Follistatin and follistatin like-3 differentially regulate adiposity and glucose homeostasis.
Follistatin and follistatin like-3 differentially regulate adiposity and glucose homeostasis.
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DOI：
10.1038/oby.2011.97
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发表时间：
2011-10
期刊：
影响因子：
6.9
通讯作者：
Schneyer, Alan
中科院分区：
文献类型：
--
作者：
Brown, Melissa L.;Bonomi, Lara;Ungerleider, Nathan;Zina, Jessica;Kimura, Fuminori;Mukherjee, Abir;Sidis, Yisrael;Schneyer, Alan
TGFβ超家族配体，包括激活素和肌肉生长抑制素，调节机体组成、胰岛功能和葡萄糖稳态。它们的生物活性由拮抗剂卵泡listatin （FST）和卵泡listatin like-3 （FSTL3）控制。假设FST和FSTL3通过调节激活素和肌肉生长抑制素的生物活性，在调节机体成分、葡萄糖稳态和胰岛功能方面具有不同的作用。三个基因突变的小鼠系被创造出来。FSTL3敲除（FSTL3 KO），一个只产生FST288亚型（FST288-only）的小鼠系和一个双突变体（2xM），其中这些系交叉。仅fst288的雄性比WT幼崽更轻，而FSTL3 KO和2xM的雄性比WT幼崽更轻。然而，通过qNMR，只有2xM小鼠全身脂肪质量增加，瘦体重减少。FSTL3 WT和KO小鼠的空腹血糖水平在年轻动物中低于FST小鼠，但在老年小鼠中较高。2xM小鼠血清胰岛素和胰腺胰岛素含量明显高于其他基因型。然而，与仅fst288和WT小鼠相比，2xM小鼠相对胰岛素抵抗和葡萄糖不耐受。FSTL3 KO和2xM小鼠的胰岛部分面积和β-细胞/胰岛比例增加，但仅fst288小鼠没有增加。尽管FSTL3 KO和2xM小鼠的胰岛体积更大，但与WT小鼠相比，它们的功能并未增强。这些结果表明，FST和FSTL3对身体成分和葡萄糖稳态的调节是不同的，尽管胰岛素分泌增加，但它们的联合损失与脂肪量增加和胰岛素抵抗有关。
TGFβ superfamily ligands, including activin and myostatin, modulate body composition, islet function, and glucose homeostasis. Their bioactivity is controlled by the antagonists follistatin (FST) and follistatin like-3 (FSTL3). The hypothesis tested was that FST and FSTL3 have distinct roles in regulating body composition, glucose homeostasis and islet function through regulation of activin and myostatin bioactivity. Three genetic mutant mouse lines were created. FSTL3 knockout (FSTL3 KO), a mouse line producing only the FST288 isoform (FST288-only) and a double mutant (2xM) in which the lines were crossed. FST288-only males were lighter that WT littermates while FSTL3 KO and 2xM males had reduced perigonadal fat pad weights. However, only 2xM mice had increased whole body fat mass and decreased lean mass by qNMR. Fasting glucose levels in FSTL3 WT and KO mice were lower than FST mice in younger animals but were higher in older mice. Serum insulin and pancreatic insulin content in 2xM mice was significantly elevated over other genotypes. Nevertheless, 2xM mice were relatively insulin resistant and glucose intolerant compared to FST288-only and WT mice. Fractional islet area and proportion of β-cells/islet were increased in FSTL3 KO and 2xM, but not FST288-only mice. Despite their larger size, islets from FSTL3 KO and 2xM mice were not functionally enhanced compared to WT mice. These results demonstrate that body composition and glucose homeostasis are differentially regulated by FST and FSTL3 and that their combined loss is associated with increased fat mass and insulin resistance despite elevated insulin production.
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影响因子：
10.9
作者：
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通讯作者：
Schneyer, Alan L.
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