Recent research implicated somatostatin-expressing neurons within the tuberal nucleus (SSTtn) of the hypothalamus as modulators of food intake. As feeding varies between females and males, we investigated whether SSTtn neurons exhibit functional differences across sex and the estrous cycle.
SSTtn neurons were manipulated by stereotaxic delivery of Cre-dependent viral vectors to the tuberal nucleus of female and male mice expressing Cre from the Sst locus.
Chemogenetic activation by Gq-coupled DREADDs was sufficient to increase food intake during the daytime hours in both sexes. Cell-specific ablation via a modified caspase decreased food intake in females only, indicating that SSTtn neurons are necessary to maintain food intake in females but not males. SSTtn neuronal ablation also revealed an effect of estrous cycle stage in female mice: while food intake in control females did not vary with the estrous cycle, nighttime food intake was lower in caspase females during stages of high estradiol. However, we observed limited colocalization of Sst and ERα in the tuberal nucleus of female mice, suggesting that estradiol may act elsewhere in the feeding circuit. Caspase females and males did not differ on any other metabolic measure examined.
It appears that SSTtn neurons differentially control feeding across the sexes, whereby these neurons are sufficient for food intake in both sexes but are necessary in females and dispensable in males. Ongoing studies are investigating SSTtn neurons at the cellular, circuit, system, and behavioral levels to pinpoint the sex difference in SSTtn neuron function and how they interact with feeding and estrogen-responsive circuitry.