Both atherosclerosis and obesity, an independent atherosclerotic risk factor, are associated with enhanced systemic inflammation. Obesity is also characterised by increased adipose tissue inflammation. However, the molecular mechanism underlying the accelerated atherosclerosis in obesity remains unclear. In obesity, activation of c-Jun N-terminal kinase (JNK) contributes to adipose tissue inflammation. 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 adipose tissue with JNK activation.
- Adipose tissue
- ©2016 The Author(s)
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