Understanding How Brain Goo Traps Hunger Neurons and Fuels Obesity

Summary: A new study shows that the brain’s hunger switch is trapped by sticky material when fed by a high-calorie diet. This prevents insulin from reaching the hunger switch, resulting in dysregulated metabolic rate and insulin resistance. Reducing this brain goo seems to enhance insulin sensitivity, energy expenditure, and metabolic rate.

 More than one-third of adults in the US are obese and living with metabolic disorders. However, metabolic disorders are quite complex and occur due to multiple factors, which means that overcoming the condition also requires a multi-dimensional approach. Additionally, science needs to understand various factors causing metabolic disorders.

When it comes to changes in appetite, researchers have long proposed that it is due to specific brain changes occurring due to specific lifestyle choices. Many obese individuals or those living with diabetes and insulin resistance find it challenging to reduce their total calorie intake.

Now, one of the new studies shows that this is because sticky goo traps the neurons in the brain’s appetite control center. This prevents insulin from reaching those neurons. The results of the study done in animal models were published in the journal Nature.

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People become obese and develop diabetes as their bodies become insensitive to insulin. However, this insulin resistance not only occurs in peripheral tissues like skeletal muscles but also in the brain. It appears that the arcuate nucleus (AN) of the hypothalamus, which is a collection of neurons acting as a hunger switch, becomes particularly resistant to insulin, causing dysregulation of hunger sensation and energy management.

This new study in mice models shows that insulin resistance develops due to an accumulation of sticky substances around these neurons or hunger switches. This is not the first time researchers have noticed AN changes when mice were fed a high-calorie diet.

Although previous studies showed changes in AN, researchers were unsure if it has to do something with insulin resistance, too. So, in this latest study, researchers fed mice with a high-fat and high-sugar diet for 12 weeks and monitored this subset of neurons for changes.

They found that scaffolding became thicker and stickier. They found that mice also started gaining weight and developing insulin resistance as these subsets of neurons or AN or hunger switch became trapped in thicker and stickier goo.

Researchers think that this stickier goo prevents insulin from reaching AN. This means that the hunger switch progressively loses its ability to regulate insulin levels in the body when animals are continuously fed with a high-calorie diet.

Next, researchers had to confirm their hypothesis. So, they injected mice with an enzyme or fluorosamine that could digest this sticky goo. These approaches could reduce the accumulation of this sticky material, thus allowing insulin uptake by these brain cells. Consequently, animals increased their energy expenditure and started losing body weight.

Researchers say that this study again proves that changes in the hunger switch directly affect resting metabolic rate, and it drives disease. Further, they also noticed that this accumulation of sticky material around the hunger switch in the hypothalamus occurs due to inflammation. Since glial cells play a vital role in brain inflammation, researchers further need to understand their role in brain inflammation, insulin resistance, and the development of metabolic disorders.

Researchers do accept that it is still unclear what or how big this accumulation of brain goo or sticky material around hunger switch or AN plays in the development of metabolic diseases. Nevertheless, these findings open doors for further investigations, and managing this brain goo could be one of the ways to manage metabolic disorders.

Source:

Beddows, C. A., Shi, F., Horton, A. L., Dalal, S., Zhang, P., Ling, C.-C., Yong, V. W., Loh, K., Cho, E., Karagiannis, C., Rose, A. J., Montgomery, M. K., Gregorevic, P., Watt, M. J., Packer, N. H., Parker, B. L., Brown, R. M., Moh, E. S. X., & Dodd, G. T. (2024). Pathogenic hypothalamic extracellular matrix promotes metabolic disease. Nature, 633(8031), 914–922. https://doi.org/10.1038/s41586-024-07922-y