miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function

Area of Science:

• Adipose tissue biology
• Molecular endocrinology
• MicroRNA regulation

Background:

• Brite (brown-in-white) adipocytes emerge in white adipose tissue (WAT) and contribute to thermogenesis, offering protection against obesity.
• MicroRNAs are key regulators of adipose tissue development and function.
• Understanding microRNA roles in brite adipocyte formation is crucial for metabolic disease research.

Purpose of the Study:

• To investigate the role of microRNAs in controlling the formation and function of brite adipocytes.
• To identify specific microRNAs involved in the browning of white adipose tissue.

Main Methods:

• Utilized human multipotent adipose-derived stem cells for in vitro studies.
• Analyzed microRNA expression in human and rodent adipose tissues (BAT and WAT).
• Performed in vitro gain- and loss-of-function experiments for miR-125b-5p.
• Administered miR-125b-5p mimic and inhibitor in vivo into rodent WAT.

Main Results:

• miR-125b-5p was downregulated during brite adipocyte formation and expressed lower in brown adipose tissue (BAT) than WAT.
• In vitro, miR-125b-5p overexpression reduced, while knockdown increased, mitochondrial biogenesis.
• In vivo, miR-125b-5p levels decreased in WAT and BAT after beta-3 adrenergic receptor stimulation.
• Direct miR-125b-5p manipulation in WAT affected UCP1 induction, brite adipocyte markers, and mitochondrial function.

Conclusions:

• miR-125b-5p acts as a repressor of brite adipocyte function.
• This microRNA modulates oxygen consumption and mitochondrial gene expression in thermogenic adipocytes.
• Targeting miR-125b-5p may offer a strategy to enhance brite adipocyte activity.