29 results on '"Spinedi E"'
Search Results
2. 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
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- 2022
3. 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.
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- 2006
4. 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
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- 2006
5. 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.
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- 2015
6. 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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7. 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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8. 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.
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- 1996
9. 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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10. 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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11. 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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12. Corrigendum to "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
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[This corrects the article DOI: 10.1155/2016/7838290.].
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- 2018
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13. The Polycystic Ovary Syndrome and the Metabolic Syndrome: A Possible Chronobiotic-Cytoprotective Adjuvant Therapy.
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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.
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- 2018
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14. 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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15. 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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16. 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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17. 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
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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.
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- 2016
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18. 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
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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.
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- 2015
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19. Relationship between impaired adipogenesis of retroperitoneal adipose tissue and hypertrophic obesity: role of endogenous glucocorticoid excess.
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Zubiría MG, Vidal-Bravo J, Spinedi E, and Giovambattista A
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- 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.)
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- 2014
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20. Excess fructose intake-induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals.
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Zubiría MG, Fariña JP, Moreno G, Gagliardino JJ, Spinedi E, and Giovambattista A
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- 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.)
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- 2013
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21. Impact of neonatal manipulation of androgen receptor function on endocrine-metabolic programming in the juvenile female rat.
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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.
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- 2013
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22. Fructose rich diet-induced high plasminogen activator inhibitor-1 (PAI-1) production in the adult female rat: protective effect of progesterone.
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Castrogiovanni D, Alzamendi A, Ongaro L, Giovambattista A, Gaillard RC, and Spinedi E
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- 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.
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- 2012
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23. Effect of pioglitazone on the fructose-induced abdominal adipose tissue dysfunction.
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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.
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- 2012
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24. Oral metformin treatment prevents enhanced insulin demand and placental dysfunction in the pregnant rat fed a fructose-rich diet.
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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.
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- 2012
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25. Increased male offspring's risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother.
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Alzamendi A, Castrogiovanni D, Gaillard RC, Spinedi E, and Giovambattista A
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- Adipokines blood, Animals, Animals, Newborn, Blotting, Western, Body Weight drug effects, Body Weight physiology, Dietary Carbohydrates administration & dosage, Eating drug effects, Eating physiology, Female, Fructose administration & dosage, Gene Expression drug effects, Hypothalamus drug effects, Hypothalamus metabolism, Leptin blood, Leptin pharmacology, Male, Metabolic Diseases blood, Neurosecretory Systems drug effects, Pregnancy, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Sex Factors, Time Factors, Lactation physiology, Metabolic Diseases physiopathology, Neurosecretory Systems physiopathology, Overweight physiopathology
- Abstract
An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and Western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis or digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49-60 d), and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life.
- Published
- 2010
- Full Text
- View/download PDF
26. Parametrial adipose tissue and metabolic dysfunctions induced by fructose-rich diet in normal and neonatal-androgenized adult female rats.
- Author
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Alzamendi A, Castrogiovanni D, Ortega HH, Gaillard RC, Giovambattista A, and Spinedi E
- Subjects
- Adipocytes pathology, Adipokines metabolism, Adiponectin metabolism, Adiposity, Animals, Body Weight, Dietary Sucrose administration & dosage, Dietary Sucrose pharmacology, Disease Models, Animal, Energy Intake, Fatty Acids, Nonesterified blood, Female, Genitalia, Female, Glucose Metabolism Disorders blood, Glucose Metabolism Disorders metabolism, Hyperandrogenism blood, Insulin metabolism, Leptin blood, Leptin genetics, Obesity blood, Plasminogen Activator Inhibitor 1 blood, Rats, Rats, Sprague-Dawley, Risk Factors, Testosterone Propionate metabolism, Triglycerides blood, Adipose Tissue metabolism, Androgens metabolism, Fructose pharmacology, Glucose Metabolism Disorders etiology, Hyperandrogenism complications, Obesity etiology
- Abstract
Hyperandrogenemia predisposes an organism toward developing impaired insulin sensitivity. The aim of our study was to evaluate endocrine and metabolic effects during early allostasis induced by a fructose-rich diet (FRD) in normal (control; CT) and neonatal-androgenized (testosterone propionate; TP) female adult rats. CT and TP rats were fed either a normal diet (ND) or an FRD for 3 weeks immediately before the day of study, which was at age 100 days. Energy intake, body weight (BW), parametrial (PM) fat characteristics, and endocrine/metabolic biomarkers were then evaluated. Daily energy intake was similar in CT and TP rats regardless of the differences in diet. When compared with CT-ND rats, the TP-ND rats were heavier, had larger PM fat, and were characterized by basal hypoadiponectinemia and enhanced plasma levels of non-esterified fatty acid (NEFA), plasminogen activator inhibitor-1 (PAI-1), and leptin. FRD-fed CT rats, when compared with CT-ND rats, had high plasma levels of NEFA, triglyceride (TG), PAI-1, leptin, and adiponectin. The TP-FRD rats, when compared with TP-ND rats, displayed enhanced leptinemia and triglyceridemia, and were hyperinsulinemic, with glucose intolerance. The PM fat taken from TP rats displayed increase in the size of adipocytes, decrease in adiponectin (protein/gene), and a greater abundance of the leptin gene. PM adipocyte response to insulin was impaired in CT-FRD, TP-ND, and TP-FRD rats. A very short duration of isocaloric FRD intake in TP rats induced severe metabolic dysfunction at the reproductive age. Our study supports the hypothesis that the early-androgenized female rat phenotype is highly susceptible to developing endocrine/metabolic dysfunction. In turn, these abnormalities enhance the risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease.
- Published
- 2010
- Full Text
- View/download PDF
27. Direct effect of ghrelin on leptin production by cultured rat white adipocytes.
- Author
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Giovambattista A, Piermaría J, Suescun MO, Calandra RS, Gaillard RC, and Spinedi E
- Subjects
- Animals, Cells, Cultured, Cycloheximide pharmacology, Dactinomycin pharmacology, Dexamethasone pharmacology, Dose-Response Relationship, Drug, Drug Synergism, Ghrelin, Insulin pharmacology, Male, Peptide Hormones antagonists & inhibitors, RNA, Messenger metabolism, Rats, Rats, Inbred F344, Adipocytes metabolism, Leptin biosynthesis, Peptide Hormones pharmacology, Protein Synthesis Inhibitors pharmacology
- Abstract
Objective: Because ghrelin is known to stimulate adipogenesis, we tested whether ghrelin could contribute to the maintenance of homeostasis, directly affecting rat white adipocyte leptin production., Research Methods and Procedures: Isolated retroperitoneal adipocytes were cultured for 0.5 to 48 hours without (baseline) or with (0.001 to 1 nM) ghrelin alone or in combination with insulin (0.01 to 10 nM) or dexamethasone (1 to 100 nM). Adipocytes were also incubated with ghrelin and inhibitors either of RNA (actinomycin D) or protein synthesis (cycloheximide) or with several concentrations (10 to 1000 nM) of a specific ghrelin antagonist. When cultures were terminated, we evaluated adipocyte leptin secretion and ob mRNA expression., Results: Our data indicate that ghrelin directly enhanced adipocyte leptin release and ob mRNA expression, that the leptin-releasing activity of ghrelin was additive to the action of both insulin and dexamethasone and was abrogated by protein synthesis inhibitors, and that effects of ghrelin on adipocyte ob mRNA expression and release were blocked by coincubation with the specific growth hormone secretagogue receptor 1a antagonist., Discussion: Our study supports the ability of ghrelin to enhance white adipose tissue leptin production by a direct receptor-mediated effect. This activity of ghrelin could play a potentially significant role in rapid restoration of homeostasis after food intake.
- Published
- 2006
- Full Text
- View/download PDF
28. A regulatory loop between the hypothalamo-pituitary-adrenal (HPA) axis and circulating leptin: a physiological role of ACTH.
- Author
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Spinedi E and Gaillard RC
- Subjects
- Adrenalectomy, Adrenocorticotropic Hormone blood, Animals, Corticosterone pharmacology, Dexamethasone pharmacology, Glucocorticoids pharmacology, Leptin, Male, Rats, Rats, Wistar, Adrenocorticotropic Hormone physiology, Hypothalamo-Hypophyseal System physiology, Pituitary-Adrenal System physiology, Proteins metabolism
- Abstract
The product of the ob/ob gene, leptin, is known to be able to exert a modulator, role on HPA axis function. The aim of the present study was to determine whether endogenous ACTH and glucocorticoids exert any regulatory effect on leptin secretion. For this purpose bilaterally adrenalectomized (ADX) or sham operated (Sham) adult male rats were implanted with an indwelling i.v. catheter. A subgroup of ADX animals received, at the same time of surgery, a s.c. corticosterone (B) pellet (75 mg) (ADX+B). All animals were subjected to experimental designs 7 days after surgery. Our results indicate, as expected, that 7-day ADX animals have several fold increased basal ACTH plasma levels and non detectable circulating B, whereas ADX+B rats showed basal plasma ACTH levels in the range of Sham values and plasma B concentrations of about 5 microg/dl. Interestingly, basal plasma leptin levels were significantly (P < 0.05) decreased by 7 days post ADX, and B replacement therapy (ADX+B) restored circulating leptin to Sham levels. Acute dexamethasone (Dxmn, 30 microg/kg body weight, i.v.) treatment induced a very rapid decrease in plasma ACTH concentrations in both Sham and ADX rats, as well as a decrease in plasma B levels in Sham rats. Interestingly, Dxm test had no effect on plasma leptin levels in Sham animals; however, in ADX rats, the synthetic glucocorticoid increased plasma leptin concentrations, restoring the levels observed in Sham rats. This effect occurred at the same time when plasma ACTH levels were decreasing toward basal Sham values. These results clearly indicate that, beside the known effects of leptin on HPA axis function, circulating ACTH and glucocorticoid are able to modulate leptin secretion in plasma. The lack of circulating glucocorticoid and/or increased plasma ACTH concentrations, are responsible for decreasing leptin output, whereas decreased plasma ACTH concentrations allow an increase of leptin secretion in blood. Our data strongly support the existence of a closed, bi-directional, circuit between HPA axis function and adipose tissue metabolism. They further indicate the physiological relevance of different types of stress associated with many phenotypes of obesity.
- Published
- 1998
- Full Text
- View/download PDF
29. A phospholipase A2-related snake venom (from Crotalus durissus terrificus) stimulates neuroendocrine and immune functions: determination of different sites of action.
- Author
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Chisari A, Spinedi E, Voirol MJ, Giovambattista A, and Gaillard RC
- Subjects
- Adrenal Glands metabolism, Adrenocorticotropic Hormone metabolism, Animals, Arginine Vasopressin metabolism, Corticotropin-Releasing Hormone metabolism, Female, Glucocorticoids metabolism, Hypothalamo-Hypophyseal System drug effects, Hypothalamus metabolism, Median Eminence metabolism, Mice, Mice, Inbred BALB C, Monocytes metabolism, Phospholipases A2, Pituitary Gland, Anterior metabolism, Pituitary-Adrenal System drug effects, Tumor Necrosis Factor-alpha metabolism, Crotalid Venoms pharmacology, Immune System drug effects, Neurosecretory Systems drug effects, Phospholipases A pharmacology
- Abstract
Immune neuroendocrine interactions are vital for the individual's survival in certain physiopathological conditions, such as sepsis and tissular injury. It is known that several animal venoms, such as those from different snakes, are potent neurotoxic compounds and that their main component is a specific phospholipase A type 2 (PLA2). It has been described recently that the venom from Crotalus durissus terrificus [snake venom (SV), in the present study] possesses some cytotoxic effect in different in vitro and in vivo animal models. In the present study, we investigated whether SV and its main component, PLA2 (obtained from the same source), are able to stimulate both immune and neuroendocrine functions in mice, thus characterizing this type of neurotoxic shock. For this purpose, several in vivo and in vitro designs were used to further determine the sites of action of SV-PLA2 on the hypothalamo-pituitary-adrenal (HPA) axis function and on the release of the pathognomonic cytokine, tumor necrosis factor alpha (TNF alpha), of different types of inflammatory stress. Our results indicate that SV (25 microg/animal) and PLA2 (5 microg/animal), from the same origin, stimulate the HPA and immune axes when administered (i.p.) to adult mice; both preparations were able to enhance plasma glucose, ACTH, corticosterone (B), and TNF alpha plasma levels in a time-related fashion. SV was found to activate CRH- and arginine vasopressin-ergic functions in vivo and, in vitro, SV and PLA2 induced a concentration-related (0.05-10 microg/ml) effect on the release of both neuropeptides. SV also was effective in changing anterior pituitary ACTH and adrenal B contents, also in a time-dependent fashion. Direct effects of SV and PLA2 on anterior pituitary ACTH secretion also were found to function in a concentration-related fashion (0.001-1 microg/ml), and the direct corticotropin-releasing activity of PLA2 was additive to those of CRH and arginine vasopressin; the corticotropin-releasing activity of both SV and PLA2 were partially reversed by the specific PLA2 inhibitor, manoalide. On the other hand, neither preparation was able to directly modify spontaneous and ACTH-stimulated adrenal B output. The stimulatory effect of SV and PLA2 on in vivo TNF alpha release was confirmed by in vitro experiments on peripheral mononuclear cells; in fact, both PLA2 (0.001-1 microg/ml) and SV (0.1-10 microg/ml), as well as concavalin A (1-100 microg/ml), were able to stimulate TNF alpha output in the incubation medium. Our results clearly indicate that PLA2-dependent mechanisms are responsible for several symptoms of inflammatory stress induced during neurotoxemia. In fact, we found that this particular PLA2-related SV is able to stimulate both HPA axis and immune functions during the acute phase response of the inflammatory processes.
- Published
- 1998
- Full Text
- View/download PDF
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