What is it about?
Body weight is regulated by groups of neurons in a region of the brain known as the hypothalamus. Our study found that eating high-fat foods increases an inflammatory molecule called prostaglandin E2 (PGE2) in the hypothalamus, which directly activates melanin-concentrating hormone (MCH) neurons that induce appetite and weight gain. Mice that lack certain receptors for PGE2 in MCH neurons do not become obese or get fatty liver even when eating high-fat food. Thus, our results show a direct link between hypothalamic inflammation and weight gain.
Photo by Irham Setyaki on Unsplash
Why is it important?
Inflammation in the hypothalamus is generally associated with sickness and weight loss. Therefore, it was perplexing that hypothalamic inflammation conversely causes excess weight gain. Our study provides an explanation for this conundrum by showing that PGE2, which is a key mediator of fever and weight loss during inflammatory diseases, can instead induce weight gain when it is increased by high-fat diets. This shows that reducing inflammation in the hypothalamus by targeting PGE2 signaling may be a promising path towards treatments for obesity.
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This page is a summary of: Prostaglandin E
activates melanin-concentrating hormone neurons to drive diet-induced obesity, Proceedings of the National Academy of Sciences, July 2023, Proceedings of the National Academy of Sciences,
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