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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.

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