PuSH - Publication Server of Helmholtz Zentrum München

Gil Lozano, M. ; Simoes Fernandez, E. ; Wu, M. ; Wiedemann, T. ; Kwon, Y. ; Sekar, R. ; Morigny, P. ; Troullinaki, M. ; Merl-Pham, J. ; Buettner, M.* ; Feuchtinger, A. ; Jouffe, C. ; Maida, A. ; Hass, D, ; Samaga, D. ; Wolff, G. ; Machado, J. ; Giroud, M. ; Klepac, K. ; Cummins, C.L.* ; Rios Garcia, M. ; Weber, P. ; Zeigerer, A. ; Uhlenhaut, N.H. ; Szendroedi, J. ; Blüher, M. ; Herzig, S.

Combinatorial targeting of the miR-379/miR-410 cluster normalizes glucose and lipid homeostasis in male models of diabetes and obesity.

Nat. Commun. 17:10014 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Non-coding RNAs from the Dlk1-Dio3 locus are critical for the maturation of metabolic tissues in early stages of postnatal development; however, their role in the mature organs remains elusive. Herein, we show that microRNAs from the miR-379/miR-410 cluster are robustly upregulated in livers of subjects with obesity and various mouse models of metabolic dysfunction. Adult-onset, combinatorial inhibition of this miRNA cluster by hepatocyte-specific expression of a decoy sequence reduces triglyceride, total and LDL cholesterol circulating levels, decreases basal glycemia and improves glucose tolerance and insulin sensitivity irrespective of sex. Consistent with the decoy-triggered enhancement of PI3K/mTOR signaling in these mice, hepatocytes expressing the combinatorial decoy show augmented mitochondrial mass and function. Notably, decoy therapy also ameliorates glucose and lipid homeostasis in both type 1 diabetic and diet-induced, type 2 pre-diabetic, obese male animals. Collectively, our results demonstrate that microRNAs from the miR-379/miR-410 cluster are critical regulators of metabolic homeostasis in the mature liver. Given the preservation of miRNA dysfunction in human obesity, hepatocyte-specific combinatorial inhibition of a large miRNA cluster represents an approach towards multi-parameter improvements in diabetes and obesity.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Glucose Homeostasis ; Microrna ; Homeostasis ; Decoy ; Type 2 Diabetes ; Downregulation And Upregulation ; Diabetes Mellitus ; Insulin ; Cluster (spacecraft)
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 17, Issue: 1, Pages: , Article Number: 10014 Supplement: ,
Publisher Springer
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
Core Facility Metabolomics and Proteomics (CF-MPC)
Core Facilty Pathology and Tissue Analytics (CF-PTA)
Translational Metabolic Oncology (IDC-TMO)
Institute of Diabetes and Endocrinology (IDE)
Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG)
Grants European Foundation for the Study of Diabetes (EFSD)
Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
Deutsche Forschungsgemeinschaft (German Research Foundation)