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Let-7i-5p represses brite adipocyte function in mice and humans
Maude Giroud1,2,3, Michael Karbiener4, Didier F Pisani1,2,3
1Univ. Nice Sophia Antipolis, iBV, UMR 7277, Nice, 06100, France.
Scientific Reports
|June 28, 2016
Summary
MicroRNAs regulate brown fat activation. Let-7i-5p is downregulated in brite adipocytes, inhibiting thermogenesis and UCP1 expression, suggesting a role in obesity treatment.
Area of Science:
- Cell Biology
- Metabolism
- Molecular Biology
Background:
- Brown adipose tissue (BAT) facilitates non-shivering thermogenesis for energy expenditure.
- The discovery of thermogenic brite/beige adipocytes offers new strategies for combating obesity.
- Identifying regulators of the brite adipogenic program is crucial for therapeutic development.
Purpose of the Study:
- To identify microRNAs (miRNAs) involved in the white to brite adipocyte conversion.
- To investigate the role of differentially expressed miRNAs in human adipocytes.
Main Methods:
- Global miRNA expression profiling of human adipocytes.
- Analysis of Let-7i-5p and UCP1 expression in vitro and in vivo.
- Functional studies using Let-7i-5p mimics in human and murine models.
Main Results:
- Let-7i-5p was found to be downregulated in brite adipocytes.
- Inverse correlation observed between Let-7i-5p and UCP1 expression.
- Let-7i-5p mimic reduced UCP1 expression and oxygen consumption in human brite adipocytes.
- Inhibition of the browning process upon beta-3 adrenergic stimulation in mice.
Conclusions:
- Let-7i-5p plays a role in regulating brite adipocyte function and recruitment.
- Targeting Let-7i-5p may offer a novel therapeutic approach for obesity and related metabolic disorders.

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