Gaby
Weight gain as we age is so common worldwide that it has almost become a cliché. The average person at 50 years old gains about 15 extra pounds.
A recent study by researchers from Nagoya and Osaka Universities in Japan has shed light on why we tend to gain weight as we get older. The team claims that significant changes in the shape of neurons in the part of the brain responsible for appetite and metabolism may be a key factor in this weight gain.
Researchers consider this topic highly significant, given that age-related weight gain poses numerous health risks, ranging from type 2 diabetes to cardiovascular diseases, as reported by ScienceAlert.
While poor diet and a sedentary lifestyle certainly play a major role in midlife weight gain, scientists also warn that losing weight becomes significantly more challenging as we age.
How the Study Was Conducted
The team focused on the neurons in a part of the brain known as the hypothalamus, as well as a protein called the melanocortin-4 receptor (MC4R). This receptor plays a crucial role in slowing down energy expenditure relative to energy intake, thus controlling appetite and regulating metabolism. The researchers were curious: what if the cellular dynamics of this receptor correlate with metabolic changes, particularly age-related weight gain?
The team tested their hypothesis on laboratory rats. They administered antibodies designed to isolate MC4R proteins. The scientists identified tiny projections—known as primary cilia—on both sides of certain hypothalamic cells that contain the MC4R protein.
Then came the most intriguing part. The researchers compared the levels of MC4R in the brains of young and adult rats and found differences in the shape of hypothalamic neurons, particularly in the length of the cilia. As the rats aged, these projections gradually shortened and virtually disappeared in many older and heavier rodents.
To determine the relationship between the disappearing cilia and diet, the team raised the test rats on different types of food. The rodents that consumed higher amounts of fat experienced a faster reduction in the length of their hypothalamic neuron cilia compared to those that ate a low-fat diet.
In the next phase of the study, the scientists turned to genetic engineering and artificially reduced the length of the cilia in the hypothalamus of young rats. As a result, these rodents ate more and burned less fat, leading to an increase in their body weight.
This weight gain occurred even with injections of the hormone leptin, which suppresses appetite. Thus, MC4R emerged as a critical link in the chain of appetite control.
What the Team Reported
“This phenomenon, known as leptin resistance, is often observed in patients with excess weight. It poses a barrier to obesity treatment. Until recently, the reason for weight gain was unknown,” noted Manami Oya, a co-author of the study from Nagoya University.
The research showed that in individuals aged 40 to 50, the shape of hypothalamic neurons changes—their cilia significantly shorten, while the content of MC4R steadily declines. As a result, individuals gain weight. The team emphasized that a person’s inclination toward fatty foods guarantees rapid weight gain in midlife, which, unfortunately, is quite difficult to shed.
On the other hand, a habit of moderate eating can help delay the shortening of cilia with the MC4R protein for a considerable time. A proper diet helps the brain resist obesity even in middle age, noted senior author Kazuhiro Nakamura from Nagoya University.
The results of the study were published in the journal Cell Metabolism.
