Scientists Find Clues to Why Males and Females Respond Differently to Overeating

Could just one day of eating a high-fat diet change how the brain controls hunger and body weight? Scientists have discovered that certain brain cells respond to high-fat food within just 24 hours, with surprisingly different effects in males and females.

Published in The Journal of Neuroscience, the study conducted by researchers Yi Lu and Mark Rossi at Rutgers University investigated how high-fat diets influence brain circuits involved in appetite regulation and metabolism.

Researchers focused on a group of excitatory neurons in the lateral hypothalamus, a region of the brain involved in controlling feeding behaviour and energy balance.

These neurons help suppress food intake and regulate metabolic processes, making them important for understanding how the brain responds to excessive calorie consumption.

Using experiments in mice, researchers examined differences in neuronal activity between males and females before and after exposure to a high-fat diet.

The findings revealed that under normal dietary conditions, these neurons were more easily activated in female mice than in males.

However, after just one day of consuming a high-fat diet, the neurons became more excitable in male mice.

Interestingly, the researchers observed different changes in the signals regulating these neurons.

In males, the excitatory signals that activate the neurons became weaker, while in females, inhibitory signals that normally reduce neuronal activity became weaker.

Importantly, when researchers artificially increased the activity of these neurons, male mice gained less weight while consuming a high-fat diet.

In female mice, increasing neuronal activity actually produced weight loss despite continued consumption of the high-fat diet.

Researchers suggested that these sex-specific neural adaptations may help explain differences in how the brain responds to excess dietary fat and regulates body weight.

However, the experiments were conducted in mice, and the findings cannot yet be directly applied to humans.

REFERENCE: Lu, Y., & Rossi, M. A. (2026). High-fat diet feeding rapidly induces sex-specific neuronal plasticity in lateral hypothalamic glutamatergic neurons. The Journal of Neuroscience. DOI: 10.1523/JNEUROSCI.0781-26.2026.