Hedonic eating declines with obesity
New research published in Nature reveals that chronic exposure to high-fat diets diminishes the brain's reward response to food, reducing the pleasure associated with eating.
The study, which investigated neural mechanisms in mice, highlights the role of the neuropeptide neurotensin (NTS) in restoring hedonic feeding behaviours.
Obesity is often linked to excessive consumption of high-calorie foods due to their rewarding effects. However, researchers have discovered that prolonged high fat diets exposure weakens this pleasure response, leading to changes in feeding behaviour.
The mesolimbic dopamine system, responsible for processing food-related rewards, is significantly affected by diet. Specifically, the study focused on neural projections from the lateral nucleus accumbens (NAcLat) to the ventral tegmental area (VTA), a pathway involved in food motivation. In mice fed a high-fat diet, this pathway exhibited uncoupled neural activity, meaning their brains no longer signalled enjoyment when consuming calorie-rich foods.
Researchers found that:
Mice on an HFD showed reduced interest in palatable foods in a no-effort setting but consumed them in familiar environments, indicating a shift in food motivation.
Optogenetic stimulation (artificially activating the NAcLat→VTA pathway with light) failed to restore hedonic feeding in mice.
Returning to a regular diet over two weeks helped reinstate normal feeding behaviour and neural responses.
RNA sequencing and fluorescence-based sensors confirmed that HFDs significantly reduced neurotensin release, impairing the brain's reward system.
Neurotensin (NTS), a neuropeptide involved in feeding regulation, was identified as a crucial factor in hedonic eating. When NTS expression was restored in mice, their hedonic feeding behaviours returned, suggesting a potential avenue for treating obesity-related reward deficits.
Blocking NTS receptors in the VTA eliminated food pleasure responses, while boosting NTS signaling improved motivation, food enjoyment, and even anxiety-related behaviors. This suggests that obesity’s impact on the brain extends beyond weight gain, influencing emotional and behavioural patterns.
This research provides valuable insights into how obesity alters reward pathways and identifies neurotensin as a potential target for therapeutic interventions. If similar mechanisms exist in humans, developing treatments that restore NTS function could help address obesity-related changes in food motivation, reducing overeating driven by diminished pleasure responses.
Future studies will explore whether neurotensin modulation can be leveraged to improve weight management strategies in clinical settings.