Key result
PAFR deficiency reduces adipose inflammation and improves glucose homeostasis in mice fed a high-carbohydrate diet.
Why the study?
The role of platelet-activating factor on diet-induced inflammatory and metabolic dysfunction was unknown.
PAFR deficiency in mice protects against diet-induced adipose inflammation and insulin resistance despite increased adiposity.
PAFR deletion exacerbates diet-induced adiposity in mice; hypothesis-generating for its role in human metabolic disease.
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 (PPARγ) 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 PPARγ expression, and lower inflammatory milieu in adipose tissue.
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Menezes‐Garcia et al. (2013) studied Diet-induced inflammatory and metabolic dysfunction. PAF receptor deletion (PAFR(-/-)) and high-refined carbohydrate diet vs. Wild-type mice and chow diet was evaluated on Adiposity, glucose tolerance, insulin sensitivity, and adipose tissue inflammation. PAFR deficiency in mice fed a high-carbohydrate diet resulted in less adipose tissue inflammation and improved glucose homeostasis despite higher adiposity.
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