We might finally grasp why weight loss methods, such as exercise, often don’t succeed for all individuals with obesity
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Understanding obesity is proving to be more complex than previously recognized, with various types potentially stemming from different biological mechanisms.
“It transcends just body mass index and physical appearance; it delves into the biology driving it and its connection to health risks,” says Akl Fahed from the Broad Institute in Cambridge, Massachusetts.
The World Health Organization defines obesity as accumulating fat that poses a health threat. Determining if someone is obese involves calculating their Body Mass Index (BMI), which compares weight to height.
Since not all individuals with obesity experience health issues, some researchers have recently suggested introducing a “preclinical” obesity category. This approach separates individuals with medical complications related to excess fat, such as breathing difficulties or heart conditions, from those who currently show no symptoms but may develop them in the future. Yet, according to research by Fahed and his team, these classifications are still evolving.
The scientists executed genome-wide association studies involving over 2 million obese individuals, seeking connections between genetics and metrics such as BMI, waist circumference, waist-to-hip ratios, and hip circumference across diverse ancestry. They identified 743 genetic regions linked to obesity, with 86 of them being novel discoveries.
Subsequently, researchers investigated which tissues showed obesity-related effects from genetic alterations in these regions, focusing on processes like insulin production, the hormone that regulates blood sugar levels. They found that these genes fall into 11 distinct clusters, each linked to a unique biological pathway.
The pathways include: metabolically unhealthy obesity, metabolically healthy obesity, and six types associated with insulin secretion, immune system regulation, appetite control, body weight management, and lipid metabolism.
The team designates these clusters as “endotypes” rather than “subtypes” to highlight that while subtypes are typically mutually exclusive, endotypes reflect identifiable biological mechanisms that can coexist in individuals with varying impacts.
Using data from over 48,000 individuals, the researchers validated their endotypes through the Mass General Brigham Biobank.
“Clearly, there are numerous forms of obesity,” states Frank Greenway of Louisiana State University in Baton Rouge. Some obese individuals may not lose weight even with GLP-1 medications like Ozempic or Wegovy.
Gaining a deeper understanding of obesity and its various forms might refine our approach to treatment. “Recognizing the diverse types of obesity may lead to more targeted interventions and personalized care,” says Laura Gray from the University of Sheffield, UK.
Six of the 11 endotypes relate to insulin regulation, suggesting that some interventions might be effective across multiple clusters, according to team member Min Seo Kim at the Broad Institute.
The findings could reshape our understanding of research exploring the interplay of genetics and lifestyle in obesity, traditionally regarded as a singular condition, potentially influencing future research methodologies, Kim remarks.
Gray suggests that there may exist more than 11 endotypes. This figure was constrained by the genetic regions currently known to affect obesity, she notes. Kim shares this sentiment, expressing the likelihood of discovering additional endotypes as genetic research progresses.
Conversely, Henriet Kirchner from the University of Lübeck in Germany believes there could be fewer than 11 endotypes. She emphasizes the need for further replication of these findings in the scientific community to enhance understanding. “The concept of obesity clusters is appealing, but it must be refined in the future to be beneficial in clinical settings,” she states.
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Source: www.newscientist.com
