Artículo
Bsx, a novel hypothalamic factor linking feeding with locomotor activity, is regulated by energy availability
Autor
Nogueiras, Ruben;#0000-0002-9976-9930
LOPEZ GUERRERO, MIGUEL; 123111
Lage Fernandez, Ricardo;#0000-0002-8779-7723
Perez-Tilve, Diego;#0000-0002-0351-4133
Pfluger, Paul;#0000-0002-8118-7588
Mendieta Zerón, Hugo; 45175
Sakkou, Maria;#0000-0003-3616-3277
Wiedmer, Petra;#0000-0001-7284-7823
Benoit, Stephen;#0000-0003-3455-133X
Datta, Rakesh;#0000-0002-5695-3017
Dong, Jesse;#0000-0002-4877-852X
Culler, Michael D.;#0000-0001-5168-8739
Sleeman, Mark;#0000-0002-3329-0919
Vidal-Puig, Antonio;#0000-0003-4220-9577
Horváth, Tamás;#0000-0003-3038-8643
Treier, Mathias;#0000-0002-8751-1246
DIEGUEZ VAZQUEZ, JOSE CARLOS; 787416
Tschöp, Matthias;x1350427
Nogueiras, Ruben
LOPEZ GUERRERO, MIGUEL
Lage Fernandez, Ricardo
Perez-Tilve, Diego
Pfluger, Paul
Mendieta Zerón, Hugo
Sakkou, Maria
Wiedmer, Petra
Benoit, Stephen
Datta, Rakesh
Dong, Jesse
Culler, Michael D.
Sleeman, Mark
Vidal-Puig, Antonio
Horváth, Tamás
Treier, Mathias
DIEGUEZ VAZQUEZ, JOSE CARLOS
Tschöp, Matthias
Institución
Resumen
Es un estudio en modelos de rata acerca del papel de BSX, la actividad y la alimentación. 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.