TWO TYPES OF OBESITY, AND ONE IS WORSE FOR OUR HEALTH

20 SEPT 2022

A new study splits obesity into two distinct subtypes, each with their own effects on our body’s functioning. Not only could the finding inform a more nuanced approach to diagnosing health conditions associated with weight, it could lead to more personalized ways of treating them.

At the moment, obesity is diagnosed using body mass index (BMI) measurements, but the team behind the new research says that this approach is too simplistic and risks being misleading by ignoring individual biological variations.

One of the newly identified obesity types is characterized by greater fat mass, the other by both fat and lean muscle mass. To their surprise, the researchers found the second type was associated with increased inflammation, which has been linked to a greater risk of cancer and other diseases.

“Using a purely data-driven approach, we see for the first time that there are at least two different metabolic subtypes of obesity, each with their own physiological and molecular features that influence health,” says J. Andrew Pospisilik, an epigenetics researcher studying metabolic disease at the Van Andel Institute in Michigan.

Translating these findings into a clinically usable test could help doctors provide more precise care for patients.”

The scientists tapped into data from 153 pairs of twins collected by the TwinsUK research project, coming up with four metabolic subtypes that influence body mass: two prone to leanness, and two prone to obesity.

These results were then verified in mouse models in the lab, using mice that were genetically identical, grew up in the same environment, and ate the same amount of food.

These controls suggest that something else is happening beyond those diet, surroundings, and inheritance. One likely explanation involves epigenetic markers – non-coding modifications made to DNA molecules that change how genes are read. Epigenetics is the reason why twins with the same DNA code aren’t always identical.

Our findings in the lab almost carbon copied the human twin data,” says Pospisilik.

“We again saw two distinct subtypes of obesity, one of which appeared to be epigenetically triggerable, and was marked by higher lean mass and higher fat, high inflammatory signals, high insulin levels, and a strong epigenetic signature.”

From what the researchers can tell so far, the second type of obesity – the one linked to inflammation – appears to be triggered by chance. That means these findings could also be useful in the study of what’s known as unexplained phenotypic variation (UPV), the idea that other factors beyond genetics and our environment make us who we are.

Scientists have been thinking about UPV for more than a hundred years, and this study hints at epigenetics are linked to UPV.

“Today’s findings underscore the power of recognizing these subtle differences between people to guide more precise ways to treat disease,” says Pospisilik.

If two (or more) types of obesity can be confirmed in future human validation studies, then it follows that various obesity treatments – changes in diet, for example, or weight loss surgeries – might have different effects depending on the obesity type. A whole new field of research just opened up.

Now the researchers want to study the two obesity types that they’ve identified in more detail – which further down the line could lead to guidelines that doctors can use to diagnose them differently.

Nearly two billion people worldwide are considered overweight and there are more than 600 million people with obesity, yet we have no framework for stratifying individuals according to their more precise disease etiologies,” says Pospisilik.

 

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