Activation of PPARγ at an Early Stage of Differentiation Enhances Adipocyte Differentiation of MEFs Derived from Type II Diabetic TSOD Mice and Alters Lipid Droplet Morphology
Activation of PPARγ at an Early Stage of Differentiation Enhances Adipocyte Differentiation of MEFs Derived from Type II Diabetic TSOD Mice and Alters Lipid Droplet Morphology
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DOI：
10.1248/bpb.b17-00030
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发表时间：
2017-06-01
影响因子：
2
通讯作者：
Atsumi, Gen-ichi
中科院分区：
文献类型：
--
作者：
Ishibashi, Kenichi;Takeda, Yoshihiro;Atsumi, Gen-ichi
与相应的津村、铃木、非肥胖(TSNO)对照小鼠相比，2型糖尿病津村、铃木、肥胖、糖尿病(TSOD)小鼠的体重逐渐增加，并产生胰岛素抵抗。尽管 2 型糖尿病的发生与脂肪细胞功能障碍有关，但人们对 TSOD 小鼠脂肪细胞的特性知之甚少。因此，我们尝试使用体外小鼠胚胎成纤维细胞（MEF）分化的脂肪细胞来去除体内因素并阐明TSOD小鼠脂肪细胞的固有特性。在这里，我们表明 TSOD 的 MEF 分化为脂肪细胞的能力较低。 TSOD的MEF分化的细胞中油红O染色的细胞百分比和脂肪形成标志物的水平低于TSNO的MEF分化的细胞。我们进一步表明，在分化早期使用过氧化物酶体增殖物激活受体-γ (PPARγ) 激动剂（罗格列酮）进行治疗可增加 TSOD-MEF 中油红 O 染色细胞分化为脂肪细胞的百分比。此外，这些脂肪细胞中的脂滴尺寸大于从TSNO的MEF分化的脂肪细胞中的脂滴尺寸。尽管在分化过程中用罗格列酮持续处理TSOD的MEF增加了油红O染色细胞的百分比，但如此处理的脂肪细胞中的脂滴大小并未达到仅在早期处理的脂肪细胞的大小。因此，在分化的早期阶段，其激动剂激活PPARγ可补偿TSOD小鼠MEF的脂肪形成分化的低效力，并加速在来自TSOD小鼠MEF的脂肪细胞中形成扩大的脂滴。
Type 2 diabetic Tsumura, Suzuki, obese, diabetes (TSOD) mice gradually gain weight as compared to corresponding Tsumura, Suzuki, non-obesity (TSNO) control mice, and develop insulin resistance. Although development of type 2 diabetes mellitus is associated with dysfunction of adipocytes, little is known about the properties of adipocytes from TSOD mice. Therefore, we attempted to remove intracorporeal factors and elucidate inherent properties of adipocytes of TSOD mice using adipocytes differentiated from mouse embryonic fibroblasts (MEFs) in vitro. Here, we show that MEFs of TSOD have low potency for differentiation into adipocytes. The percentage of Oil red O-stained cells and levels of adipogenic markers in cells differentiated from MEFs of TSOD are lower than those in cells differentiated from MEFs of TSNO. We further show that treatment with an agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma) (rosiglitazone) at an early stage of differentiation increases the percentage of Oil red O-stained cells in TSOD-MEFs differentiated into adipocytes. Moreover, the lipid droplet size in those adipocytes is larger than that in the adipocytes differentiated from MEFs of TSNO. Although persistent treatment of MEFs of TSOD with rosiglitazone during differentiation increases the percentage of Oil red O-stained cells, the lipid droplet size in adipocytes treated as such does not reach the size of those treated in early stage only. Thus, activation of PPAR gamma by its agonist at an early stage of differentiation compensates for the low potency toward adipogenic differentiation of, and accelerates formation of enlarged lipid droplets in adipocytes derived from, MEFs of TSOD mice.