Researchers at this facility have made a significant discovery in rats, uncovering an age-related change in specific neuron structures that contribute to increased calorie intake and metabolic dysfunction by suppressing satiation feedback. By manipulating this mechanism through diet and genetics, the research team observed varying rates of weight gain and metabolic abnormalities in older rats. While this finding sheds light on the proximate cause of metabolic regulation issues, the deeper mechanisms of aging, such as chronic inflammation and mitochondrial dysfunction, remain unclear in their relation to this discovery.
As we age, the propensity for overweight and obesity increases, making individuals more vulnerable to chronic diseases like diabetes and hyperlipidemia. Previous studies have suggested that middle-age weight gain stems from a decline in overall metabolism due to aging, though the specific mechanism was unknown. One key player in metabolism and appetite regulation is the melanocortin-4 receptor (MC4R), which detects overnutrition and prevents obesity by stimulating metabolism and curbing food intake in response to signals from melanocortin.
In a research endeavor, the team utilized a specific antibody to visualize MC4Rs and found them exclusively present in primary cilia of certain hypothalamic neurons in rat brains. Their subsequent investigation into the length of MC4R+ cilia in 9-week-old (young) and 6-month-old (middle-age) rats revealed a significant shortening in middle-aged rats, resulting in reduced metabolism and fat-burning capacity compared to their younger counterparts.
Furthermore, the team studied the effects of different diets on MC4R+ cilia length, noting that cilia shortened with age on a normal diet, accelerated on a high-fat diet, and slowed on a restricted diet. Intriguingly, MC4R+ cilia were regenerated in rats under two months of dietary restriction after disappearing with age. By using genetic technologies to shorten MC4R+ cilia in young rats, the team observed increased food intake, decreased metabolism, and subsequent weight gain.
Overall, this research sheds light on the neural regulation of metabolism and appetite in aging rats, providing valuable insights into the mechanisms underlying age-related metabolic changes. For more information, refer to the provided link: https://www.eurekalert.org/news-releases/1037463.
