Endocrinology
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In the brain of medaka (Oryzias latipes), a teleost fish, we recently found that the supracommissural/posterior nuclei of the ventral telencephalic area (Vs/Vp) and the magnocellular/gigantocellular portions of the magnocellular preoptic nucleus (PMm/PMg) express estrogen receptor (ER) and androgen receptor (AR) specifically in females. This finding led us to postulate that sex steroid hormones might induce gene expression unique to females in these nuclei. In the present study, we searched for genes differentially expressed between the sexes in the medaka brain and identified the gene encoding neuropeptide B (npb) as being female-specifically expressed in Vs/Vp and PMm/PMg. ⋯ Subsequent analyses provided evidence that the female-specific expression of npb in Vs/Vp and PMm/PMg results from the reversible and transient action of estrogens secreted from the ovary and that this estrogenic action is most likely mediated by the direct transcriptional activation of npb through an estrogen-responsive element in its proximal promoter region. Vs/Vp and PMm/PMg are generally recognized in teleost fish as the sites where neurons expressing 2 other neuropeptides, isotocin and vasotocin, are present, but the female-specific npb/ER/AR-expressing neurons were distinct from, although adjacent to, isotocin and vasotocin neurons. Taken together, these data demonstrate that npb is female-specifically expressed in novel, as-yet undefined populations of Vs/Vp and PMm/PMg neurons, resulting from the direct stimulatory action of ovarian estrogens via female-specific ER in these neurons.
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The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with interscapular BAT morphologic abnormalities and thermogenic dysfunction. ⋯ Brown fat dysfunction and age-related assimilation of fat mass were accelerated in mice in which OX-producing neurons were ablated. Conversely, OX injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.
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Although IGF-1 has been implicated in mediating hypersensitivity to pain, the underlying mechanisms remain unclear. We identified a novel functional of the IGF-1 receptor (IGF-1R) in regulating A-type K(+) currents (IA) as well as membrane excitability in small trigeminal ganglion neurons. Our results showed that IGF-1 reversibly decreased IA, whereas the sustained delayed rectifier K(+) current was unaffected. ⋯ Functionally, we observed a significantly increased action potential firing rate induced by IGF-1; pretreatment with 4-aminopyridine abolished this effect. Taken together, our results indicate that IGF-1 attenuates IA through sequential activation of the PI3K- and c-Raf-dependent ERK1/2 signaling cascade. This occurred via the activation of IGF-1R and might contribute to neuronal hyperexcitability in small trigeminal ganglion neurons.
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Variants in the fat mass- and obesity-associated (FTO) gene are associated with obesity and body fat mass in genome-wide association studies. However, the mechanism by which FTO predisposes individuals to obesity is not clear so far. First mechanistic evidence was shown in Fto-negative mice. ⋯ The up-regulation of UCP-1 in FTO-deficient adipocytes resulted in enhanced mitochondrial uncoupling. We conclude that FTO deficiency leads to the induction of a brown adipocyte phenotype, thereby enhancing energy expenditure. Further understanding of the signaling pathway connecting FTO with UCP-1 expression might lead to new options for obesity and overweight treatment.