This article delves into a groundbreaking study published in Nature titled “Changes in neurotensin signalling drive hedonic devaluation in obesity.” Contrary to the common belief that indulging in junk food leads to obesity, the research presents a counterintuitive perspective: the enjoyment of food, even junk food, plays a crucial role in maintaining a healthy weight. By exploring the neural mechanisms underlying obesity, the study reveals that a decrease in neurotensin levels in the brain due to long - term high - fat diets impairs the body’s hedonic response to food, exacerbating obesity. Restoring neurotensin levels not only reignites the interest in high - calorie foods but also brings about multiple health benefits. This discovery not only offers new insights into obesity treatment but also paves the way for understanding the brain’s regulation of eating behavior, challenging existing perceptions of obesity and diet.
In today’s modern society, junk food has become omnipresent, infiltrating every corner of our daily lives. From fast - food restaurants on every street corner to vending machines in workplaces and schools, its convenience and affordability make it an easy choice for many. The dopamine - induced pleasure it provides has long been blamed as the primary culprit behind the global obesity epidemic. However, a revolutionary study published in Nature, titled “Changes in neurotensin signalling drive hedonic devaluation in obesity,” shatters this conventional wisdom, presenting a paradigm - shifting perspective that could redefine our understanding of weight management.
Obesity has emerged as one of the most pressing global health challenges of our time. According to the World Health Organization, the number of obese adults worldwide has nearly tripled since 1975, with millions suffering from obesity - related health problems such as diabetes, heart disease, and certain types of cancer. Despite widespread awareness of the detrimental effects of junk food, the allure of these high - calorie, low - nutrient foods remains strong.
Why do we find it so difficult to resist the temptation of a juicy burger or a decadent slice of cake? And perhaps even more intriguingly, why do many obese individuals seem to lose their passion for food over time, despite the body’s innate desire for pleasurable eating experiences? These puzzling questions have puzzled scientists for years, driving them to explore the complex interplay between the brain, behavior, and metabolism. This latest study finally begins to shed light on the mysterious mechanisms behind this “pleasure paradox,” offering a glimmer of hope for more effective obesity treatment.
The Crucial Role of Neurotensin in Obesity
The study’s key discovery lies in the role of neurotensin, a brain peptide that has long been overlooked in the context of obesity research. The researchers found that a long - term high - fat diet causes a significant decrease in neurotensin levels in the brains of mice. Neurotensin interacts closely with the dopamine network, a complex system of neurons responsible for regulating feelings of pleasure, reward, and motivation.
Chronic HFD promotes uncoupling of NAcLat→VTA activity during hedonic eating
Dopamine is often referred to as the “feel - good” neurotransmitter, as it is released in response to pleasurable activities such as eating, exercise, and social interaction. When neurotensin levels drop, it disrupts the normal functioning of the dopamine network, leading to a phenomenon known as hedonic devaluation.
In simple terms, this means that obese mice start to lose interest in high - calorie foods, despite their biological need for energy. This change in food preference not only affects their eating behavior but also has far - reaching consequences for their overall health, potentially contributing to further weight gain and the development of obesity - related complications.
Restoring Neurotensin: A Promising Approach to Obesity Treatment
To test the hypothesis that restoring neurotensin levels could reverse these effects, the researchers employed advanced genetic techniques to manipulate the expression of the neurotensin gene in obese mice. The results were nothing short of remarkable. Once the neurotensin levels were restored, the mice not only regained their appetite for high - calorie foods but also showed significant improvements in other aspects of their health.
Their body weight decreased steadily over time, as they began to consume more balanced diets and engage in increased physical activity. Additionally, the mice exhibited reduced levels of anxiety, as measured by various behavioral tests, and showed enhanced mobility and overall well - being. These findings suggest that targeting neurotensin could be a promising new approach to treating obesity, offering a more holistic and personalized treatment strategy that addresses both the physical and psychological aspects of the disease.
Another fascinating aspect of the study was the observation of contrasting food - seeking behaviors in obese mice. In the familiar environment of their home cages, obese mice showed a clear preference for high - fat foods over regular chow, gobbling up every last crumb with enthusiasm. However, when placed in a novel, open environment filled with a variety of high - calorie treats, their behavior changed dramatically. Instead of indulging in the feast of delicious foods, the obese mice showed little interest, barely touching the offerings. This paradoxical behavior caught the attention of the researchers, who suspected that it might be related to the disrupted neurotensin - dopamine signaling in their brains.
To investigate this further, the team utilized cutting - edge optogenetics techniques, which allow for precise control of neural activity using light. In normal - diet mice, stimulating the neural circuits connected to the dopamine network led to an immediate increase in their desire for high - calorie foods. They would actively seek out and consume more treats, driven by the heightened sense of pleasure and reward. In stark contrast, the same stimulation had no effect on obese mice.
Their lack of response suggested a fundamental impairment in the dopamine - mediated reward system, which was later confirmed by genetic sequencing analysis. The analysis revealed a significant reduction in neurotensin levels in the brains of obese mice, providing strong evidence that the decline in neurotensin is the key factor responsible for their diminished food enjoyment and altered eating behavior.
NAcLat→VTA NTS is necessary for hedonic feeding and dopamine cell excitation.
The implications of this study extend far beyond the realm of obesity research. By uncovering the intricate relationship between neurotensin, dopamine, and eating behavior, the researchers have opened up new avenues for understanding and treating a wide range of metabolic and neurological disorders. For instance, future studies could explore the role of neurotensin in diabetes, where abnormal eating patterns and insulin resistance are common symptoms. Additionally, the findings may have important implications for the treatment of eating disorders such as anorexia and bulimia, which are characterized by distorted perceptions of food and body image.
Looking ahead, the research team plans to conduct further studies to explore the long - term effects of neurotensin modulation on health and metabolism. They also aim to develop targeted therapies that can safely and effectively restore neurotensin levels in humans, without causing unwanted side effects. While there is still a long way to go before these treatments become widely available, the results of this study offer a beacon of hope for millions of people struggling with obesity and related health problems.
Conclusion
In conclusion, this groundbreaking study challenges our long - held beliefs about the relationship between food, pleasure, and obesity. It reminds us that enjoying food is not a vice but an essential part of a healthy life. By understanding the complex neural mechanisms that underlie our eating behavior, we can develop more effective strategies for managing weight and promoting overall well - being. As we continue to explore the mysteries of the brain and the body, we move one step closer to unlocking the secrets of obesity and finding a cure for this global health crisis.
References
Gazit Shimoni, N., Tose, A.J., Seng, C. et al. Changes in neurotensin signalling drive hedonic devaluation in obesity. Nature (2025). doi：10.1038/s41586-025-08748-y