Lack of Platelet-Activating Factor Receptor Protects Mice Against Diet-Induced Adipose Inflammation and Insulin-Resistance Despite Fat Pad Expansion

Objective: The role of platelet-activating factor (PAF) on diet-induced inflammatory and metabolic dysfunction is unknown. The effects of diet-induced metabolic and inflammatory dysfunction in mice with deletion of the PAF receptor (PAFR(-/-)) were evaluated in this study. Methods: Wild-type and PAFR(-/-) mice were fed chow (WT-C and PAFR(-/-)-C) or high-refined carbohydrate-containing diet (WT-HC and PAFR(-/-)-HC). PAFR(-/-)- Results: HC mice gained more weight and adiposity than PAFR(-/-)-C and WT-HC mice. Lipogenesis increased and hormone-sensitive lipase expression decreased in PAFR(-/-)-HC compared to WT-HC mice. WT-HC mice had impaired glucose tolerance and insulin sensitivity compared to WT-C mice. In contrast, glucose tolerance and insulin sensitivity in PAFR(-/-)-HC mice were similar to that of lean littermates. PAFR(-/-)-HC mice expressed significantly more peroxisome proliferator-activator receptor gamma (PPARc) than PAFR(-/-)-C and WT-C mice. Resistin increased in WT-HC mice compared to WT-C mice. However, the levels of resistin were 35% lower in PAFR(-/-)-HC mice than WT-HC mice. PAFR(-/-) presented with less HC diet-induced adipose tissue inflammation than WT mice. Adipocytes isolated from PAFR(-/-) mice incubated in media containing normal or high levels of glucose secreted less interleukin-6 and tumor necrosis factor alpha and presented lower rate of lipolysis than WT mice. Conclusion: PAFR deficiency resulted in less inflammation in adipose tissue and improvement in glucose homeostasis when fed the HC diet. The higher adiposity observed in PAFR(-/-) mice fed HC diet could be owing to the maintenance of insulin sensitivity, decreased adipocyte lipolysis rate, high lipogenesis and PPAR gamma expression, and lower inflammatory milieu in adipose tissue.