Table 2.
Summary of studies that used cell-specific PPARγ knockout mouse models to assess the contribution of PPARγ in macrophages, HSC and hepatocytes in different models of fatty liver disease.
| Year [Ref] | Model | Hepatic PPARγ expression | Cre, mouse line. | Results of PpargΔ Mac | Results of TZD treatment (Macrophage-PPARγ dependent) |
| 2007 (Odegaard et al. 2007) | Balb/c HFD (18 weeks) | ns | LysM-Cre, 1 | Insulin resistance | NA |
| 2011 (Morán-Salvador et al. 2011) | HFD (12 weeks) | ↑ PPARγ1 and 2 | LysM-Cre, 2 | Glucose intolerance (chow) and ↓ steatosis (HFD) | NA |
| 2013 (Moran-Salvador et al. 2013) | CCl4 (8 weeks) | ↑ PPARγ2 | LysM-Cre, 2 | ↑ Liver damage and fibrosis | NA |
| 2018 (Heming et al. 2018) | Bone marrow cells | ns | LysM-Cre, ns | Pro-inflammatory phenotype. | NA |
| 2022 (Ni et al. 2022) | MCD (4weeks) | ns | LysM-Cre, 3 | ↑ inflammation and fibrosis | NA |
| Ref. | Model | Hepatic PPARγ expression | Cre, mouse line. | Results of PpargΔHSC | Results of TZD treatment (HSC-PPARγ dependent), dose |
| 2013 (Moran-Salvador et al. 2013) | CCl4 (8 weeks) | ↑ PPARγ2 | aP2-Cre, 2 | ↑ Liver damage and fibrosis | NA |
| 2020 (Liu et al. 2020) | CCl4 + recovery | ns | Lrat-Cre, 2 | ↑ fibrosis | Accelerated regression of liver fibrosis. |
| Ref. | Model | Hepatic PPARγ expression | Cre, mouse line. | Results of PpargΔHep | Results of TZD treatment [dose] (Hepatocyte-PPARγ dependent) |
| 2003 (Matsusue et al. 2003) | ob/ob | ↑ PPARγ | Alb-Cre, 1 | ↓ steatosis. Impaired glucose homeostasis, and chylomicrons remnants clearance. | ↑ steatosis by rosiglitazone [~3 mg/kg/day, 3 weeks] in PPARγ-intact ob/ob mice. |
| 2003 (Gavrilova et al. 2003) | A/ZIP | ↑ PPARγ2 | Alb-Cre, 1 | ↓ steatosis. Impaired triglyceride clearance. | ↑ steatosis by rosiglitazone [~3 mg/kg/day, 5 weeks] in PPARγ-intact A/ZIP mice. |
| 2011 (Morán-Salvador et al. 2011) | HFD (12 weeks) | ↑ PPARγ1 and 2 | Alb-Cre, 2 | ↓ steatosis. Improved glucose homeostasis. | ↑ steatosis by rosiglitazone [10μM] in PPARγ-intact PCLS |
| 2013 (Moran-Salvador et al. 2013) | CCl4 (8 weeks) | ↑ PPARγ2 | Alb-Cre, 2 | ↑ hepatic IL1B, TIMP1 expression. | NA |
| 2016 (Zhang et al. 2016) | Alcohol (8 weeks) | ↑t PARγ2 | Alb-Cre, 2 | ↓ steatosis and inflammation | NA |
| 2017 (Wang et al. 2017) | HFD-Alcohol (3 months) | ↑ PPARγ | Alb-Cre, 2 | ↓ steatosis and fibrosis, but ↑ neutrophil infiltration | NA |
| 2017 (Wolf Greenstein et al. 2017) | HFD (14 weeks) | ↑ PPARγ | AAV8-TBG-Cre, 2 | ↓ steatosis | NA |
| 2020 (Cordoba-Chacon 2020) | MCD (3 weeks) | ↑ PPARγ | AAV8-TBG-Cre, 2 | ↓ fibrosis | NA |
| 2020 (Kulkarni et al. 2020) | HFD (3 months) | ↑ PPARγ | Alb-Cre | ↓ steatosis | ↑ steatosis by pioglitazone [100 mg/Kg diet, 3 months] in PPARγ-intact mice. |
| 2021 (Lee et al. 2021a) | HFD (23 weeks) | ↑ PPARγ2 | AAV8-TBG-Cre, 2 | ↓ steatosis in severe obese mice, and ↑ adiposity | ↑ steatosis by rosiglitazone [70 mg/Kg diet, 6 weeks] in PPARγ-intact severe obese mice. |
| 2021 (Lee et al. 2021b) | HFCF (24/34 weeks) | ↑ PPARγ in male mice | AAV8-TBG-Cre, 2 | ↓ steatosis and NASH in male mice | Rosiglitazone [50 mg/Kg diet, 8 weeks] efficiently decreases NASH in PpargΔHepmice |
| 2022 (Lee et al. 2023) | HFD-HFCF (18–16 weeks) | ↑ PPARγ2 | AAV8-TBG-Cre, 2 | ↓ steatosis in HFD-fed and NASH in HFCF-fed male and female mice | NA |
Models: ob/ob, leptin-deficient hyperphagic mouse model with severe obesity; A/ZIP, lipodystrophie mouse model; HFD, high-fat diet-induced obese mouse model; CCl4, carbon tetrachloride-induced hepatoxicity; MCD: methionine and choline-deficient diet; Alcohol, alcoholic liver disease- induced by Lieber-deCarli diet; HFD-Alcohol, high-fat diet plus binge ethanol mouse model; MCD, methionine and choline-deficient diet-induced steatohepatitis; HFCF, high-fat, cholesterol, and fructose diet-induced non-alcoholic steatohepatitis. ↑, increased; ↓, decreased. Ns, not shown or described. NA, not applicable to this study. IL1B: Interleukin 1B, TIMP1: Tissue inhibitor of metalloproteinase 1. PCLS: Precision-cut liver slices. PPARγ floxed mouse line: 1, mouse line developed by Akiyama et al (Akiyama et al. 2002); 2, mouse line developed by He et al (He et al. 2003) (Jackson Laboratories Strain #:004584); 3, mouse line obtained in GemPharmatech (Nanjing, China).