Researchers at UC Berkeley have discovered that a reduction in neurotensin levels within the brain’s dopamine network may explain why people with obesity find less pleasure in eating. This groundbreaking study suggests that restoring neurotensin levels could enhance eating enjoyment and aid in weight management.
A study led by researchers at the University of California, Berkeley, has revealed a surprising brain mechanism behind why people with obesity may experience less pleasure from eating. This discovery offers new insights into how chronic high-fat diets affect the brain and opens exciting pathways for obesity treatments.
The study, published in the journal Nature, found that long-term consumption of high-fat food diminishes levels of neurotensin, a brain peptide involved in modulating dopamine — the “feel-good” neurotransmitter. Paradoxically, while a high-fat diet typically spurs weight gain, it simultaneously lowers the desire to eat, compounding the obesity problem.
“A natural inclination toward junk food is not inherently bad — but losing it could further exacerbate obesity,” senior author Stephan Lammel, a professor in UC Berkeley’s Department of Neuroscience, said in a news release. “A high-fat diet changes the brain, leading to lower neurotensin levels, which in turn alters how we eat and respond to these foods. We found a way to restore the desire for high-calorie foods, which may actually help with weight management.”
The team’s research utilized advanced techniques like optogenetics — which allows scientists to control brain circuits using light. They observed that neurotensin levels were significantly reduced in obese mice, disrupting the dopamine-related pleasure experienced when eating high-fat foods.
“Imagine eating an amazing dessert at a great restaurant in Paris — you experience a burst of dopamine and happiness,” added co-first author Neta Gazit Shimoni, a postdoctoral fellow at UC Berkeley. “We found that this same feeling occurs in mice on a normal diet, but is missing in those on a high-fat diet. They may keep eating out of habit or boredom, rather than genuine enjoyment.”
To probe deeper, Lammel’s team restored neurotensin levels in the obese mice through dietary changes and genetic manipulations. These alterations not only reinstated the pleasure response but also led to weight loss, decreased anxiety and improved mobility.
“Bringing back neurotensin seems to be very, very critical for preventing the loss of desire to consume high-calorie foods,” Lammel added. “It doesn’t make you immune to getting obese again, but it would help to control eating behavior, to bring it back to normal.”
The implications of this discovery are far-reaching.
For decades, obesity treatments have struggled to provide sustained results. While interventions like GLP-1 agonists (e.g., Ozempic) show some success by curbing appetite, the team’s findings suggest a complementary approach that restores the intrinsic pleasure of eating, potentially breaking the persistent cycle of overeating.
Moving forward, the researchers plan to investigate the genetic pathways that regulate neurotensin in greater detail.
“We now have the full genetic profile of these neurons and how they change with high-fat diets,” added Lammel. “The next step is to explore pathways upstream and downstream of neurotensin to find precise therapeutic targets.”
The study also has broader implications for understanding how different conditions impact eating behavior.
“The bigger question is whether these systems interact across different conditions,” Shimoni added. “How does starvation affect dopamine circuits? What happens in eating disorders? These are the questions we’re looking at next.”
Supported by a range of organizations, including the McKnight Foundation, One Mind Foundation and the National Institutes of Health, this groundbreaking work may pave the way for innovative treatments that reinvigorate the joy of eating, ultimately helping combat the global obesity epidemic.