Human miR-1 Stimulates Metabolic and Thermogenic-Related Genes in Adipocytes

Int J Mol Sci. 2024 Dec 31;26(1):276. doi: 10.3390/ijms26010276.

Abstract

MicroRNAs play a pivotal role in the regulation of adipose tissue function and have emerged as promising therapeutic candidates for the management of obesity and associated comorbidities. Among them, miR-1 could be a potential biomarker for metabolic diseases and contribute to metabolic homeostasis. However, thorough research is required to fully elucidate the impact of miR-1 on human adipocyte thermogenesis and metabolism. This study aimed to explore the effect of miR-1 on human adipocyte browning, a process whose activation has been linked to obesity protection and counteraction. Human multipotent adipose-derived stem cells, hMADS cells, were differentiated into white and brown-like adipocytes and transfected with miR-1 mimics for gene expression and western blotting analyses. miR-1 inhibited the expression of its previously validated target PTK9/TWF1 and modulated the expression profile of key genes involved in thermogenesis and adipocyte browning (increased UCP1 at mRNA and protein level, increased CPT1M, decreased HIF3A), adipocyte differentiation and metabolism (decreased PLIN1, FASN, RXRA, PPARG, FABP4, MAPKAPK2), as well as genes related to the cytoskeleton (decreased ACTB) and extracellular matrix (decreased COL1A1). These findings suggest that miR-1 can modulate the expression of adipocyte human genes associated with thermogenesis and metabolism, which could hold value for eventual therapeutic potential in obesity.

Keywords: PTK9; TWF1; UCP1; adipocyte browning; brown adipocyte; miR-1; microRNA; white adipocyte.

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes, Brown / metabolism
  • Cell Differentiation* / genetics
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Thermogenesis* / genetics

Substances

  • MicroRNAs
  • MIRN1 microRNA, human