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  • Sex-specific, reciprocal regulation of ERα and miR-22 controls muscle lipid metabolism in male mice.

Sex-specific, reciprocal regulation of ERα and miR-22 controls muscle lipid metabolism in male mice.

The EMBO journal (2017-03-21)
Judith Schweisgut, Christian Schutt, Stas Wüst, Astrid Wietelmann, Bart Ghesquière, Peter Carmeliet, Stefan Dröse, Kenneth S Korach, Thomas Braun, Thomas Boettger
ABSTRACT

Control of energy homeostasis and metabolism is achieved by integrating numerous pathways, and miRNAs are involved in this process by regulating expression of multiple target genes. However, relatively little is known about the posttranscriptional processing of miRNAs and a potential role for the precursors they derive from. Here, we demonstrate that mature miRNA-22 is more abundant in muscle from male mice relative to females and that this enables sex-specific regulation of muscular lipid metabolism and body weight by repressing estrogen receptor alpha (ERα) expression. We found that the ERα adjusts its own activity by preventing processing of miR-22 via direct binding to a conserved ERα-binding element within the primary miR-22 precursor. Mutation of the ERα binding site within the pri-miR-22 in vivo eliminates sex-specific differences in miR-22 expression. We reason that the resulting tissue selective negative feedback regulation is essential to establish sex-specific differences in muscle metabolism and body weight development.

MATERIALS
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Product Description

Sigma-Aldrich
Anti-LDHD antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)