Sato Daisuke, Oda Kanako, Kusunoki Masataka, Nishina Atsuyoshi, Takahashi Kazuaki, Feng Zhonggang, Tsutsumi Kazuhiko, Nakamura Takao
Department of Biomedical Information Engineering, Graduate School of Medical Science, Yamagata University, 2-2-2, Iida-nishi, Yamagata 990-9585, Japan.
Department of Biomedical Information Engineering, Graduate School of Medical Science, Yamagata University, 2-2-2, Iida-nishi, Yamagata 990-9585, Japan.
Eur J Pharmacol. 2016 Feb 15;773:71-7. doi: 10.1016/j.ejphar.2016.01.012. Epub 2016 Jan 26.
It was reported that adipocyte size is potentially correlated in part to amount of long chain polyunsaturated fatty acids (PUFAs) and insulin resistance because several long chain PUFAs can be ligands of peroxisome proliferator-activated receptors (PPARs). In our previous study, marked reduction of PUFAs was observed in insulin-resistant high-fat fed rats, which may indicate that PUFAs are consumed to improve insulin resistance. Although PPARγ agonist, well known as an insulin sensitizer, proliferates small adipocytes, the effects of PPARγ agonist on FA composition in adipose tissue have not been clarified yet. In the present study, we administered pioglitazone, a PPARγ agonist, to high-fat fed rats, and measured their FA composition of triglyceride fraction in adipose tissue and adipocyte diameters in pioglitazone-treated (PIO) and non-treated (control) rats. Insulin sensitivity was obtained with hyperinsulinemic euglycemic clamp. Average adipocyte diameter in the PIO group were smaller than that in the control one without change in tissue weight. In monounsaturated FAs (MUFAs), 14:1n-5, 16:1n-7, and 18:1n-9 contents in the PIO group were lower than those, respectively, in the control group. In contrast, 22:6n-3, 20:3n-6, 20:4n-6, and 22:4n-6 contents in the PIO group were higher than those, respectively, in the control group. Insulin sensitivity was higher in the PIO group than in the control one. These findings suggest that PPARγ activation lowered MUFAs whereas suppressed most of C20 or C22 PUFAs reduction, and that the change of fatty acid composition may be relevant with increase in small adipocytes.
据报道，脂肪细胞大小可能部分与长链多不饱和脂肪酸（PUFAs）的含量及胰岛素抵抗相关，因为几种长链PUFAs可以是过氧化物酶体增殖物激活受体（PPARs）的配体。在我们之前的研究中，观察到胰岛素抵抗的高脂喂养大鼠体内PUFAs显著减少，这可能表明PUFAs被消耗以改善胰岛素抵抗。尽管PPARγ激动剂作为一种胰岛素增敏剂可使小脂肪细胞增殖，但PPARγ激动剂对脂肪组织中脂肪酸组成的影响尚未阐明。在本研究中，我们给高脂喂养大鼠施用吡格列酮（一种PPARγ激动剂），并测量了吡格列酮处理组（PIO）和未处理组（对照组）大鼠脂肪组织中甘油三酯部分的脂肪酸组成及脂肪细胞直径。通过高胰岛素正常血糖钳夹术获得胰岛素敏感性。PIO组的平均脂肪细胞直径小于对照组，而组织重量无变化。在单不饱和脂肪酸（MUFAs）中，PIO组的14:1n - 5、16:1n - 7和18:1n - 9含量分别低于对照组。相反，PIO组的22:6n - 3、20:3n - 6、20:4n - 6和22:4n - 6含量分别高于对照组。PIO组的胰岛素敏感性高于对照组。这些发现表明，PPARγ激活降低了MUFAs，同时抑制了大多数C20或C22 PUFAs的减少，并且脂肪酸组成的变化可能与小脂肪细胞的增加有关。
