Fábio Lima - Academia.edu (original) (raw)

Papers by Fábio Lima

Jornal de Pediatria, 2007

To describe the advances in research into the physiological role of white adipose tissue, with em... more To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity.

American Journal of Hypertension, 1997

The effect of sodium chloride salt restriction and overload on insulin sensitivity is still an op... more The effect of sodium chloride salt restriction and overload on insulin sensitivity is still an open question.Some authors have shown that NaCl salt restriction increases insulin resistance, whereas others have reported the opposite. In the present study, the objective was to get some more insight on this issue by studying the influence of dietary salt content on glucose uptake in isolated adipocytes.Male Wistar rats were fed from weaning either low (0.15%) or high (7.94%) salt diets. On the 12th week of age, weight and tail-cuff blood pressure were measured, followed 10 days later by an intravenous glucose tolerance test with concomitant insulin determinations. One week later, the rats were killed by decapitation and epididymal adipocytes were obtained for glucose metabolism evaluation.No weight differences were observed between both groups of animals. Blood pressure was significantly higher (P < .001) on salt overloaded rats (146 ± 11 mm Hg) than on salt restricted ones (115 ± 5 mm Hg). Dietary salt content did not influence the area under the curve of plasma glucose. Area under the curve of insulin levels was lower (P = .023) on the high than on the low salt diet. A higher (P < .001) glucose uptake in the absence and in the presence of insulin was observed in adipocytes from rats on the high salt diet. The median effective concentration (EC50) from the dose-response curves of glucose uptake was the same on both groups of animals. Glucose oxidation and incorporation into lipids was also enhanced by salt overload. High salt increased insulin receptor density (P < .001).In conclusion, salt overload increased blood pressure, and high and low salt dietary content did not influence insulin sensitivity based on the unchanged EC50 from the in vitro studies. However, insulin-independent glucose uptake, oxidation, and incorporation into lipids were enhanced in adipocytes from rats on the high salt diet. The lower levels of insulin during the glucose tolerance test on salt-loaded animals may be a consequence of the higher insulin-independent glucose uptake in that group.

Journal of Pineal Research, 2006

Abstract: Considering the cyclic characteristic of production and secretion of pineal melatonin,... more Abstract: Considering the cyclic characteristic of production and secretion of pineal melatonin, it is reasonable to assume that this oscillation might be important in determining the variety of its circadian and seasonal effects. To simulate this physiological condition in vitro, isolated adipocytes were exposed to melatonin in a circadian-like pattern by adding the hormone to the incubating medium during 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day). This intermittent procedure was interrupted when three cycles with melatonin were fulfilled (60-hr incubation). Here, we report the effects of melatonin (1 nM) added intermittently or continuously to the incubating medium alone or in combination with insulin (5 nM) and/or dexamethasone (7 nM) on leptin release and expression by rat adipocytes. After acute 12-hr incubation neither melatonin nor insulin alone affected leptin expression, but together they increased it by 105%. Dexamethasone increased leptin mRNA content and release (70%) but this effect was not enhanced by melatonin. Nevertheless, after 60 hr under intermittent melatonin, we observed a synergism between melatonin and dexamethasone. This interaction promoted an increment (75% compared with dexamethasone alone) in leptin release and expression. Our results suggest that circadian-like exposure to melatonin potentiates the dexamethasone action and is important to the effects promoted by insulin on leptin expression. Based on an in vitro approach, this work helps to clarify the physiological relevance and the repercussions of the in vivo circadian pattern of melatonin secretion.

Jornal De Pediatria, 2007

To describe the advances in research into the physiological role of white adipose tissue, with em... more To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity.

European Journal of Biochemistry, 2000

The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases e... more The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases even disappearance of fat tissue. Here, we report the effects of leptin (10 and 100 ng´mL 21 ) on isolated rat adipocytes maintained for 15 h in culture. Leptin decreased the incorporation of acetate into total lipids by 30%. A reduction in this incorporation (42%) was still observed after the leptin-cultivated adipocytes were exposed to a supraphysiological insulin concentration (10 000 mU´mL 21 ). On the other hand, leptin increased acetate degradation by 69% and the maximal activity of citrate synthase by 50% in isolated adipocytes. It also increased oleate degradation by 35 and 50% at concentrations of 10 and 100 ng´mL 21 , respectively. Eventually, leptin upregulated the uncoupling protein-2 (UCP2) mRNA level by 63% and had no effect on uncoupling protein-3 (UCP3) mRNA in isolated adipocytes. The upregulation of UCP2 mRNA might have contributed to the stimulation of acetate and fatty acid degradation by leptin. The peripheral effects of leptin observed in this study are in line with the general energy dissipating role postulated for this hormone and for UCP2. They suggest mechanisms by which adipocytes regulate their fat content by an autocrine pathway without the participation of the central nervous system.

Journal of Pineal Research, 2008

Abstract: The aim of this work was to investigate the effect of the in vitro circadian-like expo... more Abstract: The aim of this work was to investigate the effect of the in vitro circadian-like exposure to melatonin [in the presence or absence of insulin (Ins)] on the metabolism and clock gene expression in adipocytes. To simulate the cyclic characteristics of the daily melatonin profile, isolated rat adipocytes were exposed in a circadian-like pattern to melatonin added to the incubating medium for 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day) combined or not with Ins. This intermittent incubation was interrupted when four and a half 24-hr cycles were fulfilled. At the end, either during the induced night (melatonin present) or the induced day (melatonin absent), the rates of lipolysis and D-[U-14C]-glucose incorporation into lipids were estimated, in addition to the determination of lipogenic [glucose-6-phosphate dehydrogenase and fatty acid synthase (FAS)] and lipolytic (hormone sensitive lipase) enzymes and clock gene (Bmal-1b, Clock, Per-1 and Cry-1) mRNA expression. The leptin release was also measured. During the induced night, the following effects were observed: an increase in the mRNA expression of Clock, Per-1 and FAS; a rise in lipogenic response and leptin secretion; and a decrease in the lipolytic activity. The intermittent exposure of adipocytes to melatonin temporally and rhythmically synchronized their metabolic and hormonal function in a circadian fashion, mimicking what is observed in vivo in animals during the daily light–dark cycle. Therefore, this work helps to clarify the physiological relevance of the circadian pattern of melatonin secretion and its interactions with Ins, contributing to a better understanding of the adipocyte biology.

Metabolism-clinical and Experimental, 2004

This study investigated the effects of pinealectomy and fasting on rat adipose tissue metabolism,... more This study investigated the effects of pinealectomy and fasting on rat adipose tissue metabolism, as well as on profiles of the hormones directly involved in its regulation (insulin, leptin, and corticosterone). Pinealectomized (PINX) and sham-operated (CONTROL) adult male Wistar rats were killed 6 weeks after surgery, in either fed or fasted (12 and 36 hours) states. Blood samples (for glucose and hormone determinations) and peri-epididymal adipocytes (for in vitro insulin-stimulated glucose uptake, oxidation, and incorporation into lipids) were collected. Pineal ablation decreased insulin-stimulated glucose uptake in adipocytes of both fed and fasted animals without affecting insulin-binding capacity. Pinealectomy attenuated the reduction in the ability to oxidize glucose in both basal and insulin-stimulated states during fasting. This alteration in the ability of adipocytes to oxidize glucose appeared together with a decrease in insulin-induced glucose incorporation into lipids in PINX animals. Additionally, pinealectomized rats showed higher corticosterone levels in both fed and fasted states, and a lower leptinemia with 36 hours of fasting, in comparison to CONTROLs. In conclusion, our data reinforce the hypothesis that the pineal gland has a role in the modulation of adipocyte metabolism, and its absence alters metabolic adaptation to fasting in rats.

Journal of Pineal Research, 2005

Abstract: This study investigated the effects of pinealectomy and exercise training on rat adipo... more Abstract: This study investigated the effects of pinealectomy and exercise training on rat adipose tissue metabolism. Pinealectomized (PINX) and sham-operated (CONTROL) adult male Wistar rats were subdivided into four subgroups, including PINX untrained, PINX trained, CONTROL untrained and CONTROL trained. At the end of the training period (8 wk), the rats were killed and peri-epididymal adipocytes were isolated for in vitro insulin-stimulated glucose uptake, conversion of d-[U-14C]-glucose, l-[U-14C]-lactate, [2-14C]-acetate and [1-14C]-palmitate into 14CO2, and insulin binding. Pinealectomy resulted in a significantly decreased insulin-stimulated glucose uptake in adipocytes without affecting insulin-binding capacity. However, in intact control animals only, training promoted a higher baseline glucose uptake in adipocytes. Training influenced the adipocyte ability to oxidize the different substrates: the rates of glucose and palmitate oxidation increased while the rates of lactate and acetate diminished. Nevertheless, these effects of exercise training were not seen in pinealectomized rats. Additionally, an increase in palmitate oxidation was observed in sedentary pinealectomized animals. In conclusion, these data show that the pineal gland alters the patterns of substrate utilization by the adipocyte, in such a way that its absence disrupts the ability to adapt to the metabolic demands evoked by exercise training in rats.

Metabolism-clinical and Experimental, 2007

The use of experimental models of diabetes mellitus (DM) has been useful in understanding the com... more The use of experimental models of diabetes mellitus (DM) has been useful in understanding the complex pathogenesis of DM. Streptozotocin (STZ) injected in rats during the neonatal period has usually led to the major features described in diabetic patients (hyperglycemia, polyphagia, polydipsia, polyuria, and abnormal glucose tolerance) in a short period. Diabetes mellitus is a product of low insulin sensibility and pancreatic beta-cell dysfunction. Its process is characterized by a symptomless prediabetic phase before the development of the disease. In this study, we investigated the long-term effects of diabetes induction regarding the cellular metabolic aspects of this model and its similarities with diabetes found in humans. Male Wistar rats (5-day old) were intraperitoneally injected with STZ (150 mg/kg) and followed up for 12 weeks. On the 12th week, animals were decapitated and peri-epididymal fat pads were excised for adipocyte isolation. The following studies were performed: insulin-stimulated 2-deoxy-d-[3H]glucose uptake; incorporation of d-[U-14C]-glucose into lipids and conversion into 14CO2; and insulin binding. The weight gain rate of the STZ-treated group became significantly lower by the eighth week. These rats developed polyphagia, polydipsia, polyuria, and glycosuria, and impaired glucose tolerance. Biological tests with isolated adipocytes revealed a reduction in the insulin receptor number and an impairment in their ability to oxidize glucose as well as to incorporate it into lipids. Interestingly, parallel to reduced body weight, the adipocyte size of STZ rats was significantly small. We concluded that apart of a decrease in pancreatic insulin content, this experimental model of DM promotes a remarkable and sustained picture of insulin resistance in adulthood that is strongly related to a loss in adipose mass.

European Journal of Pharmacology, 1979

... North-Holland Biomedical Press GASTRIC EMPTYING EFFECT OF d,I-TRANYLCYPROMINE AND ITS STEREOI... more ... North-Holland Biomedical Press GASTRIC EMPTYING EFFECT OF d,I-TRANYLCYPROMINE AND ITS STEREOISOMERS REGINA SCIVOLETTO, NAOMI S. HELL ... in inhibiting MAO whereas 1-Tc blocks catecholamine uptake more strikingly (Escobar et al., 1974; Fuentes et al ...

Arquivos Brasileiros de Endocrinologia & Metabologia, 2014

Jornal de Pediatria, 2007

To describe the advances in research into the physiological role of white adipose tissue, with em... more To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity.

American Journal of Hypertension, 1997

The effect of sodium chloride salt restriction and overload on insulin sensitivity is still an op... more The effect of sodium chloride salt restriction and overload on insulin sensitivity is still an open question.Some authors have shown that NaCl salt restriction increases insulin resistance, whereas others have reported the opposite. In the present study, the objective was to get some more insight on this issue by studying the influence of dietary salt content on glucose uptake in isolated adipocytes.Male Wistar rats were fed from weaning either low (0.15%) or high (7.94%) salt diets. On the 12th week of age, weight and tail-cuff blood pressure were measured, followed 10 days later by an intravenous glucose tolerance test with concomitant insulin determinations. One week later, the rats were killed by decapitation and epididymal adipocytes were obtained for glucose metabolism evaluation.No weight differences were observed between both groups of animals. Blood pressure was significantly higher (P < .001) on salt overloaded rats (146 ± 11 mm Hg) than on salt restricted ones (115 ± 5 mm Hg). Dietary salt content did not influence the area under the curve of plasma glucose. Area under the curve of insulin levels was lower (P = .023) on the high than on the low salt diet. A higher (P < .001) glucose uptake in the absence and in the presence of insulin was observed in adipocytes from rats on the high salt diet. The median effective concentration (EC50) from the dose-response curves of glucose uptake was the same on both groups of animals. Glucose oxidation and incorporation into lipids was also enhanced by salt overload. High salt increased insulin receptor density (P < .001).In conclusion, salt overload increased blood pressure, and high and low salt dietary content did not influence insulin sensitivity based on the unchanged EC50 from the in vitro studies. However, insulin-independent glucose uptake, oxidation, and incorporation into lipids were enhanced in adipocytes from rats on the high salt diet. The lower levels of insulin during the glucose tolerance test on salt-loaded animals may be a consequence of the higher insulin-independent glucose uptake in that group.

Journal of Pineal Research, 2006

Abstract: Considering the cyclic characteristic of production and secretion of pineal melatonin,... more Abstract: Considering the cyclic characteristic of production and secretion of pineal melatonin, it is reasonable to assume that this oscillation might be important in determining the variety of its circadian and seasonal effects. To simulate this physiological condition in vitro, isolated adipocytes were exposed to melatonin in a circadian-like pattern by adding the hormone to the incubating medium during 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day). This intermittent procedure was interrupted when three cycles with melatonin were fulfilled (60-hr incubation). Here, we report the effects of melatonin (1 nM) added intermittently or continuously to the incubating medium alone or in combination with insulin (5 nM) and/or dexamethasone (7 nM) on leptin release and expression by rat adipocytes. After acute 12-hr incubation neither melatonin nor insulin alone affected leptin expression, but together they increased it by 105%. Dexamethasone increased leptin mRNA content and release (70%) but this effect was not enhanced by melatonin. Nevertheless, after 60 hr under intermittent melatonin, we observed a synergism between melatonin and dexamethasone. This interaction promoted an increment (75% compared with dexamethasone alone) in leptin release and expression. Our results suggest that circadian-like exposure to melatonin potentiates the dexamethasone action and is important to the effects promoted by insulin on leptin expression. Based on an in vitro approach, this work helps to clarify the physiological relevance and the repercussions of the in vivo circadian pattern of melatonin secretion.

Jornal De Pediatria, 2007

To describe the advances in research into the physiological role of white adipose tissue, with em... more To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity.

European Journal of Biochemistry, 2000

The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases e... more The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases even disappearance of fat tissue. Here, we report the effects of leptin (10 and 100 ng´mL 21 ) on isolated rat adipocytes maintained for 15 h in culture. Leptin decreased the incorporation of acetate into total lipids by 30%. A reduction in this incorporation (42%) was still observed after the leptin-cultivated adipocytes were exposed to a supraphysiological insulin concentration (10 000 mU´mL 21 ). On the other hand, leptin increased acetate degradation by 69% and the maximal activity of citrate synthase by 50% in isolated adipocytes. It also increased oleate degradation by 35 and 50% at concentrations of 10 and 100 ng´mL 21 , respectively. Eventually, leptin upregulated the uncoupling protein-2 (UCP2) mRNA level by 63% and had no effect on uncoupling protein-3 (UCP3) mRNA in isolated adipocytes. The upregulation of UCP2 mRNA might have contributed to the stimulation of acetate and fatty acid degradation by leptin. The peripheral effects of leptin observed in this study are in line with the general energy dissipating role postulated for this hormone and for UCP2. They suggest mechanisms by which adipocytes regulate their fat content by an autocrine pathway without the participation of the central nervous system.

Journal of Pineal Research, 2008

Abstract: The aim of this work was to investigate the effect of the in vitro circadian-like expo... more Abstract: The aim of this work was to investigate the effect of the in vitro circadian-like exposure to melatonin [in the presence or absence of insulin (Ins)] on the metabolism and clock gene expression in adipocytes. To simulate the cyclic characteristics of the daily melatonin profile, isolated rat adipocytes were exposed in a circadian-like pattern to melatonin added to the incubating medium for 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day) combined or not with Ins. This intermittent incubation was interrupted when four and a half 24-hr cycles were fulfilled. At the end, either during the induced night (melatonin present) or the induced day (melatonin absent), the rates of lipolysis and D-[U-14C]-glucose incorporation into lipids were estimated, in addition to the determination of lipogenic [glucose-6-phosphate dehydrogenase and fatty acid synthase (FAS)] and lipolytic (hormone sensitive lipase) enzymes and clock gene (Bmal-1b, Clock, Per-1 and Cry-1) mRNA expression. The leptin release was also measured. During the induced night, the following effects were observed: an increase in the mRNA expression of Clock, Per-1 and FAS; a rise in lipogenic response and leptin secretion; and a decrease in the lipolytic activity. The intermittent exposure of adipocytes to melatonin temporally and rhythmically synchronized their metabolic and hormonal function in a circadian fashion, mimicking what is observed in vivo in animals during the daily light–dark cycle. Therefore, this work helps to clarify the physiological relevance of the circadian pattern of melatonin secretion and its interactions with Ins, contributing to a better understanding of the adipocyte biology.

Metabolism-clinical and Experimental, 2004

This study investigated the effects of pinealectomy and fasting on rat adipose tissue metabolism,... more This study investigated the effects of pinealectomy and fasting on rat adipose tissue metabolism, as well as on profiles of the hormones directly involved in its regulation (insulin, leptin, and corticosterone). Pinealectomized (PINX) and sham-operated (CONTROL) adult male Wistar rats were killed 6 weeks after surgery, in either fed or fasted (12 and 36 hours) states. Blood samples (for glucose and hormone determinations) and peri-epididymal adipocytes (for in vitro insulin-stimulated glucose uptake, oxidation, and incorporation into lipids) were collected. Pineal ablation decreased insulin-stimulated glucose uptake in adipocytes of both fed and fasted animals without affecting insulin-binding capacity. Pinealectomy attenuated the reduction in the ability to oxidize glucose in both basal and insulin-stimulated states during fasting. This alteration in the ability of adipocytes to oxidize glucose appeared together with a decrease in insulin-induced glucose incorporation into lipids in PINX animals. Additionally, pinealectomized rats showed higher corticosterone levels in both fed and fasted states, and a lower leptinemia with 36 hours of fasting, in comparison to CONTROLs. In conclusion, our data reinforce the hypothesis that the pineal gland has a role in the modulation of adipocyte metabolism, and its absence alters metabolic adaptation to fasting in rats.

Journal of Pineal Research, 2005

Abstract: This study investigated the effects of pinealectomy and exercise training on rat adipo... more Abstract: This study investigated the effects of pinealectomy and exercise training on rat adipose tissue metabolism. Pinealectomized (PINX) and sham-operated (CONTROL) adult male Wistar rats were subdivided into four subgroups, including PINX untrained, PINX trained, CONTROL untrained and CONTROL trained. At the end of the training period (8 wk), the rats were killed and peri-epididymal adipocytes were isolated for in vitro insulin-stimulated glucose uptake, conversion of d-[U-14C]-glucose, l-[U-14C]-lactate, [2-14C]-acetate and [1-14C]-palmitate into 14CO2, and insulin binding. Pinealectomy resulted in a significantly decreased insulin-stimulated glucose uptake in adipocytes without affecting insulin-binding capacity. However, in intact control animals only, training promoted a higher baseline glucose uptake in adipocytes. Training influenced the adipocyte ability to oxidize the different substrates: the rates of glucose and palmitate oxidation increased while the rates of lactate and acetate diminished. Nevertheless, these effects of exercise training were not seen in pinealectomized rats. Additionally, an increase in palmitate oxidation was observed in sedentary pinealectomized animals. In conclusion, these data show that the pineal gland alters the patterns of substrate utilization by the adipocyte, in such a way that its absence disrupts the ability to adapt to the metabolic demands evoked by exercise training in rats.

Metabolism-clinical and Experimental, 2007

The use of experimental models of diabetes mellitus (DM) has been useful in understanding the com... more The use of experimental models of diabetes mellitus (DM) has been useful in understanding the complex pathogenesis of DM. Streptozotocin (STZ) injected in rats during the neonatal period has usually led to the major features described in diabetic patients (hyperglycemia, polyphagia, polydipsia, polyuria, and abnormal glucose tolerance) in a short period. Diabetes mellitus is a product of low insulin sensibility and pancreatic beta-cell dysfunction. Its process is characterized by a symptomless prediabetic phase before the development of the disease. In this study, we investigated the long-term effects of diabetes induction regarding the cellular metabolic aspects of this model and its similarities with diabetes found in humans. Male Wistar rats (5-day old) were intraperitoneally injected with STZ (150 mg/kg) and followed up for 12 weeks. On the 12th week, animals were decapitated and peri-epididymal fat pads were excised for adipocyte isolation. The following studies were performed: insulin-stimulated 2-deoxy-d-[3H]glucose uptake; incorporation of d-[U-14C]-glucose into lipids and conversion into 14CO2; and insulin binding. The weight gain rate of the STZ-treated group became significantly lower by the eighth week. These rats developed polyphagia, polydipsia, polyuria, and glycosuria, and impaired glucose tolerance. Biological tests with isolated adipocytes revealed a reduction in the insulin receptor number and an impairment in their ability to oxidize glucose as well as to incorporate it into lipids. Interestingly, parallel to reduced body weight, the adipocyte size of STZ rats was significantly small. We concluded that apart of a decrease in pancreatic insulin content, this experimental model of DM promotes a remarkable and sustained picture of insulin resistance in adulthood that is strongly related to a loss in adipose mass.

European Journal of Pharmacology, 1979

... North-Holland Biomedical Press GASTRIC EMPTYING EFFECT OF d,I-TRANYLCYPROMINE AND ITS STEREOI... more ... North-Holland Biomedical Press GASTRIC EMPTYING EFFECT OF d,I-TRANYLCYPROMINE AND ITS STEREOISOMERS REGINA SCIVOLETTO, NAOMI S. HELL ... in inhibiting MAO whereas 1-Tc blocks catecholamine uptake more strikingly (Escobar et al., 1974; Fuentes et al ...

Arquivos Brasileiros de Endocrinologia & Metabologia, 2014