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Scientists identify two different subtypes of obesity
A team led by scientists at the Van Andel Institute has identified two distinct types of obesity with physiological and molecular differences that can have lifelong consequences for health, disease and drug response. The findings, published today in the journal Nature Metabolism, provide a more nuanced understanding of obesity than current definitions and could one day provide more accurate ways to diagnose and treat obesity and related metabolic disorders. The study also reveals new details about the role of epigenetics and chance in health and provides insights into the connection between insulin and...
Scientists identify two different subtypes of obesity
A team led by scientists at the Van Andel Institute has identified two distinct types of obesity with physiological and molecular differences that can have lifelong consequences for health, disease and drug response.
The findings, published today in the journal Nature Metabolism, provide a more nuanced understanding of obesity than current definitions and could one day provide more accurate ways to diagnose and treat obesity and related metabolic disorders.
The study also reveals new details about the role of epigenetics and chance in health and provides insights into the connection between insulin and obesity.
Nearly two billion people worldwide are considered overweight and there are more than 600 million people with obesity, but we have no framework for stratifying individuals according to their precise causes of disease. Using a purely data-driven approach, we see for the first time that there are at least two distinct metabolic subtypes of obesity, each with their own physiological and molecular characteristics that influence health. Translating these findings into a clinically useful test could help physicians provide more precise care to patients.”
J. Andrew Pospisilik, Ph.D., chair of the Department of Epigenetics at the Van Andel Institute and corresponding author of the study
Currently, obesity is diagnosed using body mass index (BMI), an index correlated with body fat that is generated by comparing weight and height. It's an imperfect measure, Pospisilik says, because it doesn't take into account underlying biological differences and can misrepresent a person's health status.
Using a combination of laboratory studies in mouse models and an in-depth analysis of data from TwinsUK, a groundbreaking research resource and study cohort developed in the United Kingdom, Pospisilik and his collaborators discovered four metabolic subtypes that influence individual body types: two prone to leanness and two prone to obesity.
One obesity subtype is characterized by greater fat mass, while the other was characterized by both greater fat mass and lean muscle mass. Surprisingly, the team found that the second type of obesity was also associated with increased inflammation, which can increase the risk of certain cancers and other diseases. Both subtypes have been observed in several study cohorts, including children. These findings are an important step in understanding how these different types impact disease risk and response to treatment.
After identifying the subtypes in the human data, the team verified the results in mouse models. This approach allowed scientists to compare individual mice that were genetically identical, raised in the same environment and fed the same amounts of food. The study found that the inflammatory subtype appears to result from epigenetic changes that were triggered purely by chance. They also found that there seems to be no middle ground -; The genetically identical sibling mice either grew larger or stayed smaller, with no gradient between them. A similar pattern was seen in data from more than 150 pairs of human twins, each of which was genetically virtually identical.
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"Our results in the laboratory almost copied the human twin data. We again saw two different subtypes of obesity, one of which appeared to be epigenetically 'triggerable' and was characterized by higher lean mass and fat, high inflammatory signals, high insulin levels and a strong epigenetic signature," Pospisilik said.
Depending on the calculation and the traits in question, only 30%-50% of human trait results can be linked to genetic or environmental influences. This means that half of us are controlled by something else. This phenomenon is called unexplained phenotypic variation (UPV), and it offers both a challenge and untapped potential to scientists like Pospisilik and his collaborators.
The study suggests that the roots of UPV likely lie in epigenetics, the processes that determine when and to what extent the instructions in DNA are used. Epigenetic mechanisms are the reason why people with the same genetic instructions, such as B. Twins can take on different characteristics such as eye and hair color. Epigenetics also offers tantalizing targets for precision treatment.
“This inexplicable variation is difficult to study, but the gain in deeper understanding is immense,” Pospisilik said. “Epigenetics can act like a light switch, turning genes “on” or “off,” which can promote health or, if something goes wrong, disease. Consideration of UPV does not currently exist in precision medicine, but it looks like it could be half the puzzle. Today’s results highlight the power of identifying these subtle differences between people to guide more precise ways to treat disease.”
Pospisilik hopes the team's findings will inform the development of future precision medicine strategies and lead to a version of their method that can be used in doctor's offices to better understand the health of individual patients and inform care.
Source:
Reference:
Yang, CH., et al. (2022) Independent phenotypic plasticity axes define distinct obesity subtypes. Natural metabolism. doi.org/10.1038/s42255-022-00629-2.
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