TABLE 1.
Phenotypes of genetic variants in murine and human PNPLAs
| Protein | Mouse Models | Human Mutations | Human Polymorphisms |
|---|---|---|---|
| PNPLA2 | Global deletion: decreased plasma FA levels, TG accumulation in multiple tissues, obesity, premature death from heart failure, defective cold adaptation, enhanced glucose and insulin tolerance (13). | Neutral lipid storage disease with myopathy, further various symptoms: cardiomyopathy, short stature, hepatomegaly, splenomegalie, diabetes, chronic pancreatitis (18, 20). | Association with decreased plasma FA and TG as well as increased fasting plasma glucose and risk for type 2 diabetes (22). |
| ATGL (7) | |||
| Desnutrin (5) | |||
| iPLA2ζ (6) | |||
| PEDF-R (9) | |||
| PLA2GVIE (47) | |||
| PNPLA3 | Association with hepatosteatosis and nonalcoholic fatty liver disease (25), liver transaminases (26), obesity, insulin secretion (27). | ||
| Adiponutrin (24) | |||
| iPLA2ɛ (6) | |||
| PLA2GVID (47) | |||
| PNPLA6 | Global deletion: embryonic lethality (30). | NTE-related motor neuron disease: distal muscle wasting, progressive spastic paraplegia (34). | |
| NTE (31) | Brain-specific deletion: neurodegeneration, vacuolation of nerve cell bodies, disruption of ER (33). | ||
| iPLA2δ (47) | |||
| PLA2GVIC (47) | |||
| PNPLA8 | Global deletion: mitochondrial dysfunction, decreased myocardial cardiolipin content, altered cardiolipin molecular species composition, multiple bioenergetic defects (39). | ||
| iPLA2γ (36) | Cardiac overexpression: decreased phospholipid mass, impaired mitochondrial function, fasting-induced TG accumulation and hemodynamic dysfunction (37). | ||
| PLA2GVIB (41) | |||
| PNPLA9 | Global deletion: reduced male fertility, decreased glucose tolerance, impaired insulin secretion (41, 44), age-related loss of bone mass (43), and neurodegeneration (45). | INAD and idiopathic NBIA (46). | |
| iPLA2β (41) | β-Cell-specific overexpression: increased glucose tolerance and insulin secretion (44). | ||
| PLA2G6 | |||
| PLA2GVIA (47) |