Lack of platelet‐activating factor receptor protects mice against diet‐induced adipose inflammation and insulin‐resistance despite fat pad expansion

Z Menezes‐Garcia, MC Oliveira, RL Lima, FM Soriani… - …, 2014 - Wiley Online Library
Z Menezes‐Garcia, MC Oliveira, RL Lima, FM Soriani, D Cisalpino, LM Botion, MM Teixeira
Obesity, 2014Wiley Online Library
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 …
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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