Genetic alterations stops obesity onset in mice, study shows

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.

miR-155 knock-out​

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