ApoE and the role of very low density lipoproteins in adipose tissue inflammation

Objective: To identify the role of triglyceride-rich lipoproteins (TGRLs) and apoE, a major apolipoprotein in TGRLs, in adipose tissue inflammation with high-fat diet (HFD)-induced obesity. Methods: Male apoE^-/- and C57BL/6J wild-type (WT) mice fed HFD for 12 weeks were assessed for metabolic and inflammatory parameters. ApoE^-/- and WT mice were orally gavaged with [³H]palmitic acid to examine the role of apoE in fat delivery to adipose tissue. VLDL from obese apoE^-/- mice were intravenously injected into lean WT or apoE^-/- mice to test potential contribution of TGRLs-derived fat delivery to inflammation in adipose tissue and the role of apoE. Results: ApoE^-/- mice gained less body weight, and had less fat mass and lower triglyceride levels in skeletal muscle than WT. ApoE^-/- mice on HFD had better insulin sensitivity than WT even when comparing body weight-matched mice. Compared to WT mice, apoE^-/- mice on HFD had lower levels of inflammatory cytokines/chemokines and CD11c in adipose tissue, and lower levels of inflammatory markers in skeletal muscle. At 6 h after oral gavage with [³H]palmitic acid, incorporation of [³H]palmitic acid into adipose tissue and skeletal muscle was lower in apoE^-/- mice. After repeated daily injection for 3 days, VLDL from obese apoE^-/- mice induced inflammation in adipose tissue of recipient WT but not apoE^-/- mice. Conclusion: In HFD-induced obesity, apoE plays an important role in inflammation in adipose tissue and skeletal muscle, likely by mediating TGRL-derived fat delivery to these tissues.