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Previous studies have indicated that obesity affects men and women differently. Now, a new animal-based study may have found a potential explanation for why that's the case.
Researchers at the University of California, Riverside, found that, in mice, the difference could partially come down to a certain kind of immune cell, one which they found behaved differently in male and female mice.
The experts said this finding could challenge the traditionally held assumption that eosinophils, a type of white blood cell involved in fighting parasites, bacteria and allergens, are uniform between men and women, and potentially offer new possibilities for more targeted treatment.
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"The main takeaway is that biological sex plays a fundamental role in shaping how immune cells function, meaning male and female immune systems cannot be treated as identical," study author Meera Nair, a professor of biomedical sciences at the University of California Riverside, told Newsweek.
She added that immune cells like eosinophils may be "flexible" as "their function and gene expression profiles are responsive to their surrounding tissue environment, biological sex, and external factors like infections."
"Ultimately, our metabolic health is dictated by how immune cells behave inside our fat tissue, providing the opportunity to target and reprogram them for better outcomes," she said.
The study was published in the journal PNAS Nexus in November.
Research has previously identified that while women tend to show higher overall prevalence of obesity, men are more susceptible to fat accumulation deep in the abdomen (what is known as visceral fat), which increases risk of cardiovascular disease, type 2 diabetes, and other complications.
Some explanations for this have included the role the hormone estrogen plays in fat storage in women, differences in gut microbiome, as well as sociocultural factors like body image perception and healthcare-seeking behavior.
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What The Study Found
The researchers found that in the mice studied, there were six distinct clusters of eosinophils in adipose (fat) tissue, and each of the clusters had slightly different functions—some of which the experts said could protect against obesity.
Nair said that under healthy conditions, eosinophils "help ‘calm’ the fat tissue environment, controlling inflammation, and maintaining metabolic balance to protect against diet-induced obesity."
"In other words, they can be viewed as cellular caretakers who have an important job to keep inflammation at bay by co-ordinating the other cell-types in the fat tissue to function optimally, preventing metabolic and cardiovascular diseases, such as diabetes, stroke and heart attacks," she said.
She said that the findings of the study suggest that "'quality’ is maybe just as important as ‘quantity’" when it comes to eosinophils and obesity.
While female mice had a higher overall number of eosinophils in fat tissue, the researchers found they had one cluster of eosinophils which worked effectively alongside macrophages, another type of immune cell found in fat tissue, to maintain healthy metabolism.
Meanwhile, in male mice, the researchers found a cluster of eosinophils that tended to develop more when they were fed a diet high in fat, and that these populations of immune cells were pro-inflammatory.
This meant that the female mice maintained a "homeostatic immune environment that protects them against weight gain-induced inflammation and metabolic disease," Nair said, while male mice developed "inflammatory eosinophil populations and altered cell communication networks that causes tissue inflammation during obesity."
What Do The Findings Mean?
Nair said that "rather than simply trying to increase the total eosinophil count, our findings point toward targeted cellular reprogramming as a new therapeutic strategy," adding they also "highlight the necessity of sex-specific medicine."
She said that treatments could be "designed to alter the genetic programming of inflammatory eosinophils so they behave more like the protective eosinophils found in females."
While these findings were only found in mice, and have not yet been validated in human populations, previous research has identified the presence of eosinophils in human fat tissue, and that higher eosinophil count is associated with an increased likelihood of being overweight.
Dr. Caroline Apovian, the director of the Mass General Brigham Weight Center, told Newsweek that it is already understood that "women are protected from visceral body fat and inflammation via hormonal differences than men (at least until menopause)," due to estrogen.
"Fat tissue is an endocrine organ and hormones and immune cells are intimately involved in endocrine communication from fat to brain heart lungs liver in a systemic fashion," she said.
She added that this new study provides "more evidence that obesity is a disease and energy regulation is controlled by hormones that are secreted from fat tissue and other organs including sex organs, GI tract, and brain."
Reference
Rebecca E Ruggiero-Ruff, Xinru Qiu, Lauren Vance, Yuxin He, Djurdjica Coss, Adam Godzik, Meera G Nair, (2026) Single-cell heterogeneity of adipose eosinophils is shaped by sex and RELMα and linked to macrophage communication networks in obesity, PNAS Nexus. https://doi.org/10.1093/pnasnexus/pgag365
Contact Newsweek editors on this story: Kara Dolman and Paul Donnelley.
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