Increased energy expenditure and leptin sensitivity account for low fat mass in myostatin-deficient mice
Increased energy expenditure and leptin sensitivity account for low fat mass in myostatin-deficient mice
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DOI：
10.1152/ajpendo.00656.2010
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发表时间：
2011-06-01
影响因子：
5.1
通讯作者：
Wisse, Brent E.
中科院分区：
文献类型：
--
作者：
Choi, Sun Ju;Yablonka-Reuveni, Zipora;Wisse, Brent E.
肌生长抑制素缺乏症导致骨骼肌质量显著增加和脂肪质量减少。以前，据报道，肌肉生长抑制素缺陷小鼠在标准化为体重后具有出乎意料的低总能量消耗（EE），因此，低脂肪量的代谢原因被忽视。为了阐明肌肉生长抑制素缺乏如何影响体脂量和能量平衡的控制，我们比较了年轻肌肉生长抑制素缺乏小鼠相对于野生型（WT）和杂合型（HET）对照的耗氧量、身体组成和食物摄入率。我们报告说，在使用回归分析调整总体重后，年轻的肌肉生长抑制素缺陷小鼠相对于WT（+/-0.81 +/-0.28千卡/天，P = 0.004）和HET对照（+0.92 +/-0.31千卡/天，P = 0.005）显示出显著增加的EE。由于两组之间的食物摄入量无差异，因此EE增加可能导致体脂量降低（KO：8.8 +/- 1.1% vs. WT：14.5 +/-1.3%，P = 0.003）和循环瘦素水平降低（KO：0.7 +/- 0.2 ng/ml vs. WT：1.9 +/- 0.3 ng/ml，P = 0.008）。有趣的是，尽管行走活动水平显著降低，但在肌生长抑制素缺陷型小鼠中观察到的调整后的EE增加（相对于WT为~ 50%，P < 0.05）。肌生长抑制素缺乏小鼠的食欲不振和EE增加表明瘦素敏感性增加可能导致其瘦型。事实上，与WT对照相比，瘦素诱导的厌食症（KO：-17 +/-1.2% vs. WT：-5 +/-0.3%）和体重减轻（KO：-2.2 +/-0.2 g vs. WT：-1.6 +/-0.1，P < 0.05）在肌生长抑制素缺陷小鼠中增加。我们的结论是，增加EE，加上增加瘦素敏感性，有助于低脂肪量缺乏肌肉生长抑制素的小鼠。
Myostatin deficiency causes dramatically increased skeletal muscle mass and reduced fat mass. Previously, myostatin-deficient mice were reported to have unexpectedly low total energy expenditure (EE) after normalizing to body mass, and thus, a metabolic cause for low fat mass was discounted. To clarify how myostatin deficiency affects the control of body fat mass and energy balance, we compared rates of oxygen consumption, body composition, and food intake in young myostatin-deficient mice relative to wild-type (WT) and heterozygous (HET) controls. We report that after adjusting for total body mass using regression analysis, young myostatin-deficient mice display significantly increased EE relative to both WT (+/- 0.81 +/- 0.28 kcal/day, P = 0.004) and HET controls (+0.92 +/- 0.31 kcal/day, P = 0.005). Since food intake was not different between groups, increased EE likely accounts for the reduced body fat mass (KO: 8.8 +/- 1.1% vs. WT: 14.5 +/- 1.3%, P = 0.003) and circulating leptin levels (KO: 0.7 +/- 0.2 ng/ml vs. WT: 1.9 +/- 0.3 ng/ml, P = 0.008). Interestingly, the observed increase in adjusted EE in myostatin-deficient mice occurred despite dramatically reduced ambulatory activity levels (-50% vs. WT, P < 0.05). The absence of hyperphagia together with increased EE in myostatin-deficient mice suggests that increased leptin sensitivity may contribute to their lean phenotype. Indeed, leptin-induced anorexia (KO: -17 +/- 1.2% vs. WT: -5 +/- 0.3%) and weight loss (KO: -2.2 +/- 0.2 g vs. WT: -1.6 +/- 0.1, P < 0.05) were increased in myostatin-deficient mice compared with WT controls. We conclude that increased EE, together with increased leptin sensitivity, contributes to low fat mass in mice lacking myostatin.