Exploring sex differences in how the brain adapts to overeating

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by Society for Neuroscience

edited by Swati Mestri, reviewed by Andrew Zinin

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Top: Compared to controls (black), male mice on a high-fat diet have limited weight gain when excitatory neurons in the hypothalamus are more easily activated (red). Bottom: Female mice on a high-fat diet experience weight loss when excitatory neurons in the hypothalamus are more easily activated (red) compared to controls (black). Credit: Lu and Rossi, 2026.

Overeating alters neural pathways involved in feeding and metabolism, but how fast do these adaptive changes occur? And do these adaptations occur similarly in males and females?

In a new study in JNeurosci, Yi Lu and Mark Rossi at Rutgers University used mice to advance understanding, focusing on changes to a key neuron population that suppresses feeding and is involved in metabolism: excitatory neurons in the lateral hypothalamus.

The researchers first discovered that, at baseline, these neurons are more easily excitable in females than males. After males consumed a high-fat diet for just one day, their neurons had increased excitability. The strength of inputs targeting these lateral hypothalamic neurons changed in both males and females, but in different ways: Inputs that trigger neuron activation weakened in males and inputs that inhibit their activity were weakened in females. When Lu and Rossi artificially increased excitatory lateral hypothalamic neuron activity, this change limited weight gain during high-fat diet consumption in males and led to weight loss in females on the high-fat diet.

According to the research team, this work shows this neuron population that suppresses feeding adapts to diets high in fat differently in males and females, at least in mice. These neurons may make female mice less susceptible to obesity from overeating while limiting weight gain in males. This study may inform future work exploring whether manipulating this neuron population suppresses weight gain in males and females.

Publication details

High-Fat Diet Feeding Rapidly Induces Sex-Specific Neuronal Plasticity in Lateral Hypothalamic Glutamatergic Neurons, JNeurosci (2026). DOI: 10.1523/JNEUROSCI.0781-26.2026

Journal information: Journal of Neuroscience

Key medical concepts

Diet, High-FatWeight GainWeight Loss

Clinical categories

Weight managementNeurologyEndocrinologyHealthy living Provided by Society for Neuroscience Who's behind this story?

Swati Mestri

Swati Mestri holds a bachelor's degree in Electronics Engineering and has worked as a content editor since 2019. She has experience editing research documents across technology, health care, and materials science, and has a particular interest in technology and space. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

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