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.

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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.


This work represents many years of collective effort by many members of our team. In particular, Victoria Linehan discovered the key role of PGE2 in MCH activation and Lisa Fang identified its consequence on body weight regulation. We hope that our study will help inform future therapies for obesity.

Michiru Hirasawa
Memorial University of Newfoundland

Read the Original

This page is a summary of: Prostaglandin E 2 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,
DOI: 10.1073/pnas.2302809120.
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