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    Friday Séminaire 18/11/2016

    Friday Séminaire 18/11/2016

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    Séminaire de Eric J. BELIN de CHANTEMELE

    Invité par Sébastien Faure

    Le 18 novembre 2016

    Un séminaire sera donné par Eric J. BELIN de CHANTEMELE, Vascular Biology center, Medical College of Georgia, Augusta University.

    «Sexual dimorphism in obesity-and leptin-mediated cardiovascular disease»

    Les étudiants de médecine/pharmacie devant valider certains modules (M1 et M2) devront impérativement venir avec leur fiche personnelle de validation des séminaires qui sera alors tamponnée.

    12h00 - 13h00
    ICO site Paul Papin, amphithéâtre

     secr-inserm-angers @ contact.univ-angers.fr

    Obesity causes hypertension in males and females. While leptin contributes to obesityinduced hypertension by increasing sympathetic activity, in males, it is unknown whether similar mechanisms trigger hypertension in obese females. Females secrete 3 to 4 times more leptin than males, but do not exhibit high sympathetic tone with obesity. They however show inappropriately high aldosterone levels that positively correlate with adiposity and blood pressure (BP). We hypothesized that leptin induces hypertension by increasing aldosterone production in obese females. Hypersensitivity to leptin, in lean mice deficient in protein tyrosine phosphatase 1B (PTP1B) or high leptin levels, in obese Agouti (Ay/a) mice induced hypertension (WT: 115±2; KO: 124±2; a/a: 113±1; Ay/a: 128±7mmHg, p<0.05) but did not increase sympathetic control of BP (response to ganglionic blockade). Leptin sensitization and obesity however elevated plasma aldosterone levels and adrenal aldosterone synthase (CYP11B2) expression, in females. Chronic leptin (KO+AA: 115±5; Ay/a+AA: 114±5mmHg) or mineralocorticoid (KO+spiro:111±5; Ay/a+spiro: 121±6mmHg) receptors inhibition restored BP to baseline levels in females PTP1B KO and obese agouti mice. Leptin or leptin receptor deficiency in female ob/ob and db/db mice, abolished obesity-induced increases in adrenal CYP11B2 and plasma aldosterone while chronic leptin infusion in female mice triggered a dose-dependent increase in adrenal CYP11B2 and plasma aldosterone levels. Leptin-mediated aldosterone secretion was independent of changes in plasma angiotensin II, potassium and corticosterone (index of ACTH levels) and preserved in the presence of losartan or alpha and beta adrenergic receptors antagonists. Stimulation of human adrenocortical cells with leptin dose-dependently increased CYP11B2 expression and aldosterone production. While investigating the interaction between percentage of body fat, leptin and aldosterone levels in young healthy adult Caucasians we reported a positive correlation between adiposity and aldosterone, and between leptin and aldosterone in adult women only. Together these data suggest that leptin directly regulates aldosterone secretion and that leptin induces hypertension via aldosteronedependent mechanisms in obese females.