The metabolome is the sum of all the small-molecule chemicals found in a biological sample, often the blood plasma. These chemicals include fatty acids, amino acids, sugars, and vitamins, to name a few. The metabolome changes in response to interactions between the genome and the environment. Those who study metabolomics say its poised to become an important part of personalized medicine, along with genomics, proteomics, and analysis of the microbiome.
In the current study, the investigators used data from TwinsUK, a multiyear study examining the genetic and environmental influences on human health and aging. They analyzed body and metabolic measures from nearly 2,000 adult twins that had been collected at three time points over an average of 13 years. They also used data from a single time point for 427 volunteers. They found that about one-third of the metabolites included in the study were associated with changes in BMI.
“For most people, we found the metabolome is tied very closely to weight and BMI,” Telenti explains. “Every time someone gains or loses a pound, their metabolome changes. Its almost linear.” But at the same time, he adds, “correlating well is not the same as correlating perfectly, and thats where this work became very interesting.”
“There have been studies before of individuals whose BMI doesnt match their metabolic health, but this is a new way of defining who is metabolically healthy,” says first author Liz Cirulli, a research scientist at Human Longevity Inc. “All across the weight spectrum, we found people who were heavier or lighter than expected based on their metabolome.” These differences were found in a range of metabolites linked to various diseases.
A surprising finding was that genetics didnt correlate nearly as closely as expected. Differences in genetics between obese and non-obese populations didnt show patterns that were distinct enough to be predictive. The exception was with a few particular genes known to be connected with extreme obesity, such as mutations in MC4R. This gene is known to play a critical role in regulating food intake and energy balance.
Telenti stresses that the metabolome tests developed for this paper are still an academic development, and much more research is needed before they can be validated and established for clinical use. But eventually, the hope is that it will be possible for someone to get a comprehensive analysis of all the metabolites in their body with one blood test, rather than the battery of tests thats currently part of a standard physical exam.
Cirulli says that future work will look at defining metabolic signatures for other traits, including blood pressure and android/gynoid ratios—a measure of different types of body fat. In addition, she explains, “Its important to collect additional longitudinal data in bigger cohorts to see what the long-term health consequences of different metabolic states are.” Explore further: Study identifies processes in the gut that drive fat build-up around the waist
Our society seems to have accepted that gaining weight is an inevitable consequence of growing up in a place with easy access to calories and where physical activity plays a declining role in our professional and private lives. Aging just makes weight loss even more difficult.
In the short term, the consequences of excess weight seem remote or unimportant; a problem of aesthetics, a minor limitation in mobility. But it may eventually lead to higher rates of diabetes and heart disease, and present a significant challenge for enjoying an active lifestyle.
My own work and that of my collaborators here and in the UK shows that obesity is more than just some more fat under the skin – it is a true modification of our metabolism.
It alters the way we process nutrients and modifies the chemical reactions that sustain our existence.
Our most recent work, published in Cell Metabolism, examined the consequences of obesity on our metabolism.
My colleagues and I undertook this project because we recognized that there are many types of obesity – each one has different consequences for each persons health. This is what we call disease heterogeneity. If we understand heterogeneity, we can personalize obesity treatments, hopefully with more success.