Adipose-Specific Inactivation of JNK Alleviates Atherosclerosis in ApoE-deficient Mice

This study investigated whether the suppression of fat inflammation through adipose-specific JNK inactivation could protect against atherosclerosis in mice. ApoE-/- mice were crossbred with transgenic mice with adipose-specific expression of a dominant negative form of JNK (dnJNK) to generate apoE-/-/dnJNK (ADJ) mice. High-fat-high-cholesterol diet-treated ADJ mice exhibited significant attenuations of visceral fat and systemic inflammation without changes in lipid or glucose metabolism, and were protected against atherosclerosis, when compared to apoE-/- mice. Lean apoE-/- mice that received transplantation of visceral fat from obese wild-type donor mice for 4 weeks showed exacerbated systemic inflammation and atherosclerotic plaque formation. Conversely, apoE-/- recipients carrying visceral fat graft from obese dnJNK donors were protected against enhanced systemic inflammation and atherogenesis. The beneficial effects of adipose-specific JNK inactivation on atherogenesis in apoE-/- recipients were significantly compromised by continuous infusion of recombinant adipocyte-fatty acid binding protein (A-FABP), previously shown to interact with JNK via a positive feedback loop to modulate inflammatory responses. Together these data suggested that enhanced atherosclerosis in obesity can be attributed, at least in part, to a distant cross-talk between visceral fat and the vasculature, mediated by the release of pro-inflammatory cytokines, such as A-FABP, from the inflamed visceral...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research