CARDIAC LEPTIN-TRH INTERACTION IN THE LEFT VENTRICULAR HYPERTROPHY OF THE OBESE MOUSE.

MAIA AISICOVICH; PERES DIAZ LUDMILA; MARIANO L. SCHUMAN; JORGE E TOBLLI; MARÍA S. LANDA; SILVIA I GARCÍA

Mar del Plata

Congreso; XXVI Congreso Argentino de Hipertension Arterial; 2019

Sociedad Argentina de Hipertensión Arterial- International Society of Hypertension

Cardiac TRH induces left ventricular hypertrophy (LVH)and fibrosis, its inhibition prevents hypertrophy. The adiponectin leptininduces TRH in CNS. We hypothesized that in obesity, the increase of TRHinduced by hyperleptinemia is responsible for the LVH, until now mostlyattributed to  pressure load. We studied obese Agouti mice sufferinghypertension with hyperleptinemia and found LVH with increased TRH gene expression.Consequently we found higher (p<0.05) fibrotic (type I and III collagen andTGFβ) and hypertrophic markers (BNP and βMHC) vs lean (BL/6J). As pressurecould explain results, we treated obese mice with diuretic (hydroclorothiazide 20mg/kg/day) since weaning (n=9), the diuretic group was normotensive in contrastto control obese mice. Nevertheless both groups developed (p<0.05): LVH,higher cardiac TRH gene and elevated fibrotic and hypertrophic markerssuggesting that LVH is not induced by hypertension. In contrast to Agouti, westudied obese ob/ob mice lacking leptin due to a disruption in their gene. Miceare normotensive, without LVH despite their obesity. We treated 2 groups withleptin (sc. 80 ug/kg/day) or saline since weaning for 15 days. Only the grouptreated with leptin developed LVH (LV weight/tibia length, p< 0.05, n=7) vssaline, pointing out that LVH is leptin dependant. As hypothesized, in thisgroup we found an increase (p<0.05) in cardiac TRH accompanied by higherexpression of type III collagen,  TGFβand BNP suggesting that leptin-TRH interaction is required for obesity-inducedLVH. To confirm TRH's leptin induction in cardiac cells, 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 leptintreatment at both concentrations. Moreover we developed cardiomiocytes primaryculture from neonates, in which leptin stimulus (80 ng/ml, 24 hs) increased(p<0.05) TRH content vs controls confirming the direct TRH induction byleptin in heart cells.Finally, obese-induced LVH is leptin-dependent, whichprobably stimulates hypertrophy and fibrosis by its TRH induction.