) | Fibrosis has portal origin; leptin important during fibrogenesis; could be applicable on an ALMN diet |
| Db/db | Mice (115, 116) | Absent on feed pellet diet; mild perisinusoidal fibrosis in portal areas on HFD (week 12); central and portal fibrosis on MCD diet (week 4) | Fibrosis has portal origin and is only mild/moderate; leptin important during fibrogenesis; not applicable |
| Fa/fa | Rats (117) | Mild periportal fibrosis on HFD (week 8); resistant to MCD-induced fibrosis | Fibrosis has portal origin and is only mild; leptin important during fibrogenesis; not applicable |
| Foz/foz (Alms1) | Mice (118, 119) | Portal and central perisinusoidal fibrosis (week 24) | Fibrosis is only mild/moderate; not applicable |
| KK-ay | Mice (97, 120) | Fibrosis absent on feed pellet diet; mild/moderate fibrosis on MCD diet (week 8); mild/moderate fibrosis on CDAA diet (week 30) | Weight loss and decreased glucose concentrations on MCD diet; CDAA decreased insulin/glucose concentrations and fibrosis not increased in KK-ay compared with wild-type; not applicable |
| Mc4r−/− | Mice (121) | Periportal and -central fibrosis (week 20) | Could be applicable if advance fibrosis develops with longer study duration |
1 Alms1, Alström gene; AMLN, Amylin liver NASH; CDAAD, choline-deficient, l-amino acid–defined; CCl4, carbon tetrachloride; DEN, diethylnitrosamine; DMN, dimethylnitrosamine; HFD, high-fat diet; MCD, methionine and choline deficient; Mc4r, melanocortin 4 receptor; NASH, nonalcoholic steatohepatitis; Ref, reference; TTA, thioacetamide.