Styner Maya, Pagnotti Gabriel M, McGrath Cody, Wu Xin, Sen Buer, Uzer Gunes, Xie Zhihui, Zong Xiaopeng, Styner Martin A, Rubin Clinton T, Rubin Janet
Department of Medicine, Division of Endocrinology and Metabolism, University of North Carolina, Chapel Hill, NC, USA.
Department of Biomedical Engineering, State University of New York, Stony Brook, Stony Brook, NY, USA.
J Bone Miner Res. 2017 Aug;32(8):1692-1702. doi: 10.1002/jbmr.3159. Epub 2017 May 4.
The relationship between marrow adipose tissue (MAT) and bone health is poorly understood. We used running exercise to ask whether obesity-associated MAT can be attenuated via exercise and whether this correlates with gains in bone quantity and quality. C57BL/6 mice were divided into diet-induced obesity (DIO, n = 14) versus low-fat diet (LFD, n = 14). After 3 months, 16-week-old mice were allocated to an exercise intervention (LFD-E, DIO-E) or a control group (LFD, DIO) for 6 weeks (4 groups, n = 7/group). Marrow adipocyte area was 44% higher with obesity (p < 0.0001) and after exercise 33% lower in LFD (p < 0.0001) and 39% lower in DIO (p < 0.0001). In LFD, exercise did not affect adipocyte number; however, in DIO, the adipocyte number was 56% lower (p < 0.0001). MAT was 44% higher in DIO measured by osmium-μCT, whereas exercise associated with reduced MAT (-23% in LFD, -48% in DIO, p < 0.05). MAT was additionally quantified by 9.4TMRI, and correlated with osmium-µCT (r = 0.645; p < 0.01). Consistent with higher lipid beta oxidation, perilipin 3 (PLIN3) rose with exercise in tibial mRNA (+92% in LFD, +60% in DIO, p < 0.05). Tibial µCT-derived trabecular bone volume (BV/TV) was not influenced by DIO but responded to exercise with an increase of 19% (p < 0.001). DIO was associated with higher cortical periosteal and endosteal volumes of 15% (p = 0.012) and 35% (p < 0.01), respectively, but Ct.Ar/Tt.Ar was lower by 2.4% (p < 0.05). There was a trend for higher stiffness (N/m) in DIO, and exercise augmented this further. In conclusion, obesity associated with increases in marrow lipid-measured by osmium-μCT and MRI-and partially due to an increase in adipocyte size, suggesting increased lipid uptake into preexisting adipocytes. Exercise associated with smaller adipocytes and less bone lipid, likely invoking increased ß-oxidation and basal lipolysis as evidenced by higher levels of PLIN3. © 2017 American Society for Bone and Mineral Research.
骨髓脂肪组织(MAT)与骨骼健康之间的关系目前尚不清楚。我们通过跑步运动来探究与肥胖相关的MAT是否可以通过运动得到缓解,以及这是否与骨量和骨质量的增加相关。将C57BL/6小鼠分为饮食诱导肥胖组(DIO,n = 14)和低脂饮食组(LFD,n = 14)。3个月后,将16周龄的小鼠分为运动干预组(LFD-E、DIO-E)或对照组(LFD、DIO),为期6周(4组,每组n = 7)。肥胖小鼠的骨髓脂肪细胞面积高出44%(p < 0.0001),运动后,LFD组降低33%(p < 0.0001),DIO组降低39%(p < 0.0001)。在LFD组,运动不影响脂肪细胞数量;然而,在DIO组,脂肪细胞数量降低56%(p < 0.0001)。通过锇μCT测量,DIO组的MAT高出44%,而运动与MAT降低相关(LFD组降低23%,DIO组降低48%,p < 0.05)。另外通过9.4T MRI对MAT进行定量,其与锇μCT相关(r = 0.645;p < 0.01)。与较高的脂质β氧化一致,胫骨mRNA中的 perilipin 3(PLIN3)随运动增加(LFD组增加92%,DIO组增加60%,p < 0.05)。胫骨μCT得出的骨小梁体积(BV/TV)不受DIO影响,但运动后增加了19%(p < 0.001)。DIO分别与较高的皮质骨膜和内膜体积相关,增加了15%(p = 0.012)和35%(p < 0.01),但皮质骨面积/总面积(Ct.Ar/Tt.Ar)降低了2.4%(p < 0.05)。DIO组有更高硬度(N/m)的趋势,运动进一步增强了这种趋势。总之,肥胖与通过锇μCT和MRI测量的骨髓脂质增加相关,部分原因是脂肪细胞大小增加,表明脂质摄取到已有的脂肪细胞中。运动与较小的脂肪细胞和较少骨脂质相关,可能是由于PLIN3水平升高导致β氧化和基础脂解增加。© 2017美国骨与矿物质研究学会