The global obesity epidemic is a pressing concern, affecting over a billion people [1].

Researchers at the Center for Cognition and Sociality (CCS) in the Institute for Basic Science (IBS) recently discovered the brain’s role in regulating fat metabolism.

While previous studies mainly focused on neurons in the brain concerning obesity, this study has shifted the spotlight to star-shaped non-neuronal cells called ‘astrocytes.’ [2]

Traditionally, the hypothalamus was considered the control center for managing food consumption and energy expenditure. Scientists were particularly intrigued by neurons in the lateral hypothalamus, but their exact function in fat metabolism remained unclear.

The breakthrough came when the research team identified a unique group of neurons in the hypothalamus that expressed receptors for the inhibitory neurotransmitter ‘GABA.’ This cluster, the GABRA5 cluster, played a pivotal role in weight regulation.

When these neurons fired more slowly in diet-induced obese mice, it led to weight gain. Conversely, stimulating these neurons resulted in weight loss.

Surprisingly, the study revealed that astrocytes in the lateral hypothalamus directly influenced the activity of the GABRA5 neurons. Reactive astrocytes produced an MAO-B enzyme, which generated significant GABA, inhibiting the GABRA5 neurons.

When the researchers reduced the expression of the MAO-B gene in these astrocytes, it increased energy consumption and led to weight loss in obese mice, even on high-calorie diets.

This finding suggests a potential revolutionary treatment for obesity that targets the MAO-B enzyme in astrocytes without affecting appetite. A drug named ‘KDS2010,’ a selective MAO-B inhibitor, has been developed and is undergoing clinical trials. In tests on obese mice, KDS2010 significantly reduced weight without altering food intake.

Previous obesity treatments focused on neuronal mechanisms related to appetite regulation [3]. However, this study’s emphasis on non-neuronal astrocytes offers a fresh perspective on combating obesity.

Given the World Health Organization‘s designation of obesity as a ’21st-century emerging infectious disease,’ KDS2010 holds promise as a next-generation treatment that can effectively combat obesity.

This breakthrough challenges conventional approaches and provides hope to the millions worldwide battling obesity. It marks a new chapter in understanding the intricate interplay between the brain and the body, offering a potential solution to a global health crisis.

The obesity epidemic has seen a dramatic rise in obesity rates globally, affecting both developed and developing nations.

According to the World Health Organization (WHO), obesity rates have nearly tripled since 1975, with nearly one billion adults currently classified as obese.

This epidemic is not limited to adults; there is a growing number of overweight or obese children and adolescents, leading to health complications and a higher risk of adult obesity [4].

Obesity is linked to various health problems, including heart disease, type 2 diabetes, certain cancers and respiratory and musculoskeletal disorders.

It also reduces overall life expectancy and exerts a significant economic toll on healthcare systems due to treating obesity-related diseases [5]. Additionally, it results in decreased workforce productivity and increased absenteeism.

Several factors contribute to the obesity epidemic, including dietary changes characterized by increased consumption of high-fat, high-sugar, low-nutrient foods, sedentary lifestyles due to changing transportation modes and urbanization, genetic predisposition and societal and environmental factors like limited access to healthy foods and cultural norms promoting obesity [6].

In conclusion, the discovery of the role of astrocytes in regulating fat metabolism and the development of KDS2010 as a potential treatment represent significant strides in addressing the global obesity epidemic, which continues to pose a substantial health and economic burden on societies worldwide. Understanding and combatting obesity remain crucial in promoting public health and well-being.

[1] https://www.worldobesity.org/about/about-obesity/prevalence-of-obesity
[2] https://www.nature.com/articles/s42255-023-00877-w
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111219/
[4] https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409636/
[6] https://www.ncbi.nlm.nih.gov/books/NBK278977/