Protein found to protect females from obesity

Mouse study reveals sex differences in obesity mechanisms.

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Obesity is increasing in the US and is linked to worse health outcomes and a lower quality of life. Over 30% of American individuals are currently considered fat. Obesity is a significant and expanding public health issue since it is a risk factor for several diseases, including diabetes, cardiovascular disease, and COVID-19.

In the United States, where over 30% of adults are considered obese, obesity is a significant public health concern. Researchers from the University of California, Riverside, discovered that female mice’s release of the immunological protein RELMalpha shields them from inflammation and fat.

Meera G. Nair, an associate professor of biomedical sciences in the School of Medicine, who co-led the study published in Life with Djurdjica Coss, a professor of biomedical sciences, said, “Our study identifies immune cells and RELMalpha in causing these sex-specific differences in the immune response to obesity.”

Mammal secreted proteins known as RELMalpha and resistin-like molecules are widely expressed in inflammatory and infectious illnesses. Following infection, the mouse body swiftly activates one of these proteins, RELMalpha, to defend the body’s tissues. Its sequence and functionality are comparable to those of human resistin.

Macrophages and eosinophils are disease-fighting white blood cells that can harm the body when not infected. Nair said, “RELMalpha regulates two immune cell types: the anti-inflammatory macrophage and the eosinophil. In contrast, males expressed less RELMalpha, had less eosinophils, and had inflammatory macrophages that promoted obesity.”

They discovered that female mice with RELMalpha deleted were no longer protected from obesity, had comparable levels of inflammatory macrophages and eosinophils to male mice, and had less eosinophils. However, by administering eosinophils or RELMalpha to these female mice, the researchers were able to reduce obesity, indicating potential therapeutic targets. This work is the first to map the female version of the route that guards against obesity.

The discovery is groundbreaking because it demonstrates a sex-dependent, hitherto unrecognized role for RELMalpha in modifying metabolic and inflammatory responses during diet-induced obesity. The findings point to a crucial ‘RELMalpha-eosinophil-macrophage axis’ that works in females to protect against diet-induced inflammation and obesity. Promoting these pathways might lead to new treatments for obesity.

The new study aimed to investigate sex differences in obesity pathogenesis and elucidate immune mechanisms underlying female-specific protection from adipose inflammation, cardiovascular disease, and metabolic syndrome.

The National Institutes of Health funded the study.

Journal Reference:

  1. Jiang Li, Rebecca E Ruggiero-Ruff, etal. Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils. eLife. DOI: 10.7554/eLife.86001
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