Table 1.

The influence of the ATX-LPA-LPP3 signaling axis on energy metabolism and diet-induced obesity, impaired glucose homeostasis, and metabolic comorbidities based on studies involving mice with genetic or pharmacological ATX, LPA receptor, and LPP3 modulation. HF, high fat; n.d., not determined; ↑, increased effect; ↓, decreased effect; ↔, no effect.

Mouse Model	Obesity/ Adiposity	Insulin Resistance/Glucose Intolerance	Other Comorbidities, Metabolic Parameters	Ref
HF-fed global ATX+/− mice	↓	↓	Lipid accrual in muscle, liver, heart ↔	[59]
HF-fed global ATX+/− mice	↓	↓	Lipid accrual in muscle ↔, liver ↓, cardiomyopathy ↓, mitochondrial dysfunction ↓	[57]
HF-fed global ATX−/− mice (postnatal KO)	↔ (adipocyte size ↓)	↓	Lipid accrual in liver ↓, inflammation ↓	[72]
HF-fed global ATX over-expressing mice	↑	↔	Inflammation ↔	[73]
HF-fed FATX−/− mice	↑	↓	n.d.	[18]
HF-fed FATX−/− mice	↓	↓	Inflammation ↓, mitochondrial dysfunction ↓	[59]
HF-fed FATX−/− mice	↔ (adipocyte size ↓)	↔	Lipid accrual in liver ↓, inflammation ↓	[72]
HF-fed adipose ATX over-expressing mice	↑	n.d.	n.d.	[59]
Western diet/HF-fed FLPP3−/− mice	↔	↓	n.d.	[29]
Chow-fed CMLPP3−/− mice	n.d.	n.d.	Cardiomyopathy ↑, mitochondrial dysfunction ↑	[30]
LF-fed LPA1−/− mice	↑	n.d.	n.d.	[74]
HF-fed LPA1−/− mice	↓	n.d.	n.d.	[75]
HF-fed LPA4−/− mice	↑	↓	Lipid accrual in liver ↓, inflammation ↓	[74]
Db/db mice with LPA1/3 inhibition (Ki16425)	↔	↓	Fibrosis in WAT ↓, liver ↔	[76]
HF-fed C57Bl6 mice wtih LPA1/3 inhibition (Ki16425)	↔	↓	Lipid accrual in muscle, liver ↔	[34]
HF-fed C57Bl6 mice with LPA1/3 inhibition (Ki16425)	n.d.	↓	Inflammation ↓ (adipose macrophage infiltration)	[33]
HF-fed C57Bl6 mice with SC144-induced ATX reduction	↔	↓	Inflammation ↓ (adipose macrophage infiltration)	[33]
HF-fed C57Bl6 mice with ATX inhibition (PF8380)	↔	n.d.	Cardiomyopathy ↓	[35]
HF-fed C57Bl6 mice with siRNA mediated ATX silencing in WAT	↔	n.d.	Lipid accrual in heart ↓, cardiac fibrosis ↓, cardiomyopathy ↓, mitochondrial dysfunction ↓	[58]