Association between diencephalic thyroliberin and arterial blood pressure in agouti-yellow and ob/ob mice may be mediated by leptin.
Leptin, a hormone secreted by the adipose tissue, stimulates anorexigenic peptides and also inhibits orexigenic peptides in hypothalamic arcuate nuclei-located neurons. It also counteracts the starvation-induced suppression of thyroid hormones by up-regulating the expression of preproTRH gene. On the other hand, in addition to its role as a modulator of the thyroid-hypothalamic-hypophysial axis, thyrotropin-releasing hormone (TRH) acts as a modulator of the cardiovascular system. In fact, we reported that overexpression of diencephalic TRH (dTRH) induces hypertension. We have recently shown that, in rats with obesity-induced hypertension, hyperleptinemia may produce an increase of dTRH together with an elevation of arterial blood pressure (ABP) through an increase of sympathetic activity and that these alterations were reversed by antisense oligonucleotide and small interfering RNA against preproTRH treatments. Here we explore the possible role of dTRH as a mediator involved in leptin-induced hypertension in 2 obesity mouse models: agouti-yellow mice, which are hyperleptinemic and hypertensive, and ob/ob mice, which lack functional circulating leptin. These 2 models share some characteristics, but ob/ob mice show lower ABP and plasma catecholamines levels. Then, for the first time, we report that there is a clear association between ABP and dTRH levels in both mouse models, as we have found that dTRH content was elevated in agouti-yellow mice and diminished in ob/ob mice compared with their controls. We also show that, after 3 days of subcutaneous leptin injections (10 microg/12 hours), ABP and dTRH increased significantly in ob/ob mice with no alterations of thyroid hormone levels. These results add evidence to the putative molecular mechanisms for the strong association between obesity and hypertension.
Burgueño
Adriana L
AL
Cardiología Molecular, Instituto de Investigaciones Médicas A Lanari, Universidad de Buenos Aires, Buenos Aires, Argentina.
Landa
Maria S
MS
Schuman
Mariano L
ML
Alvarez
Azucena L
AL
Carabelli
Julieta
J
García
Silvia I
SI
Pirola
Carlos J
CJ
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D004027:Diencephalon / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D020738:Leptin; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013974:Thyroxine