特发性中枢性性早熟女童血清不饱和游离脂肪酸谱的变化及其与体质量指数、性激素水平的相关性分析

doi:10.3969/j.issn.1674-8115.2021.11.001

摘要/Abstract

摘要：

目的·分析特发性中枢性性早熟（idiopathic central precocious puberty，ICPP）女童不饱和游离脂肪酸谱的变化及其与体质量指数（body mass index，BMI）、性激素水平的相关性。方法·选取2020年8月—2021年1月至上海交通大学附属儿童医院住院的56例ICPP女童及46例同龄正常未发育女童为研究对象，分别纳入ICPP组和对照组。收集2组女童的身高、体质量，计算BMI及体质量指数标准差评分（body mass index standard deviation score，BMI SDS）；检测所有女童的血清不饱和游离脂肪酸谱的浓度，检测ICPP组女童的血清黄体生成素（luteinizing hormone，LH）、促卵泡生成激素（follicle stimulating hormone，FSH）的基础值和峰值，以及雌二醇（estradiol，E₂）、性激素结合球蛋白（sex hormone-binding globulin，SHBG）、胰岛素样生长因子-1（insulin-like growth factor-1，IGF-1）水平。对接受促性腺激素释放激素类似物（gonadotropin releasing-hormone analogues，GnRHa）治疗的女童随访3个月，比较完成随访的48例ICPP女童治疗前后血清不饱和游离脂肪酸谱的浓度。采用多元逐步回归分析血清不饱和游离脂肪酸谱与各项指标的相关性。结果·①ICPP组女童的BMI、BMI SDS高于对照组（P<0.05），但各种不饱和游离脂肪酸与BMI均无相关性（均P>0.05）。②与对照组相比，ICPP组的花生四烯酸（arachidonic acid，AA；P=0.001）、n-6二十二碳五烯酸（n-6 docosapentenoic acid，n-6DPA；P=0.000）、n-3二十二碳五烯酸（n-3 docosapentenoic acid，n-3DPA；P=0.005）、二十碳五烯酸（eicosapentaenoic acid，EPA；P=0.010）、二十二碳六烯酸（docosahexaenoic acid，DHA；P=0.003）、总n-6多不饱和游离脂肪酸（n-6 polyunsaturated fatty acids，n-6PUFA；P=0.049）水平明显降低，差异具有统计学意义。③油酸（oleic acid，C18：1n-9；P=0.036）、巨头鲸鱼酸（gondoic acid，C20：1n-9；P=0.030）、亚油酸（linoleic acid，LA；P=0.020）、γ-亚麻酸（γ-linolenic acid，GLA；P=0.010）、α-亚麻酸（α-linolenic acid，ALA；P=0.009）及总n-6PUFA（P=0.041）水平，与LH峰值呈正相关；EPA（P=0.049）、DHA（P=0.046）水平与LH基础值呈负相关；EPA（P=0.020，P=0.002）、n-3DPA（P=0.003，P=0.001）、DHA（P=0.007，P=0.028）、总n-3PUFA（P=0.012，P=0.011）水平与FSH、E2基础值呈负相关；总n-6PUFA/总n-3PUFA比值与FSH基础值呈正相关（P=0.002）；FSH峰值、SHBG、IGF-1水平与各种游离脂肪酸均无相关性（均P>0.05）。④经3个月GnRHa治疗后，ICPP女童C16：1（P=0.001）、C18：1（P=0.001）、C20：1（P=0.001）、LA（P=0.013）、GLA（P=0.013）、ALA（P=0.032）水平较治疗前明显下降，而AA（P=0.001）、EPA（P=0.000）、DHA（P=0.025）水平较治疗前明显升高。结论·ICPP女童普遍存在超重或肥胖，但各种不饱和游离脂肪酸水平与BMI均无相关性；性发育及GnRHa治疗可影响ICPP女童体内不饱和游离脂肪酸的代谢，多种不饱和游离脂肪酸水平与性激素水平具有相关性。

关键词: 特发性中枢性性早熟, 女童, 血清不饱和游离脂肪酸谱, 相关性

Abstract:

Objective·To analyze the changes of unsaturated free fatty acid profiles and their correlations with body mass index (BMI) and sex hormones in idiopathic central precocious puberty (ICPP) girls.

Methods·Fifty-six ICPP girls who were hospitalized in Children's Hospital of Shanghai Jiao Tong University from August 2020 to January 2021 and 46 normal undeveloped girls at the same age were selected, respectively included in the ICPP group and the control group. The height and weight of the two groups were collected, and the BMI and body mass index standard deviation score (BMI SDS) were calculated. The concentration of serum unsaturated free fatty acid profiles of all the girls as well as the basic and peak values of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol (E₂), sex hormone-binding globulin (SHBG), and insulin-like growth factor-1 (IGF-1) in ICPP girls were detected. The girls who received gonadotropin releasing-hormone analogues (GnRHa) treatment were followed up for 3 months. Finally, 48 ICPP girls were enrolled in the follow-up study. The concentrations of serum unsaturated free fatty acid profiles before and after treatment in 48 ICPP girls who completed the follow-up were compared. Multivariate stepwise regression was used to analyze the correlation between serum unsaturated free fatty acid profiles and various indicators.

Results·①BMI and BMI SDS of the ICPP group were higher than those of the control group (P<0.05), but there was no correlation between the levels of various unsaturated free fatty acids and BMI(P>0.05). ②Compared with the control group, the levels of arachidonic acid (AA, P=0.001), n-6 docosapentenoic acid (n-6DPA, P=0.000), n-3 docosapentaenoic acid (n-3DPA, P=0.005), eicosapentaenoic acid (EPA, P=0.010), docosapentaenoic acid (DHA, P=0.003) and total n-6 polyunsaturated fatty acids (n-6PUFA, P=0.049) were significantly reduced. ③The levels of oleic acid (C18:1n-9, P=0.036), gondoic acid (C20:1n-9, P=0.030), linoleic acid (LA, P=0.020), γ-Linolenic acid (GLA, P=0.010), α-linolenic acid (ALA, P=0.009) and total n-6PUFA (P=0.041) were positively correlated with the peak values of LH. The levels of EPA (P=0.049) and DHA (P=0.046) were negatively correlated with the basic values of LH. The levels of EPA (P=0.020, P=0.002), n-3DPA (P=0.003, P=0.001), DHA (P=0.007, P=0.028) ), and total n-3PUFA (P=0.012, P=0.011) were negatively correlated with the basic values of FSH and E₂. The ratio of total n-6PUFA/total n-3PUFA was positively correlated with the basic values of FSH (P=0.002). The peak vaules of FSH, SHBG, and IGF-1 had no correlation with various unsaturated free fatty acids (all P>0.05). ④After 3 months of GnRHa treatment, the levels of C16:1 (P=0.001), C18:1 (P=0.001), C20:1 (P=0.001), LA (P=0.013), GLA (P= 0.013), and ALA (P=0.032) in ICPP girls were significantly lower than those before treatment, while the levels of AA (P=0.001), EPA (P=0.000), and DHA (P=0.025) were significantly higher than those before treatment.

Conclusion·ICPP girls were generally overweight or obese, but there was no correlation between the levels of various unsaturated free fatty acids and BMI. Sexual development and GnRHa treatment could affect the metabolism of unsaturated free fatty acids in ICPP girls, and sex hormones were related to a variety of unsaturated free fatty acids.

Key words: idiopathic central precocious puberty, girl, serum unsaturated free fatty acid profile, correlation

中图分类号:

R725.8

黎琳琳, 胡韶华, 尹小琴, 李嫔. 特发性中枢性性早熟女童血清不饱和游离脂肪酸谱的变化及其与体质量指数、性激素水平的相关性分析[J]. 上海交通大学学报(医学版), 2021, 41(11): 1405-1411.

Lin-lin LI, Shao-hua HU, Xiao-qin YIN, Pin LI. Changes of serum unsaturated free fatty acid profiles in girls with idiopathic central precocious puberty and their correlations with body mass index and sex hormones[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(11): 1405-1411.

图/表 6

参考文献 27

1	Dahl RE, Allen NB, Wilbrecht L, et al. Importance of investing in adolescence from a developmental science perspective[J]. Nature, 2018, 554(7693): 441-450.
2	中华医学会儿科学分会内分泌遗传代谢学组, «中华儿科杂志»编辑委员会. 中枢性性早熟诊断与治疗共识(2015)[J]. 中华儿科杂志, 2015, 53(6):412-418.
3	Li W, Liu Q, Deng X, et al. Association between obesity and puberty timing: a systematic review and meta-analysis[J]. Int J Environ Res Public Health, 2017, 14(10):1266.
4	Chen C, Zhang Y, Sun W, et al. Investigating the relationship between precocious puberty and obesity: a cross-sectional study in Shanghai, China[J]. BMJ Open, 2017, 7(4): e014004.
5	Dai YL, Fu JF, Liang L, et al. Association between obesity and sexual maturation in Chinese children: a muticenter study[J]. Int J Obes (Lond), 2014, 38(10): 1312-1316.
6	傅君芬, 周雪莲. 肥胖对儿童青春期性发育的影响及作用机制[J]. 中华实用儿科临床杂志, 2014, 29(8): 574-577.
7	Cheng G, Buyken AE, Shi L, et al. Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty[J]. Nutr Rev, 2012, 70(3): 133-152.
8	Prentice AM, Jebb SA. Beyond body mass index[J]. Obes Rev, 2001, 2(3): 141-147.
9	郑淑容. 脂肪酸的营养功能[J]. 畜禽业, 2012(9): 55-57.
10	韩宏毅, 王剑. 多不饱和脂肪酸及其生理功能[J]. 中国临床研究, 2010, 23(6): 523-525.
11	Nguyen NTK, Fan HY, Tsai MC, et al. Nutrient intake through childhood and early menarche onset in girls: systematic review and meta-analysis[J]. Nutrients, 2020, 12(9):2544.
12	Duan R, Chen Y, Qiao T, et al. Modern dietary pattern is prospectively associated with earlier age at menarche: data from the CHNS 1997-2015[J]. Nutr J, 2020, 19(1): 95.
13	Maclure M, Travis LB, Willett W, et al. A prospective cohort study of nutrient intake and age at menarche[J]. Am J Clin Nutr, 1991, 54(4): 649-656.
14	Rogers IS, Northstone K, Dunger DB, et al. Diet throughout childhood and age at menarche in a contemporary cohort of British girls[J]. Public Health Nutr, 2010, 13(12): 2052-2063.
15	Moisan J, Meyer F, Gingras S. A nested case-control study of the correlates of early menarche[J]. Am J Epidemiol, 1990, 132(5): 953-961.
16	Calder PC. Functional roles of fatty acids and their effects on human health[J]. J Parenter Enteral Nutr, 2015, 39(1): 18S-32S.
17	申甜. 营养对青春期性发育影响及机理研究[D]. 上海: 上海交通大学, 2007.
18	de Mello AH, Uberti MF, de Farias BX, et al. N-3 PUFA and obesity: from peripheral tissues to the central nervous system[J]. Br J Nutr, 2018, 119(11): 1312-1323.
19	Shaikh SR, Shaver PR, Shewchuk BM. High fat diet dysregulates hypothalamic-pituitary axis gene expression levels which are differentially rescued by EPA and DHA ethyl esters[J]. Mol Nutr Food Res, 2018, 62(13): e1800219.
20	Calcaterra V, Cena H, Regalbuto C, et al. The role of fetal, infant, and childhood nutrition in the timing of sexual maturation[J]. Nutrients, 2021, 13(2): 419.
21	Shahidi F, Ambigaipalan P. Omega-3 polyunsaturated fatty acids and their health benefits[J]. Annu Rev Food Sci Technol, 2018, 9: 345-381.
22	郭盛, 李嫔. 营养与青春期性发育[J]. 中国中西医结合儿科学, 2016, 8(3): 249-252, 244.
23	崔璐璐, 李嫔, 许丽雅, 等. 哺乳期不同营养状态对雌鼠性发育及下丘脑促性腺激素释放激素神经元表达的影响[J]. 实用儿科临床杂志, 2009, 24(20): 1557-1559.
24	Heras V, Castellano JM, Fernandois D, et al. Central ceramide signaling mediates obesity-induced precocious puberty[J]. Cell Metab, 2020, 32(6): 951-966.e8.
25	Pusceddu MM, Kelly P, Stanton C, et al. N-3 polyunsaturated fatty acids through the lifespan: implication for psychopathology[J]. Int J Neuropsychopharmacol, 2016, 19(12): pyw078.
26	Anderson BM, MacLennan MB, Hillyer LM, et al. Lifelong exposure to n-3 PUFA affects pubertal mammary gland development[J]. Appl Physiol Nutr Metab, 2014, 39(6): 699-706.
27	Meng Y, Zhang J, Yuan C, et al. Oleic acid stimulates HC11 mammary epithelial cells proliferation and mammary gland development in peripubertal mice through activation of CD36-Ca²⁺ and PI3K/Akt signaling pathway[J]. Oncotarget, 2018, 9(16): 12982-12994.

Item	Control group （n=46）	ICPP group （n=56）
Age/year	8.23±1.45	8.28±0.59
Height/cm	124.10±9.81	134.63±5.84^①
Weight/kg	24.64±5.46	31.15±4.70^①
BMI/（kg·m^-2）	15.92±1.88	17.12±1.84^②
BMI SDS	-0.34±0.96	0.28±0.95^②

Item	Control group （n=46）	ICPP group （n=56）
Age/year	8.23±1.45	8.28±0.59
Height/cm	124.10±9.81	134.63±5.84^①
Weight/kg	24.64±5.46	31.15±4.70^①
BMI/（kg·m^-2）	15.92±1.88	17.12±1.84^②
BMI SDS	-0.34±0.96	0.28±0.95^②

FFA	Control group		ICPP group
FFA	r value	P value	r value	P value
C16：1	-0.012	0.935	-0.247	0.066
C18：1	0.062	0.682	-0.092	0.499
C20：1	0.077	0.610	-0.128	0.347
LA	-0.022	0.885	-0.138	0.310
GLA	0.250	0.093	-0.192	0.156
AA	-0.102	0.501	-0.147	0.279
n-6DPA	-0.095	0.531	-0.091	0.506
ALA	-0.050	0.743	-0.155	0.254
EPA	0.131	0.384	-0.074	0.589
n-3DPA	0.107	0.477	-0.103	0.451
DHA	-0.158	0.296	-0.185	0.172
Tn-6	-0.048	0.753	-0.133	0.327
Tn-3	-0.057	0.704	-0.194	0.153
Tn-6/Tn-3	0.052	0.729	0.087	0.524

FFA	Control group		ICPP group
FFA	r value	P value	r value	P value
C16：1	-0.012	0.935	-0.247	0.066
C18：1	0.062	0.682	-0.092	0.499
C20：1	0.077	0.610	-0.128	0.347
LA	-0.022	0.885	-0.138	0.310
GLA	0.250	0.093	-0.192	0.156
AA	-0.102	0.501	-0.147	0.279
n-6DPA	-0.095	0.531	-0.091	0.506
ALA	-0.050	0.743	-0.155	0.254
EPA	0.131	0.384	-0.074	0.589
n-3DPA	0.107	0.477	-0.103	0.451
DHA	-0.158	0.296	-0.185	0.172
Tn-6	-0.048	0.753	-0.133	0.327
Tn-3	-0.057	0.704	-0.194	0.153
Tn-6/Tn-3	0.052	0.729	0.087	0.524

FFA	LHB	FSHB	LHB/FSHB	LHP	FSHP	LHP/FSHP	E₂	SHBG	IGF-1
C16：1	0.098	-0.066	0.230	0.219	-0.001	0.220	-0.032	0.037	0.095
C18：1	0.068	0.001	0.226	0.281^⑩	0.089	0.214	-0.032	0.036	0.189
C20：1	0.140	0.049	0.206	0.290^⑪	0.055	0.214	0.039	0.105	0.180
LA	-0.001	-0.035	0.170	0.311^⑫	0.143	0.179	-0.101	-0.022	0.182
GLA	-0.088	-0.175	0.089	0.343^⑬	0.142	0.239	-0.209	0.046	0.108
AA	-0.231	-0.172	-0.204	-0.064	0.073	-0.146	-0.198	-0.166	0.007
n-6DPA	-0.135	-0.160	-0.109	-0.021	0.079	-0.210	-0.223	-0.114	0.049
ALA	-0.005	-0.100	0.194	0.348^⑭	0.066	0.315^⑯	-0.087	-0.038	0.195
EPA	-0.268^①	-0.309^③	-0.323^⑧	-0.137	-0.007	-0.187	-0.406^⑦	-0.163	-0.103
n-3DPA	-0.239	-0.395^④	-0.219	0.121	0.018	0.072	-0.426^⑰	-0.158	0.195
DHA	-0.273^②	-0.356^⑤	-0.252	-0.074	-0.018	-0.152	-0.294^⑱	-0.097	-0.099
Tn-6	-0.047	-0.071	0.113	0.274^⑮	0.148	0.122	-0.131	-0.050	0.166
Tn-3	-0.209	-0.333^⑥	-0.081	0.164	0.031	0.090	-0.338^⑲	-0.113	0.059
Tn-6/Tn-3	0.228	0.410^⑦	0.312^⑨	0.124	0.169	0.004	0.216	0.057	0.208