The results once again highlight the influence that genes have in regulating signalling pathways involved in the development and maintenance of obesity.
It may be that research on a genetic level could provide new therapeutic targets that may prove effective in managing obesity.
Researchers from The Ohio State University Wexner Medical Center deleted a specific microRNA (miR), a small, non-coding RNA that influences and regulates gene transcription in cells and affects how they function.
This microRNA - miR-155 – is thought to regulate the development and maintenance of obesity. It has been previously linked with the development of hepatic steatosis associated with obesity.
Female wild-type (unaltered) mice and miR-155 knockout mice were fed a control diet or a high-fat diet for 12 weeks. Researchers observed no signs of obesity in the miR-155 knockout mice.
Compared to wild-type mice, weight gain in miR-155 knockout mice was reduced 56% with a 74% reduction in fat accumulation. Experiments using male mice produced similar results.
Compared to female wild-type mice, miR-155 knockout mice lost 78% more body weight after overnight fast, and miR-155 knockout mice increased energy expenditure by 14% over wild-type mice.
"MicroRNAs target hundreds of mRNAs simultaneously, so they represent a promising class of molecules for improving outcomes of disease," said lead author Andrew Gaudet.
"Our study shows that manipulating miR-155 improves how cells respond to high fat intake. This suggests that altering microRNA expression is an attractive potential therapy for obesity."
miR-155 conductor-like role
Researchers believe that the obesity resistance of miR-155 KO female mice was not due to altered energy intake or activity; rather, miR-155 KO mice fed on the high fat diet increased energy release compared to wild-type mice.
The data suggested miR-155 deletion improved obesity resistance, by reducing white fat tissue inflammation and steering non-defined fat cells to develop into brown fat cells that used more energy.
The efficacy of miR-155 deletion in females is impressive considering it did not affect body weight during development or in adults maintained on standard food. miR-155 deletion abolishes high-fat diet induced body weight gain in female mice.
This contrasts with other obesity-resistant transgenic models that display only partial protection against diet-induced obesity.
Source: Nature/Scientific Reports
Published online ahead of print, doi:10.1038/srep22862
“miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity.”
Authors: Andrew D. Gaudet, Laura K. Fonken, Liubov V. Gushchina, Taryn G. Aubrecht, Santosh K. Maurya, Muthu Periasamy, Randy J. Nelson & Phillip G. Popovich