American Diabetes Association
Online_Supplemental_Material_8-11-22.pdf (802.88 kB)

miR-130b/301b is a Negative Regulator of Beige Adipogenesis and Energy Metabolism in vitro and in vivo

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posted on 2022-08-24, 18:06 authored by Wenyi Luo, Youngsil Kim, Mary Ellen Jensen, Oana Herlea-Pana, Weidong Wang, Michael C. Rudolph, Jacob E. Friedman, Steven D. Chernausek, Shaoning Jiang

Thermogenic brown or beige adipocytes dissipate energy in the form of heat and thereby counteract obesity and related metabolic complications. The microRNA cluster, miR-130b/301b, is highly expressed in adipose tissues and has been implicated in metabolic diseases as a post-transcriptional regulator of mitochondrial biogenesis and lipid metabolism. We investigated the roles of miR-130b/301b in regulating beige adipogenesis in vivo and in vitro. miR-130b/301b declined in adipose progenitor cells during beige adipogenesis, while forced overexpression of miR-130b-3p or miR-301b-3p suppressed uncoupling protein 1 (UCP1) and mitochondrial respiration, suggesting a decline in miR-130b-3p or miR-301b-3p is required for adipocyte precursors to develop the beige phenotype. Mechanistically, miR-130b/301b directly targeted AMP-activated protein kinase (AMPKα1) and suppressed peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α), key regulators of brown adipogenesis and mitochondrial biogenesis. Mice lacking the miR-130b/301b microRNA cluster showed reduced visceral adiposity and less weight gain. miR-130b/301b null mice exhibited improved glucose tolerance, increased UCP1 and AMPK activation in subcutaneous fat (iWAT), and increased response to cold-induced energy expenditure. Together, these data identify the miR-130b/301b cluster as a new regulator that suppresses beige adipogenesis involving PGC-1α and AMPK signaling in iWAT and is therefore a potential therapeutic target against obesity and related metabolic disorders.


This publication was made possible by NIH Grant Number 5P30GM122744 from the COBRE Program of the National Institute of General Medical Services. The XFe96 seahorse equipment provided by the Cancer Functional Genomics core was supported partly by the National Institute of General Medical Sciences Grant P20GM103639 and National Cancer Institute Grant P30CA225520 of the National Institutes of Health, Stephenson Cancer Functional Genomics Core, the University of Oklahoma.


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