Cardiac Hypertrophy in obesity: Leptin-TRH interaction.

AISICOVICH MAIA; PERES DIAZ LUDMILA; SCHUMAN, MARIANO LUIS; TOBLLI, J; LANDA, MARIA SILVINA; GARCÍA SILVIA INES

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

SAIC

Cardiac Hypertrophyin obesity: Leptin-TRH interaction.Maia Aisicovich, Ludmila Pers Diaz,  Mariano Schuman, Jorge Toblli, Maria S Landa ySilvia García.Cardiac TRH induce leftventricular hypertrophy (LVH) and fibrosis, its inhibition prevent hypertrophy.Theadiponectin leptin induces TRH in CNS. We hypothesized that in obesity, theincrease of TRH induced by  hyperleptinemia is responsible of the LVH,until now mostly attributed to  pressure load. We studied obese Agoutimice suffering hypertension with hyperleptinemia and found LVH with increasedTRH gene expression. Consequently we found higher (p<0.05) fibrotic andhypertrophic markers vs lean (BL/6J). As pressure could explain results wetreated obese mice with diuretic (hydroclorothiazide 20 mg/kg/day) from weaning(n=9), the diuretic group was normotensive in contrast to control obese mice.Nevertheless both groups developed (p<0.05): LVH, higher TRH gene andelevated fibrotic and hypertrophic markers suggesting that LVH is not inducedby hypertension. In contrast to Agouti, we studied obese Ob/Ob mice lackingleptin due to a disruption in their gene. Mice are normotensive, without LVHdespite their obesity. We treated 2 groups with leptin (sc. 80 ug/kg/day) orsaline from weaning for 15 days. Only the group treated with leptin developedLVH (LV weight/tibia length, p< 0.05, n=7) vs saline, pointing out that LVHis leptin dependant. As hypothesized, in this group we found an increase(p<0.05) in cardiac TRH accompanied by higher expression of type IIIcollagen suggesting that leptin-TRH interaction is required for obesity-inducedLVH. To confirm cardiac cells TRH´s leptin induction, cardiomyocytes derivedcell line H9C2 (n=6) was stimulated with leptin (10 and100 ng/ml). TRHexpression (rt-PCR) and peptide (WB) were increased (p<0.05) post leptin atboth concentrations. Moreover we developed cardiomiocytes primary culture fromneonates, in which leptin stimulus (80 ng/ml, 24 hs) increased (p<0.05) TRHcontent vs controls confirming the direct TRH induction by leptin in heartcells. Finally, obese-induced LVHis leptin-dependent, who probably stimulates hypertrophy and fibrosis by itsTRH induction.