Japan Team Finds Mechanism behind Middle-Age Weight Gain

Jiji Press

17:51 JST, March 7, 2024

Nagoya (Jiji Press)—A Japanese research team has discovered a mechanism apparently behind why people gain weight easily in middle age.

Nagoya University professor Kazuhiro Nakamura and his team found in experiments using rats that primary cilia of neurons in the area of the brain known as the hypothalamus, which controls metabolism and food intake, become shorter with age.

A similar mechanism is believed to exist in humans. It is hoped that the discovery will lead to a fundamental treatment for obesity.

The results of the research will be published in the U.S. journal Cell Metabolism on Thursday.

Although a decline in overall metabolism due to aging has been cited as a cause of middle-age weight gain, no detailed mechanism had been known.

Nakamura’s team focused on melanocortin 4 receptors, or MC4Rs, found in neurons in the hypothalamus. The receptors detect excess nutrients and stimulate the metabolism.

A study of rats given an antibody developed to make MC4Rs visible found that the receptors were concentrated in primary cilia that extended from some hypothalamus neurons like antennas.

Comparisons of rats of various ages showed that the primary cilia gradually shortened with age. When the team shortened the primary cilia in rats through genetic modification, the rats displayed lower metabolism and increased food intake, resulting in weight gain.

The team also found that the primary cilia shrank faster in rats on a high-fat diet. Meanwhile, the primary cilia became shorter at a slower pace or even grew longer when rats’ diets were restricted.

“Overeating leads to the antiobesity mechanism wearing out,” Nakamura said. “By maintaining a moderate diet and not consuming too many calories, we may be able to keep the antiobesity effect even as we age.”