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ResearchIn-Press PreviewCell biologyMetabolism Open Access | 10.1172/JCI175566

The microRNA miR-30a blocks adipose tissue fibrosis accumulation in obesity

Pradip K. Saha,1 Robert Sharp,1 Aaron R. Cox,2 Rabie Habib,2 Michael J. Bolt,3 Jessica B. Felix,1 Claudia E. Ramirez Bustamante,1 Xin Li,2 Sung Yun Jung,4 Kang Ho Kim,5 Kai Sun,2 Huaizhu Wu,6 Samuel Klein,7 and Sean M. Hartig1

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Saha, P. in: PubMed | Google Scholar

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Sharp, R. in: PubMed | Google Scholar

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

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1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Habib, R. in: PubMed | Google Scholar

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Bolt, M. in: PubMed | Google Scholar

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Felix, J. in: PubMed | Google Scholar |

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Ramirez Bustamante, C. in: PubMed | Google Scholar

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Li, X. in: PubMed | Google Scholar

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Jung, S. in: PubMed | Google Scholar |

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Kim, K. in: PubMed | Google Scholar

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Sun, K. in: PubMed | Google Scholar |

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Wu, H. in: PubMed | Google Scholar

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Klein, S. in: PubMed | Google Scholar |

1Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States of America

2Center for Metabolic and Degenerative Diseases, the Brown Foundation Instit, University of Texas Health Science Center, Houston, United States of America

3Advanced Technology Core Labs, Baylor College of Medicine, Houston, United States of America

4Department of Biochemistry, Baylor College of Medicine, Houston, United States of America

5Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Me, University of Texas Health Science Center, Houston, United States of America

6Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, United States of America

7Center for Human Nutrition, Washington University School of Medicine, St Louis, United States of America

Find articles by Hartig, S. in: PubMed | Google Scholar |

Published June 5, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI175566.
Copyright © 2025, Saha et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 5, 2025 - Version history
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Abstract

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic co-morbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved microRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed high fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits pro-fibrotic programs in subcutaneous WAT, at least in part, by repressing PAI-1, a dominant regulator of fibrinolysis and biomarker of insulin resistance. Conversely, mouse adipocytes lacking miR-30a exhibited greater expression of fibrosis markers with disrupted cellular metabolism. Lastly, miR-30a expression negatively correlates with PAI-1 levels in subcutaneous WAT from people with obesity, further supporting an anti-fibrotic role for miR-30a. Together, these findings uncover miR-30a as a critical regulator of adipose tissue fibrosis that predicts metabolically healthy obesity in people and mice.

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  • Version 1 (June 5, 2025): In-Press Preview
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