基底体相关蛋白复合体在儿童肥胖及其代谢性疾病中的作用机制

doi:10.11852/zgetbjzz2025-0283

中国儿童保健杂志 ›› 2025, Vol. 33 ›› Issue (10): 1066-1069.DOI: 10.11852/zgetbjzz2025-0283

基底体相关蛋白复合体在儿童肥胖及其代谢性疾病中的作用机制

詹舒敏, 傅君芬

浙江大学医学院附属儿童医院,国家儿童健康与疾病临床医学研究中心,浙江杭州 310051

收稿日期:2025-03-24 修回日期:2025-06-05 发布日期:2025-10-11
通讯作者: 傅君芬,E-mail: fjf68@zju.edu.cn
作者简介:詹舒敏(1992—),女,博士,主要研究方向为儿童肥胖和生长发育。
基金资助:
国家重点研发计划(2021YFC2701900);浙江省“尖兵”“领雁”研发攻关计划(2023C03047);国家自然科学基金(82370863)

Mechanisms of Bardet-Biedl syndrome protein complex in childhood obesity and associated metabolic diseases

ZHAN Shumin, FU Junfen

Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang 310051, China

Received:2025-03-24 Revised:2025-06-05 Published:2025-10-11
Contact: FU Junfen, E-mail: fjf68@zju.edu.cn

摘要/Abstract

摘要： 基底体相关蛋白复合体(BBSome)是一种由 8 种 Bardet-Biedl 综合征 (BBS) 蛋白组成的复合物,参与纤毛功能。BBSome已成为能量平衡的重要调节器,与肥胖、2型糖尿病和非酒精性脂肪肝等代谢性疾病密切相关。研究表明,BBSome在中枢能量代谢、脂肪酸代谢、葡萄糖稳态、瘦素受体运输等过程中起重要作用。尽管大部分研究集中在成年模型上,但儿童期的BBS症状同样严重,未来应加强对幼年期代谢性疾病的研究,以揭示BBSome在代谢调节中的复杂角色。

Abstract: Bardet-Biedl syndrome protein complex (BBSome) is a complex composed of eight proteins associated with Bardet-Biedl syndrome (BBS) that plays a crucial role in ciliary function.It has emerged as an important regulator of energy balance and is closely linked to metabolic diseases such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease.Research indicates that BBSome is involved in central energy metabolism, fatty acid metabolism, glucose homeostasis, and the transport of leptin receptors.While most studies have focused on adult models, the symptoms of BBS can be severe in childhood as well.Future research should enhance the understanding of metabolic diseases in early life to elucidate the complex role of BBSome in metabolic regulation.

Key words: Bardet-Biedl syndrome protein complex, Bardet-Biedl syndrome, cilia, childhood obesity, metabolic diseases

中图分类号:

R179

詹舒敏, 傅君芬. 基底体相关蛋白复合体在儿童肥胖及其代谢性疾病中的作用机制[J]. 中国儿童保健杂志, 2025, 33(10): 1066-1069.

ZHAN Shumin, FU Junfen. Mechanisms of Bardet-Biedl syndrome protein complex in childhood obesity and associated metabolic diseases[J]. Chinese Journal of Child Health Care, 2025, 33(10): 1066-1069.

参考文献

[1] Chandra B, Tung ML, Hsu Y,et al.Retinal ciliopathies through the lens of Bardet-Biedl Syndrome: Past, present and future[J].Prog Retin Eye Res, 2022, 89: 101035.
[2] Tian X, Zhao H, Zhou J.Organization, functions, and mechanisms of the BBSome in development, ciliopathies, and beyond[J].Elife, 2023, 12: e87623.
[3] Zhong BH, Nie N, Dong M.Molecular mechanisms of the obesity associated with Bardet-Biedl syndrome: An update[J].Obes Rev, 2025, 26(3): e13859.
[4] Niederlova V, Modrak M, Tsyklauri O, et al.Meta-analysis of genotype-phenotype associations in Bardet-Biedl syndrome uncovers differences among causative genes[J].Hum Mutat, 2019, 40(11): 2068-2087.
[5] Sun WY, Xue B, Liu YX, et al.Chlamydomonas LZTFL1 mediates phototaxis via controlling BBSome recruitment to the basal body and its reassembly at the ciliary tip[J].Proc Natl Acad Sci U S A, 2021, 118(35): e2101590118.
[6] Nachury MV, Loktev AV, Zhang Q, et al.A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis[J].Cell, 2007, 129(6): 1201-1213.
[7] Guo DF, Cui H, Zhang Q, et al.The BBSome controls energy homeostasis by mediating the transport of the leptin receptor to the plasma membrane[J].PLoS Genet, 2016, 12(2): e1005890.
[8] Leitch CC, Lodh S, Prieto-Echagüe V, et al.Basal body proteins regulate Notch signaling through endosomal trafficking[J].J Cell Sci, 2014, 127(Pt 11): 2407-2419.
[9] Starks RD, Beyer AM, Guo DF, et al.Regulation of insulin receptor trafficking by Bardet Biedl syndrome proteins[J].PLoS Genet, 2015, 11(6): e1005311.
[10] Nowak-Ciołek M, Ciołek M, Tomaszewska A, et al.Collaborative effort: Managing Bardet-Biedl syndrome in pediatric patients.Case series and a literature review[J].Front Endocrinol (Lausanne), 2024, 15: 1424819.
[11] DeMars KM, Ross MR, Starr A, et al.Neuronal primary cilia integrate peripheral signals with metabolic drives[J].Front Physiol, 2023, 14: 1150232.
[12] Guo DF, Lin Z, Wu Y, et al.The BBSome in POMC and AgRP neurons is necessary for body weight regulation and sorting of metabolic receptors[J].Diabetes, 2019, 68(8): 1591-1603.
[13] Rouabhi M, Guo DF, Morgan DA, et al.BBSome ablation in SF1 neurons causes obesity without comorbidities[J].Mol Metab, 2021, 48: 101211.
[14] Siljee JE, Wang Y, Bernard AA, et al.Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity[J].Nat Genet, 2018, 50(2): 180-185.
[15] Zhao Y, Rahmouni K.BBSome: A new player in hypertension and other cardiovascular risks[J].Hypertension, 2022, 79(2): 303-313.
[16] Seo S, Guo DF, Bugge K, et al.Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling[J].Hum Mol Genet, 2009, 18(7): 1323-1331.
[17] Wang L, Liu Y, Stratigopoulos G, et al.Bardet-Biedl syndrome proteins regulate intracellular signaling and neuronal function in patient-specific iPSC-derived neurons[J].J Clin Invest, 2021, 131(8).
[18] Masek M, Etard C, Hofmann C, et al.Loss of the Bardet-Biedl protein Bbs1 alters photoreceptor outer segment protein and lipid composition[J].Nat Commun, 2022, 13(1): 1282.
[19] Aksanov O, Green P, Birk RZ.BBS4 directly affects proliferation and differentiation of adipocytes[J].Cell Mol Life Sci, 2014, 71(17): 3381-3392.
[20] Jiang J, Reho JJ, Bhattarai S, et al.Endothelial BBSome is essential for vascular, metabolic, and retinal functions[J].Mol Metab, 2021, 53: 101308.
[21] Rouabhi Y, Guo DF, Zhao Y, et al.Metabolic consequences of skeletal muscle-and liver-specific BBSome deficiency[J].Am J Physiol Endocrinol Metab, 2023, 325(6): e711-e722.
[22] Hilgendorf KI.Primary cilia are critical regulators of white adipose tissue expansion[J].Front Physiol, 2021, 12: 769367.
[23] Wachten D, Mick DU.Signal transduction in primary cilia-analyzing and manipulating GPCR and second messenger signaling[J].Pharmacol Ther, 2021, 224: 107836.
[24] Vourdoumpa A, Paltoglou G, Charmandari E.The genetic basis of childhood obesity: A systematic review[J].Nutrients, 2023, 15(6): 1416.

基底体相关蛋白复合体在儿童肥胖及其代谢性疾病中的作用机制

Mechanisms of Bardet-Biedl syndrome protein complex in childhood obesity and associated metabolic diseases

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	许玥, 郜统勋, 胡思源, 李梅芳, 栾奕博, 许晨霞. ω-3/6多不饱和脂肪酸与儿童肥胖的两样本孟德尔随机化研究[J]. 中国儿童保健杂志, 2025, 33(8): 841-847.
[2]	刘璐洁, 徐东, 肖延风, 尹春燕. 肥胖伴非酒精性脂肪肝儿童的血清脂质代谢特征[J]. 中国儿童保健杂志, 2025, 33(2): 136-141.
[3]	郭锡熔. 多系统交互网络视角下儿童肥胖相关代谢性疾病的免疫-代谢-力学三维机制解析[J]. 中国儿童保健杂志, 2025, 33(10): 1052-1055.
[4]	王同帅, 郭锡熔. 超级增强子与肥胖相关代谢性疾病的研究进展[J]. 中国儿童保健杂志, 2025, 33(10): 1079-1081.
[5]	高建芳, 单小玉, 郭锡熔. 染色质三维结构与基因调控网络在儿童代谢性疾病中的遗传学机制进展[J]. 中国儿童保健杂志, 2025, 33(10): 1082-1085.
[6]	彭舟, 王晓雨, 郭锡熔. 细胞生物力学视角下的儿童肥胖研究进展[J]. 中国儿童保健杂志, 2025, 33(10): 1086-1090.
[7]	王瑞, 郭锡熔. 物质跨物种传输与肥胖[J]. 中国儿童保健杂志, 2025, 33(10): 1091-1094.
[8]	陈垚, 刘长青, 朱谦让, 刘怡娅, 田美娜, 王宏伟, 于连龙. 膳食支链氨基酸对儿童青少年血脂异常的影响[J]. 中国儿童保健杂志, 2025, 33(10): 1101-1107.
[9]	陈瑜洁, 李晓南. 行为干预在儿童肥胖管理中的应用进展[J]. 中国儿童保健杂志, 2024, 32(8): 875-880.
[10]	何雨桦, 熊菲. 端粒在生命早期不良环境和代谢性疾病关系中的作用[J]. 中国儿童保健杂志, 2024, 32(8): 886-890.
[11]	刘军廷, 李少丽, 陈芳芳, 宗心南, 黄春雷, 张彤, 邰隽, 谷庆隆, 代表北京儿童青少年健康队列研究组. 北京市儿童青少年自然人群队列基线特征分析[J]. 中国儿童保健杂志, 2024, 32(11): 1212-1218.
[12]	陈敬, 单蕊, 肖伍才, 宋洁云, 刘峥. 多基因风险评分在儿童肥胖干预效果可持续性中的作用[J]. 中国儿童保健杂志, 2024, 32(1): 16-20.
[13]	牛婉侠, 梁爽, 王一彪. 儿童肥胖相关心肌病的分子机制[J]. 中国儿童保健杂志, 2023, 31(5): 507-511.
[14]	肖伍才, 刘峥, 陈敬, 王辉, 宋洁云, 周双, 高爱钰, 张芳, 王海俊. MAP2K5基因rs2241423多态性与儿童肥胖干预效果的关系[J]. 中国儿童保健杂志, 2022, 30(9): 952-955.
[15]	李燕, 罗燕飞, 孙光辉, 迪丽胡麻·居来提, 沈亦平, 米热古丽·买买提. Bardet-Biedl综合征3个家系报告[J]. 中国儿童保健杂志, 2022, 30(5): 575-580.