Diminished satellite cells and elevated adipogenic gene expression in muscle as caused by ovariectomy are averted by low-magnitude mechanical signals
Diminished satellite cells and elevated adipogenic gene expression in muscle as caused by ovariectomy are averted by low-magnitude mechanical signals
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DOI：
10.1152/japplphysiol.01020.2014
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发表时间：
2015-07-01
影响因子：
3.3
通讯作者：
Rubin, Clinton T.
中科院分区：
文献类型：
--
作者：
Frechette, Danielle M.;Krishnamoorthy, Divya;Rubin, Clinton T.
更年期加速的与年龄相关的肌肉骨骼系统退化，由于全身和肌肉肥胖的增加而进一步复杂化。这项研究的目的是在分子、细胞和组织水平上确定卵巢切除对小鼠肥胖和卫星细胞数量的影响，以及机械信号是否会影响任何结果。8周龄C57BL/6小鼠摘除卵巢，其中一半接受低强度振动(LIV；0.3g/90 Hz，15min/d，5d/wk；n=10)6wk，其余一半为假振动(OVX；n=10)。将数据与年龄匹配的完整对照(AC；n=10)进行比较。体内MU CT分析显示，6wk后，去卵巢小鼠的总肥胖率(P<；0.001)和内脏肥胖度(P<；0.001)分别增加了43%和125%，而LIV仅增加了21%(P=0.001)。与AC相比，成脂基因(PPARγ、FABP4、PPAR Delta和FoxO1)在OVX肌肉中的表达上调(P<；0.05)，而LIV则降低了这些水平(P<；0.05)。成脂基因的表达与肌肉中总卫星细胞和储备卫星细胞的百分比呈负相关，与AC相比，OVX组和AC组均下降(分别为-21%和-28%，P<；0.01)。LIV缓解了这些下降(分别为-11%和-17%)。这些结果为雌激素缺乏的负面后果提供了进一步的证据，并表明机械信号有可能中断随后的成脂基因表达和卫星细胞抑制，强调了物理信号在保护肌肉骨骼完整性和减缓脂肪表型方面的重要性。
Age-related degeneration of the musculoskeletal system, accelerated by menopause, is further complicated by increased systemic and muscular adiposity. The purpose of this study was to identify at the molecular, cellular, and tissue levels the impact of ovariectomy on adiposity and satellite cell populations in mice and whether mechanical signals could influence any outcomes. Eight-week-old C57BL/6 mice were ovariectomized, with one half subjected to low-intensity vibration (LIV; 0.3 g/90 Hz, 15 min/day, 5 day/wk; n = 10) for 6 wk and the others sham vibrated (OVX; n = 10). Data are compared with age-matched, intact controls (AC; n = 10). In vivo mu CT analysis showed that OVX mice gained 43% total (P < 0.001) and 125% visceral adiposity (P < 0.001) compared with their baseline after 6 wk, whereas LIV gained only 21% total (P = 0.01) and 70% visceral adiposity (P < 0.01). Relative to AC, expression of adipogenic genes (PPAR gamma, FABP4, PPAR delta, and FoxO1) was upregulated in OVX muscle (P < 0.05), whereas LIV reduced these levels (P < 0.05). Adipogenic gene expression was inversely related to the percentage of total and reserve satellite cell populations in the muscle, with both declining in OVX compared with AC (-21 and -28%, respectively, P < 0.01). LIV mitigated these declines (-11 and -17%, respectively). These results provide further evidence of the negative consequences of estrogen depletion and demonstrate that mechanical signals have the potential to interrupt subsequent adipogenic gene expression and satellite cell suppression, emphasizing the importance of physical signals in protecting musculoskeletal integrity and slowing the fat phenotype.