Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, United States.
Center for Healthy Aging Research, Oregon State University, Corvallis, OR, United States.
Front Endocrinol (Lausanne). 2020 Mar 17;11:117. doi: 10.3389/fendo.2020.00117. eCollection 2020.
Growing female mice housed at room temperature (22°C) weigh the same but differ in body composition compared to mice housed at thermoneutrality (32°C). Specifically, mice housed at room temperature have lower levels of white adipose tissue (WAT). Additionally, bone marrow adipose tissue (bMAT) and cancellous bone volume fraction in distal femur metaphysis are lower in room temperature-housed mice. The metabolic changes induced by sub-thermoneutral housing are associated with lower leptin levels in serum and higher levels of gene expression in brown adipose tissue. Although the precise mechanisms mediating adaptation to sub-thermoneutral temperature stress remain to be elucidated, there is evidence that increased sympathetic nervous system activity acting via β-adrenergic receptors plays an important role. We therefore evaluated the effect of the non-specific β-blocker propranolol (primarily β and β antagonist) on body composition, femur microarchitecture, and bMAT in growing female C57BL/6 mice housed at either room temperature or thermoneutral temperature. As anticipated, cancellous bone volume fraction, WAT and bMAT were lower in mice housed at room temperature. Propranolol had small but significant effects on bone microarchitecture (increased trabecular number and decreased trabecular spacing), but did not attenuate premature bone loss induced by room temperature housing. In contrast, propranolol treatment prevented housing temperature-associated differences in WAT and bMAT. To gain additional insight, we evaluated a panel of genes in tibia, using an adipogenesis PCR array. Housing temperature and treatment with propranolol had exclusive as well as shared effects on gene expression. Of particular interest was the finding that room temperature housing reduced, whereas propranolol increased, expression of the gene for acetyl-CoA carboxylase (), the rate-limiting step for fatty acid synthesis and a key regulator of β-oxidation. Taken together, these findings provide evidence that increased activation of β and/or β receptors contributes to reduced bMAT by regulating adipocyte metabolism, but that this pathway is unlikely to be responsible for premature cancellous bone loss in room temperature-housed mice.
在室温（22°C）下饲养的雌性生长小鼠体重相同，但与在热中性（32°C）下饲养的小鼠相比，身体成分存在差异。具体而言，在室温下饲养的小鼠白色脂肪组织（WAT）水平较低。此外，在室温下饲养的小鼠的骨髓脂肪组织（bMAT）和远端股骨干骺端松质骨体积分数较低。亚热中性饲养引起的代谢变化与血清中瘦素水平降低和棕色脂肪组织中基因表达水平升高有关。尽管介导适应亚热中性温度应激的精确机制仍有待阐明，但有证据表明，增加的交感神经系统活性通过β-肾上腺素能受体发挥重要作用。因此，我们评估了非特异性β-阻断剂普萘洛尔（主要是β和β拮抗剂）对生长的 C57BL/6 雌性小鼠在室温或热中性温度下的身体成分、股骨微观结构和 bMAT 的影响。正如预期的那样，在室温下饲养的小鼠的骨小梁体积分数、WAT 和 bMAT 较低。普萘洛尔对骨微观结构有微小但显著的影响（增加了小梁数量，减少了小梁间距），但不能减弱室温饲养引起的早期骨丢失。相比之下，普萘洛尔治疗可防止与室温有关的 WAT 和 bMAT 差异。为了获得更多的见解，我们使用脂肪生成 PCR 阵列评估了胫骨中的一组基因。饲养温度和普萘洛尔治疗对基因表达有独特的影响，也有共同的影响。特别有趣的是，室温饲养降低了乙酰辅酶 A 羧化酶（）的基因表达，而普萘洛尔增加了该基因的表达，乙酰辅酶 A 羧化酶是脂肪酸合成的限速步骤，也是β氧化的关键调节剂。综上所述，这些发现提供了证据表明，增加β和/或β受体的激活通过调节脂肪细胞代谢有助于减少 bMAT，但该途径不太可能是室温饲养小鼠的皮质骨丢失的原因。
