Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion.

Animals Basic Helix-Loop-Helix Transcription Factors / metabolism Cell Line Diet, High-Fat Disease Models, Animal Forkhead Box Protein O1 / metabolism Frizzled Receptors / metabolism Gene Deletion Gene Silencing Insulin / genetics Insulin Resistance / genetics Insulin Secretion / genetics Insulin-Secreting Cells / metabolism Male Mice, Inbred C57BL Mice, Knockout Mice, Obese MicroRNAs / genetics Models, Biological Nerve Tissue Proteins / metabolism Obesity / genetics Transcription, Genetic Up-Regulation / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
14 04 2020
Historique:
received: 06 04 2019
accepted: 17 03 2020
entrez: 15 4 2020
pubmed: 15 4 2020
medline: 22 7 2020
Statut: epublish

Résumé

B cell dysfunction due to obesity can be associated with alterations in the levels of micro-RNAs (miRNAs). However, the role of miRNAs in these processes remains elusive. Here, we show that miR-802 is increased in the pancreatic islets of obese mouse models and demonstrate that inducible transgenic overexpression of miR-802 in mice causes impaired insulin transcription and secretion. We identify Foxo1 as a transcription factor of miR-802 promoting its transcription, and NeuroD1 and Fzd5 as targets of miR-802-dependent silencing. Repression of NeuroD1 in β cell and primary islets impairs insulin transcription and reduction of Fzd5 in β cell, which, in turn, impairs Ca

Identifiants

DOI: 10.1038/s41467-020-15529-w PMID: 32286278 PMC: PMC7156651
pubmed: 32286278
doi: 10.1038/s41467-020-15529-w
pii: 10.1038/s41467-020-15529-w
pmc: PMC7156651
doi:

Substances chimiques

Basic Helix-Loop-Helix Transcription Factors 0
Forkhead Box Protein O1 0
Foxo1 protein, mouse 0
Frizzled Receptors 0
Fzd5 protein, mouse 0
Insulin 0
MIRN802 microRNA, mouse 0
MicroRNAs 0
Nerve Tissue Proteins 0
Neurogenic differentiation factor 1 169238-82-8

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1822

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Auteurs

Fangfang Zhang (F)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.
ORCID: 0000-0002-1954-4345

Dongshen Ma (D)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.
Department of Pathology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

Wanli Zhao (W)

Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China.

Danwei Wang (D)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Tingsheng Liu (T)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Yuhong Liu (Y)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Yue Yang (Y)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Yue Liu (Y)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Jinming Mu (J)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Bingbing Li (B)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Yanfeng Zhang (Y)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Yi Pan (Y)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Changying Guo (C)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China.

Hong Du (H)

Department of Endocrinology, Nanjing Jinling Hospital. 305 Zhongshan East Road, Nanjing, jiangsu, PR China.

Ling Li (L)

Department of Endocrinology, School of Medicine, Zhongda Hospital, Southeast University, 87 DingJiaQiao Rd, Nanjing, Nanjing, Jiangsu, PR China.

Xianghui Fu (X)

Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, Sichuan, China. xfu@scu.edu.cn.
ORCID: 0000-0001-9808-3892

Zhengyu Cao (Z)

Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China. zycao1999@hotmail.com.
ORCID: 0000-0002-2692-2949

Liang Jin (L)

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of life Science and Technology, China Pharmaceutical University. 24 Tongjiaxiang, Jiangsu province, Nanjing, PR China. ljstemcell@cpu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Alimentation riche en graisse › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif hélice ailée › Facteurs de transcription Forkhead › Protéine O1 à motif en tête de fourche › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs Wnt › Récepteurs Frizzled › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Délétion de séquence › Délétion de gène › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones pancréatiques › Insulines › Insuline › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Insulinorésistance › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Phénomènes physiologiques › Sécrétion d'insuline › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules entéroendocrines › Cellules à insuline › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris obèse › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Transcription génétique › Obesity-induced overexpression of miR-802...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › Obesity-induced overexpression of miR-802...