Turning Muscle Stem Cells into Brown Fat

Michael Rudnicki’s laboratory at the Ottawa Hospital Research Institute has managed to convert stem cells from skeletal muscle into brown fat. Because brown fat burns calories, studies have shown that trimmer people tend to have more brown fat, Therefore, Rudnicki’s findings are being viewed as a potential treatment for obesity.

According to Rudnicki, “This discovery significantly advances our ability to harness this good fat in the battle against bad fat and all the associated health risks that come with being overweight and obese. Rudnicki is a senior scientist and director for the Regenerative Medicine Program and Sprott Center for Stem Cell Research at the Ottawa Hospital Research Institute.

Obesity is the fifth leading risk death, globally speaking, and an estimated 2.8 million people dying every year from the effects of being overweight or obese, according to the World Health Organization. The Public Health Agency of Canada estimates that 25% of Canadian adults are obese.

in 2007, Rudnicki and his research team demonstrated the existence of a stem cell population in skeletal muscle. In this new publication, Rudnicki and others show that these adult muscle stem cells not only have the ability to produce muscle fibers, but can also make brown fat.

An even more important aspect of this paper (Yin, et al., Cell Metabolism 17(2) 2013: 210), is that it shows how adult muscle stem cells become brown fat. The main switch is a regulatory molecule called microRNA-133 or miR-133. When miR-133 is present, the muscle stem cells produce muscle fibers, but when the intracellular concentration of miR-133 is reduced, the muscle stem cells form brown fat.

Graphic Abstract

Rudnicki’s research staff developed a molecule that could reduce the concentration of miR-133 in cells. This molecule an antisense oligonucleotide or ASO that is complementary to miR-133. When injected into mice, the ASO caused the mice to produce more brown fat and prevented obesity. Additionally, when injected into the hind leg muscle, the metabolism of the mouse increased, and this effect lasted for four months after the ASO injection.

Even though antisense oligonucleotides are being used in clinical trials, such trials with miR-133 ASOs are still years away.

Rudnicki noted that “we are very excited by this breakthrough.” He continued: “While we acknowledge that it’s a first step there are still many questions to be answered, such as: Will it help adults who are already obese to lose weight? How should it be administered? How long do the effects last? Are there any adverse effects we have not yet observed?”

Surely these questions will be addressed in good time, and Rudnicki’s lab is probably working on them as you read this entry.