First Author | Sprenkle NT | Year | 2023 |
Journal | Cell Rep | Volume | 42 |
Issue | 8 | Pages | 112928 |
PubMed ID | 37542720 | Mgi Jnum | J:344664 |
Mgi Id | MGI:7525085 | Doi | 10.1016/j.celrep.2023.112928 |
Citation | Sprenkle NT, et al. (2023) The miR-23-27-24 clusters drive lipid-associated macrophage proliferation in obese adipose tissue. Cell Rep 42(8):112928 |
abstractText | Identifying molecular circuits that control adipose tissue macrophage (ATM) function is necessary to understand how ATMs contribute to tissue homeostasis and obesity-induced insulin resistance. In this study, we find that mice with a myeloid-specific knockout of the miR-23-27-24 clusters of microRNAs (miRNAs) gain less weight on a high-fat diet but exhibit worsened glucose and insulin tolerance. Analysis of ATMs from these mice shows selectively reduced numbers and proliferation of a recently reported subset of lipid-associated CD9(+)Trem2(+) ATMs (lipid-associated macrophages [LAMs]). Leveraging the role of miRNAs to control networks of genes, we use RNA sequencing (RNA-seq), functional screens, and biochemical assays to identify candidate target transcripts that regulate proliferation-associated signaling. We determine that miR-23 directly targets the mRNA of Eif4ebp2, a gene that restricts protein synthesis and proliferation in macrophages. Altogether, our study demonstrates that control of proliferation of a protective subset of LAMs by noncoding RNAs contributes to protection against diet-induced obesity metabolic dysfunction. |