MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix compositionResearch in context
Background: Abdominal fat mass is associated with metabolic risk whilst gluteal femoral fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human fat distribution remains largely unexplored. Methods: An initial m...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S235239641930355X |
| _version_ | 1818116343994515456 |
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| author | Catriona Hilton Matt J. Neville Laura B.L. Wittemans Marijana Todorcevic Katherine E. Pinnick Sara L. Pulit Jian'an Luan Agné Kulyté Ingrid Dahlman Nicholas J. Wareham Luca A. Lotta Peter Arner Cecilia M. Lindgren Claudia Langenberg Fredrik Karpe |
| author_facet | Catriona Hilton Matt J. Neville Laura B.L. Wittemans Marijana Todorcevic Katherine E. Pinnick Sara L. Pulit Jian'an Luan Agné Kulyté Ingrid Dahlman Nicholas J. Wareham Luca A. Lotta Peter Arner Cecilia M. Lindgren Claudia Langenberg Fredrik Karpe |
| author_sort | Catriona Hilton |
| collection | DOAJ |
| description | Background: Abdominal fat mass is associated with metabolic risk whilst gluteal femoral fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human fat distribution remains largely unexplored. Methods: An initial microarray screen of abdominal subcutaneous and gluteal adipose tissue, with validatory qPCR, identified microRNA-196a as being strongly differentially expressed between gluteal and abdominal subcutaneous adipose tissue. Findings: We found that rs11614913, a SNP within pre-miR-196a-2 at the HOXC locus, is an eQTL for miR-196a expression in abdominal subcutaneous adipose tissue (ASAT). Observations in large cohorts showed that rs11614913 increased waist-to-hip ratio, which was driven specifically by an expansion in ASAT. In further experiments, rs11614913 was associated with adipocyte size. Functional studies and transcriptomic profiling of miR-196a knock-down pre-adipocytes revealed a role for miR-196a in regulating pre-adipocyte proliferation and extracellular matrix pathways. Interpretation: These data identify a role for miR-196a in regulating human body fat distribution. Fund: This work was supported by the Medical Research Council and Novo Nordisk UK Research Foundation (G1001959) and Swedish Research Council. We acknowledge the OBB-NIHR Oxford Biomedical Research Centre and the British Heart Foundation (BHF) (RG/17/1/32663). Work performed at the MRC Epidemiology Unit was funded by the United Kingdom's Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1. Keywords: Abdominal, Adipocyte, Body fat distribution, Gluteal, Human adipose tissue, MicroRNA |
| first_indexed | 2024-12-11T04:21:01Z |
| format | Article |
| id | doaj.art-132352bcea1b412e8fe99d6280bbbd8f |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T04:21:01Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-132352bcea1b412e8fe99d6280bbbd8f2022-12-22T01:21:06ZengElsevierEBioMedicine2352-39642019-06-0144467475MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix compositionResearch in contextCatriona Hilton0Matt J. Neville1Laura B.L. Wittemans2Marijana Todorcevic3Katherine E. Pinnick4Sara L. Pulit5Jian'an Luan6Agné Kulyté7Ingrid Dahlman8Nicholas J. Wareham9Luca A. Lotta10Peter Arner11Cecilia M. Lindgren12Claudia Langenberg13Fredrik Karpe14Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UKOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK; NIHR Oxford Biomedical Research Centre, OUH Trust, Oxford OX3 7LE, UK; Corresponding author at: Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK.Wellcome Trust Centre for Human Genetics, Oxford University, Oxford OX3 7BN, UK; Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UKOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UKOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UKBig Data Institute, University of Oxford, Oxford OX3 7FZ, UK; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford OX3 7BN, UK; Department of Genetics, University Medical Center Utrecht, Utrecht, the NetherlandsMedical Research Council Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UKDepartment of Medicine (H7), Karolinska Institutet at Karolinska University Hospital - Huddinge, 141 86 Stockholm, SwedenDepartment of Medicine (H7), Karolinska Institutet at Karolinska University Hospital - Huddinge, 141 86 Stockholm, SwedenMedical Research Council Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UKMedical Research Council Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UKDepartment of Medicine (H7), Karolinska Institutet at Karolinska University Hospital - Huddinge, 141 86 Stockholm, SwedenBig Data Institute, University of Oxford, Oxford OX3 7FZ, UK; Wellcome Trust Centre for Human Genetics, Oxford University, Oxford OX3 7BN, UKMedical Research Council Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UKOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK; NIHR Oxford Biomedical Research Centre, OUH Trust, Oxford OX3 7LE, UK; Corresponding author at: Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK.Background: Abdominal fat mass is associated with metabolic risk whilst gluteal femoral fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human fat distribution remains largely unexplored. Methods: An initial microarray screen of abdominal subcutaneous and gluteal adipose tissue, with validatory qPCR, identified microRNA-196a as being strongly differentially expressed between gluteal and abdominal subcutaneous adipose tissue. Findings: We found that rs11614913, a SNP within pre-miR-196a-2 at the HOXC locus, is an eQTL for miR-196a expression in abdominal subcutaneous adipose tissue (ASAT). Observations in large cohorts showed that rs11614913 increased waist-to-hip ratio, which was driven specifically by an expansion in ASAT. In further experiments, rs11614913 was associated with adipocyte size. Functional studies and transcriptomic profiling of miR-196a knock-down pre-adipocytes revealed a role for miR-196a in regulating pre-adipocyte proliferation and extracellular matrix pathways. Interpretation: These data identify a role for miR-196a in regulating human body fat distribution. Fund: This work was supported by the Medical Research Council and Novo Nordisk UK Research Foundation (G1001959) and Swedish Research Council. We acknowledge the OBB-NIHR Oxford Biomedical Research Centre and the British Heart Foundation (BHF) (RG/17/1/32663). Work performed at the MRC Epidemiology Unit was funded by the United Kingdom's Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1. Keywords: Abdominal, Adipocyte, Body fat distribution, Gluteal, Human adipose tissue, MicroRNAhttp://www.sciencedirect.com/science/article/pii/S235239641930355X |
| spellingShingle | Catriona Hilton Matt J. Neville Laura B.L. Wittemans Marijana Todorcevic Katherine E. Pinnick Sara L. Pulit Jian'an Luan Agné Kulyté Ingrid Dahlman Nicholas J. Wareham Luca A. Lotta Peter Arner Cecilia M. Lindgren Claudia Langenberg Fredrik Karpe MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix compositionResearch in context EBioMedicine |
| title | MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix compositionResearch in context |
| title_full | MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix compositionResearch in context |
| title_fullStr | MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix compositionResearch in context |
| title_full_unstemmed | MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix compositionResearch in context |
| title_short | MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix compositionResearch in context |
| title_sort | microrna 196a links human body fat distribution to adipose tissue extracellular matrix compositionresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S235239641930355X |
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