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Diet and lifestyle

Biomarkers can help maintain a healthy body weight

A better understanding of biomarkers holds the key to improving healthy weight management by making it more personalized and relevant. This will save many people from frustrating weight-loss processes that do not work out as planned. This is the message from Professor Eric Ravussin, who has researched the role of energy metabolism in controlling body weight for more than 30 years.

Human metabolism is essentially a converter. It converts food into energy in our bodies and ultimately determines whether we lose or gain weight. Nevertheless, the underlying mechanisms are difficult to figure out, because metabolism differs from person to person. This means that there is a very individual response to a very essential question: how much energy should we consume to stay at a healthy weight?

The answer to this question is key for research on obesity and related diseases such as type 2 diabetes and cardiovascular diseases. This was one issue discussed at the Copenhagen Bioscience Conference in October 2019 with the overall theme of Metabolism in Action.

One keynote speaker was Eric Ravussin, Professor and Associate Executive Director, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. For more than 30 years, he has been researching the role of energy metabolism in controlling body weight. In his current research, he is striving to better understand the mechanisms behind metabolism.

“Expenditure of energy is not the same as expenditure of calories, because the calories come from carbohydrate, from fat and from protein. The body regulates each of these macronutrients differently. What we have learned is that those who are low-fat burners are also likely to gain weight. The question is, what are the mechanisms behind this? This is what the science from the past 20 years has been really starting to look at,” says Eric Ravussin.

As many categories as there are people

The low-energy or low-fat burners that Eric Ravussin mentions, comprise one of two phenotypes metabolic research has identified so far: the thrifty phenotype. The second phenotype is called spendthrift and comprises people who are high-energy or high-fat burners. Eric Ravussin and his colleagues used these phenotypes as a basis for a controlled overfeeding study in which 35 people (29 men and 6 women) consumed 40% above their baseline energy requirements for 8 weeks and were then asked to come back for follow-up 6 months later.

The study showed that the subjects who had a lower-than-predicted sleeping metabolic rate – the thrifty phenotype – retained more of the fat gained during the overfeeding period, whereas the subjects with a higher-than-expected sleeping metabolic rate – the spendthrift phenotype – lost significantly more weight during the 6-month follow-up.

The results, which were published in the American Journal of Clinical Nutrition in October 2019, suggest that individual metabolic phenotypes can influence long-term regulation of body weight.

The two phenotypes can explain why people on the same diet react differently to the same restrictions in calorie intake. But the two phenotypes only explain some of the differences in people’s metabolism, and Eric Ravussin wants to understand even better the underlying mechanisms that can help explain these differences.

“We can categorize people into thrifty and spendthrift phenotypes, but this is still very crude. Instead of two categories, we should ideally have as many categories as we have people. This is what precision medicine is all about. Some strategies will be good for a proportion of people engaging in weight loss and some will not. The goal is to identify many more groups. We are certainly not there yet, but I think we can start to find groups of people who are more alike,” says Eric Ravussin.

Biomarkers can help customize treatment

Eric Ravussin and his colleagues are participating in the Molecular Transducers of Physical Activity Consortium (MoTrPAC). The aim of the project is to reveal how exercise improves and preserves the health of the body’s tissues and organs at the molecular level. The studies are examining the endurance and resistance of 3000 people in connection with exercise training. According to Eric Ravussin, the approach used in these studies should be transferred to research on nutrition and weight management.

“We perform the examinations by collecting biological samples such as blood, saliva and stool for the microbiome before, during and after exercise. We perform all the -omics you can think of – genomics, transcriptomics, lipidomics and metabolomics – and look at the variability in those molecular responses to exercise. Based on these results, we can identify biomarkers. We should do the same thing when it comes to management of weight, so we can understand the molecular transducers of the response in different people,” explains Eric Ravussin.

He emphasizes the importance of finding and understanding relevant biomarkers for maintaining a healthy weight. Researchers must currently get people to fast or overfeed them to determine whether they have a thrifty or spendthrift phenotype. Using simpler biomarkers such as blood, saliva or hair samples would enable identification and subsequent treatment to be more custom designed for individual needs and preferences.

“There is a lot of interindividual variability. Some people are going to lose weight easily, and some have great difficulty. Some people prefer a low-fat diet and some a low-carbohydrate or ketogenic diet. This sells books but frustrates many people because they do not know how to manage it. I think we need to move towards more personalized medicine and identify potential responders to the different types of diets and interventions. I see the research moving towards precision medicine where we can really use biomarkers to decide which strategy would be better for a specific person to follow,” elaborates Eric Ravussin.

Let data be the driver of discoveries

Technological development will aid the researchers in finding and using these biomarkers to enable people to maintain healthy weight. Eric Ravussin predicts that the future for this field will take a more unconventional approach to data than we are used to.

“With the technology we have now, and especially the power of digital data analysis, we should be non-targeted: we should be totally agnostic and open to any data that come out. We should go from educated guesses to a non-targeted blind approach. Let the data drive what we are going to discover,” concludes Eric Ravussin.

Metabolic adaptation is not observed after 8 weeks of overfeeding but energy expenditure variability is associated with weight recovery” has been published in the American Journal of Clinical Nutrition. The Copenhagen Bioscience Conferences are a series of scientific conferences within biomedicine and biotechnology. The Conferences bring together some of the world’s top researchers and young talent to discuss the latest scientific results and hottest topics within a particular field. The purpose of the Conferences is to enable participants to build an international network and relationships and to exchange knowledge and ideas.

Eric Ravussin
Boyd Professor, Director, Douglas L. Gordon Chair in Diabetes and Metabolism
Dr. Ravussin is a world expert in the conduct of translational research in obesity and type 2 diabetes. Over his more than 30 year career, he has conducted numerous clinical investigations on measures of energy expenditure, body composition, carbohydrate metabolism and biomarkers of aging in health and disease states. More specifically over the past 15 years he has established a wet lab studying skeletal muscle and adipose tissue cross talks and the relationship of these two tissues on inflammation, nutrient partitioning and insulin sensitivity. He has published more than 450 peer reviewed manuscripts in the field of obesity, type 2 diabetes and aging. He has mentored more than 60 postdoctoral fellows. Over the past 10 years he has conducted translational research on the impact of caloric restriction on biomarkers of aging, looked at the impact of weight loss and weight gain (overfeeding) in the cross talk between adipose and skeletal muscle and has conducted randomized clinical trial on the impact of dietary, activity, surgical and pharmacological interventions on insulin sensitivity.