Table 1. Comparison of CGI-58 and ATGL mouse models.
| Endpoint | Mouse model | Phenotype vs. control mice |
|---|---|---|
| Obesity and adipose tissue |
ASO-mediated CGI-58 knockdown2 |
Complete prevention of HFD-induced obesity 50% lower fat mass on both chow and HFD No difference in BW on chow diet |
| Adipose-specific CGI-58 overexpression36 |
No difference in BW or HFD-induced obesity No difference in lipolysis No difference in fat mass or adipocyte size |
|
| Whole-body ATGL knockout18,45 |
Higher rate of HFD-induced obesity Higher fat mass Larger adipocyte size Blunted lipolysis |
|
| Adipose-specific ATGL knockout32 |
Higher rate of HFD-induced obesity Higher fat mass Larger adipocyte size Blunted lipolysis |
|
| Adipose-specific ATGL overexpression33 |
Attenuated HFD-induced obesity Lower fat mass Smaller adipocyte size Lower adipocyte TAG content Increased lipolysis |
|
| Liver lipid metabolism |
Whole-body CGI-58 knockout9 |
Higher TAG Lower TAG hydrolase activity |
| ASO-mediated CGI-58 knockdown1,2 |
Higher TAG, DAG, and ceramides Lower TAG hydrolase activity Lower VLDL-TAG secretion Lower β-oxidation |
|
| Whole-body ATGL knockout9,18,40 |
Higher TAG Lower TAG hydrolase activity |
|
| Liver-specific ATGL knockout41 |
Higher TAG Lower TAG hydrolase activity No difference in VLDL-TAG secretion No difference in DAG and ceramides |
|
| Adenovirus-mediated ATGL knockdown42 |
Higher TAG Lower TAG hydrolase activity No difference in VLDL-TAG secretion |
|
| Adenoviral ATGL overexpression21,44 |
Lower TAG No difference in VLDL-TAG secretion Higher rate of NEFA release into plasma Higher rate of FA oxidation |
|
| Insulin signaling |
ASO-mediated CGI-58 knockdown1,2 |
Improved whole-body glucose tolerance on chow and HFD Improved whole-body insulin tolerance on HFD Improved hepatic insulin signaling |
| Whole-body ATGL knockout18,40,44,45 |
Improved whole-body glucose tolerance on chow and HFD Improved whole-body insulin tolerance on chow and HFD Unchanged or slightly impaired hepatic insulin signaling No difference in insulin signaling in primary hepatocytes |
|
| Adenoviral ATGL overexpression44 |
Slight improvement in insulin signaling |
|
| Lipid signaling | ASO-mediated CGI-58 knockdown1,2 |
Lower PPARα target gene expression in liver Altered hepatic glycerophospholipids Prevention of hepatic stress kinase activation and inflammatory signaling |
| Whole-body ATGL knockout60 |
Lower PPARα target gene expression in liver Steatosis and cardiomyopathy prevented by PPARα agonist |
|
| Adenovirus-mediated ATGL knockdown42 | Lower PPARα target gene expression in liver |
ASO, antisense oligonucleotide; HFD, high fat diet; BW, body weight; TAG, triacylglycerol; DAG, diacylglycerol; FA, fatty acid; NEFA, non-esterified fatty acid; VLDL, very low density lipoprotein.