image: 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? New 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 just one day of consuming a high-fat diet, the neurons had increased excitability in males. 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.
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About JNeurosci
JNeurosci was launched in 1981 as a means to communicate the findings of the highest quality neuroscience research to the growing field. Today, the journal remains committed to publishing cutting-edge neuroscience that will have an immediate and lasting scientific impact, while responding to authors' changing publishing needs, representing breadth of the field and diversity in authorship.
About The Society for Neuroscience
The Society for Neuroscience is the world's largest organization of scientists and physicians devoted to understanding the brain and nervous system. The nonprofit organization, founded in 1969, now has nearly 35,000 members in more than 95 countries.
Journal
JNeurosci
Article Title
High-Fat Diet Feeding Rapidly Induces Sex-Specific Neuronal Plasticity in Lateral Hypothalamic Glutamatergic Neurons
Article Publication Date
2-Nov-2026
COI Statement
The authors declare no competing financial interests.