Brain changes linked to middle-age weight gain, study finds

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Researchers from Nagoya University and various other institutions in Japan have made a new discovery in the battle against obesity, particularly as it affects people in middle age.

Their study, focusing on rats but believed to be applicable to humans, pinpoints a significant change in brain structure as a key factor in age-related weight gain.

Published in the journal Cell Metabolism, this research sheds light on the complex relationship between our brains and our waistlines as we grow older.

At the heart of their findings is a protein known as the melanocortin-4 receptor (MC4R), which plays a crucial role in managing our metabolism and appetite.

MC4Rs are found in the primary cilia, which are tiny, antenna-like structures on certain neurons in the hypothalamus—the part of the brain that regulates hunger and energy use.

The study revealed that these primary cilia, and consequently the MC4Rs, shorten with age. This reduction appears to disrupt the body’s ability to regulate weight, leading to increased obesity risk in middle age.

Professor Kazuhiro Nakamura, the study’s lead author, believes that this mechanism is not exclusive to rats but also exists in humans.

“We hope our finding will lead to a fundamental treatment for obesity,” he stated. The implications of this research are significant, as obesity is closely linked to various chronic diseases, including diabetes and heart disease.

Previously, the prevailing theory was that middle-aged weight gain stemmed from a general slowdown in metabolism as part of the aging process. However, this new study provides a more detailed understanding of the biological changes that contribute to this phenomenon.

The research team embarked on a series of experiments to examine how the length of MC4R-containing cilia affects the body’s ability to manage weight.

They compared young rats, aged 9 weeks, with middle-aged rats, aged 6 months, and found that the cilia in the older rats were notably shorter. This was associated with a decrease in metabolism and the body’s fat-burning capabilities.

Further, the study explored how diet affects the length of these crucial cilia. Rats on a high-fat diet saw a faster shortening of the MC4R+ cilia, whereas a restricted diet slowed down the process. Remarkably, dietary restriction could even regenerate MC4R+ cilia that had shortened due to age.

An intriguing aspect of the study involved exploring the role of leptin, a hormone associated with reducing appetite.

In rats with artificially shortened MC4R+ cilia, leptin was unable to curb appetite, suggesting a link to leptin resistance—a common issue in obese patients. This resistance has long puzzled scientists, but the study’s findings offer new insights into its possible causes.

The conclusion that dietary habits can significantly impact the brain’s structure—and, by extension, its ability to regulate weight—is a pivotal finding. “Moderate eating habits could maintain MC4R+ cilia long enough to keep the brain’s anti-obesity system in good shape even as we age,” says Prof. Nakamura.

This research not only provides a better understanding of the biological underpinnings of middle-age obesity but also highlights potential pathways for prevention and treatment, emphasizing the importance of dietary choices in maintaining a healthy weight throughout life.

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The research findings can be found in Cell Metabolism.

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