A recent study conducted by the University of California, Berkeley, sheds light on the paradoxical relationship between obesity and the pleasure derived from food consumption. Researchers have identified a potential cause for the decreased enjoyment of eating in obese individuals: a decline in neurotensin, a brain peptide associated with the dopamine network, crucial for experiencing pleasure.
UC Berkeley researchers investigated the impact of diet on the brain’s response to high-fat foods. Their study suggests that the chronic consumption of high-calorie foods diminishes desires for such foods, which could exacerbate weight gain. Stephan Lammel, a professor in the Department of Neuroscience at UC Berkeley, explains, “A natural inclination toward junk food is not inherently bad — but losing it could further exacerbate obesity.”
Their research indicates that the drop in neurotensin within a specific brain region might explain why people with obesity find less pleasure in eating. By restoring neurotensin levels through dietary adjustment or genetic methods, the researchers saw a revival of food enjoyment and potential aid in weight management. “A high-fat diet changes the brain,” Lammel stated, “leading to lower neurotensin levels, which in turn alters how we eat and respond to these foods.”
Collaborators Neta Gazit Shimoni and Amanda Tose, under Lammel’s senior authorship, contributed to the study, which is published in Nature. They note that while mice on high-fat diets preferred high-fat foods over normal chow, their interest waned when offered high-calorie treats outside their normal environment. This behavior diverges from mice on regular diets, which consume these treats readily, according to findings reported by Gazit Shimoni.
Using optogenetics, the team demonstrated that high-fat diet mice saw reduced effects of dopamine stimulation, undermining their motivation for high-calorie foods. Lammel states, “Neurotensin is this missing link. Normally, it enhances dopamine activity to drive reward and motivation. But in high-fat diet mice, neurotensin is downregulated.”
Restoring neurotensin returned normal feeding motivation and reduced anxiety in mice. However, maintaining healthy eating behavior becomes crucial as direct neurotensin restoration could trigger side effects. The researchers are now targeting specific genes and pathways to regulate neurotensin more precisely without adverse effects. “The next step is to explore pathways upstream and downstream of neurotensin to find precise therapeutic targets,” Lammel explained.
The research, supported by several foundations and the National Institutes of Health, sets a potential path for new obesity treatments. It also opens avenues for studying neurotensin’s role in other conditions like diabetes and eating disorders.
For more details on the research and related studies, visit the Nature journal or the Stephan Lammel lab website.
