Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance
Summary: While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as a likely target for treatment of cardiovascular diseases. However, the deleterious effects o...
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Elsevier
2018-02-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718301384 |
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doaj-e344e7cdc5634e7db68d175d5c1581a0 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nathan L. Price Abhishek K. Singh Noemi Rotllan Leigh Goedeke Allison Wing Alberto Canfrán-Duque Alberto Diaz-Ruiz Elisa Araldi Ángel Baldán Joao-Paulo Camporez Yajaira Suárez Matthew S. Rodeheffer Gerald I. Shulman Rafael de Cabo Carlos Fernández-Hernando |
spellingShingle |
Nathan L. Price Abhishek K. Singh Noemi Rotllan Leigh Goedeke Allison Wing Alberto Canfrán-Duque Alberto Diaz-Ruiz Elisa Araldi Ángel Baldán Joao-Paulo Camporez Yajaira Suárez Matthew S. Rodeheffer Gerald I. Shulman Rafael de Cabo Carlos Fernández-Hernando Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance Cell Reports miR-33 obesity insulin-resistance food-consumption metabolism micro-RNA |
author_facet |
Nathan L. Price Abhishek K. Singh Noemi Rotllan Leigh Goedeke Allison Wing Alberto Canfrán-Duque Alberto Diaz-Ruiz Elisa Araldi Ángel Baldán Joao-Paulo Camporez Yajaira Suárez Matthew S. Rodeheffer Gerald I. Shulman Rafael de Cabo Carlos Fernández-Hernando |
author_sort |
Nathan L. Price |
title |
Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance |
title_short |
Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance |
title_full |
Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance |
title_fullStr |
Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance |
title_full_unstemmed |
Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance |
title_sort |
genetic ablation of mir-33 increases food intake, enhances adipose tissue expansion, and promotes obesity and insulin resistance |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-02-01 |
description |
Summary: While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as a likely target for treatment of cardiovascular diseases. However, the deleterious effects of long-term anti-miR-33 therapies and predisposition of miR-33−/− mice to obesity and metabolic dysfunction exemplify the possible pitfalls of miRNA-based therapies. Our work provides an in-depth characterization of miR-33−/− mice and explores the mechanisms by which loss of miR-33 promotes insulin resistance in key metabolic tissues. Contrary to previous reports, our data do not support a direct role for SREBP-1-mediated lipid synthesis in promoting these effects. Alternatively, in adipose tissue of miR-33−/− mice, we observe increased pre-adipocyte proliferation, enhanced lipid uptake, and impaired lipolysis. Moreover, we demonstrate that the driving force behind these abnormalities is increased food intake, which can be prevented by pair feeding with wild-type animals. |
topic |
miR-33 obesity insulin-resistance food-consumption metabolism micro-RNA |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718301384 |
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doaj-e344e7cdc5634e7db68d175d5c1581a02020-11-25T03:07:18ZengElsevierCell Reports2211-12472018-02-012282133214510.1016/j.celrep.2018.01.074Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin ResistanceNathan L. Price0Abhishek K. Singh1Noemi Rotllan2Leigh Goedeke3Allison Wing4Alberto Canfrán-Duque5Alberto Diaz-Ruiz6Elisa Araldi7Ángel Baldán8Joao-Paulo Camporez9Yajaira Suárez10Matthew S. Rodeheffer11Gerald I. Shulman12Rafael de Cabo13Carlos Fernández-Hernando14Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USAVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USAVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USADepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USAIntegrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Molecular, Cellular, and Developmental Biology, Yale University School of Medicine, New Haven, CT, USAVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USATranslational Gerontology Branch, National Institute of Aging, NIH, Baltimore, MD, USAVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USAEdward A. Doisy Department of Biochemistry and Molecular Biology and Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, USADepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USAVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT, USAIntegrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Molecular, Cellular, and Developmental Biology, Yale University School of Medicine, New Haven, CT, USADepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Cellular and Molecular Physiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USATranslational Gerontology Branch, National Institute of Aging, NIH, Baltimore, MD, USAVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; Corresponding authorSummary: While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as a likely target for treatment of cardiovascular diseases. However, the deleterious effects of long-term anti-miR-33 therapies and predisposition of miR-33−/− mice to obesity and metabolic dysfunction exemplify the possible pitfalls of miRNA-based therapies. Our work provides an in-depth characterization of miR-33−/− mice and explores the mechanisms by which loss of miR-33 promotes insulin resistance in key metabolic tissues. Contrary to previous reports, our data do not support a direct role for SREBP-1-mediated lipid synthesis in promoting these effects. Alternatively, in adipose tissue of miR-33−/− mice, we observe increased pre-adipocyte proliferation, enhanced lipid uptake, and impaired lipolysis. Moreover, we demonstrate that the driving force behind these abnormalities is increased food intake, which can be prevented by pair feeding with wild-type animals.http://www.sciencedirect.com/science/article/pii/S2211124718301384miR-33obesityinsulin-resistancefood-consumptionmetabolismmicro-RNA |