Modulating fibroblast growth factor 21 in hyperphagic OLETF rats with daily exercise and caloric restriction.
Modulating fibroblast growth factor 21 in hyperphagic OLETF rats with daily exercise and caloric restriction.
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通过日常运动和热量限制，在倍感OLETF大鼠中调节成纤维细胞生长因子21。
DOI：
10.1139/h2012-091
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Rector RS
中科院分区：
文献类型：
--
作者：
Fletcher JA;Meers GM;Laughlin MH;Ibdah JA;Thyfault JP;Rector RS
长期使用成纤维细胞生长因子21 （FGF-21）治疗可改善肥胖和非酒精性脂肪性肝病（NAFLD）结局；然而，肥胖情况下，FGF-21的表达矛盾地升高。在这里，我们试图确定通过日常运动（EX）和热量限制（CR）预防肥胖对贪食大鼠肝脏FGF-21的影响，大鼠Long-Evans德岛脂肪（OLETF）。4周龄的雄性OLETF大鼠被随机分为任意进食、久坐（OLETF-SED）、自愿轮式跑步（OLETF- ex）或CR （OLETF-CR；占SED的70%）组（每组n = 7-8），直到40周龄。非贪食大鼠Long-Evans Tokushima Otsuka （LETO-SED）作为对照组。在OLETF-SED动物中观察到，每日EX和CR均可预防肥胖和NAFLD的发展。与OLETF-SED大鼠相比，OLETF-EX和OLETF-CR大鼠血清FGF-21（降低~80%）和肝脏FGF-21 mRNA表达（降低~65%）显著降低（p < 0.01）。然而，肝脏FGF-21蛋白含量在OLETF-EX动物中降低的程度最大（OLETF-SED的50%），并且在OLETF-SED和OLETF-CR大鼠之间没有差异。肝脏FGF-21信号介质——肝脏FGF-21受体2 （FGFR2， mRNA表达）、肝脏FGF-21受体底物2 （FRS2，蛋白含量）和共受体β-Klotho（蛋白含量）——在OLETF-EX和OLETF-CR动物中与OLETF-SED动物相比均升高（分别为60%-100%、~40%和+ 30%-50%）。日常运动和热量限制可调节贪食OLETF大鼠肝脏FGF-21及其主要信号介质。增强FGF-21的代谢作用可能部分解释了运动和热量限制对NAFLD结果的益处。
Chronic treatment with fibroblast growth factor 21 (FGF-21) favorably improves obesity and nonalcoholic fatty liver disease (NAFLD) outcomes; however, FGF-21 expression is paradoxically elevated in obese conditions. Here, we sought to determine the effects of obesity prevention by daily exercise (EX) vs. caloric restriction (CR) on hepatic FGF-21 in the hyperphagic, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Four-week-old male OLETF rats were randomized into groups (n = 7–8 per group) of ad libitum fed, sedentary (OLETF-SED), voluntary wheel running exercise (OLETF-EX), or CR (OLETF-CR; 70% of SED) until 40 weeks of age. Nonhyperphagic, Long-Evans Tokushima Otsuka (LETO-SED) rats served as controls. Both daily EX and CR prevented obesity and NAFLD development observed in the OLETF-SED animals. This was associated with significantly (p < 0.01) lower serum FGF-21 (~80% lower) and hepatic FGF-21 mRNA expression (~65% lower) in the OLETF-EX and OLETF-CR rats compared with the OLETF-SED rats. However, hepatic FGF-21 protein content was reduced to the greatest extent in the OLETF-EX animals (50% of OLETF-SED) and did not differ between the OLETF-SED and OLETF-CR rats. Hepatic FGF-21 signaling mediators — hepatic FGF-21 receptor 2 (FGFR2, mRNA expression), hepatic FGF-21 receptor substrate 2 (FRS2, protein content), and co-receptor β-Klotho (protein content) — were all elevated (60%–100%, ~40%, and +30%–50%, respectively) in the OLETF-EX and OLETF-CR animals compared with the OLETF-SED animals. Daily exercise and caloric restriction modulate hepatic FGF-21 and its primary signaling mediators in the hyperphagic OLETF rat. Enhanced metabolic action of FGF-21 may partially explain the benefits of exercise and caloric restriction on NAFLD outcomes.
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影响因子：
120.7
作者：
Flegal, Katherine M.;Carroll, Margaret D.;Curtin, Lester R.
通讯作者：
Curtin, Lester R.
DOI：
10.1016/j.bbrc.2007.06.068
发表时间：
2007-08-24
影响因子：
3.1
作者：
Lundasen, Thomas;Hunt, Mary C.;Rudling, Mats
通讯作者：
Rudling, Mats
影响因子：
2.2
作者：
Moran, Timothy H.;Bi, Sheng
通讯作者：
Bi, Sheng
DOI：
10.1073/pnas.0701600104
发表时间：
2007-05-01
影响因子：
11.1
作者：
Ogawa, Yasushi;Kurosu, Hiroshi;Kuro-o, Makoto
通讯作者：
Kuro-o, Makoto
影响因子：
3.7
作者：
Uebanso T;Taketani Y;Yamamoto H;Amo K;Ominami H;Arai H;Takei Y;Masuda M;Tanimura A;Harada N;Yamanaka-Okumura H;Takeda E
通讯作者：
Takeda E