Exercise training for bone and lipid metabolisms: exercise intensity and duration are important factors

doi:10.3969/j.issn.2095-4344.0830

Abstract

Abstract:

BACKGROUND: Rational exercise training promotes bone and lipid metabolisms, while over-trained exercise makes negative effect. There are many biomarkers and pathways in the progress of bone and lipid metabolisms, which have been explored in different suitable studies.
OBJECTIVE: To summarize the indexes and pathways of bone and lipid metabolisms, especially the common biomarkers and pathways, and to explore the effects of exercise on bone and lipid metabolisms.
METHODS: PubMed and CNKI databases were retrieved with the keywords of “exercise training, bone metabolism, lipid metabolism, index, pathway” in English and Chinese, respectively. Finally, 52 eligible articles were enrolled for result analysis.
RESULTS AND CONCLUSION: Bone metabolic indexes include 25-hydroxy-vitamin-D, calcitonin, parathyroid hormone, tumor necrosis factor, interleukin 1, 2, 4, 6 and 11, insulin-like growth factor 1, transforming growth factor-beta, bone morphogenetic protein, interferon, macrophage colony-stimulating factor, fibroblast growth factor, platelet fireworks growth factor, tartrate-resistant acid phosphatase, collagen I telopeptide, pyridinoline, urinary deoxypyridinoline, alkaline phosphatase, osteocalcin, osteoporogeterin, carboxyterminal propeptide of type I procollagen and so on. While lipid metabolic indexes contain triacylglycerol, serum total cholesterol, high density lipoprotein, low density lipoprotein, leptin, adiponectin, apolipoprotein, oxidized low density lipoprotein, and low density lipoprotein receptor related protein. Exercise intensity and duration are important factors for bone and lipid metabolisms. While a long-term high-intensity exercise will do harm to bone and lipid metabolisms, and a short-time high-intensity exercise is beneficial for bone metabolism. The interaction of exercise intensity and duration on bone and lipid metabolisms still needs to be further studied.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Bone and Bones, Metabolism, Lipid Metabolism, Signal Transduction, Tissue Engineering

CLC Number:

R318

Hou Xi-he, Zhang Ling-li, Li Hui, Wu Wei. Exercise training for bone and lipid metabolisms: exercise intensity and duration are important factors[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(12): 1950-1955.

Figures/Tables 5

此外，应用型研究发现，不同运动项目对骨代谢影响也存在差异。长期运动训练运动员的骨形态结构、骨量、骨密度不同于普通人。运动员之间，也由于其专项和训练强度不同，其骨形态结构、骨量、骨密度也会出现差异。Ari等[16]对女子定向越野、自行车、滑雪和举重运动员的研究得出，举重运动员的骨密度高于其他项目运动员。Jürim等[17]比较女子优秀足球运动员和女子优秀游泳运动员骨密度之间的差异，在身高和体质量无差异的情况下，得出女子优秀足球运动员的骨密度显著高于游泳运动员。Min等[18]比较了跑步、摔跤和高尔夫女子运动员，得出摔跤运动员所测定骨密度要高于跑步和高尔夫运动员。Morel等[19]研究发现，划艇、游泳运动员的全身骨密度和下肢骨密度较低，而橄榄球、足球、拳击运动爱好者的全身骨密度以及下肢骨密度较高；足球、田径运动员的下肢骨密度占全身百分比较高，从事健美、拳击、攀岩和游泳的则是上肢骨密度比率大，橄榄球运动员的脊柱骨密度比率较大。不同运动项目对骨代谢影响有所不同，对骨组织产生相对较大应力的项目(举重、摔跤等)更有利于骨生长及骨量的累积。需注意的是，在运动训练中，大强度的运动不宜进行过长时间，并且间隔不宜太过频繁，以免造成细胞机械磨损和氧化应激损伤而不利于骨生长和骨量的累积。 2.2 运动训练对脂代谢的影响 2.2.1 脂代谢相关检测指标脂代谢过程中，常用的指标有三酰甘油、血清总胆固醇、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)等。此外，瘦素、脂联素、载脂蛋白E(APOE)、氧化型低密度脂蛋白胆固醇(oxLDL-C)和低密度脂蛋白受体相关蛋白5(LPR5)等既可作为脂代谢指标，又可影响骨代谢[20-24]。其中瘦素和脂联素较为重要。瘦素和脂联素是脂肪细胞分泌的两个重要因子，共同参与维持脂肪代谢的平衡，对骨代谢也产生一定影响(表3)。"

瘦素主要由脂肪细胞分泌的多功能蛋白类激素，可抑制食欲减少能量摄入、抑制脂肪合成和增加能量的消耗。肥胖程度越高，瘦素水平也越高，且常伴有瘦素抵抗[25]。瘦素对骨代谢的调节作用主要有中枢调控和外周调控作用，中枢调控主要通过下丘脑交感神经系统，其过程较为复杂，既可激活相应的交感神经(β2)引起骨流失，也可激活相应交感神经(β1)引起骨形成[26]；外周调控中瘦素通过OPG/RANKL信号通路可作用于骨髓间充质干细胞使骨保护素分泌增多，RANKL分泌减少，抑制破骨细胞分化，促进成骨细胞的增殖分化[26]。同时，瘦素可抑制骨髓间充质干细胞向脂肪细胞分化，促进骨髓间充质干细胞向成骨细胞分化[27]。而近期研究中还发现，瘦素还可通过ERK信号通路(MAPK家族，可诱导碱性磷酸酶表达，使基质矿化增强、向成骨方向分化速率加快[28])对软骨细胞上的雌激素受体的表达调控骨代谢[29]。瘦素分泌浓度对骨代谢产生不同的影响，少量或适量分泌可促进骨形成，当瘦素分泌过量(30 nmol/L)时，可使骨髓间充质干细胞凋亡，促进骨吸收，导致了骨量流失[30]。总之，瘦素对骨代谢的影响是一个十分复杂的过程，通过各个信号通路的综合作用，作用性质可能取决于分泌浓度。脂联素是脂肪组织表达、分泌的拮抗炎症因子，主要通过靶细胞膜上的脂联素受体结合而参与糖脂代谢的调节，可促进胰岛素增敏[31]。脂联素对骨代谢的调节作用主要3方面：①骨骼局部产生的脂联素促进骨形成，②循环中的脂联素抑制骨形成，③脂联素通过影响胰岛素(insulin)信号通路促进骨形成[32]。其中主要涉及的信号通路包括JNK信号通路(MAPK家族，在转导胞外信号至核转录因子时起着重要的作用，可以提高转录的能力[33])、P38信号(MAPK家族，可促进骨髓间充质干细胞向成骨细胞分化，抑制骨髓间充质干细胞向脂肪细胞分化[34])通路及RANKL/RANK/OPG信号通路。脂联素可通过JNK及P38促进成骨细胞的增殖分化；诱导NF-κB受体活化素配体(receptor activator of NF-kappaβ ligand，RANKL)表达，阻断骨保护素表达，促进骨吸收[35-36]。此外，脂联素可促进胰岛素分泌及增加其活性，胰岛素可促进成骨细胞及骨钙素含量，促进骨形成[37-38]。脂联素对骨代谢的影响也是一个复杂的过程，通过不同的信号通路产生不同的作用，其关键因素可能与脂联素的浓度、持续作用时间及变化量有关，作用机制有待进一步研究。瘦素与脂联素对骨代谢的影响是一个复杂的过程，与其浓度、作用时间等关系密切。 2.2.2 运动训练对脂代谢的影响运动训练对脂代谢常规指标具有改善作用。Saremi等[39]研究中发现，12周有氧运动(每周5 d)可以显著降低低密度脂蛋白胆固醇的水平，改善腰臀比(WHR)。在动物实验中，John等[40]研究发现，中等强度运动可降低胰岛素抵抗小鼠的血清三酰甘油和总胆固醇浓度，并适当提高高密度脂蛋白胆固醇水平。运动对三酰甘油、血清总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇具有一定改善作用，长期有规律的运动习惯可以改善身体形态，消耗多余的脂肪。运动强度和运动训练持续时间是影响脂肪代谢的两个重要因素。一般而言，中低强度的运动可以使脂肪分解加快、加速脂肪氧化，大强度运动则会减少脂肪氧化。脂肪氧化分解产生能量需要经过一定时间段的持续运动累积，一般而言，运动后30 min脂肪氧化分解产能的效率将显著提高。运动训练对瘦素和脂联素的影响由诸多因素决定，除了运动强度及持续时间外，体质量、体脂和体质水平都会对其影响，而且是综合多方面的共同影响。适宜的运动可以降低血瘦素水平，改善瘦素抵抗，并增加血液脂联素水平。一次性大强度运动后，体内的瘦素和脂联素水平变化不明显或易恢复到原有水平。Jurmae等[41]研究发现，优秀男性划船运动员在一次性极限运动后血清脂联素并未出现明显变化。Zaccaria等[42]研究发现，短时间一次性大强度运动后(60 min)，体内的瘦素水平没有显著改变；而长期运动对瘦素和脂联素的水平变化还需取决于其体质量和体脂是否在长期运动的过程有所改变，对于体质量较大、体脂含量较高的人，长期运动对其瘦素及脂联素将产生积极影响，有利于过剩脂肪消耗及骨形成、骨量累积。Hulver等[43]研究发现，6个月的中等强度运动可使减重者脂联素显著上升，而体质量没有变化者其脂联素没有明显变化。同样，持续有氧运动4-10个月，肥胖者的瘦素水平下降，Hermoso等[44]推测体脂变化时导致瘦素变化的关键因素。长期坚持运动人群其体内瘦素和脂联素水平变化不会太大，脂代谢和骨代谢处于良好的动态平衡中。运动强度过大时，脂质易受氧化应激影响，过剩的ROS与多不饱和脂肪酸生成次级氧化产物丙二醛与低密度脂蛋白结合生成氧化低密度脂蛋白[45]，过多的氧化低密度脂蛋白不仅可以造成脂质异变，而且也可抑制骨髓间充质干细胞向成骨细胞分化，不利于骨形成[46]。这个与上述骨代谢中ROS恶性效果相似，因此，无论是脂代谢还是骨代谢，当运动强度过大或大强度运动持续时间较长，都将不利于代谢，产生不利影响。 2.3 运动训练对骨代谢和脂代谢影响中的思考运动强度和持续时间是影响骨代谢及脂代谢的两个重要因素，前文中表明，当运动强度过大时，会造成细胞的机械磨损及氧化损伤，甚至出现氧化损伤标志物，如丙二醛、H2O2、共轭二烯(conjugated diolefins，CD)等。当细胞损伤得不到修复或者氧化损伤标志物在体内的含量达到一定值时，不仅不利于骨代谢及脂代谢，乃至对身体健康状况造成伤害[47]。而运动持续时间对骨代谢的影响，目前较少，Ghorbanzadeh等[48]认为，在剧烈运动过程中，初期对骨代谢的影响最为明显，随着运动持续时间的增加而有所下降；运动时体内脂肪大量动员，血浆游离脂肪酸浓度上升，为肌肉组织和其他器官提供了氧化代谢的底物，随着脂肪酸的浓度增高，对肌肉组织、器官又是一种不良作用[49]。如果运动强度过大、持续时间较长，有氧氧化较弱，体内的脂肪酸含量高而无法被很有效地分解产生能量，则导致血液脂肪酸含量越来越高，给机体带来巨大负担，引起机能下降。此外，血浆游离脂肪酸含量增高也易诱导丙二醛的生成，最终结合成氧化低密度脂蛋白，抑制了骨髓间充质干细胞向成骨细胞分化[50]。因此，从分子机制角度来讲，运动训练时，运动强度过大则只能持续短暂时间，运动强度较大时，也不能持续太长时间。以免造成细胞机械磨损、氧化损伤及过量血浆脂肪酸堆积，不利于骨代谢和脂代谢(图2)。除了运动强度和持续时间这两个重要因素外，运动"

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