Nonogaki K, Kaji T, Yamazaki T, Murakami Mari
Department of Diabetes Technology, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi, Japan.
Nutr Diabetes. 2016 Nov 28;6(11):e233. doi: 10.1038/nutd.2016.41.
Expression of β-Kotho, fibroblast growth factor receptor (FGFR)-1c and 2c, which bind FGF21, is decreased in the white adipose tissue of obese mice. The aim of the present study was to determine the role of FGFR2c in the development of obesity and diabetes in KKA mice. Treatment with mouse monoclonal FGFR2-IIIc antibody (0.5 mg kg) significantly suppressed body weight gain and epididymal white adipose tissue weight in individually housed KKA mice while having no effect on daily food intake. In addition, treatment with FGFR2-IIIc antibody significantly increased plasma-free fatty acid levels while having no effect on blood glucose or plasma FGF21 levels. Moreover, treatment with FGFR2-IIIc antibody had no significant effect on the expression of uncoupling protein-1, uncoupling protein-2 or peroxisome proliferator-activated receptor-γ coactivator 1α in the epididymal white adipose tissue. The treatment with FGFR2-IIIc antibody had no significant effects on daily food intake and body weight gain in individually housed KK mice. These findings suggest that FGFR2-IIIc upregulates the adiposity induced by social isolation in KKA mice, and that decreased expression and/or function of FGFR2c might be a compensatory response to enhanced adiposity. Inhibition of FGFR2-IIIc function might be a novel therapeutic approach for obesity.
与成纤维细胞生长因子21（FGF21）结合的β-Kotho、成纤维细胞生长因子受体（FGFR）-1c和2c在肥胖小鼠白色脂肪组织中的表达降低。本研究的目的是确定FGFR2c在KKA小鼠肥胖和糖尿病发生发展中的作用。用小鼠单克隆FGFR2-IIIc抗体（0.5mg/kg）治疗可显著抑制单独饲养的KKA小鼠的体重增加和附睾白色脂肪组织重量，而对每日食物摄入量无影响。此外，用FGFR2-IIIc抗体治疗可显著提高血浆游离脂肪酸水平，而对血糖或血浆FGF21水平无影响。此外，用FGFR2-IIIc抗体治疗对附睾白色脂肪组织中解偶联蛋白-1、解偶联蛋白-2或过氧化物酶体增殖物激活受体-γ共激活因子1α的表达无显著影响。用FGFR2-IIIc抗体治疗对单独饲养的KK小鼠的每日食物摄入量和体重增加无显著影响。这些发现表明，FGFR2-IIIc上调了KKA小鼠因社会隔离诱导的肥胖，FGFR2c表达和/或功能的降低可能是对肥胖增强的一种代偿反应。抑制FGFR2-IIIc功能可能是一种治疗肥胖的新方法。
