| Background:Adolescent overweight and obesity have become important public health issues for society as a whole.The conventional wisdom is that while obesity is a risk factor for many chronic diseases,the mechanical load associated with body weight facilitates bone formation.However,adipocytes and osteoblasts originate from a common pluripotent mesenchymal stem cell,and obesity can increase adipocyte differentiation as well as fat accumulation,thus hindering osteoblast differentiation and bone formation.The chronic inflammatory environment of the obese body may promote osteoclast activity and bone resorption through the OPG/RANKL/RANK pathway.miRNA is a type of small non-coding RNA that can regulate cell proliferation,differentiation,apoptosis and inflammatory response.Among them,miR-374a-5p has been widely studied in the field of cancer,but in recent years it has been found that it can negatively regulate inflammatory factors such as CCL2 and TNF-α,and these inflammatory mediators happen to be the key tandem factors of obesity and bone.Therefore,some researchers have proposed that miRNA-374a may be involved in the regulation of bone metabolism through inflammatory factors.Because of the complex interaction between adipose tissue and bone metabolism,the bone health of obese people,particularly the effect of exercise combined with diet on their bone health,is attracting attention.Objective:To observe the effect of exercise combined with dietary intervention on bone status and bone metabolism in obese male adolescents,and to further explore the mediating effect of miRNA374/inflammatory factors,to provide support and basis for improving bone metabolism and bone health in obese male adolescents.Methods:Obese male adolescents from the Wuhan Haoqian Weight Loss Training Camp were screened.A total of 14 adolescents aged 12-18 years were selected according to BMI as the intervention group（group E）through physical and morphological index tests.Another 6adolescents of similar age and normal weight were selected as the control group（Group C）.The intervention group underwent a 4-week exercise combined dietary intervention under the centralised closed management of the Haoqian Weight Loss Training Camp.On the first day of the camp and at the end of the first day before the camp,body shape,body composition,bone mineral density,blood biochemical indices and bone metabolism related indices were measured.Body composition was measured using a Korean Jevon X-SCAN PLUS II electrical impedance body composition meter,bone mineral density was measured by Osteo Sys SONOST 3000 ultrasound bone densitometer,biochemical parameters related to glucolipid metabolism were measured using a fully automated biochemical analyzer and an electrochemiluminescent immunoassay analyzer,and parameters related to bone resorption,bone formation and serum inflammatory factors were measured by enzyme-linked immunoassay（ELISA）.ELISA was used to determine bone resorption,bone formation and serum inflammatory factors.Peripheral blood mononuclear cell miRNA-374a-5p was measured by real-time fluorescence quantitative PCR.Findings:（1）Before the intervention,weight,body fat percentage,body fat mass,BMI,waist circumference,abdominal circumference,hip circumference,and waist-to-hip ratio were extremely significantly higher in group E than in group C（P<0.001）;subjects in group E had significantly lower weight,body fat percentage,BMI,body fat mass,waist circumference,hip circumference,and abdominal circumference after the 4-week exercise combined with diet intervention（P<0.001）,suggesting that central obesity in obese adolescents was effectively improved.（2）Before exercise combined with dietary intervention,FINS in group E was extremely significantly higher than that in group C（225.90±107.34 pmol/L&72.74±25.71pmol/L,P<0.01）.The insulin resistance index of E was significantly higher than that of group C（6.45±2.78&2.17±0.79,P<0.05）.（3）Bone mineral density tests showed that the bone mass index（78.75±6.21&109.58±8.15）,T-value（-1.35±0.33&0.27±0.41）,and Z-value（-1.36±0.37&0.57±0.50）were significantly lower in group E than in group C before the exercise combined with dietary intervention（P<0.05）,indicating that all subjects in group E had reduced bone mass;the bone mass index（78.75±6.21&90.77±7.18）,T-value（-1.35±0.33&-0.71±0.39）and Z-value（-1.36±0.37&-0.63±0.43）were highly significant higher in group E after the intervention（P<0.001）,and all subjects in the group had T-values≥-1,suggesting that their bone mass reduction improved and reached the normal range.（4）The results of bone conversion index test showed that after 4 weeks of exercise combined with dietary intervention,calcium and phosphorus metabolism related indexes in group E,1,25（OH）2D3（21.59±4.00 ng/ml&25.91±4.34 ng/ml）,PTH（19.77±9.03 pg/ml&51.43±17.94 pg/ml）,total calcium（1.91±0.57 mmol/L&2.46±0.07 mmol/L）were significantly increased（P<0.05）.While analysis of bone formation indexes revealed a significant decrease in BGP（22.21±22.33 ng/ml&16.68±17.82 ng/ml,P<0.05）,OPG（8.76±3.00 ng/ml&6.16±3.82 ng/ml,P<0.01）and bone resorption index TRACP-5b（69.46±10.53 pg/ml&74.37±8.85 pg/ml）,β-CTX（1539.49±703.28 pg/ml&1623.73±651.86 pg/ml）were not significant before and after intervention（P>0.05）;while bone conversion-related index RANKL was significantly reduced after intervention（186.33±57.28 pg/ml&149.56±31.61 pg/ml,P<0.01）.（5）The results of miR-374a-5p and inflammatory factor-related assays showed that after 4 weeks of exercise combined with dietary intervention,blood miR-374a-5p levels（0.56±0.37&0.83±0.42）were significantly increased in group E（P<0.05）;inflammation-related indexes NF-κB-p65（0.24±0.13 ng/ml&0.15±0.09 ng/ml）was highly significantly reduced（P<0.001）,CCL2（253.77±123.35 pg/ml&228.63±106.57 pg/ml）,IL-17A（46.09±20.80 pg/ml&43.56±24.31 pg/ml）was significantly reduced（P<0.05）,while SOST（51.84±32.33 pg/ml&52.08±24.06 pg/ml）,STEAP2（0.32±0.11 ng/ml&0.37±0.14ng/ml）were not significantly different before and after intervention（P>0.05）.Conclusion:Obese adolescents have insulin resistance and poor bone status.Abdominal obesity and bone health can be improved by exercise combined with dietary intervention.The mechanism may be to upregulate miR-374a-5p levels,reduce levels of inflammatory factors such as CCL2,improve the body’s inflammatory state,and further influence osteoblast and osteoclast formation and differentiation,affecting bone remodeling and improving bone status. |
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