CD36-facilitated fatty acid uptake inhibits leptin production and signaling in adipose tissue
CD36-facilitated fatty acid uptake inhibits leptin production and signaling in adipose tissue
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DOI：
10.2337/db06-1699
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发表时间：
2007-07-01
期刊：
影响因子：
7.7
通讯作者：
Abumrad, Nada A.
中科院分区：
文献类型：
--
作者：
Hajri, Tahar;Hall, Angela M.;Abumrad, Nada A.
瘦素在调节能量消耗以应对食物摄入方面起着重要作用，但对瘦素的营养调节尚不完全了解。在这项研究中，我们使用体内和体外方法，研究了脂肪酸摄取在调节瘦素表达和产生中的作用。cd36缺失小鼠的瘦素水平增加了一倍，尽管脂肪量减少了40%，但细胞脂肪酸摄取受损。cd36缺失的小鼠不受饮食引起的体重增加的影响，但不受瘦素缺乏引起的体重增加的影响。cd36缺失小鼠的瘦素分泌对葡萄糖摄入有强烈反应，而野生型小鼠的反应则迟钝。这表明瘦素调节整合了葡萄糖和脂肪酸的相反影响，脂肪酸抑制的丧失允许葡萄糖/胰岛素的非抑制刺激。脂肪酸抑制基础和胰岛素刺激的瘦素释放与cd36促进的脂肪酸通量有关，这对于过氧化物酶体增殖物激活受体7的脂肪酸激活很重要，可能有助于脂肪细胞的营养感知功能。脂肪酸摄取也可能调节脂肪细胞瘦素信号。在cd36缺失的脂肪组织中，磷酸化与非磷酸化的信号转导因子和转录激活因子3的比值与瘦素水平不成比例地增加，这是瘦素活性的一个指标。此外，瘦素敏感脂肪酸氧化酶的表达增强。靶向脂肪细胞CD36可能提供一种解耦瘦素产生和肥胖的方法。
Leptin plays an important role in regulating energy expenditure in response to food intake, but nutrient regulation of leptin is incompletely understood. In this study using in vivo and in vitro approaches, we examined the role of fatty acid uptake in modulating leptin expression and production. Leptin levels are doubled in the CD36-null mouse, which has impaired cellular fatty acid uptake despite a 40% decrease in fat mass. The CD36-null mouse is protected from diet-induced weight gain but not from that consequent to leptin deficiency. Leptin secretion in the CD36-null mouse is strongly responsive to glucose intake, whereas a blunted response is observed in the wild-type mouse. This indicates that leptin regulation integrates opposing influences from glucose and fatty acid and loss of fatty acid inhibition allows unsuppressed stimulation by glucose/insulin. Fatty acid inhibition of basal and insulin-stimulated leptin release is linked to CD36-facilitated fatty acid flux, which is important for fatty acid activation of peroxisome proliferator-activated receptor 7 and likely contributes to the nutrient sensing function of adipocytes. Fatty acid uptake also may modulate adipocyte leptin signaling. The ratio of phosphorylated to unphosphorylated signal transducer and activator of transcription 3, an index of leptin activity, is increased in CD36-null fat tissue disproportionately to leptin levels. In addition, expression of leptin-sensitive fatty acid oxidative enzymes is enhanced. Targeting adipocyte CD36 may offer a way to uncouple leptin production and adiposity.