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Une mesure précise de l’activité physique en conditions de vie libre est nécessaire pour une meilleure compréhension de ses relations avec la santé. Le premier objectif de ce travail thèse a été de valider l’Actiheart (qui combine la mesure de la fréquence cardiaque et du mouvement par accélérométrie) par rapport à l’eau doublement marquée (EDM). Nous montrons un bon niveau de concordance entre la dépense énergétique liée à l’activité physique (DEAP) estimée par l’Actiheart et l’EDM. Une individualisation de la relation entre la fréquence cardiaque et de la DEAP par un test d’effort est nécessaire pour une estimation fiable de la DEAP au niveau individuel et pour évaluer des changements de DEAP tels qu’induits par une intervention. En laboratoire, nous montrons que la précision de l’Actiheart est activité dépendante. Ceci nécessite la mise en place de leur reconnaissance par de nouveaux capteurs et modèles mathématiques. L’adiponectine est une hormone du tissu adipeux qui a un rôle dans le métabolisme énergétique et dont la sécrétion diminue avec l’obésité. Les effets de l’activité physique sont en revanche contradictoires dans la littérature. Le second objectif de ce travail a été d’évaluer l’effet de l’activité physique et d’une intervention avec contrôle du poids sur les taux plasmatiques d’adiponectine. Nous montrons que l’adiponectine totale et à haut poids moléculaire sont associées négativement à la variation du niveau d’activité physique. D’autres travaux sont cependant nécessaires pour comprendre les mécanismes qui sous-tendent cette modulation de l’adiponectine plasmatique qui ne semble pas liée à des variations de synthèse dans le tissu adipeux ou musculaire. / Accurate measurements of physical activity in free living are needed to establish what dose of physical activity is necessary for obtaining a specific health benefits. The first aim of this work was to validate the Actiheart (which combines heart rate and accelerometry sensors) with doubly labeled water (DLW). We show a good level of concordance between physical activity energy expenditure (PAEE) estimated by Actiheart and DLW. Individualization of the relationship between heart rate and PAEE by an incremental test is needed for an accurate estimate of the PAEE at the individual level and to evaluate changes induced by an intervention. In laboratory, we show that the accuracy of Actiheart is activitydependent. This requires the establishment of their recognition from new sensors and mathematical models. Adiponectin, hormone secreted by adipose tissue, has a role in energy metabolism and its secretion decreases with obesity. However the effects of physical activity remain in contradiction in published studies. The second objective of this work was to evaluate the effect of physical activity and intervention with weight control on plasma adiponectin. We show that the total and high molecular weight adiponectin were negatively associated with modifications of the physical activity level. Further work is however necessary to understand the mechanisms underlying this modulation of plasma adiponectin which does not seem related to changes in synthesis in adipose tissue or muscle.

La déficience partielle en lipoprotéine lipase (LPLD) est associée à une augmentation du risque cardiométabolique chez les hommes et les femmes. L’adiponectine, le syndrome métabolique et la ménopause sont des modulateurs importants de ce risque. L’objectif de cette étude était d’évaluer la contribution de l’adiponectine au profil de risque cardiométabolique de femmes porteuses de variants dans le gène LPL connus pour être associés avec la LPLD. L'échantillon étudié comprenait 568 femmes d'origine canadienne-française, dont 127 avec une LPLD et 441 non LPLD (contrôles). L'influence de l'adiponectine sur le risque associé à la LPLD a été évaluée en utilisant des analyses de régression multiples prenant en compte l’influence du statut ménopausique, des variables anthropométriques, du bilan lipidique, de la glycémie à jeun et du tabagisme. Les résultats montrent que les niveaux d'adiponectine étaient significativement plus faibles dans les groupes LPLD. La contribution des valeurs faibles d’adiponectine au profil de risque cardiométabolique des sujets LPLD était indépendante du statut ménopausique et de toutes les autres covariables étudiées. Cela suggère que l'adiponectine contribue au profil de risque cardiométabolique chez les femmes porteuses d’une mutation connue pour être associée avec la LPLD. / The cardiovascular risk significantly increases after menopause. Lipoprotein lipase (LPL) is a key enzyme in the metabolism of triglyceride (TG)-rich lipoproteins which contributes to cardiometabolic homeostasis. Adiponectin is an adipocytokine which also influences the cardiometabolic status. The objective of this study was to evaluate the contribution of plasma adiponectin to the cardiometabolic status of women carrying loss-of-function LPL gene variants (LPLD). A total of 568 French Canadian women (127 LPLD and 441 controls) were included. The association of plasma adiponectin with LPLD was assessed using multiple regression models. Cardiometabolic covariates included anthropometrics, lipids (TG, HDL-C, LDL-C, apo B), fasting glucose and smoking. Mean plasma adiponectin concentration was significantly lower in women with LPLD. Women carrying loss-of function LPL gene mutations also presented a significantly higher risk of coronary artery disease. In conclusion, these results suggest that low plasma adiponectin significantly contributes to the cardiometabolic risk profile of postmenopausal women carrying loss-of-function LPL gene mutations, independently of anthropometrics, lipids and other covariates.

Obesity is recognized as an important risk factor for the development of many chronic diseases such as hypertension, Type 2 diabetes mellitus (T2DM) cardiovascular disease, cancer, renal disease, neurologic dysfunction, metabolic syndrome and asthma (3, 4). Circulating serum adiponectin levels in obese asthmatics have been reported to be low. Therefore, we aimed to investigate the role of adiponectin in a mucus hypersecretion model and hypothesized that adiponectin would decrease IL-13 induced MUC5AC expression from differentiated NHBE cells and that increasing concentrations of IL-13 would cause a decrease in Adipo R1 and Adipo R2 expression. MUC5AC expression with exposure to adiponectin was not significant. However, mRNA expression of Adipo R1 and Adipo R2 was significantly decreased by stimulation of IL-13 for acute (24 hours) and chronic (14 days) exposure. Therefore, the obese state and specifically IL-13 concentration could play a role in Adipo R1 and Adipo R2 expression within NHBE cells.

Le récepteur éboueur CD36 facilite l’internalisation des acides gras libres non estérifiés (AGNE) au niveau des tissus cardiaque et périphériques. Lors d’une ischémie-reperfusion du myocarde (MI/R), les dommages produits sont en partie liés à l’internalisation des AGNE et à la production d’espèces réactives de l’oxygène, contrairement à ce qui est observé chez des souris déficientes en CD36 (CD36-/-). Nous avons émis l’hypothèse selon laquelle le CP-3(iv), un ligand synthétique du récepteur CD36, exercerait un effet cardioprotecteur en réduisant la taille de la zone myocardique infarcie lors d’une ischémie transitoire du myocarde. Nos objectifs étaient 1) de déterminer l’effet cardioprotecteur du CP-3(iv) et 2) de définir son mécanisme. Pour cela, des études in vivo et ex vivo ont été faites. Des souris de type sauvage ont été traitées avec le CP-3(iv) (289 nmol/kg) par voie sous-cutanée pendant 14 jours avant d’être soumises à 30 minutes d’ischémie suivant la ligature de l’artère coronaire gauche descendante et de sa reperfusion pendant une période de 6 ou 48 heures. De plus, des coeurs isolés de souris ont été perfusés 30 minutes, suivi de 40 minutes à faible débit (10%) et de 30 minutes de reperfusion pendant laquelle le coeur est perfusé avec le CP-3(iv) à une concentration de 10-6 M. Nos travaux ont montré que l’effet cardioprotecteur d’un traitement préventif par le CP-3(iv) permet de diminuer la taille de l’infarctus et préserve l’hémodynamie cardiaque de façon dépendante du CD36 puisque cet effet est non visible chez les souris CD36-/-. De plus, le CP-3(iv) exerce non seulement un effet systémique, mais aussi un effet cardioprotecteur direct sur le coeur isolé. / The scavenger receptor CD36 facilitates the internalization of non-esterified fatty acids (NEFA) on cardiac and peripheral tissues. During myocardial ischemia and reperfusion (MI/R), the damage induced is in part related to the internalization of NEFA and the production of reactive oxygen species, in opposition to what is observed in CD36-deficient mice (CD36-/-). We hypothesized that CP-3(iv), a synthetic ligand of the CD36 receptor, provides a cardioprotective effect by reducing the infarct area during a transient myocardial ischemia. Our objectives were 1) to determine the cardioprotective effect of CP-3(iv) and 2) to define its mechanism. For this, in vivo and ex vivo studies have been done. Wild-type mice were treated with CP-3(iv) (289 nmol/kg) subcutaneously during 14 days before being submitted to 30 minutes of ischemia following left anterior descending coronary artery ligature and reperfusion for a period of 6 to 48 hours. In addition, isolated mouse hearts were perfused 30 minutes, followed by 40 minutes with low flow (10%) and 30 minutes of reperfusion during which the heart is perfused with CP-3(iv) at a concentration of 10-6 M. Our work has shown that the cardioprotective effect of preventive treatment with CP-3(iv) reduces the infarct size and preserves cardiac hemodynamics in a CD36-dependent manner because this effect is not visible in CD36-/- mice. In addition, CP-3(iv) not only exerts a systemic effect, but also a direct cardioprotective effect on the isolated heart.

O tecido adiposo é considerado não somente uma fonte de energia estocável, mas principalmente um órgão endócrino que secreta várias citoquinas, as quais podem contribuir para o desenvolvimento de doenças relacionadas à obesidade, incluindo o diabetes mellitus e a doença vascular aterosclerótica. Dentre esse pool de moléculas, a adiponectina (Arcp30, AdipoQ, apM1, ou GBP28), uma nova proteína semelhante ao colágeno, foi descoberta como uma citoquina específica do adipócito. Neste estudo, realizamos a determinação dos níveis séricos da adiponectina em uma amostra de pacientes hospitalizados com SCA e, posteriormente, avaliamos a associação com os eventos cardiovasculares no seguimento clínico. Método: avaliamos 114 pacientes com SCA de ambos os sexos neste estudo de corte transversa com seguimento clínico mediano de 18 meses. Realizamos análise de regressão multivariada de Cox para identificar associação independente entre adiponectina e o risco subsequente de óbito CV, IAM não-fatal, AVE não-fatal, e rehospitalização com revascularização. Também comparamos os diversos biomarcadores metabólicos, inflamatórios, de coagulação e de necrose miocárdica por quartis de adiponectina. Resultados: Adiponectina não correlacionou-se de modo independente com o risco CV, tanto na análise univariada quanto nos modelos de Cox. Das variáveis metabólicas, a única com valor preditivo para os desfechos primário e co-primário foi a glicemia de jejum, com OR ajustado=1,06 (IC95% 1,01-1,11), p=0,016, e OR ajustado=1,10 (IC95% 1,03-1,17), p=0,003, ambos para incrementos de 10 na glicemia de jejum. Conclusões: Adiponectina não se mostrou variável independente de risco cardiovascular nesta amostra de pacientes com SCA. A glicemia de jejum foi a única variável metabólica com valor preditivo independente para os desfechos cardiovasculares. / Background: The adipose tissue is considered not only an energy resource stock, but mainly an endocrine organ that secretes several cytokines, which may contribute to the development of diseases related to obesity, including diabetes mellitus and the atherosclerotic vascular diseases. Within this pool of molecules, adiponectin (Arcp30, AdipoQ, apM1, or GBP28), a novel protein similar to collagen, was discovered as an adipocyte-specific cytokine. In this study, we determined the serum levels of adiponectin in a sample of patients hospitalized with acute coronary syndromes (ACS), and subsequently we evaluated the association with the cardiovascular events during the follow-up phase. Methods: we evaluated 114 patients with ACS of both genders in this cross-sectional study with a median follow-up of 18 months. We performed a proportional multiple regression analysis of Cox to identify independent association between adiponectina and risk of cardiovascular death, non-fatal acute MI, non-fatal CVA, and rehospitalization requiring revascularization. We also compared the various biomarkers of metabolism, inflammation, coagulation, and of myocardial necrosis divided by quartiles of adiponectin. Results: Adiponectin did not correlate independently with CV risk, either on univariate analysis or on the multiple regression models of Cox. Among the metabolic biomarkers, the only variable with predictive value for the primary and co-primary endpoints was fasting glucose, with an adjusted OR=1,06 (95%CI 1,01-1,11), p=0,016, and adjusted OR=1,10 (95%CI 1,03-1,17), p=0,003, both for increments of 10. Conclusions: Adiponectin was not an independent risk factor for cardiovascular risk in this sample of ACS patients. Fasting glucose was the only metabolic biomarker with a significant and independent predictive value for cardiovascular outcomes.

A obesidade é tida como o principal preditor para o desenvolvimento da apnéia obstrutiva do sono (AOS). Tanto a obesidade, como a AOS estão associadas a maior prevalência de doenças cardiovasculares e alguns fatores comuns às duas doenças são considerados como responsáveis por esta ligação, como o aumento no stress oxidativo, do tônus simpático e da resistência à insulina. Para o tratamento da AOS, o uso do CPAP é a principal escolha, melhorando a qualidade do sono destes indivíduos. No entanto, os efeitos fisiológicos sobre outras variáveis vêm sendo bastante pesquisados nos últimos anos. Dessa forma, o objetivo do presente trabalho foi verificar o efeito do CPAP sobre o stress oxidativo e níveis de adiponectina em pacientes obesos portadores de AOS. Foram estudados pesquisa 29 pacientes, classificados como obesos (IMC = 30kg/m2), do sexo masculino, com idade entre 25-70 anos, divididos em 3 grupos: a) Grupo I: 10 indivíduos sem AOS (índice apnéia-hipopnéia-IAH = 5), que não tiveram AOS diagnosticada após a realização da polissonografia; b) Grupo 2: 10 portadores de AOS de moderada a grave (IAH = 20) que não fizeram o uso do CPAP, por não se adaptarem ao aparelho ou por terem optado pelo tratamento cirúrgico, após o prazo de 2 meses; c) Grupo 3: 9 portadores de AOS de moderada a grave (IAH = 20) que fizeram o uso do CPAP. Foram pacientes com indicação, acesso e adaptação (no mínimo 4h por noite, durante dois meses) ao CPAP. O grupo 3 apresentou diferenças significativas antes e após o uso do CPAP, nas seguintes variáveis: redução na produção de superóxido [13,2 (10,3-19,6) vs. 10,5 (5,8-11,8) nmoles O2- /2x106 PMN] e aumento na síntese de nitritos e nitratos séricos [24,5 (16,7-33,5) vs. 49,5 (39,3-58,1) uM] e nos níveis plasmáticos de adiponectina [4,4 (4,2-5,6) vs. 5,3 (4,4-6,1) ug/mL]. Também foram verificadas correlações positivas entre a produção de superóxido e o índice apnéia-hipopnéia (IAH) (r= 0,726154; p= 0,000431), entre os níveis de nitritos e nitratos séricos e de adiponectina (r= 0,68809886; p= 0,001127), entre a produção de superóxido e o HOMA-IR (r= 0,833409; p= 0,000009), entre o entre o IAH e o HOMA-IR (r= 0,8570778; p= 0,000002). Foram observadas correlações negativas entre o índice IAH e os níveis de nitritos e nitratos séricos (r= -0,867078; p= 0,000002), entre a produção de superóxido e de óxido nítrico (r= -0,92733221; p= 0,000000), entre a produção de superóxido e os níveis de adiponectina (r= -0,77373778; p= 0,000102), entre o IAH e os níveis de adiponectina (r= -0,70782095; p= 0,000698) entre a os níveis de nitritos e nitratos séricos e o HOMA-IR (r= -0,813984; p= 0,000002). De acordo com os resultados do presente trabalho, podemos concluir que: a) Os indivíduos obesos portadores de AOS apresentam aumento na produção de superóxido, redução nos níveis de nitritos e nitratos séricos e adiponectina, e resistência à insulina; b) As alterações na produção de superóxido, nos níveis de nitritos e nitratos séricos e de adiponectina e a resistência à insulina presentes na obesidade, são agravadas pela apnéia obstrutiva do sono e c) O uso do CPAP é capaz de melhorar as elevações na produção de superóxido, as reduções nos níveis de nitritos e nitratos séricos e adiponectina e as alterações metabólicas presentes nos pacientes obesos portadores de AOS. / Obesity is viewed as the main factor for the obstructive sleep apnea (OSA) development. Obesity and the OSA are both associated with the major cardiovascular illnesses prevalence and certain common factors they are considered responsible for, such as the stress oxidative increase, the sympathetic tonus and the resistance to insulin. For the OSA treatment, CPAP usage is the first choice in enhancing these individuals sleeping quality. Meanwhile, the physiological effects on other variables are being actively searched for these last years. Thus, the objective of this paper was to check CPAP effect on oxidative stress and the adiponectin levels in obese patients with OSA. Twenty nine male patients considered obese (BMI = 30kg/m2) and between the ages of 25-70 were analyzed, then divided into 3 groups: a) Group I: 10 OSA free patients (apnea-hipopnea index (AHI) = 5), after a polysomnography diagnostic; b) Group 2: 10 with moderate to serious OSA (AHI = 20) and CPAP free usage for failure to adapt to the machine or, for having chosen surgical treatment after two months; c) Group 3: 9 with OSA from moderate to serious (AHI = 20) using CPAP. They were patients with sign, access and adaptation (in minimum 4 hours/night, during 2 months) to CPAP. Significant differences were observed in group 3, before and after CPAP usage in the following variables: reduction of superoxide production [13,2 (10,3-19,6) vs. 10,5 (5,8-11,8) n moles O2- /2x106 PMN] and increase in serum nitrite/nitrates levels [24,5 (16,7-33,5) vs. 49,5 (39,3-58,1) ug/mL] and the adiponectin plasmatic levels [4,4 (4,2-5,6) vs. 5,3 (4,4-6,1) ug/mL]. Positive correlations between superoxide production and Apnea-Hypopnea Index (AHI) (r= 0,726154; p= 0,000431) were verified, as well as between serum nitrite/nitrates levels and adiponectin levels (r= 0,68809886; p= 0,001127); superoxide production and HOMA(IR) (r= 0,833409; p= 0,000009); AHI and HOMA(IR) (r= 0,8570778; p= 0,000002). Negative correlations were observed between AHI and serum nitrite/nitrates levels (r= -0,867078; p= 0,000002); superoxide and serum nitrite/nitrates levels (r= -0,92733221; p= 0,000000); superoxide production and adiponectin levels (r= -0,77373778; p= 0,000102); AHI and adiponectin levels (r= -0,70782095; p= 0,000698); serum nitrite/nitrates levels and HOMA(IR) (r= -0,813984; p= 0,000002). According to our results we can conclude that: a) obese individuals with OSA have superoxide production, serum nitrite/nitrates levels and adiponectin reduction, and resistance to insulin; b) alterations in superoxide production, serum nitrite/nitrates levels, adiponectin and the resistance to insulin present in obesity, are all worsen by the sleep obstructive apnea; c) CPAP usage can improve rises in superoxide production, reductions serum nitrite/nitrates levels and adiponectin, and the metabolic alterations present in obese patients with OSA.

Perivascular adipose tissue (PVAT) and vascular endothelial cells both have important structural and functional roles in blood vessels and are the focus of this doctoral thesis. Firstly, PVAT has been rediscovered as an endocrine organ, releasing vasorelaxing substances. Secondly, the endothelial monolayer functions as an important barrier, the role of which is to restrict the transfer of molecules or even blood-borne cells between the lumen of the blood vessel and the surrounding tissue. In my main study, the presence of PVAT caused 'anti-contractile' effects, which were reversed by nitric oxide synthase (NOS) inhibition in rat mesenteric arteries and were lost in adiponectin-knockout mice. The β3 adrenoceptor agonist CL-316,243 increased PVAT-dependent anti-contractile effects and caused myocyte hyperpolarisation. Hyperpolarisation to CL-316,243 could be mimicked by the adipokine, adiponectin, and by the 5'AMP kinase (AMPK) activator, A-769662. In addition, the AMPK inhibitor, dorsomorphin, and the selective BKCa channel blocker, iberiotoxin, each blocked hyperpolarisations to CL-316,243, adiponectin and A-769662. The anti-contractile effects of CL-316,243 could also be mimicked by A-769662 but were not blocked by dorsomorphin. Moreover CL-316,243 still had anti-contractile effects in adiponectin-knockout mice. However, inhibiting the production of both NO and hydrogen peroxide reduced anti-contractile effects of CL-316,243. In obese Sprague Dawley rats both the hyperpolarising and the anti-contractile effects to CL-316,243 were impaired, while hyperpolarisation to A-769662 were unchanged. Western blots revealed that NOS, a possible downstream target of AMPK, was phosphorylated in PVAT control samples, a form which was decreased in PVAT from obese rats. These results collectively indicate that the anti-contractile and hyperpolarising effects observed following stimulation with CL-316,243 are due to activation of different PVAT-dependent pathways, both of which probably contribute to vasodilatation in blood vessels. Understanding these pathways is crucial for the development of improved treatments for obesity and hypertension. During my work at Novartis, I found that activation of sphingosine-1-receptors type 1 (S1P1) with the activator FTY720 (Fingolimod, Novartis; used in multiple sclerosis treatment) caused closure of the endothelial barrier in human umbilical vein cells. This effect could be mimicked with a recombinant peptide of nectin, an adherens junction protein. The novel S1P1 antagonists 'A1' and 'A2' (Novartis) inhibited the effect of FTY720, but not those of nectin. The discovery of nectin as a potential barrier closure modulator might contribute to the development of additional treatments for use in multiple sclerosis.

Η αντιπονεκτίνη και οι υποδοχείς αντιπονεκτίνης, AdipoR1 και AdipoR2, αποτελούν συστατικά στοιχεία των ενεργειακών ομοιοστατικών μηχανισμών στους περιφερικούς ιστούς. Σύμφωνα με πρόσφατες μελέτες, η αντιπονεκτίνη φαίνεται, επιδρώντας σε κεντρικά νευρωνικά κυκλώματα, να συμμετέχει στη ρύθμισης πρόσληψης τροφής και κατανάλωσης ενέργειας. Σκοπός της παρούσας μελέτης ήταν η διερεύνηση της πιθανής έκφρασης και της κατανομής της αντιπονεκτίνης και των υποδοχέων της στην ανθρώπινη υπόφυση, στον υποθάλαμο και σε άλλες περιοχές του ανθρώπινου εγκεφάλου. Τομές υπόφυσης, υποθαλάμου και της παρακείμενης βασικής τηλεγκεφαλικής περιοχής, εγκεφαλικού φλοιού και παρεγκεφαλίδας μονιμοποιημένες σε ουδέτερη φορμόλη και εγκλεισμένες σε παραφίνη, από σαράντα περιστατικά, μελετήθηκαν ιστολογικά με τη χρήση ηωσίνης-αιματοξυλίνης, και των ειδικών χρώσεων PAS-orange G και luxol fast blue-cresyl violet. Εν συνεχεία, εφαρμόσθηκε απλή και διπλή ανοσοϊστοχημική μέθοδος, χρησιμοποιώντας ειδικά αντισώματα έναντι της αντιπονεκτίνης, του AdipoR1 και AdipoR2, της ακετυλομεταφοράσης της χολίνης, της FSH, LH, TSH, GH, ACTH και προλακτίνης. Ο μέσος όρος (± SD) ηλικίας και δείκτη μάζας σώματος (ΒΜΙ) των υπό εξέταση περιπτώσεων ήταν 56 (±18) έτη και 27 (±5) kg/m2, αντίστοιχα. Έντονη έκφραση της αντιπονεκτίνης παρατηρήθηκε στον πρόσθιο λοβό (pars distalis/PD) της υπόφυσης και στο χοανικό δακτύλιο (pars tuberalis/PT). Ειδικότερα, ισχυρή ανοσοϊστοχημική χρώση για την αντιπονεκτίνη παρατηρήθηκε στα κύτταρα που παράγουν GH, FSH, LH , TSH και FSH, LH, TSH, στον πρόσθιο λοβό και στο χοανικό δακτύλιο αντίστοιχα.. Στο PD, ισχυρή έως μέτρια έκφραση του AdipoR1 και AdipoR2 ανιχνεύθηκε στους ίδιους κυτταρικούς τύπους στους οποίους εντοπίσθηκε και η αντιπονεκτίνη. Δεν παρατηρήθηκε ανοσοθετικότητα για τους υποδοχείς της αντιπονεκτίνης στα κύτταρα του ΡT. Έντονη ανοσοϊστοχημική χρώση για τον AdipoR1 παρουσίασαν οι νευρώνες της πλάγιας υποθαλαμικής περιοχής και του βασικού πυρήνα του Meynert (NBM). Η έκφραση της αντιπονεκτίνης και των υποδοχέων της στην ανθρώπινη υπόφυση ενδεχομένως αποτελεί μία ένδειξη της ύπαρξης ενός τοπικού ρυθμιστικού συστήματος, το οποίο ασκεί τροποποιητικές δράσεις στους ενδοκρινικούς άξονες. Επιπρόσθετα, η παρουσία του AdipoR1 στον υποθάλαμο και στο NBM υποδεικνύει ότι η αντιπονεκτίνη μπορεί να 118 συμμετέχει σε κεντρικά νευρωνικά σηματοδοτικά μονοπάτια, ελέγχοντας την ενεργειακή ομοιόσταση και άλλες εγκεφαλικές λειτουργίες. / Adiponectin and its receptors, AdipoR1 and AdipoR2, constitute integral components of energy homeostatic mechanism, in peripheral tissues. Recent studies have implicated adiponectin in central neural networks regulating food intake and energy expenditure. The present study aimed at investigating the possible expression and distribution of adiponectin and its receptors in human pituitary gland, hypothalamus and different brain areas. Sections of the pituitary gland, hypothalamus and adjacent basal forebrain area, cerebrum and cerebellum from forty autopsy cases, were examined using H&E, PAS-Orange G, luxol fast blue/cresyl violet stains and single and double immunohistochemistry using adiponectin, AdipoR1, AdipoR2, choline acetyltransferase, FSH, LH, TSH, GH, ACTH and prolactinspecific antibodies. Age and BMI mean values ± SD of the autopsy cases were 56±18 years and 27±5 kg/m2, respectively. Strong adiponectin expression was observed in pituitary gland. In pars distalis (PD), adiponectin localized in GH, FSH, LH and TSH-producing cells and in pars tuberalis (PT) in FSH, LH and TSH-producing cells. Strong to moderate expression of AdipoR1 and AdipoR2 was observed in PD by the same cell types as adiponectin. No immunoreactivity for adiponectin receptors was noted in cells of PT. Intense AdipoR1 immunostaining was observed in neurons of lateral hypothalamic area and of nucleus basalis of Meynert (NBM). Adiponectin and its receptors expression in human pituitary might indicate the existence of a local system, modulating endocrine axes. Furthermore, the presence of AdipoR1 in hypothalamus and NBM suggests that adiponectin may participate in central neural signaling pathways controlling energy homeostasis and higher brain functions.