Research on plasma brain-derived neurotrophic factor level and its correlation with metabolic abnormalities in obese children

doi:10.3877/cma.j.issn.1673-5250.2024.01.011

Objective

To explore the differences in plasma brain-derived neurotrophic factor (BDNF) level between obese and normal children, and its relationship with different metabolic phenotypes and factors.

Methods

A total of 41 obese children who attended the pediatric outpatient clinic of West China Second University Hospital, Sichuan University from March to October 2022 were selected for the study and included in the obese group. Another 11 cases of non-obese healthy children who underwent routine physical examinations in outpatient clinic of our hospital during the control same period were selected as controls and included in the control group. Physical growth indicators, clinical examination results and plasma muscle factors [BDNF, irisin, fibroblast growth factor (FGF)-21 and interleukin (IL)-6 and -15] levels were collected from the 2 groups. Plasma BDNF levels were compared between the 2 groups by Mann-Whitney U test. Plasma BDNF levels were analysed for fold-change (FC) in children between 2 groups and children with abnormal lipid, glucose and purine metabolism versus normal children, and were judged to have a significant FC if FC was >1.20 or <0.83. Correlations of body mass index (BMI), BMI standard deviation scores (BMI-SDS), and plasma levels of IL-6 and irisin with plasma BDNF level in two groups were analyzed by Spearman′s rank correlation test. The study was approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Approval No. 2022-084). The baseline information was not significantly different between the obese and control group (P>0.05), including age, gender ratio, and height.

Results

①The weight and BMI of the obese group were significantly higher than those in the control group (t=4.30, P<0.001; Z=-5.05, P<0.001). ②The median plasma BDNF level of children in obese group was 2 402.0 pg/mL (1 370.0 pg/mL, 3 958.5 pg/mL), which was significantly higher than that of control group 442.0 pg/mL (933.2 pg/mL, 1 688.0 pg/mL), with a statistically significant difference (Z=-2.10, P=0.036); and there was a significant FC between BDNF levels of obese group and control group (FC=1.42). ③Plasma BDNF levels in obese children with abnormal lipid, glucose and purine metabolism were significantly higher than those in obese children with normal lipid, glucose and purine metabolism, with significant FC (FC=1.43, 1.47, 1.98). ④Plasma BDNF level was lower in male than that in female children and had significant FC (FC=0.69). The plasma BDNF levels of children with severe plasma 25-hydroxy vitamin D [25-(OH)-D] deficiency and insufficiency were higher than those of children with normal plasma 25-(OH)-D, and both had significant FC (FC=1.39, 1.51). Children with elevated platelet counts had higher plasma BDNF levels compared to those with normal platelet counts, with a significant FC (FC=2.77). ⑤In 2 groups of children, BMI, BMI-SDS, plasma IL-6 and irisin levels were positively correlated with their plasma BDNF levels (r=0.396, 0.343, 0.326, 0.656; P=0.004, 0.013, 0.018, <0.001).

Conclusions

BDNF may be involved in the occurrence and development of obesity and obesity-related metabolic disorders, and it may be influenced by factors such as gender, serum 25-(OH)-D levels, platelet counts, and levels of muscle factors such as IL-6 and irisin.

Key words: Pediatric obesity, Brain-derived neurotrophic factor, Muscle factor, Metabolic abnormalities, Lipid metabolism disorders, Glucose metabolism disorders

表1 肥胖症组及对照组受试儿相关临床资料比较

组别	例数	性别[例数(%)]		年龄(岁，±s)	身高(cm，±s)	体重(kg，±s)	BMI[kg/m²，M(Q₁，Q₃)]
组别	例数	男	女	年龄(岁，±s)	身高(cm，±s)	体重(kg，±s)	BMI[kg/m²，M(Q₁，Q₃)]
肥胖症组	41	10(24.4)	31(75.6)	10.0±2.5	145.0±14.0	55.3±20.4	23.8(22.0，27.5)
对照组	11	6(54.5)	5(45.5)	9.6±2.1	143.5±12.1	43.6±10.0	14.5(14.1，14.8)
统计量		χ²＝3.70		t＝0.51	t＝0.30	t＝4.30	Z＝－5.05
P值		0.054		0.614	0.762	<0.001	<0.001

表1 肥胖症组及对照组受试儿相关临床资料比较

组别	例数	性别[例数(%)]		年龄(岁，±s)	身高(cm，±s)	体重(kg，±s)	BMI[kg/m²，M(Q₁，Q₃)]
组别	例数	男	女	年龄(岁，±s)	身高(cm，±s)	体重(kg，±s)	BMI[kg/m²，M(Q₁，Q₃)]
肥胖症组	41	10(24.4)	31(75.6)	10.0±2.5	145.0±14.0	55.3±20.4	23.8(22.0，27.5)
对照组	11	6(54.5)	5(45.5)	9.6±2.1	143.5±12.1	43.6±10.0	14.5(14.1，14.8)
统计量		χ²＝3.70		t＝0.51	t＝0.30	t＝4.30	Z＝－5.05
P值		0.054		0.614	0.762	<0.001	<0.001

图1 肥胖症组与对照组受试儿血浆BDNF水平比较(图1A：2组受试儿血浆BDNF水平四分位数箱式图；图1B：2组受试儿血浆BDNF水平中位数及其FC值)注：BDNF为脑源性神经营养因子，FC为差异倍数

表2 各代谢指标异常与正常肥胖症患儿血浆BDNF水平比较及其FC分析

代谢指标结果	异常		正常		FC值	Z值	P值
代谢指标结果	例数	[pg/mL，M(Q₁，Q₃)]	例数	[pg/mL，M(Q₁，Q₃)]	FC值	Z值	P值
总代谢	12	2 086.0(1 449.0，4 469.3)	29	1 976.5(1 338.5，3 861.0)	1.06	－0.49	0.641
脂代谢	17	2 462.0(1 720.0，4 252.5)	24	1 713.5(1 260.2，3 289.2)	1.43^a	－1.35	0.177
HDL-C	2	3 152.0(2 619.0，3 685.0)	37	1 820.0(1 338.5，3 601.5)	1.73^a	－0.83	0.456
LDL-C	4	2 805.5(1 097.1，4 269.8)	35	1 911.0(1 347.0，3 504.0)	1.46^a	－0.05	0.982
TG	6	2 274.0(1 682.9，3 828.8)	33	1 765.0(1 338.5，3 895.5)	1.29^a	－0.51	0.635
脂肪肝	8	3 413.5(1 352.0，11 563.3)	33	1 911.0(1 370.0，3 141.0)	1.79^a	－1.35	0.186
糖代谢	21	2 462.0(1 658.5，4506.5)	20	1 677.0(1 200.3，2 566.5)	1.47^a	－1.69	0.090
2 h PBG	2	2 659.5(2 139.8，3 179.3)	36	2 064.0(1 403.8，4 039.5)	1.29^a	－0.13	0.922
HOMA-IR	12	1 976.5(1 449.8，4 469.3)	29	2 086.0(1 338.5，3 861.0)	0.94	－0.49	0.641
嘌呤代谢	7	3 699.0(1 697.0，4 726.0)	34	1 865.5(1 306.8，2 959.5)	1.98^a	－1.66	0.101

表2 各代谢指标异常与正常肥胖症患儿血浆BDNF水平比较及其FC分析

代谢指标结果	异常		正常		FC值	Z值	P值
代谢指标结果	例数	[pg/mL，M(Q₁，Q₃)]	例数	[pg/mL，M(Q₁，Q₃)]	FC值	Z值	P值
总代谢	12	2 086.0(1 449.0，4 469.3)	29	1 976.5(1 338.5，3 861.0)	1.06	－0.49	0.641
脂代谢	17	2 462.0(1 720.0，4 252.5)	24	1 713.5(1 260.2，3 289.2)	1.43^a	－1.35	0.177
HDL-C	2	3 152.0(2 619.0，3 685.0)	37	1 820.0(1 338.5，3 601.5)	1.73^a	－0.83	0.456
LDL-C	4	2 805.5(1 097.1，4 269.8)	35	1 911.0(1 347.0，3 504.0)	1.46^a	－0.05	0.982
TG	6	2 274.0(1 682.9，3 828.8)	33	1 765.0(1 338.5，3 895.5)	1.29^a	－0.51	0.635
脂肪肝	8	3 413.5(1 352.0，11 563.3)	33	1 911.0(1 370.0，3 141.0)	1.79^a	－1.35	0.186
糖代谢	21	2 462.0(1 658.5，4506.5)	20	1 677.0(1 200.3，2 566.5)	1.47^a	－1.69	0.090
2 h PBG	2	2 659.5(2 139.8，3 179.3)	36	2 064.0(1 403.8，4 039.5)	1.29^a	－0.13	0.922
HOMA-IR	12	1 976.5(1 449.8，4 469.3)	29	2 086.0(1 338.5，3 861.0)	0.94	－0.49	0.641
嘌呤代谢	7	3 699.0(1 697.0，4 726.0)	34	1 865.5(1 306.8，2 959.5)	1.98^a	－1.66	0.101

图2 不同性别、血清25-(OH)-D缺乏程度受试儿血浆BDNF水平差异分析(图2A：不同性别受试儿血浆BDNF水平中位数和FC值；图2B：不同血清25-(OH)-D水平受试儿血浆BDNF水平中位数和FC值)注：①、②、③分别指血清25-(OH)-D重度缺乏[血清25-(OH)-D水平<20 pg/mL]、不足[血清25-(OH)-D水平≥20～30 pg/mL]、正常[血清25-(OH)-D水平≥30 pg/mL]受试儿。25-(OH)-D为25-羟维生素D，BDNF为脑源性神经营养因子，FC为差异倍数

表3 不同性别、血清25-(OH)-D水平、血小板计数受试儿血浆BDNF水平比较及其FC分析

临床指标	例数	血浆BDNF水平[pg/ml，M(Q₁，Q₃)]	FC值	统计量	P值
性别			0.69^c	Z＝－0.31	0.754
男	37	1 730.0(1 283.5，2 953.0)
女	15	2 086.0(1 157.0，4 993.0)
血清25-(OH)-D ^a			—^d	H＝1.52	0.468
重度缺乏	13	1 911.0(1 197.0，3 601.5)
不足	22	2 143.5(1 678.8，4 235.0)
正常	6	1 383.0(1 023.9，6 478.5)
血小板计数^b			2.77^c	Z＝－1.71	0.090
升高	4	3 861.0(2 309.3，13 097.3)
正常	28	1 792.5(1 334.3，3 556.3)

表3 不同性别、血清25-(OH)-D水平、血小板计数受试儿血浆BDNF水平比较及其FC分析

临床指标	例数	血浆BDNF水平[pg/ml，M(Q₁，Q₃)]	FC值	统计量	P值
性别			0.69^c	Z＝－0.31	0.754
男	37	1 730.0(1 283.5，2 953.0)
女	15	2 086.0(1 157.0，4 993.0)
血清25-(OH)-D ^a			—^d	H＝1.52	0.468
重度缺乏	13	1 911.0(1 197.0，3 601.5)
不足	22	2 143.5(1 678.8，4 235.0)
正常	6	1 383.0(1 023.9，6 478.5)
血小板计数^b			2.77^c	Z＝－1.71	0.090
升高	4	3 861.0(2 309.3，13 097.3)
正常	28	1 792.5(1 334.3，3 556.3)

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