Li Naisi, Yang Qiyuan, Walker Ryan G, Thompson Thomas B, Du Min, Rodgers Buel D
Department of Animal Sciences (N.L., Q.Y., M.D., B.D.R.), Washington Center for Muscle Biology, Washington State University, Pullman, Washington 99164-7620; and Department of Molecular Genetics, Biochemistry and Microbiology (R.G.W., T.B.T.), University of Cincinnati, Cincinnati, Ohio 45267-0524.
Endocrinology. 2016 Jan;157(1):282-91. doi: 10.1210/en.2015-1546. Epub 2015 Nov 18.
A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn(-/-) (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn(-/-) BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn(-/-) animals results from nutrient partitioning away from fat and in support of muscle.
一种潜在的治疗肥胖的新方法包括减弱肌肉生长抑制素，因为这样可增加肌肉量并减少脂肪量。尽管如此，相互矛盾的研究报告称，肌肉生长抑制素可刺激或抑制脂肪生成，而且尚不清楚通过减弱肌肉生长抑制素实现的肥胖减轻是源于脂肪沉积的变化还是脂肪生成的变化。因此，我们使用标记保留野生型和mstn(-/-)（杰基尔）小鼠，对白色脂肪组织（WAT）和棕色脂肪组织（BAT）中的干细胞、过渡扩增细胞和祖细胞池的变化进行了量化。杰基尔小鼠的肌肉量更大，WAT和BAT量更小，并且野生型和杰基尔小鼠所有组织中的标记诱导情况相同。然而，标记保留细胞的数量在杰基尔小鼠的WAT和BAT中消散得更快，诱导后1个月时分别仅为野生型细胞计数的25%和17%。杰基尔小鼠的脂肪细胞密度显著更高，并且随着标记保留细胞的消失而随时间增加，这与干细胞、过渡扩增细胞和祖细胞池的扩张和分化增强一致。来自杰基尔WAT和BAT的基质血管细胞比野生型细胞更快地分化为成熟脂肪细胞，尽管杰基尔WAT细胞在体外也增殖得更快，但BAT细胞并非如此。然而，体外分化标志物表达表明，mstn(-/-) BAT前脂肪细胞对肌肉生长抑制素的抑制作用更为敏感。这些结果表明，减弱肌肉生长抑制素可在体内刺激脂肪生成，并且mstn(-/-)动物的肥胖减轻是由于营养物质从脂肪转移并支持肌肉。
