Resumen:
We recently reported that the hypothalamic homeobox domain
transcription factor Bsx plays an essential role in the central nervous system control of spontaneous physical activity
and the generation of hyperphagic responses. Moreover,
we found Bsx to be a master regulator for the hypothalamic
expression of key orexigenic neuropeptide Y and agouti
gene-related protein. We now hypothesized that Bsx, which is
expressed in the dorsomedial and arcuate nucleus (ARC) of
the hypothalamus, is regulated by afferent signals in response
to peripheral energy balance. Bsx expression was analyzed
using in situ hybridization in fed vs. fasted (24 h) and ghrelin
vs. leptin-treated rats, as well as in mice deficient for leptin or
the ghrelin signaling. Ghrelin administration increased,
whereas ghrelin receptor antagonist decreased ARC Bsx expression. Leptin injection attenuated the fasting-induced increase in ARC Bsx levels but had no effect in fed rats. Dorsomedial hypothalamic nucleus Bsx expression was unaffected by pharmacological modifications of leptin or ghrelin signaling. Obese leptin-deficient (ob/ob) mice, but not obese melanocortin 4 receptor-knockout mice, showed higher expression of Bsx, consistent with dependency from afferent leptin rather than increased adiposity per se. Interestingly, exposure to a high-fat diet triggered Bsx expression, consistent
with the concept that decreased leptin signaling due to a highfat diet induced leptin resistance. Our data indicate that ARC Bsx expression is specifically regulated by afferent energy
balance signals, including input from leptin and ghrelin. Future
studies will be necessary to test if Bsx may be involved in
the pathogenesis of leptin resistance.