157 results on '"Spinedi E"'
Search Results
2. Editorial: Hypothalamic obesity: Today and future
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van Santen, H.M., primary, Spinedi, E., additional, and Muller, H.L., additional
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- 2022
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3. Editorial: Hypothalamic obesity: Today and future
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Endocrinologie patientenzorg, Brain, Child Health, Cancer, van Santen, H M, Spinedi, E, Muller, H L, Endocrinologie patientenzorg, Brain, Child Health, Cancer, van Santen, H M, Spinedi, E, and Muller, H L
- Published
- 2022
4. Bilateral adrenal enucleation-induced changes in adenohypophyseal pro-opiomelanocortin (POMC)-related peptides synthesis and secretion: A comparative study with adrenalectomized rats
- Author
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Perone, M. J., Chisari, A. N., Dumm, C. L. Gómez, Spinedi, E., and Estivariz, F. E.
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- 1997
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5. Posters
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Yao, Y. M., Tian, H. M., Liang, H. P., Yu, Y., Lu, L. R., Wang, Y. P., Sheng, Z. Y., Reith, H. B., Holzheimer, R. G., Thiede, A., Galstian, G. M., Danilina, A. V., Gorodetsky, V. M., Tutelian, A. V., Galley, H. F., Webster, N. R., Djugehev, A. N., Fomin, M. D., Satalkin, A. A., Sokolov, V. A., Maskin, B., Fontán, P., Spinedi, E., Badolati, A., Endo, S., Kasai, T., Inada, K., Takakuwa, T., Yamada, Y., Suzuki, T., Taniguchi, S., Kern, H., Wittich, R., Schaffartzik, W., Kox, W., Spies, C., Ilkka, L., Takala, J., Paiva, J. A., Sousa-Dias, C., Bodas, A., Ramos, J. P., Candeias, J., Pereira, A. C., Torrinha, F., Ribeiro, T., Milting, K., Sanft, C., Brede, K., Beller, S., Andresen, M., Dougnac, A., Letelier, L. M., Díaz, O., Laterre, F. F., Reynaert, M., Valdivieso, A., Geppert, A., Zorn, G., Huber, K., Siostrzonek, P., Oberhoffer, M., Bögel, D., Meier-Hellmann, A., Vogelsang, H., Reinhart, K., Tsidemiadou, F., Farmakis, M., Bobota, A., Pragastis, D., Bilancia, R., Posca, A., Margiotta, D., Spampani, E., Roselli, P., Caputo, G., Thio, J. M., Sinaasappel, M., Ince, C., Berger, D., Boelke, E., Hiki, N., Poch, B., Beier, A., Graf, M., Seidelmann, M., Beger, H. G., Nuvials, X., Ruiz Rodriguez, J. C., Martin, M. C., Esteban, F., Garcia-Allut, J. L., Burgueno, M. J., Mourelle, M., Monasterio, J., Angles, A., Boveda, J. L., Salgado, A., Segura, R. M., Sauri, R., Beck, B., Schimmer, R. C., Pasch, T., Ward, P. A., Gruson, D., Hilbert, G., Roux, C., Coulon, V., Juzan, M., Laffort, P., Parrens, E., Gualde, N., Gbikpi-Benissan, G., Cardinaud, J. P., Shi, Hanping, Xu, Renbao, Gao, Han, Marenović, T., Miloŝević, D., Brkan, Z., Ŝurbatović, M., Gundelach, K., Engelmann, L., Pilz, U., Werner, M., Reiger, J., Tatzber, F., Oberbichler, A., Grimm, G., de Abreu, M. Gama, Kirschfink, M., Quintel, M., Albrecht, D. M., Ragaller, M., Nakae, H., Koike, S., Mavrommatis, A., Theodoridis, Th., Stavropoulos, G., Zakynthinos, S., Orfanidou, A., Sfyras, D., Christopoulou-Kokkinou, V., Roussos, Ch., Właszczyk, A., Adamik, B., Zimecki, M., Kübler, A., Berezowicz, P. S., Vasilcov, V., Kelina, N., Gengin, M., Mitroshina, S., Filippova, L., Levachova, O., Gürlich, R., Maruna, P., and Čermák, J.
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- 1996
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6. Testis Structure and Function in a Nongenetic Hyperadipose Rat Model at Prepubertal and Adult Ages
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França, L R., Suescun, M O., Miranda, J R., Giovambattista, A, Perello, M, Spinedi, E, and Calandra, R S.
- Published
- 2006
7. Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats
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Moreno, G, Perelló, M, Camihort, G, Luna, G, Console, G, Gaillard, R C, and Spinedi, E
- Published
- 2006
8. Sexual Dimorphism of Neuroendocrine-Immune Interactions
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Spinedi, E., primary, Gaillard, R., additional, and Chisari, A., additional
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- 2001
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9. Cytokines, Leptin, and the Hypothalamo-Pituitary-Adrenal Axis
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GAILLARD, R. C., SPINEDI, E., CHAUTARD, T., and PRALONG, F. P.
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- 2000
10. The Hypothalamo-Pituitary-Adrenal Axis of Athymic Swiss Nude Mice: The Implications of T Lymphocytes in the ACTH Release from Immune Cellsa
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GAILLARD, R. C., DANEVA, T., HADID, R., MULLER, K., and SPINEDI, E.
- Published
- 1998
11. Neonatal androgenization-induced early endocrine metabolic and ovary misprogramming in the female rat
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Ongaro, Luisina, Salvetti, N., Giovambattista, Andrés, Spinedi, E., and Ortega, H.
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Ciencias Biológicas ,Biología Celular, Microbiología ,PCOS ,glucocorticoid ,sex steroids ,glucose load ,leptin - Abstract
Aim: Androgen excess predisposes the organism to develop metabolic-endocrine and reproductive dysfunctions, among them the development of a phenotype resembling that ofhumanPolycystic Ovary Syndrome(PCOS).METHODS: We analyzed the impact of a single neonatal (5day-old)testosterone propionate(TP; s.c. 1.25mg/female pup) dose on: a) several metabolic-endocrine activities and b) ovarian steroidogenic and granulosacell(GC) functions and also follicular population in juvenile and adult TP and control (CT)rats. Key Findings: Compared to CTrats, TPanimalswere characterized by: a) acceleratedgrowth, hyperadiposity and hyperleptinemia, b) very early (pre-weaning age) vaginal opening, c)hyperinsulinemiain adult life, d) dysfunctional ovariansteroidogenesis, e) conserved GC functionality in both juveniles (in vitro) and adults (in vivo), and f)estrous cyclesarrested atestrus. Finally, histological studies of the ovaries indicated that in TP (vs. CT)rats: i) primary and antral follicle frequencies were 3- and 15-fold higher and lower, respectively, in juveniles and ii) secondary and atretic follicle frequencies were 3- and 5-fold lower and higher, respectively, in adults. Large cystic images without corpus luteum were observed in the ovaries from adult TPratsonly. Significance: Our results strongly suggest that transient neonatal hyperandrogenemia induced early misprogramming of metabolic-endocrine and ovarian (steroidogenesis/folliculogenesis) functions. Conversely, TPratspreserved their ovary GC endocrine function. Our results further support the high risk of developingovarian hyperstimulation syndromeforinfertilewomen with transient/chronic hyperandrogenemia (PCOS) subjected to assisted reproductive technologies.
- Published
- 2015
12. Angiotensin II and glucocorticoid release: Direct effect at the adrenal level and modulation of the adrenocorticotropin-induced glucocorticoid release
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Spinedi, E., Aguado, L., Basilotta, G., and Carrizo, D.
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- 1989
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13. 20. Effect of aging on 24-h pattern of stress hormones and leptin in rats
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Rios-Lugo, J., primary, Cano, P., additional, Cardinali, D.P., additional, Spinedi, E., additional, and Esquifino, A.I., additional
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- 2009
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14. Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats
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Moreno, G, primary, Perelló, M, additional, Camihort, G, additional, Luna, G, additional, Console, G, additional, Gaillard, R C, additional, and Spinedi, E, additional
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- 2005
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15. Sex- and stress-steroids interactions and the immune system: evidence for a neuroendocrine-immunological sexual dimorphism
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Gaillard, R.C., primary and Spinedi, E., additional
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- 1998
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16. Transient sex-related changes in the mice hypothalamo–pituitary–adrenal (HPA) axis during the acute phase of the inflammatory process
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Daneva, T., primary, Spinedi, E., additional, Hadid, R., additional, Jacquier, M.-C., additional, Giacomini, M., additional, and Gaillard, R. C., additional
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- 1993
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17. Effects of gonadectomy and sex hormone therapy on the endotoxin-stimulated hypothalamo-pituitary-adrenal axis: evidence for a neuroendocrine-immunological sexual dimorphism.
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Spinedi, E, primary, Suescun, M O, additional, Hadid, R, additional, Daneva, T, additional, and Gaillard, R C, additional
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- 1992
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18. Sexual Dimorphism of Neuroendocrine-Immune Interactions.
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Spinedi, E., Gaillard, R., and Chisari, A.
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- 2002
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19. The Hypothalamo-Pituitary-Adrenal Axis of Athymic Swiss Nude Mice: The Implications of T Lymphocytes in the ACTH Release from Immune Cellsa.
- Author
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GAILLARD, R. C., DANEVA, T., HADID, R., MULLER, K., and SPINEDI, E.
- Published
- 1998
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20. ENDOTOXEMIA AND LIVER RESECTION WITH TOTAL VASCULAR EXCLUSION (TVE).
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De Paula, J. A., Spinedi, E., Argibay, P., Pekolj, J., Moscone, C., Bonofiglio, C., Ciardullo, M., and De Santibañes, E.
- Published
- 1996
21. Redox potential of the small intestine lumer in a model of experimental hemorrhage in rats
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Paula, J.A.D., Spinedi, E., Dubin, A., Bustos, D., and Davolos, J.
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- 2001
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22. Dexamethasone Inhibits White Adipose Tissue Browning.
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Giordano AP, Gambaro SE, Alzamendi A, Harnichar AE, Rey MA, Ongaro L, Spinedi E, Zubiría MG, and Giovambattista A
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- Rats, Animals, Obesity metabolism, Adipogenesis, Dexamethasone pharmacology, Thermogenesis, Adipose Tissue, Brown metabolism, Adipose Tissue, White metabolism
- Abstract
White adipose tissue (WAT) regulates energy balance through energy storage, adipokines secretion and the thermogenesis process. Beige adipocytes are responsible for WAT thermogenesis. They are generated by adipogenesis or transdifferentiation during cold or β3-adrenergic agonist stimulus through a process called browning. Browning has gained significant interest for to its preventive effect on obesity. Glucocorticoids (GCs) have several functions in WAT biology; however, their role in beige adipocyte generation and WAT browning is not fully understood. The aim of our study was to determine the effect of dexamethasone (DXM) on WAT thermogenesis. For this purpose, rats were treated with DXM at room temperature (RT) or cold conditions to determine different thermogenic markers. Furthermore, the effects of DXM on the adipogenic potential of beige precursors and on mature beige adipocytes were evaluated in vitro. Our results showed that DXM decreased UCP-1 mRNA and protein levels, mainly after cold exposure. In vitro studies showed that DXM decreased the expression of a beige precursor marker ( Ebf2 ), affecting their ability to differentiate into beige adipocytes, and inhibited the thermogenic response of mature beige adipocytes ( Ucp-1 , Dio2 and Pgc1α gene expressions and mitochondrial respiration). Overall, our data strongly suggest that DXM can inhibit the thermogenic program of both retroperitoneal and inguinal WAT depots, an effect that could be exerted, at least partially, by inhibiting de novo cell generation and the thermogenic response in beige adipocytes.
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- 2024
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23. Role of Spexin in White Adipose Tissue Thermogenesis under Basal and Cold-Stimulated Conditions.
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Gambaro SE, Zubiría MG, Giordano AP, Castro PF, Garraza C, Harnichar AE, Alzamendi A, Spinedi E, and Giovambattista A
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- Animals, Humans, Male, Mice, Adipose Tissue, White metabolism, Mice, Inbred C57BL, Uncoupling Protein 1 metabolism, Adipose Tissue, Brown drug effects, Adipose Tissue, Brown physiology, Cold Temperature, Thermogenesis drug effects, Thermogenesis physiology, Peptide Hormones pharmacology, Peptide Hormones physiology
- Abstract
Spexin (SPX) is a novel adipokine that plays an emerging role in metabolic diseases due to its involvement in carbohydrate homeostasis, weight loss, appetite control, and gastrointestinal movement, among others. In obese patients, SPX plasma levels are reduced. Little is known about the relationship between SPX and white adipose tissue (WAT) thermogenesis. Therefore, the aim of the present study was to evaluate the role of SPX in this process. C57BL/6J male mice were treated or not with SPX for ten days. On day 3, mice were randomly divided into two groups: one kept at room temperature and the other kept at cold temperature (4 °C). Caloric intake and body weight were recorded daily. At the end of the protocol, plasma, abdominal (epididymal), subcutaneous (inguinal), and brown AT (EAT, IAT, and BAT, respectively) depots were collected for measurements. We found that SPX treatment reduced Uncoupling protein 1 levels in WAT under both basal and cold conditions. SPX also reduced cox8b and pgc1α mRNA levels and mitochondrial DNA, principally in IAT. SPX did not modulate the number of beige precursors. SPX decreased spx levels in IAT depots and galr2 in WAT depots. No differences were observed in the BAT depots. In conclusion, we showed, for the first time, that SPX treatment in vivo reduced the thermogenic process in subcutaneous and abdominal AT, being more evident under cold stimulation.
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- 2024
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24. Role of glucocorticoid receptor (GR) in white adipose tissue beiging.
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Martín FM, Alzamendi A, Harnichar AE, Castrogiovanni D, Zubiría MG, Spinedi E, and Giovambattista A
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- Animals, Male, Rats, Adipocytes, White metabolism, Adipose Tissue metabolism, Adipose Tissue, Brown metabolism, Adiposity, Energy Metabolism, Glucocorticoids metabolism, Mammals metabolism, Obesity metabolism, Thermogenesis, Adipose Tissue, White metabolism, Receptors, Glucocorticoid metabolism
- Abstract
Aim: Glucocorticoids (GCs) play a crucial role in energy homeostasis including white adipose tissue function; however, chronic GC excess is detrimental to mammals' health. White hypertrophic adiposity is a main factor for neuroendocrine-metabolic dysfunctions in monosodium L-glutamate (MSG)-damaged hypercorticosteronemic rat. Nevertheless, little is known about the receptor path in endogenous GC impact on white adipose tissue-resident precursor cells to bring them into beige lineage. Thus, our aim was to explore whether transient/chronic endogenous hypercorticosteronemia affects browning capacity in white adipose tissue pads from MSG rats during development., Main Methods: Control and MSG male rats aged 30 and 90 days were 7-day exposed to cold conditions in order to stimulate wet white epidydimal adipose tissue (wEAT) beiging capacity. This procedure was also replicated in adrenalectomized rats., Key Findings: Data indicated that whereas epidydimal white adipose tissue pads from prepubertal hypercorticosteronemic rats retained full expression of GR/MR genes resulting in a drastic reduction in wEAT beiging capacity, conversely, chronic hypercorticosteronemic adult MSG rats developed down-regulation of corticoid genes (and reduced GR cytosolic mediators) in wEAT pads and consequently partially restored local beiging capacity. Finally, wEAT pads from adrenalectomized rats revealed up-regulation of GR gene accompanied by full local beiging capacity., Significance: This study strongly supports a GR-dependent inhibitory effect of GC excess on white adipose tissue browning, an issue strongly supporting a key role of GR in the non-shivering thermogenic process. As a consequence, normalizing the GC milieu could be a relevant factor to handle dysmetabolism in white hyperadipose phenotypes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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25. Inhibitory effect of androgens on white adipose tissue thermogenic capacity.
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Harnichar AE, Zubiría MG, Giordano AP, Miguel I, Rey MA, Spinedi E, and Giovambattista A
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- Adipose Tissue, Brown metabolism, Adipose Tissue, White metabolism, Animals, Cold Temperature, Rats, Thermogenesis physiology, Uncoupling Protein 1 genetics, Uncoupling Protein 1 metabolism, Adipocytes, Beige metabolism, Androgens metabolism, Androgens pharmacology
- Abstract
White adipose tissue (WAT) browning has gained interest due to its impact in obesity. Here, we evaluated the effect of androgens on the Ucp1-dependent thermogenic process from inguinal (IAT) and retroperitoneal (RPAT) WAT. Surgically androgens depleted rats (ODX) showed basal thermogenic activation (room temperature) in both WAT depots, which expressed higher levels of Ucp1, Prdm16 and Pgc1a. WAT pads from ODX cold-exposed rats (ODX-C) expressed increased levels of Ucp1 and Pgc1a and showed high UCP1 protein content. In primary beige adipocyte cultures, testosterone decreased the mitochondrial marker Cox8b and mitochondrial content. Finally, testosterone and dihydrotestosterone (DHT) decreased the expression of Ucp1, Pcg1a and Prdm16 in forskolin-stimulated beige adipocytes, an effect that was prevented by the antiandrogen flutamide. In conclusion, androgen deficient rats developed WAT depots with enhanced basal and cold-stimulated thermogenic activity. Additionally, in vitro androgen treatments inhibited the thermogenic program, effect which was mediated by the androgen receptor pathway., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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26. Dexamethasone primes adipocyte precursor cells for differentiation by enhancing adipogenic competency.
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Zubiría MG, Giordano AP, Gambaro SE, Alzamendi A, Frontini-López YR, Moreno G, Spinedi E, and Giovambattista A
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- Adipocytes drug effects, Adipocytes metabolism, Adipose Tissue cytology, Animals, Biomarkers metabolism, Gene Expression Regulation drug effects, Male, Mice, PPAR gamma genetics, PPAR gamma metabolism, Rats, Sprague-Dawley, Receptors, Glucocorticoid metabolism, Receptors, Mineralocorticoid metabolism, Retroperitoneal Space, Stem Cells drug effects, Stem Cells metabolism, Transcription Factors metabolism, Adipocytes cytology, Adipogenesis drug effects, Adipogenesis genetics, Dexamethasone pharmacology, Stem Cells cytology
- Abstract
Aim: Dexamethasone (DXM) is a synthetic glucocorticoid whose effects in early and terminal adipogenesis have been addressed. In this study, we evaluated if DXM affects adipocyte precursor cells (APCs), priming them for further adipogenic differentiation. For this purpose, we analyzed APCs number and competency after DXM treatment., Materials and Methods: Adult male rats were injected for 2 or 7 days with either DXM (30 μg/kg of weight, sc.) or vehicle. Stromal vascular fraction (SVF) cells from retroperitoneal adipose tissue (RPAT) were isolated to quantify APCs by flow cytometry (CD34
+ /CD45- /CD31- ). Also, expression of competency markers (PPARγ2 and Zfp423) was assessed. Additionally, SVF cells from control rats were incubated with DXM (0.25 μM) alone or combined with a mineralocorticoid receptor (MR) antagonist (Spironolactone 10 μM) and/or a glucocorticoid receptor (GR) antagonist (RU486 1 μM) to assess APCs competency and adipocyte differentiation., Key Findings: APCs from 2 days DXM-treated rats showed increased expression of PPARγ2 and Zfp423 (competency markers), but did not affect APCs percentage by FACS analysis (CD34+ /CD45- /CD31- ). Additionally, we found that DXM treatment in SVF also increased APCs competency in vitro, predisposing APCs to further adipocyte differentiation. These effects on APCs were abrogated only when both, MR and GR, were blocked., Significance: Overall, our results suggest that DXM primes APCs for differentiation mainly by enhancing Zfp423 and PPARγ2 expressions. Also, we showed that the inhibition of MR and GR was necessary for the complete abolishment of DXM effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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27. Neuroendocrine-Metabolic Dysfunction and Sleep Disturbances in Neurodegenerative Disorders: Focus on Alzheimer's Disease and Melatonin.
- Author
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Spinedi E and Cardinali DP
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- Alzheimer Disease therapy, Amyloid beta-Peptides metabolism, Animals, Brain metabolism, Cognitive Dysfunction therapy, Humans, Melatonin metabolism, Melatonin therapeutic use, Sleep Wake Disorders therapy, Alzheimer Disease physiopathology, Brain physiopathology, Cognitive Dysfunction physiopathology, Sleep Wake Disorders physiopathology
- Abstract
Alzheimer's disease (AD) is associated with altered eating behavior and metabolic disruption. Amyloid plaques and neurofilament tangles are observed in many hypothalamic nuclei from AD brains. Some of these areas (suprachiasmatic nuclei, lateral hypothalamic area) also play a role in the regulation of the sleep/wake cycle and may explain the comorbidity of eating and sleep disorders observed in AD patients. Inadequate sleep increases the neurodegenerative process, for example, the decrease of slow-wave sleep impairs clearance of β-amyloid peptide (Aβ) and tau protein from cerebral interstitial fluid. Cerebrospinal fluid (CSF) melatonin levels decrease even in preclinical stages (Braak-1 stage) when patients manifest no cognitive impairment, suggesting that reduction of melatonin in CSF may be an early marker (the cause for which is still unknown) of oncoming AD. Melatonin administration augments glymphatic clearance of Aβ and reduces generation and deposition of Aβ in transgenic animal models of AD. It may also set up a new equilibrium among hypothalamic feeding signals. While melatonin trials performed in the clinical phase of AD have failed to show or showed only modest positive effects on cognition, in the preclinical stage of dementia (minimal cognitive impairment) the effect of melatonin is demonstrable with significant improvement of sleep and quality of life. In this review, we discuss the main aspects of hypothalamic alterations in AD, the association between interrupted sleep and neurodegeneration, and the possible therapeutic effect of melatonin on these processes., (© 2018 S. Karger AG, Basel.)
- Published
- 2019
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28. Corrigendum to "Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction".
- Author
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Villagarcía HG, Sabugo V, Castro MC, Schinella G, Castrogiovanni D, Spinedi E, Massa ML, and Francini F
- Abstract
[This corrects the article DOI: 10.1155/2016/7838290.].
- Published
- 2018
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29. The Polycystic Ovary Syndrome and the Metabolic Syndrome: A Possible Chronobiotic-Cytoprotective Adjuvant Therapy.
- Author
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Spinedi E and Cardinali DP
- Abstract
Polycystic ovary syndrome is a highly frequent reproductive-endocrine disorder affecting up to 8-10% of women worldwide at reproductive age. Although its etiology is not fully understood, evidence suggests that insulin resistance, with or without compensatory hyperinsulinemia, and hyperandrogenism are very common features of the polycystic ovary syndrome phenotype. Dysfunctional white adipose tissue has been identified as a major contributing factor for insulin resistance in polycystic ovary syndrome. Environmental (e.g., chronodisruption) and genetic/epigenetic factors may also play relevant roles in syndrome development. Overweight and/or obesity are very common in women with polycystic ovary syndrome, thus suggesting that some polycystic ovary syndrome and metabolic syndrome female phenotypes share common characteristics. Sleep disturbances have been reported to double in women with PCOS and obstructive sleep apnea is a common feature in polycystic ovary syndrome patients. Maturation of the luteinizing hormone-releasing hormone secretion pattern in girls in puberty is closely related to changes in the sleep-wake cycle and could have relevance in the pathogenesis of polycystic ovary syndrome. This review article focuses on two main issues in the polycystic ovary syndrome-metabolic syndrome phenotype development: (a) the impact of androgen excess on white adipose tissue function and (b) the possible efficacy of adjuvant melatonin therapy to improve the chronobiologic profile in polycystic ovary syndrome-metabolic syndrome individuals. Genetic variants in melatonin receptor have been linked to increased risk of developing polycystic ovary syndrome, to impairments in insulin secretion, and to increased fasting glucose levels. Melatonin therapy may protect against several metabolic syndrome comorbidities in polycystic ovary syndrome and could be applied from the initial phases of patients' treatment.
- Published
- 2018
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30. N-Acetyl-l-Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats.
- Author
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Villagarcía HG, Castro MC, Arbelaez LG, Schinella G, Massa ML, Spinedi E, and Francini F
- Subjects
- Acetylcysteine pharmacology, Animals, Antioxidants pharmacology, Antioxidants therapeutic use, Blood Glucose drug effects, Blood Glucose metabolism, Hypothalamus metabolism, Insulin Resistance physiology, Male, Obesity blood, Oxidative Stress drug effects, Oxidative Stress physiology, Prediabetic State blood, Rats, Rats, Wistar, Treatment Outcome, Acetylcysteine therapeutic use, Hypothalamus drug effects, Liver drug effects, Liver metabolism, Obesity drug therapy, Prediabetic State prevention & control
- Abstract
Aim: Hypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not., Methodology: We evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity -LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitored liver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFα protein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions (glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat)., Key Findings: Chronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides, UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISI and the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSG rats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NAC-treated MSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenic genes) expression levels., Significance: Our study strongly supports that chronic oral antioxidant therapy (NAC administration) prevented the development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats by efficiently decreasing high endogenous OS., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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31. Rejuvenating Effect of Long-Term Insulin-Like Growth Factor-I Gene Therapy in the Hypothalamus of Aged Rats with Dopaminergic Dysfunction.
- Author
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Schwerdt JI, Lopez-Leon M, Cónsole GM, Brown OA, Morel GR, Spinedi E, and Goya RG
- Subjects
- Adenoviridae genetics, Animals, Female, Hyperprolactinemia genetics, Hyperprolactinemia pathology, Hypothalamus cytology, Hypothalamus metabolism, Rats, Rats, Sprague-Dawley, Dopamine metabolism, Genetic Therapy methods, Genetic Vectors administration & dosage, Hyperprolactinemia therapy, Insulin-Like Growth Factor I genetics, Rejuvenation
- Abstract
The aging female rat constitutes an interesting model of spontaneous and progressive age-related dopaminergic dysfunction as it allows assessing new therapeutic strategies for Parkinson's disease. Insulin-like growth factor I (IGF-I) is emerging as a powerful neuroprotective molecule, strongly induced in the central nervous system after different insults. We constructed a helper-dependent recombinant adenoviral vector (HDRAd-IGFI) harboring the gene for rat IGF-I. This was used to implement long-term IGF-I gene therapy in the hypothalamus of aged female rats, which display hypothalamic dopaminergic (DA) dysfunction and, as a consequence, chronic hyperprolactinemia. Rejuvenating long-term IGF-I gene therapy was implemented in young (3 months) and aged (24 months) female rats, which received a single intrahypothalamic injection of 4 × 10
9 viral particles of either HD-RAd-IGFI or HD-RAd-DsRed (control vector) and were sacrificed 119 days postinjection. In the young animals, neither vector modified serum prolactin (PRL) levels, but in the RAd-IGFI-injected aged rats a nearly full reversion of their hyperprolactinemic status was recorded. Morphometric analysis revealed a significant increase in the total number of tyrosine hydroxylase (TH)-positive cells in the hypothalamus of experimental compared with control aged animals (5874 ± 486 and 3390 ± 498, respectively). Our results indicate that IGF-I gene therapy in aged female rats is highly effective in rejuvenating the hypothalamic DA neuron groups.- Published
- 2018
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32. IGF-1 Gene Therapy as a Potentially Useful Therapy for Spontaneous Prolactinomas in Senile Rats.
- Author
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Brown OA, Canatelli-Mallat M, Console GM, Camihort G, Luna G, Spinedi E, and Goya RG
- Subjects
- Animals, Female, Hypothalamus metabolism, Hypothalamus pathology, Prolactinoma genetics, Prolactinoma pathology, Rats, Rats, Sprague-Dawley, Genetic Therapy, Genetic Vectors administration & dosage, Insulin-Like Growth Factor I genetics, Prolactinoma therapy
- Abstract
Background: Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibular dopaminergic neuron function in aging female rats., Objective: Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile female rats., Methods: Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young (4 mo.) and aging (24 mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed and injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or the reporter red fluorescent protein DsRed. Ninety-one days post vector injection, all rats were sacrificed and their brains and pituitaries fixed. Serum prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as hypothalamic IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with an anti-rat PRL antibody and submitted to morphometric analysis., Results: DsRed expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The IGF1 treatment affected neither pituitary weight nor PRL, E2 or P4 serum levels in the young rats. In the old rats, IGF1 gene therapy reduced gland weight as compared with intact counterparts and tended to reduce PRL levels as compared with intact counterparts. The treatment significantly rescued the phenotype of the lactotropic cell population in the senile adenomas., Conclusion: We conclude that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous prolactinomas in aging female rats., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
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33. Diabetes primary prevention program: New insights from data analysis of recruitment period.
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Gagliardino JJ, Elgart JF, Bourgeois M, Etchegoyen G, Fantuzzi G, Ré M, Ricart JP, García S, Giampieri C, González L, Suárez-Crivaro F, Kronsbein P, Angelini JM, Martínez C, Martínez J, Ricart A, and Spinedi E
- Subjects
- Argentina epidemiology, Blood Glucose analysis, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 epidemiology, Female, Follow-Up Studies, Glucose Intolerance diagnosis, Glucose Intolerance epidemiology, Glucose Tolerance Test, Glycated Hemoglobin analysis, Humans, Insulin Resistance, Male, Middle Aged, Prediabetic State diagnosis, Prediabetic State epidemiology, Primary Prevention, Prognosis, Prospective Studies, Surveys and Questionnaires, Biomarkers analysis, Diabetes Mellitus, Type 2 prevention & control, Glucose Intolerance prevention & control, Mass Screening methods, Prediabetic State prevention & control
- Abstract
Background: Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina., Methods: People were recruited through population approach (house-to-house survey by FINDRISC in randomized areas) and opportunistic approach (FINDRISC completed by participants during consultations for nonrelated prediabetes/diabetes symptoms in public and private primary care centres of cities involved). In people with FINDRISC score ≥ 13 points, we evaluated blood concentrations of HbA
1c , creatinine, lipids, and an oral glucose tolerance test (OGTT)., Results: Approximately 3415 individuals completed the FINDRISC populational survey and 344 the opportunistic survey; 43% of the 2 groups scored over 13 points; 2.8 and 75.4% of them, respectively, took the prescribed OGTT. Approximately 53.7% of the OGTT showed normal values and 5.2% unknown T2D. The remaining cases showed 69.5% impaired fasting glucose, 13.6% impaired glucose tolerance, and 16.9% both impairments. HbA1c values showed significant differences compared with normal glucose tolerance (4.96 ± 0.43%), prediabetes (5.28 ± 0.51%), and T2D (5.60 ± 0.51%). Participants with prediabetes and T2D showed a predominant increase in low-density lipoprotein-cholesterol values. In prediabetes, >50% showed insulin resistance., Conclusions: People with prediabetes/T2D had dyslipidemia associated with insulin resistance, which promotes the development of T2D and cardiovascular disease. Thus, it merits its appropriate treatment., (Copyright © 2017 John Wiley & Sons, Ltd.)- Published
- 2018
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34. White Adipose Tissue and Circadian Rhythm Dysfunctions in Obesity: Pathogenesis and Available Therapies.
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Pagano ES, Spinedi E, and Gagliardino JJ
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- Animals, Chronobiology Disorders complications, Circadian Clocks genetics, Circadian Clocks physiology, Homeostasis, Humans, Hypothalamus physiopathology, Metabolic Diseases genetics, Obesity complications, Obesity genetics, Adipose Tissue, White physiopathology, Chronobiology Disorders physiopathology, Chronobiology Disorders therapy, Chronotherapy, Obesity physiopathology, Obesity therapy
- Abstract
A combined neuroendocrine, metabolic, and chronobiological view can help to better understand the multiple and complex mechanisms involved in obesity development and maintenance, as well as to provide new effective approaches for its control and treatment. Indeed, we have currently updated data on the whole adipogenic process involved in white adipose tissue (WAT) mass expansion, namely due to a mechanism whereby WAT cells become hypertrophic, thus inducing a serious local (WAT) inflammatory condition that in turn, will impair not only the cross-talk between the hypothalamus and the WAT, but also favoring the development of deep and widespread neuroendocrine-metabolic dysfunction. Moreover, we also have revisited the circadian clock genes involved in dysfunctional WAT mass expansion and the mechanisms that may lead to obesity development, including early metabolic dysfunctions, enhanced oxidative stress and distorted energy homeostasis. The epigenetic changes of clock genes driving metabolic disease and obesity development have also been included in this review. Finally, we have also underlined the relevance of metabolic homeostasis regulation by central and peripheral organ clocks, sleep disturbances, nutrients, and feeding time, as key factors in obesity development as well as both, classical and chronotherapeutic approaches for its prevention and treatment., (© 2016 S. Karger AG, Basel.)
- Published
- 2017
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35. Preface.
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Spinedi E, Cardinali DP, and Gagliardino JJ
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- Humans, Adipose Tissue physiopathology, Hypothalamus physiopathology, Obesity physiopathology, Overweight physiopathology
- Published
- 2017
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36. Relationship between the Balance of Hypertrophic/Hyperplastic Adipose Tissue Expansion and the Metabolic Profile in a High Glucocorticoids Model.
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Zubiría MG, Alzamendi A, Moreno G, Portales A, Castrogiovanni D, Spinedi E, and Giovambattista A
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- Adipocytes metabolism, Adipogenesis physiology, Adiposity physiology, Animals, Cell Differentiation physiology, Cell Proliferation physiology, Cells, Cultured, Corticosterone blood, Disease Models, Animal, Hyperplasia blood, Hyperplasia complications, Hypertrophy blood, Hypertrophy complications, Insulin blood, Leptin blood, Male, Malonates adverse effects, Rats, Rats, Sprague-Dawley, Glucocorticoids blood, Intra-Abdominal Fat metabolism, Obesity blood
- Abstract
Adipose tissue (AT) expansion is the result of two processes: hyperplasia and hypertrophy; and both, directly or indirectly, depend on the adipogenic potential of adipocyte precursor cells (APCs). Glucocorticoids (GCs) have a potent stimulatory effect on terminal adipogenesis; while their effects on early stages of adipogenesis are largely unknown. In the present work, we study, in a model of high GC levels, the adipogenic potential of APCs from retroperitoneal AT (RPAT) and its relationship with RPAT mass expansion. We employed a model of hyper-adiposity (30- and 60-day-old rats) due to high endogenous GC levels induced by neonatal treatment with l-monosodium glutamate (MSG). We found that the RPAT APCs from 30-day-old MSG rats showed an increased adipogenic capacity, depending on the APCs' competency, but not in their number. Analyses of RPAT adipocyte diameter revealed an increase in cell size, regardless of the rat age, indicating the prevalence of a hypertrophic process. Moreover, functional RPAT alterations worsened in 60-day-old rats, suggesting that the hyperplastic AT expansion found in 30-day-old animals might have a protective role. We conclude that GCs chronic excess affects APCs' adipogenic capacity, modifying their competency. This change would modulate the hyperplastic/hypertrophic balance determining healthy or unhealthy RPAT expansion and, therefore, its functionality.
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- 2016
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37. Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct Effects of Fructose on Adipocyte Precursor Cells.
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Zubiría MG, Alzamendi A, Moreno G, Rey MA, Spinedi E, and Giovambattista A
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- Adipogenesis drug effects, Animals, Body Weight, Drug Administration Schedule, Energy Intake, Fructose administration & dosage, Male, Rats, Rats, Sprague-Dawley, Adipocytes drug effects, Fructose pharmacology
- Abstract
We have previously addressed that fructose rich diet (FRD) intake for three weeks increases the adipogenic potential of stromal vascular fraction cells from the retroperitoneal adipose tissue (RPAT). We have now evaluated the effect of prolonged FRD intake (eight weeks) on metabolic parameters, number of adipocyte precursor cells (APCs) and in vitro adipogenic potential from control (CTR) and FRD adult male rats. Additionally, we have examined the direct fructose effects on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size. FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads; data is supported by high mRNA levels of competency markers: PPARγ2 and Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal APCs displayed an overall increased adipogenic capacity. We conclude that the RPAT mass expansion observed in eight week-FRD fed rats depends on combined accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct effect of fructose on APCs.
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- 2016
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38. High Risk of Metabolic and Adipose Tissue Dysfunctions in Adult Male Progeny, Due to Prenatal and Adulthood Malnutrition Induced by Fructose Rich Diet.
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Alzamendi A, Zubiría G, Moreno G, Portales A, Spinedi E, and Giovambattista A
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- Adipose Tissue physiopathology, Adiposity, Age Factors, Animals, Biomarkers blood, Blood Glucose metabolism, Energy Intake, Female, Leptin blood, Male, Malnutrition blood, Malnutrition physiopathology, Metabolic Syndrome blood, Metabolic Syndrome physiopathology, Phenotype, Pregnancy, Rats, Sprague-Dawley, Sex Factors, Weight Gain, Adipose Tissue metabolism, Animal Nutritional Physiological Phenomena, Dietary Carbohydrates toxicity, Fructose toxicity, Malnutrition etiology, Maternal Nutritional Physiological Phenomena, Metabolic Syndrome etiology, Prenatal Exposure Delayed Effects
- Abstract
The aim of this work was to determine the effect of a fructose rich diet (FRD) consumed by the pregnant mother on the endocrine-metabolic and in vivo and in vitro adipose tissue (AT) functions of the male offspring in adulthood. At 60 days of age, rats born to FRD-fed mothers (F) showed impaired glucose tolerance after glucose overload and high circulating levels of leptin (LEP). Despite the diminished mass of retroperitoneal AT, this tissue was characterized by enhanced LEP gene expression, and hypertrophic adipocytes secreting in vitro larger amounts of LEP. Analyses of stromal vascular fraction composition by flow cytometry revealed a reduced number of adipocyte precursor cells. Additionally, 60 day-old control (C) and F male rats were subjected to control diet (CC and FC animals) or FRD (CF and FF rats) for three weeks. FF animals were heavier and consumed more calories. Their metabolic-endocrine parameters were aggravated; they developed severe hyperglycemia, hypertriglyceridemia, hyperleptinemia and augmented AT mass with hypertrophic adipocytes. Our study highlights that manipulation of maternal diet induced an offspring phenotype mainly imprinted with a severely unhealthy adipogenic process with undesirable endocrine-metabolic consequences, putting them at high risk for developing a diabetic state.
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- 2016
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39. Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction.
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Villagarcía HG, Sabugo V, Castro MC, Schinella G, Castrogiovanni D, Spinedi E, Massa ML, and Francini F
- Abstract
We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing's syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation.
- Published
- 2016
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40. Neonatal androgenization-induced early endocrine-metabolic and ovary misprogramming in the female rat.
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Ongaro L, Salvetti NR, Giovambattista A, Spinedi E, and Ortega HH
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- Animals, Animals, Newborn, Disease Models, Animal, Estrous Cycle physiology, Female, Granulosa Cells metabolism, Hyperinsulinism etiology, Ovarian Hyperstimulation Syndrome etiology, Rats, Rats, Sprague-Dawley, Ovary physiopathology, Polycystic Ovary Syndrome physiopathology, Testosterone Propionate pharmacology, Virilism physiopathology
- Abstract
Aim: Androgen excess predisposes the organism to develop metabolic-endocrine and reproductive dysfunctions, among them the development of a phenotype resembling that of human Polycystic Ovary Syndrome (PCOS)., Methods: We analyzed the impact of a single neonatal (5day-old) testosterone propionate (TP; s.c. 1.25mg/female pup) dose on: a) several metabolic-endocrine activities and b) ovarian steroidogenic and granulosa cell (GC) functions and also follicular population in juvenile and adult TP and control (CT) rats., Key Findings: Compared to CT rats, TP animals were characterized by: a) accelerated growth, hyperadiposity and hyperleptinemia, b) very early (pre-weaning age) vaginal opening, c) hyperinsulinemia in adult life, d) dysfunctional ovarian steroidogenesis, e) conserved GC functionality in both juveniles (in vitro) and adults (in vivo), and f) estrous cycles arrested at estrus. Finally, histological studies of the ovaries indicated that in TP (vs. CT) rats: i) primary and antral follicle frequencies were 3- and 15-fold higher and lower, respectively, in juveniles and ii) secondary and atretic follicle frequencies were 3- and 5-fold lower and higher, respectively, in adults. Large cystic images without corpus luteum were observed in the ovaries from adult TP rats only., Significance: Our results strongly suggest that transient neonatal hyperandrogenemia induced early misprogramming of metabolic-endocrine and ovarian (steroidogenesis/folliculogenesis) functions. Conversely, TP rats preserved their ovary GC endocrine function. Our results further support the high risk of developing ovarian hyperstimulation syndrome for infertile women with transient/chronic hyperandrogenemia (PCOS) subjected to assisted reproductive technologies., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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41. Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats.
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Castrogiovanni D, Ongaro L, Zuburía G, Giovambattista A, and Spinedi E
- Abstract
Rats neonatally treated with monosodium L-glutamate (MSG) are deeply dysfunctional in adulthood. We explored the effect of an oral low dose of metformin treatment in male MSG rats on adipoinsular axis and visceral adipose tissue (VAT) dysfunctions, in both basal (nonfasting) and endotoxemia conditions. MSG rats, treated or not treated with metformin (30 days prior to experimentation), and control litter-mates (CTR) were studied at 90 days of age. Peripheral concentrations of glucose, lipids, and hormones were determined in basal and post-lipopolysaccharide (LPS) treatment conditions. Food intake and body weight (BW) were recorded and VAT mass and leptin mRNA levels were evaluated. Data indicated that MSG rats were lighter and displayed hypercorticosteronemia, hypophagia, adipoinsular axis hyperactivity, and enhanced VAT mass associated with an increased leptin gene expression. Interestingly, metformin-treated MSG rats corrected BW catch-up and counteracted VAT (mass and leptin mRNA level) and adipoinsular axis (basal and post-LPS) dysfunctions. Thus metformin treatment in MSG rats is able to correct several VAT and metabolic-endocrine dysfunctions. Our study suggests that a low-dose metformintherapy is effective to correct, at least in part, adipoinsular axis dysfunction in hypertrophic obese phenotypes, such as that of the human Cushing syndrome.
- Published
- 2015
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42. Relationship between impaired adipogenesis of retroperitoneal adipose tissue and hypertrophic obesity: role of endogenous glucocorticoid excess.
- Author
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Zubiría MG, Vidal-Bravo J, Spinedi E, and Giovambattista A
- Subjects
- Adipocytes drug effects, Adipogenesis, Adipose Tissue drug effects, Animals, Cell Differentiation drug effects, Cell Proliferation drug effects, Humans, Inflammation chemically induced, Intra-Abdominal Fat drug effects, Male, Rats, Rats, Sprague-Dawley, Stromal Cells drug effects, Adipocytes pathology, Adipose Tissue pathology, Glucocorticoids pharmacology, Intra-Abdominal Fat pathology, Obesity etiology, Obesity pathology, Stromal Cells pathology
- Abstract
Although the pro-adipogenic effect of glucocorticoid (GC) on adipose tissue (AT) precursor cell differentiation is openly accepted, the effect of chronically high peripheral levels of GC on AT mass expansion is not fully understood. In the present study, we aim to assess the in vitro adipogenic capacity of AT precursor cells isolated from retroperitoneal (RP) AT pads of the hypercorticosteronaemic, adult neonatally treated monosodium L-glutamate (MSG) male rat. To ascertain this issue, we explored the in vitro adipogenic process of stromal-vascular fraction (SVF) cells isolated from RPAT pads of 60-day-old MSG rats. The data recorded indicated that RPAT-SVF cells from hypercorticosteronaemic MSG rats, although displaying an enhanced proliferation capacity, differentiated slower than normal cells. This dysfunction was associated with a reduction in key parameters indicative of precursor cell commitment, differentiation capacity and the percentage of fully differentiated adipocytes, with a retarded maturation process. The distorted adipogenic capacity was highly conditioned by RPAT-SVF cells displaying a low committed population and both excessive and reduced expression of anti- (Pref-1 and Wnt-10b) and pro-adipogenic (mineralocorticoid receptor) signals respectively. Notably, the normalization of peripheral corticosterone levels in MSG rats, as a result of bilateral adrenalectomy combined with GC replacement therapy, fully prevented reduced RPAT precursor cell commitment and overall impaired adipogenesis. Our study strongly supports that the impaired adipogenic process observed in the adult hypertrophic obese MSG male rat is a GC-dependent mechanism, thus explaining the unhealthy RPAT expansion observed in human hypertrophic obese phenotypes, such as in the Cushing's syndrome., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Published
- 2014
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43. Two-hour insulinemia after oral glucose overload and women at risk of pregnancy-induced hypertensive disorders.
- Author
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Romero J and Spinedi E
- Subjects
- Adult, Anthropometry, Diabetes, Gestational diagnosis, Female, Glucose Tolerance Test, Humans, Insulin Resistance, Pregnancy, Pregnancy Outcome, Retrospective Studies, Risk Assessment, Blood Glucose metabolism, Diabetes, Gestational blood, Insulin blood, Pre-Eclampsia blood
- Abstract
Objective: Pregnant women with impaired insulin sensitivity are at risk for developing pregnancy-induced hypertensive disorders (PIHD). We analyzed glucose and insulin circulating levels throughout a 2-h oral 75 g glucose tolerance test in pregnant women, and related the 2-h insulinemias to PIHD prevalence., Methods: Pregnant women (gestational week 24-28) were submitted to a glucose overload, and glucose and insulin plasma concentrations were measured throughout the test. These peripheral metabolite levels, the homeostasis model assessment (HOMA) values and the glucose to insulin ratio (G:Ir) were analyzed. Anthropometric parameters and pregnancy outcome were recorded., Results: Women with normal fasting glycemia, insulinemia and HOMA values, G:Ir and 2 h-glycemia but whose 2 h-insulinemia was higher than 215.25 pM were at greater risk for developing late pregnancy hypertension and preeclampsia compared to women of similar characteristics but whose 2 h-insulinemias were lower than 215.25 pM., Conclusion: 2-h insulinemias higher than 215.25 pM after a 75 g glucose overload could be highly indicative of women at increased risk of developing PIHD.
- Published
- 2013
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44. Excess fructose intake-induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals.
- Author
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Zubiría MG, Fariña JP, Moreno G, Gagliardino JJ, Spinedi E, and Giovambattista A
- Subjects
- Adipocytes drug effects, Adipocytes metabolism, Adipocytes pathology, Adipogenesis physiology, Adipokines genetics, Adipokines metabolism, Animals, Cell Enlargement drug effects, Cell Proliferation drug effects, Dietary Carbohydrates toxicity, Fructose toxicity, Intra-Abdominal Fat metabolism, Male, PPAR gamma genetics, PPAR gamma metabolism, Rats, Rats, Sprague-Dawley, Signal Transduction drug effects, Stromal Cells drug effects, Stromal Cells metabolism, Stromal Cells pathology, Sweetening Agents administration & dosage, Sweetening Agents toxicity, Adipogenesis drug effects, Dietary Carbohydrates administration & dosage, Fructose administration & dosage, Intra-Abdominal Fat drug effects, Intra-Abdominal Fat pathology
- Abstract
We studied the effect of feeding normal adult male rats with a commercial diet supplemented with fructose added to the drinking water (10% w/v; fructose-rich diet, FRD) on the adipogenic capacity of stromal-vascular fraction (SVF) cells isolated from visceral adipose tissue (VAT) pads. Animals received either the commercial diet or FRD ad libitum for 3 weeks; thereafter, we evaluated the in vitro proliferative and adipogenic capacities of their VAT SVF cells. FRD significantly increased plasma insulin, triglyceride and leptin levels, VAT mass/cell size, and the in vitro adipogenic capacity of SVF cells. Flow cytometry studies indicated that the VAT precursor cell population number did not differ between groups; however, the accelerated adipogenic process could result from an imbalance between endogenous pro- and anti-adipogenic SVF cell signals, which are clearly shifted towards the former. The increased insulin milieu and its intracellular mediator (insulin receptor substrate-1) in VAT pads, as well as the enhanced SVF cell expression of Zpf423 and peroxisome proliferator receptor-γ2 (all pro-adipogenic modulators), together with a decreased SVF cell concentration of anti-adipogenic factors (pre-adipocyte factor-1 and wingless-type MMTV-10b), strongly supports this assumption. We hypothesize that the VAT mass expansion recorded in FRD rats results from the combination of initial accelerated adipogenesis and final cell hypertrophy. It remains to be determined whether FRD administration over longer periods could perpetuate both processes, or whether cell hypertrophy itself remains responsible for a further VAT mass expansion, as observed in advanced/morbid obesity., (© 2013 FEBS.)
- Published
- 2013
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45. Impact of neonatal manipulation of androgen receptor function on endocrine-metabolic programming in the juvenile female rat.
- Author
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Ongaro L, Giovambattista A, and Spinedi E
- Abstract
The impact of neonatal androgen receptor (AR) stimulation/blockage, due to testosterone propionate (TP)/AR antagonist treatment, on individual anthropometry and neuroendocrine-metabolic function was evaluated in the juvenile female rat. Pups (age 5 days) were s.c. injected with TP (1.25 mg), flutamide (F; 1.75 mg), and TP + F or vehicle (control, CT) and studied on day 30 of age. Body weight (BW), parametrial adipose tissue (PMAT) mass, food intake, adipoinsular axis, and steroidogenic functions were examined. Opposite to TP-rats, F-treated rats developed hypophagia, grew slowly (BW and PMAT), and displayed heightened peripheral insulin sensitivity. These F effects were abrogated in TP + F animals. Accordingly, TP rats displayed hyperleptinemia, an effect fully prevented by F cotreatment. Finally, androgen-treated animals bore an irreversible ovarian dysfunction (reduced circulating levels of 17HOP4 and ovary 17HOP4 content and P450c17 mRNA abundance). These data indicate that early stimulation of AR enhanced energy store, blockage of AR activity resulted in some beneficial metabolic effects, and neonatally androgenized rats developed a severe ovarian dysfunction. Our study highlights the important role of AR in the early organizational programming of metabolic and neuroendocrine functions.
- Published
- 2013
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46. Antioxidant treatment prevents the development of fructose-induced abdominal adipose tissue dysfunction.
- Author
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Fariña JP, García ME, Alzamendi A, Giovambattista A, Marra CA, Spinedi E, and Gagliardino JJ
- Subjects
- Acetophenones pharmacology, Adipocytes pathology, Animals, Antioxidants pharmacology, Biomarkers blood, Body Weight, Eating, Homeostasis, Male, Metabolic Diseases pathology, NADPH Oxidases metabolism, Rats, Rats, Wistar, Abdominal Fat metabolism, Fatty Acids metabolism, Fructose adverse effects, Leptin blood, Metabolic Diseases chemically induced, Oxidative Stress drug effects, Sweetening Agents adverse effects
- Abstract
In the present study, we tested the effect of OS (oxidative stress) inhibition in rats fed on an FRD [fructose-rich diet; 10% (w/v) in drinking water] for 3 weeks. Normal adult male rats received a standard CD (commercial diet) or an FRD without or with an inhibitor of NADPH oxidase, APO (apocynin; 5 mM in drinking water; CD-APO and FRD-APO). We thereafter measured plasma OS and metabolic-endocrine markers, AAT (abdominal adipose tissue) mass and cell size, FA (fatty acid) composition (content and release), OS status, LEP (leptin) and IRS (insulin receptor substrate)-1/IRS-2 mRNAs, ROS (reactive oxygen species) production, NADPH oxidase activity and LEP release by isolated AAT adipocytes. FRD-fed rats had larger AAT mass without changes in body weight, and higher plasma levels of TAG (triacylglycerol), FAs, TBARS (thiobarbituric acid-reactive substance) and LEP. Although no significant changes in glucose and insulin plasma levels were observed in these animals, their HOMA-IR (homoeostasis model assessment of insulin resistance) values were significantly higher than those of CD. The AAT from FRD-fed rats had larger adipocytes, higher saturated FA content, higher NADPH oxidase activity, greater ROS production, a distorted FA content/release pattern, lower insulin sensitivity together with higher and lower mRNA content of LEP and IRS-1-/2 respectively, and released a larger amount of LEP. The development of all the clinical, OS, metabolic, endocrine and molecular changes induced by the FRD were significantly prevented by APO co-administration. The fact that APO treatment prevented both changes in NADPH oxidase activity and the development of all the FRD-induced AAT dysfunctions in normal rats strongly suggests that OS plays an important role in the FRD-induced MS (metabolic syndrome) phenotype.
- Published
- 2013
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47. Fructose rich diet-induced high plasminogen activator inhibitor-1 (PAI-1) production in the adult female rat: protective effect of progesterone.
- Author
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Castrogiovanni D, Alzamendi A, Ongaro L, Giovambattista A, Gaillard RC, and Spinedi E
- Subjects
- Animals, Blood Glucose, Cholesterol blood, Corticosterone blood, Fatty Acids, Nonesterified blood, Female, Fructose chemistry, Gene Expression Regulation drug effects, Gene Expression Regulation physiology, Glucose Tolerance Test, Insulin blood, Leptin blood, Plasminogen Activator Inhibitor 1 genetics, Rats, Rats, Sprague-Dawley, Testosterone blood, Triglycerides blood, Diet adverse effects, Fructose pharmacology, Plasminogen Activator Inhibitor 1 metabolism, Progesterone metabolism
- Abstract
The effect of progesterone (P4) on fructose rich diet (FRD) intake-induced metabolic, endocrine and parametrial adipose tissue (PMAT) dysfunctions was studied in the adult female rat. Sixty day-old rats were i.m. treated with oil alone (control, CT) or containing P4 (12 mg/kg). Rats ate Purina chow-diet ad libitum throughout the entire experiment and, between 100 and 120 days of age drank ad libitum tap water alone (normal diet; CT-ND and P4-ND) or containing fructose (10% w/v; CT-FRD and P4-FRD). At age 120 days, animals were subjected to a glucose tolerance test or decapitated. Plasma concentrations of various biomarkers and PMAT gene abundance were monitored. P4-ND (vs. CT-ND) rats showed elevated circulating levels of lipids. CT-FRD rats displayed high (vs. CT-ND) plasma concentrations of lipids, leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1). Lipidemia and adiponectinemia were high (vs. P4-ND) in P4-FRD rats. Although P4 failed to prevent FRD-induced hyperleptinemia, it was fully protective on FRD-enhanced plasma PAI-1 levels. PMAT leptin and adiponectin mRNAs were high in CT-FRD and P4-FRD rats. While FRD enhanced PMAT PAI-1 mRNA abundance in CT rats, this effect was absent in P4 rats. Our study supports that a preceding P4-enriched milieu prevented the enhanced prothrombotic risk induced by FRD-elicited high PAI-1 production.
- Published
- 2012
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48. Effect of pioglitazone on the fructose-induced abdominal adipose tissue dysfunction.
- Author
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Alzamendi A, Giovambattista A, García ME, Rebolledo OR, Gagliardino JJ, and Spinedi E
- Abstract
Aim. To test the potential role of PPARγ in the endocrine abdominal tissue dysfunction induced by feeding normal rats with a fructose rich diet (FRD) during three weeks. Methodology. Adult normal male rats received a standard commercial diet (CD) or FRD, (10% in drinking water) without or with pioglitazone (PIO) (i.p. 0.25 mg/Kg BW/day; CD-PIO and FRD-PIO). Thereafter, we measured circulating metabolic, endocrine, and oxidative stress (OS) markers, abdominal adipose tissue (AAT) mass, leptin (LEP) and plasminogen activator inhibitor-1 (PAI-1) tissue content/expression, and leptin release by isolated adipocytes incubated with different concentrations of insulin. Results. Plasma glucose, insulin, triglyceride, TBARS, LEP, and PAI-1 levels were higher in FRD rats; PIO coadministration fully prevented all these increments. AAT adipocytes from FRD rats were larger, secreted a higher amount of LEP, and displayed decreased sensitivity to insulin stimulation; these effects were significantly ameliorated by PIO. Whereas AAT LEP and PAI-1 (mRNA) concentrations increased significantly in FRD rats, those of insulin-receptor-substrate- (IRS-) 1 and IRS-2 were reduced. PIO coadministration prevented FRD effects on LEP, PAI-1, and IRS-2 (fully) and IRS-1 (partially) mRNAs in AAT. Conclusion. PPARγ would play a relevant role in the development of the FRD-induced metabolic-endocrine dysfunction.
- Published
- 2012
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49. Oral metformin treatment prevents enhanced insulin demand and placental dysfunction in the pregnant rat fed a fructose-rich diet.
- Author
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Alzamendi A, Del Zotto H, Castrogiovanni D, Romero J, Giovambattista A, and Spinedi E
- Abstract
The intake of a fructose-rich diet (FRD) in the normal female rat induces features similar to those observed in the human metabolic syndrome phenotype. We studied the impact of FRD administration to mothers on pregnancy outcome. On gestational day (Gd) zero rats were assigned to either group: ad libitum drinking tap water alone (normal diet, ND) or containing fructose (10% w/vol; FRD) through pregnancy; all rats were fed a Purina chow diet ad libitum ND and FRD rats were daily cotreated or not with metformin (60 mg/Kg/day oral; ND + MF and FRD + MF) and submitted to a high glucose load test on Gd 14. Additionally, placentas from different groups were studied on Gd 20. Data indicated that: (1) although FRD rats well tolerated glucose overload, their circulating levels of insulin were significantly higher than in ND rats; (2) the mesometrial triangle blood vessel area was significantly lower in placentas from FRD than ND dams; (3) the detrimental effects of FRD administration to mothers were ameliorated by metformin cotreatment. Our study suggests that excessive intake of fructose during pregnancy enhanced the risk for developing gestational diabetes and subsequent preeclampsia, and that metformin prevented the poor pregnancy outcome induced by FRD.
- Published
- 2012
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50. In vitro functionality of isolated embryonic hypothalamic vasopressinergic and oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor and angiotensin II.
- Author
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Moreno G, Piermaria J, Gaillard RC, and Spinedi E
- Subjects
- Animals, Cells, Cultured, Culture Media chemistry, Female, Hypothalamus cytology, Hypothalamus drug effects, Male, Neurons drug effects, Potassium Chloride pharmacology, Rats, Rats, Sprague-Dawley, Angiotensin II pharmacology, Brain-Derived Neurotrophic Factor pharmacology, Hypothalamus embryology, Neurons metabolism, Oxytocin metabolism, Vasopressins metabolism
- Abstract
There are only a few studies on the ontogeny and differentiation process of the hypothalamic supraoptic-paraventriculo-neurohypophysial neurosecretory system. In vitro neuron survival improves if cells are of embryonic origin; however, surviving hypothalamic neurons in culture were found to express small and minimal amounts of arginine-vasopressin (AVP) and oxytocin (OT), respectively. The aim of this study was to develop a primary neuronal culture design applicable to the study of magnocellular hypothalamic system functionality. For this purpose, a primary neuronal culture was set up after mechanical dissociation of sterile hypothalamic blocks from 17-day-old Sprague-Dawley rat embryos (E17) of both sexes. Isolated hypothalamic cells were cultured with supplemented (B27)-NeuroBasal medium containing an agent inhibiting non-neuron cell proliferation. The neurosecretory process was characterized by detecting AVP and OT secreted into the medium on different days of culture. Data indicate that spontaneous AVP and OT release occurred in a culture day-dependent fashion, being maximal on day 13 for AVP, and on day 10 for OT. Interestingly, brain-derived neurotrophic factor (BDNF) and Angiotensin II (A II) were able to positively modulate neuropeptide output. Furthermore, on day 17 of culture, non-specific (high-KCl) and specific (Angiotensin II) stimuli were able to significantly (P < 0.05) enhance the secretion of both neuropeptides over respective baselines. This study suggests that our experimental design is useful for the study of AVP- and OT-ergic neuron functionality and that BDNF and A II are positive modulators of embryonic hypothalamic cell development.
- Published
- 2011
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