Multi-step regulation of microRNA expression and secretion into small extracellular vesicles by insulin

Marsel Lino; Ruben Garcia-Martin; Vitor Rosetto Muñoz; Gabriel Palermo Ruiz; Allah Nawaz; Bruna Brasil Brandão; Jonathan Dreyfus; Hui Pan; C. Ronald Kahn

Cell Reports (Jul 2024)

Multi-step regulation of microRNA expression and secretion into small extracellular vesicles by insulin

Marsel Lino,
Ruben Garcia-Martin,
Vitor Rosetto Muñoz,
Gabriel Palermo Ruiz,
Allah Nawaz,
Bruna Brasil Brandão,
Jonathan Dreyfus,
Hui Pan,
C. Ronald Kahn

Affiliations

Marsel Lino: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA
Ruben Garcia-Martin: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA
Vitor Rosetto Muñoz: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA
Gabriel Palermo Ruiz: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA
Allah Nawaz: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA
Bruna Brasil Brandão: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA
Jonathan Dreyfus: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA
Hui Pan: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA
C. Ronald Kahn: Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 7
p. 114491

Abstract

Read online

Summary: Tissues release microRNAs (miRNAs) in small extracellular vesicles (sEVs) including exosomes, which can regulate gene expression in distal cells, thus acting as modulators of local and systemic metabolism. Here, we show that insulin regulates miRNA secretion into sEVs from 3T3-L1 adipocytes and that this process is differentially regulated from cellular expression. Thus, of the 53 miRNAs upregulated and 66 miRNAs downregulated by insulin in 3T3-L1 sEVs, only 12 were regulated in parallel in cells. Insulin regulated this process in part by phosphorylating hnRNPA1, causing it to bind to AU-rich motifs in miRNAs, mediating their secretion into sEVs. Importantly, 43% of insulin-regulated sEV-miRNAs are implicated in obesity and insulin resistance. These include let-7 and miR-103, which we show regulate insulin signaling in AML12 hepatocytes. Together, these findings demonstrate an important layer to insulin’s regulation of adipose biology and provide a mechanism of tissue crosstalk in obesity and other hyperinsulinemic states.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords