Analysis of DNA from more than 85,000 people reveals two genetic variants that predispose to larger muscles without also accumulating fat around the waist.
An international genetic study with participation from researchers from the University of Copenhagen and others discovered four genetic variants, all of which predispose to larger muscles.
The researchers call two of the genetic variants “body builder” genes, since these increase muscle mass without also increasing fat mass.
Conversely, the other two genetic variants increase both muscle mass and fat mass. The researchers call these “sumo wrestler” genes.
However, although all four genes increase muscle mass, the health effects of each are very different.
“For now, the fact that we now understand better how genetics regulates the body’s composition of muscle and fat is primarily of academic interest. But knowing about the genetic variants that affect the body’s muscle mass will hopefully enable us to influence them in the future in a health-promoting direction,” explains an author, Tuomas Kilpeläinen, Associate Professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.
The research has been published in the American Journal of Clinical Nutrition.
Hard to disentangle fat and muscle genes
Researchers are generally interested in learning more about the genetic variants that somewhat determine our weight, body fat percentage, height and muscle mass.
Genetic variants are small differences in the same genes, and these small differences can make one person become obese while another does not.
Knowledge about the genetic variants that predispose to various things can therefore also make it easier to design medicine to combat everything from obesity to muscle loss.
For a long time, however, researchers have struggled to determine which genetic variants are linked to the regulation of lean body mass.
Lean body mass is the weight of everything in the body except fat: muscles, bone, blood and other tissue. Muscles are a variable that can vary considerably from person to person.
Across a population, however, disentangling lean body mass from the quantity of body fat is difficult, since overweight people generally also have more muscle.
“The reason is largely mechanical, because larger muscles are required to carry around more weight. Therefore, when we correct our analytical models for fat mass, it reduces our ability to find genetic variants that predispose for lean body mass,” explains Tuomas Kilpeläinen.
Investigated more than 85,000 Europeans
The researchers examined the genomes of more than 85,000 people of European origin to find genetic variants that predispose to higher lean body mass.
The genetic analysis compared the body weight, lean body mass and fat mass of these people measured by two methods: bioimpedance, which measures the percentage of body fat (fat conducts current worse than muscle because muscle contains more water), and DXA scanning, which uses X-rays to identify the body's various components, including muscle, fat and bone.
The researchers then used two analytical models to analyse the data: one corrected for fat mass and the other did not.
The researchers then compared the results from the two models and disentangled the genetic variants that influence fat mass and lean body mass and those that influence only lean body mass.
Four genetic variants increase lean body mass
The results identified four genetic variants, all of which were associated with increased lean body mass.
Two of the genetic variants, VCAN and ADAMTSL3, increased only lean body mass and not fat mass (body builder genes), while two genetic variants, FTO and MC4R, increased both lean body mass and fat mass (sumo wrestler genes).
Body builder genes protect against metabolic diseases
The researchers examined the participants’ health status to find associations between these genetic variants and health. They found that the sumo wrestler genes were associated with an adverse metabolic profile.
People with these genetic variants were more likely to be obese and to develop cardiovascular diseases or metabolic diseases such as diabetes.
Conversely, the body builder genes seemed to protect against these diseases.
The researchers concluded that their findings indicate that various genetic variants can increase lean body mass, but if the gene variants also increase fat mass, the effect on health can change from being protective to being harmful.
“This finding supports the assumption that muscles promote health whereas higher body fat mass is harmful,” says Tuomas Kilpeläinen.
“Disentangling the genetics of lean mass” has been published in the American Journal of Clinical Nutrition. Tuomas Kilpeläinen is an Associate Professor at the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.
