Department of Microbiology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Department of Biochemistry and Immunology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Obesity (Silver Spring). 2014 Mar;22(3):663-72. doi: 10.1002/oby.20142. Epub 2013 Dec 14.
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.
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.
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.
血小板激活因子（PAF）在饮食诱导的炎症和代谢功能障碍中的作用尚不清楚。本研究评估了 PAF 受体（PAFR）缺失对饮食诱导的代谢和炎症功能障碍的影响。
将野生型和 PAFR（-/-）小鼠分别喂食标准饲料（WT-C 和 PAFR（-/-）-C）或高精制碳水化合物饮食（WT-HC 和 PAFR（-/-）-HC）。
HC 饮食组的 PAFR（-/-）小鼠比 PAFR（-/-）-C 和 WT-HC 小鼠体重增加更多，体脂增加。与 WT-HC 相比，PAFR（-/-）-HC 小鼠的脂肪生成增加，激素敏感脂肪酶表达减少。与 WT-C 相比，WT-HC 小鼠葡萄糖耐量和胰岛素敏感性受损。相比之下，PAFR（-/-）-HC 小鼠的葡萄糖耐量和胰岛素敏感性与瘦鼠相似。与 PAFR（-/-）-C 和 WT-C 相比，PAFR（-/-）-HC 小鼠表达更多的过氧化物酶体增殖物激活受体γ（PPARγ）。与 WT-C 相比，WT-HC 小鼠的抵抗素增加。然而，PAFR（-/-）-HC 小鼠的抵抗素水平比 WT-HC 小鼠低 35%。与 WT 相比，PAFR（-/-）小鼠的高脂肪饮食诱导的脂肪组织炎症更少。与 WT 相比，在含有正常或高葡萄糖水平的培养基中孵育的 PAFR（-/-）小鼠分离的脂肪细胞分泌的白细胞介素-6 和肿瘤坏死因子-α较少，脂肪分解率较低。
当喂食 HC 饮食时，PAFR 缺乏导致脂肪组织炎症减少和葡萄糖稳态改善。与喂食 HC 饮食的 WT 相比，PAFR（-/-）小鼠的肥胖程度更高，这可能是由于胰岛素敏感性维持、脂肪细胞脂肪分解率降低、脂肪生成增加和 PPARγ表达增加以及脂肪组织中炎症环境降低所致。
