Myostatin knockout in mice increases myogenesis and decreases adipogenesis

Myostatin knockout in mice increases myogenesis and decreases adipogenesis
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DOI:
10.1006/bbrc.2002.6500
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发表时间:
2002-03-01
影响因子:
3.1
通讯作者:
Baile, CA
Baile, CA
中科院分区:
生物学4区
文献类型:
--
作者:
Lin, J;Arnold, HB;Baile, CA

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生长分化因子-8 (GDF-8),或肌肉生长抑制素,在肌肉发育过程中起重要的抑制作用。由于肌肉和脂肪组织是由相同的间充质干细胞发育而来,我们假设肌生长抑制素基因敲除可能导致肌肉形成和脂肪形成之间的转换。雄性和雌性野生型(WT)和肌肉生长抑制素敲除(KO)小鼠在4、8和12周龄时被处死。KO小鼠臀肌(GM)在8周(P < 0.01)和12周(P < 0.001)时明显大于WT小鼠。12周时,KO小鼠脂肪库明显减少(P < 0.01)。与12周龄WT小鼠相比,KO小鼠血清瘦素浓度降低(P < 0.001),腹股沟脂肪组织瘦素mRNA表达降低(P < 0.01)。与WT小鼠相比,KO小鼠脂肪组织中CCAAT/增强子结合蛋白- α (C/EBPalpha)和过氧化物酶体增殖激活受体- γ (PPARgamma)水平显著降低。因此,肌生长抑制素敲除小鼠的肌肉发育增加与脂肪生成减少有关,因此,瘦素分泌减少。(C) 2002 Elsevier Science (USA)。
Growth differentiation factor-8 (GDF-8), or Myostatin, plays an important inhibitory role during muscle development. Since muscle and adipose tissue develop from the same mesenchymal stem cells, we hypothesized that Myostatin gene knockout may cause a switch between myogenesis and adipogenesis. Male and female wild type (WT) and Myostatin knockout (KO) mice were sacrificed at 4, 8, and 12 weeks of age. The gluteus muscle (GM) was larger in KO mice compared to WT mice at 8 (P < 0.01) and 12 (P < 0.001) weeks. At 12 weeks, KO mice had decreased fat depots (P < 0.01). Compared to 12-week-old WT mice, serum leptin concentration in KO mice was lower (P < 0.001) and leptin mRNA expression was decreased (P < 0.01) in inguinal adipose tissue. CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor-gamma (PPARgamma) levels in adipose tissue were significantly lower in KO mice compared to WT mice. Thus, increased muscle development in Myostatin knockout mice is associated with reduced adipogenesis and consequently, decreased leptin secretion. (C) 2002 Elsevier Science (USA).