Search

International audience; We have studied the effects of proton source acidity and exchange duration at T=330°C. Surface SHG has shown that middle acidity is of great interest.

Estrogen receptors (ER) are used as therapeutic targets, either for contraception or for the hormonal replacement therapy in menopausal women, but also in physiopathology for breast cancer treatment. It is therefore important to understand the tissue-specificity of the actions of ERα to optimize the benefits/risks ratio in each tissue. Besides the conventional nuclear ERα acting as a transcription factor, many studies have demonstrated that ERα is also able to mediate extra nuclear signaling, enabling rapid actions of estrogen. Recently, new transgenic mouse models were used to study these effects, and allowed to genetically segregate membrane versus nuclear actions of a steroid hormone receptor, demonstrating their in vivo tissue-specific roles.

The APJ receptor cloned in 1993 found its ligand in 1998 with the discovery of apelin. The presence of APJ in the central nervous system (more particularly in the hypothalamus) and in various tissues (heart, blood vessels, stomach, etc.) makes it a potential pharmacological target. Interest in APJ has allowed the development of peptidic molecules able to stimulate and/or inhibit the receptor and, more recently, to discover another endogenous ligand: apela. Among the functions regulated by the APJ/apelin system, the control of energy metabolism appears today in the forefront. A better understanding of the pharmacology of APJ receptor should allow innovative therapeutic approaches in the treatment of metabolic diseases.

Communication orale ; http://www.lesjfn.fr

Obesity is characterized by an excessive development of fat mass which is a consequence of increased fat cell size and/or fat cell number. Several hormones and neurotransmitters are regulators of adipose tissue development and metabolism. Among them, catecholamines play a major role by acting through alpha 2- and beta-adrenergic receptors. Stimulation of alpha 2-adrenergic receptors induce inhibition of lipolysis in mature adipocytes as well as preadipocyte proliferation. The antilipolytic effect mediated by alpha 2-adrenergic receptors is in part responsible for the weak lipid mobilization of some fat deposits in humans (subcutaneous fat in particular). Changes in beta- and alpha 2-adrenergic receptors ratio and function have been proposed to explain the lipolytic disturbances described in some obese subjects. Human and rodent adipocytes differ considerably with respect to the balance between beta- and alpha 2-adrenergic receptors. Human adipocytes express mainly alpha 2- but very few beta 3-adrenergic receptors while the reverse is true for rodent adipocytes. Since no suitable animal model was available to study the contribution of alpha 2/beta-adrenergic balance in adipocytes in vivo, we combined gene targeting and transgenic approaches to create a mice with increased alpha 2/beta-adrenergic ratio in adipose tissue. Specifically, we have generated transgenic mice strains on a beta 3-adrenergic receptor knock-out background which express human alpha 2-adrenergic receptors. No particular phenotype was observed in mice maintained in normal diet whereas when fed a high fat diet, transgenic mice increased significantly body weight and fat mass. These results underline the physiologic relevance of the interaction of the presence of alpha 2-adrenergic receptors with a high fat diet in the control of adipose tissue development.

Aging is associated with a cell cycle arrest mechanism named senescence. In adipocyte, this cell state could contribute to metabolic alterations as well as a low-grade inflammatory state. In this context, visceral white adipose tissue could play a major role in age-associated setup pathologies through the loss of metabolic control. Indeed, during aging, white adipose tissue undergoes functional and morphological modifications progressively leading to altered storage and endocrine capacities. Consequently, it has been hypothesized that a new emerging adipocyte secretory profile associated with aging (SASP for senescence associated secretory phenotype) could actively participate to the progressive onset of metabolic diseases related to aging. By proteomic analysis, we identified haptoglobin as a new proinflammatory cytokine overproduced by murine adipose tissue during aging. Our results showed a regulatory feedback loop between adipocyte haptoglobin and senescence state arguing for a role of the cytokine in aging process. Moreover, haptoglobin induced adipocyte metabolic alterations in vitro targeting lipolysis and insulin sensitivity. In vivo validation of haptoglobin's role on metabolic-induced aging are currently ongoing. Our study will allow a better understanding of haptoglobin's role in age-related adipose tissue loss of function and will pave the road for a new therapeutic strategy in the field of metabolism and age-associated pathologies., Le vieillissement est associé un mécanisme d'arrêt du cycle cellulaire nommé senescence. Au niveau de l'adipocyte, cet état cellulaire semble contribuer à la survenue d'altérations métaboliques et à un état pro-inflammatoire. Dans ce contexte, le tissu adipeux blanc viscéral pourrait jouer un rôle déterminant sur la perte du contrôle métabolique et ainsi participer à l'installation de pathologies associées au vieillissement. Au cours du vieillissement, le tissu adipeux blanc subit des modifications morphologiques et physiologiques conduisant à une altération progressive des fonctions de stockage et endocrines de l'adipocyte. Ainsi, un nouveau profil sécrétoire pro-inflammatoire appelé SASP (Senescence Associated Secretory Phenotype) a pu être mis en évidence et pourrait être impliqué dans la survenue de différentes pathologies liées à l'âge (diabète, insuffisance cardiaque ou rénales, ...). Dans ce sens, l'analyse précise du SASP d'adipocytes issus de souris de différents âges nous a permis d'identifier une cytokine pro-inflammatoire, l'haptoglobine, comme un nouveau candidat potentiellement impliqué dans les désordres métaboliques et inflammatoires associés au vieillissement. Nos premiers résultats montrent que, via une boucle de régulation, la senescence augmente la production d'haptoglobine adipocytaire et que réciproquement., cette production entretien la senescence de l'adipocyte Au niveau fonctionnel, l'haptoglobine altère les principales fonctions adipocytaires métaboliques telles que la lipolyse et la sensibilité à l'insuline. Des expériences sont en cours afin de confirmer in vivo l'importance de cette adipocytokine sur les altérations métaboliques entrainant une accélération du vieillissement de l'organisme. Cette étude permettra de mieux comprendre la participation de l'haptoglobine dans la perte des fonctions du tissu adipeux afin de développer de nouvelles stratégies thérapeutiques pour ralentir les processus de vieillissement.