Summary of project PR002238
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002238. The data can be accessed directly via it's Project DOI: 10.21228/M8BK0V This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002238 |
| Project DOI: | doi: 10.21228/M8BK0V |
| Project Title: | A multi-omic census reveals obesity-associated microRNA miR-let-7 as novel instigator of adipose mitochondrial dysfunction and of intergenerational metabolic decline. |
| Project Summary: | We here describe that obesity and weight loss in male mice causes reversible abnormalities in glucose and lipid metabolism, serum metabolomes, and white adipose tissue alongside reversible reductions in activity of genes controlling mitochondrial energy dissipation. When mating obese male mice with lean females, we observed concordant reductions in mitochondrial gene expression and translation in offspring that resemble those observed in the paternal (F0) generation. When mapping miRNA responses across somatic and gametic cell types and generations, we found that obesity and weight loss reversible affected miRNA abundance, and observed miR-let7 isoforms induced in obese adipose tissues of F0 and offspring (F1) generations, as well as in sperm of obese F0 mice. Mechanistically, when overexpressing miR-let-7 in adipocytes, we found it to silence DICER1, a cellular rheostat required for adipose tissue adaptation in obesity as evidenced by functional deficiency in mitochondrial functioon following DICER1 loss. Delivery of miR-let-7 into oocytes elicited glucose intolerance and impairments in adipose mitochondrial gene expression in mice sired from miRNA-injected embryos, phenocopying aspects of paternal obesity. When performing single-cell RNA-Seq of embryos, we found that miR-let7 impaired mitochondrial gene expression, suggesting altered energy metabolism following sperm-mediated changes in zygotic miRNAs. When studying miRNA alterations in human semen, we lifestyle-induced weight loss to downregulate MIR-LET-7 in human subjects, suggesting similar roles for human MIR-LET-7 in gametic epigenomes and embryogenesis. |
| Institute: | University of Southern Denmark |
| Department: | Department of Biochemistry and Molecular Biology |
| Last Name: | Kornfeld |
| First Name: | Jan-Wilhelm |
| Address: | University of Southern Denmark (SDU), Campusvej 55, 5230 Odense M, Denmark |
| Email: | janwilhelmkornfeld@bmb.sdu.dk |
| Phone: | +4565503904 |
Summary of all studies in project PR002238
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003622 | A multi-omic census reveals obesity-associated microRNA miR-let-7 as novel instigator of adipose mitochondrial dysfunction and of intergenerational metabolic decline. | Mus musculus | University of Southern Denmark | MS | 2025-01-02 | 1 | 34 | Uploaded data (3.6G)* |
