Loss of miR-146b-3p Inhibits Perivascular Adipocyte Browning with Cold Exposure During Aging

Xiao-Xi Pan1, Jiu-Mei Cao2, Fan Cai2

  • 1State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Abstract

Insights

Aging impairs perivascular adipose tissue (PVAT) browning, a process crucial for vascular health. This study reveals that a microRNA, miR-146b-3p, plays a key role in regulating this age-related decline in PVAT browning.

Area of Science:

  • Vascular Biology
  • Adipose Tissue Biology
  • Aging Research

Background:

  • Pathological changes in perivascular adipose tissue (PVAT) are linked to increased vascular disease risk.
  • MicroRNAs are critical regulators of adipocyte differentiation and browning.
  • Understanding PVAT browning in aging is essential for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the role of miR-146b-3p in regulating perivascular adipocyte browning during aging.
  • To determine if miR-146b-3p expression changes with age in PVAT.
  • To elucidate the functional impact of miR-146b-3p on adipocyte browning in vitro and in vivo.

Main Methods:

  • Utilized a cold-induced mouse model to study aging effects on PVAT browning.
  • Quantified miR-146b-3p expression in PVAT of young and old mice post-cold stimulus.
  • Employed miRNA mimics and inhibitors in vitro and in vivo to assess miR-146b-3p's regulatory function.

Main Results:

  • Old mice exhibited reduced PVAT browning and lower miR-146b-3p expression after cold exposure.
  • Aging impaired preadipocyte to brown adipocyte differentiation, correlating with miR-146b-3p levels.
  • miR-146b-3p inhibition blocked browning in young adipocytes, while mimics restored browning in aged adipocytes.

Conclusions:

  • Aging significantly inhibits perivascular adipocyte browning.
  • Downregulation of miR-146b-3p is a key factor contributing to impaired PVAT browning in aged individuals.
  • miR-146b-3p represents a potential therapeutic target for age-related vascular dysfunction.

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