Egberto Gaspar de Moura

Publications

• 2.69

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  Maternal Tobacco Smoke Exposure During Lactation Inhibits Catecholamine Production by Adrenal Medullae in Adult Rat Offspring.

  A P Santos-Silva, P C Lisboa, C R Pinheiro, L A Maia, N Peixoto-Silva, Y Abreu-Villaça, E G Moura, E Oliveira

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 05/2012;

  Previously, we have shown that maternal smoke exposure during lactation, even when pups are not exposed, affects biochemical profiles in the offspring at weaning, eliciting lower body adiposity, hyperinsulinemia, hypocorticosteronemia and lower adrenal catecholamine content. However, the future impa... [more] Previously, we have shown that maternal smoke exposure during lactation, even when pups are not exposed, affects biochemical profiles in the offspring at weaning, eliciting lower body adiposity, hyperinsulinemia, hypocorticosteronemia and lower adrenal catecholamine content. However, the future impact of tobacco exposure is still unknown. As postnatal nicotine exposure causes short- and long-term effects on pups' biochemistry and endocrine profiles, we have now evaluated some endocrine and metabolic parameters of the adult offspring whose mothers were tobacco exposed during lactation. For this, from day 3 to 21 of lactation, rat dams were divided in: 1) SE group, cigarette smoke-exposed (1.7 mg nicotine/cigarettes for 1 h, 4 times/day, daily), without their pups, and 2) C group, exposed to air, in the same conditions. Offspring were killed at 180-days-old. Body weight and food intake were evaluated. Blood, white adipose tissue, adrenal, and liver were collected. All significant data were p<0.05. The adult SE offspring showed no change in body weight, cumulative food intake, serum hormone profile, serum lipid profile, or triglycerides content in liver. However, in adrenal gland, adult SE offspring showed lower catecholamine content ( - 50%) and lower tyrosine hydroxylase protein expression ( - 56%). Despite the hormonal alterations during lactation, tobacco smoke exposure through breast milk only programmed the adrenal medullary function at adulthood and this dysfunction can have consequence on stress response. Thus, an environment free of smoke during lactation period is essential to improve health outcomes in adult offspring.
• 2.11

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  Flaxseed bioactive compounds change milk, hormonal and biochemical parameters of dams and offspring during lactation.

  A A Troina, M S Figueiredo, M C F Passos, A M Reis, E Oliveira, P C Lisboa, E G Moura

  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 05/2012;

  We evaluated maternal intake of SDG (secoisolariciresinol diglucoside), a compound from flaxseed, and flaxseed oil + SDG on biochemical and hormonal parameters of dams and male and female offspring during lactation. Dams were fed a standard diet (C); diet added 40mg of SDG/100g diet (SDG) or diet ad... [more] We evaluated maternal intake of SDG (secoisolariciresinol diglucoside), a compound from flaxseed, and flaxseed oil + SDG on biochemical and hormonal parameters of dams and male and female offspring during lactation. Dams were fed a standard diet (C); diet added 40mg of SDG/100g diet (SDG) or diet added 40mg of SDG/100g diet and 7% of flaxseed oil (OLSDG). SDG and OLSDG dams showed hyperprolactinemia. The OLSDG milk had lower lactose and protein, while the SDG milk had lower protein on the 14(th) day of lactation. At 14 days, OLSDG male and female pups showed lower body mass, SDG and OLSDG male pups had hypoprolactinemia and lower body fat mass, but higher visceral fat mass (VFM) and hypertriglyceridemia. At 21 days, male SDG and OLSDG presented hypotriglyceridemia. At 14 days, SDG and OLSDG female offspring showed higher serum 17-β estradiol (E2); OLSDG presented hypercholesterolemia and SDG presented hypertriglyceridemia. At 21 days, SDG and OLSDG female pups showed hypotriglyceridemia and OLSDG shower lower E2. Both maternal treatments changes maternal metabolism as well as hormonal and biochemical parameters of the offspring, which are gender-dependent. Maternal hyperprolactinemia may act as an imprint factor responsible for the hormonal and metabolic changes observed in the pups.
• 2.69

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  Postnatal low protein diet programs leptin signaling in the hypothalamic-pituitary-thyroid axis and pituitary TSH response to leptin in adult male rats.

  P C Lisboa, E Oliveira, A T S Fagundes, A P Santos-Silva, E P S Conceição, M C F Passos, E G Moura

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 02/2012; 44(2):114-22.

  Maternal protein restriction (PR) during lactation programs a lower body weight, hyperthyroidism, leptin resistance, and over-expression of leptin receptor in the pituitary gland at adulthood. Because leptin regulates energy homeo-stasis and the hypothalamus-pituitary-thyroid (HPT) axis, we evaluate... [more] Maternal protein restriction (PR) during lactation programs a lower body weight, hyperthyroidism, leptin resistance, and over-expression of leptin receptor in the pituitary gland at adulthood. Because leptin regulates energy homeo-stasis and the hypothalamus-pituitary-thyroid (HPT) axis, we evaluated adipocyte morphology, the leptin signaling pathway in the HPT axis and the in vitro thyrotropin (TSH) response to leptin in adult progeny in this model. At birth, dams were separated in control diet with 23% protein or PR diet with 8% protein. After weaning, offspring received a normal diet. Adult PR offspring showed lower adipocytes area, higher leptin:visceral fat ratio, lower hypothalamic signal transducer and activator of transcription 3 (STAT3), higher pituitary leptin receptor (Ob-R) and lower thyroid janus tyrosine kinase 2 (JAK2) contents. Regarding the in vitro study, 10(-7)  M leptin stimulated TSH secretion in C offspring at 30 min, but had no effect in PR offspring. At 120 min, 10(-7)  M leptin decreased TSH secretion in C offspring and increased in PR offspring. Maternal nutritional status during lactation programs for adipocyte atrophy, higher relative leptin secretion and changes in the downstream leptin signaling in the HPT axis and the TSH response to leptin, suggesting a role for leptin in the development of the HPT axis and helping to explain thyroid dysfunction and leptin resistance in this programming model. Because leptin stimulates thyroid function, it is unlikely that these alterations were responsible for the increased in serum T4 and T3. Therefore, neonatal PR programs a hyperthyroidism, lower adipogenesis, and impairment of leptin action.
• 2.69

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  Maternal prolactin inhibition during lactation affects physical performance evaluated by acute exhaustive swimming exercise in adult rat offspring.

  G Casimiro-Lopes, P C Lisboa, J C Koury, G Boaventura, M C F Passos, E G Moura

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 02/2012; 44(2):123-9.

  Maternal prolactin inhibition at the end of lactation programs for metabolic syndrome and hypothyroidism in adult offspring, which could negatively affect exercise performance. We evaluated the effects of maternal hypoprolactinemia in late lactation on physical performance in adult progeny. Lactatin... [more] Maternal prolactin inhibition at the end of lactation programs for metabolic syndrome and hypothyroidism in adult offspring, which could negatively affect exercise performance. We evaluated the effects of maternal hypoprolactinemia in late lactation on physical performance in adult progeny. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg per day) or saline on days 19, 20, and 21 of lactation and offspring were followed until 180 days old. Physical performance was recorded in untrained rats at 90 and 180 days by an acute exhaustive swimming test (exercise group-Ex). At day 90, BRO offspring showed higher visceral fat mass, higher plasma thiobarbituric acid reactive substances, lower total antioxidant capacity, higher liver glycogen, lower glycemia, and normal insulinemia. Although thyroid hormones (TH) levels were unchanged, mitochondrial glycerol phosphate dehydrogenase (mGPD) activity was lower in muscle and in brown adipose tissue (BAT). At this age, BRO-Ex offspring showed higher exercise capacity, lower blood lactate, higher serum T3, and higher muscle and BAT mGPD activities. At day 180, BRO offspring showed central obesity, hypothyroidism, insulin resistance, and lower EDL (extensor digitorum longus) muscle glycogen with unaltered plasma oxidative stress markers. This group showed no alteration of exercise capacity or blood lactate. After exercise, EDL and liver glycogen were lower, while T3 levels, BAT and muscle mGPD activities were normalized. Liver glycogen seem to be related with higher exercise capacity in younger BRO offspring, while the loss of this temporary advantage maybe related to the hypothyroidism and insulin resistance developed with age.
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  Developmental plasticity in adrenal function and leptin production primed by nicotine exposure during lactation: gender differences in rats.

  C R Pinheiro, E Oliveira, I H Trevenzoli, A C Manhães, A P Santos-Silva, V Younes-Rapozo, S Claudio-Neto, A C Santana, C C A Nascimento-Saba, E G Moura, P C Lisboa

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 09/2011; 43(10):693-701.

  Neonate male rats whose mothers were nicotine-treated during lactation have higher adiposity, hyperleptinemia, and adrenal dysfunction. At adulthood, they still present higher adiposity and hyperleptinemia, but there was no report about their adrenal function. Also, there was no report of this devel... [more] Neonate male rats whose mothers were nicotine-treated during lactation have higher adiposity, hyperleptinemia, and adrenal dysfunction. At adulthood, they still present higher adiposity and hyperleptinemia, but there was no report about their adrenal function. Also, there was no report of this developmental plasticity on females. Here, we evaluated the adrenal function and leptin content in adipocytes and muscle of male and female adult offspring whose mothers were nicotine-treated during lactation. On the 2nd postnatal day (PN2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6 mg/kg/day) or saline for 14 days (12 litters/group and 2 rats/litter). Male and female offspring were killed on PN180. Significant data were p<0.05. Male NIC offspring presented higher adrenal catecholamine content (+ 89%) and TH expression (+ 38%), lower "in vitro" catecholamine release (- 19%), and higher adrenergic β3 receptor (ADRB3, + 59%) content in visceral adipose tissue (VAT). Serum corticosterone was higher (+ 77%) in male NIC group, coherent with the increase of both CRH and ACTH immunostaining in hypothalamus and pituitary, respectively. Leptin content was higher in VAT (+ 23%), which may justify the observed hyperleptinemia. Female NIC offspring presented lower ADRB3 content in VAT (- 39%) and lower leptin content in subcutaneous adipose tissue (SAT) (- 46%), but higher leptin content in soleus muscle (+ 22%), although leptinemia was normal. We evidenced a sex dimorphism in the model of maternal nicotine exposure during lactation. The adrenal function in adult offspring was primed only in male offspring while the female offspring displayed relevant alterations in leptin content on muscle and adipocytes.
• 2.97

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  Maternal prolactin inhibition at the end of lactation affects learning/memory and anxiety-like behaviors but not novelty-seeking in adult rat progeny.

  Mabel C Fraga, Egberto G Moura, Juliana Oliveira Silva, Isabela Teixeira Bonomo, Cláudio C Filgueiras, Yael Abreu-Villaça, Magna C F Passos, Patrícia C Lisboa, Alex C Manhães

  Pharmacology, biochemistry, and behavior. 07/2011; 100(1):165-73.

  Maternal hypoprolactinemia at the end of lactation in rats reduces milk production and is associated with offspring's malnutrition. Since malnutrition during development is also known to have long lasting effects on cognition and emotion, in the present study we tested the hypothesis that matern... [more] Maternal hypoprolactinemia at the end of lactation in rats reduces milk production and is associated with offspring's malnutrition. Since malnutrition during development is also known to have long lasting effects on cognition and emotion, in the present study we tested the hypothesis that maternal hypoprolactinemia, induced by bromocriptine treatment, at the end of the lactating period affects memory/learning, novelty-seeking and anxiety-like behaviors in adult male Wistar rats using, respectively, the radial arm water maze (RAWM), the hole board (HB) arena and the elevated plus-maze (EPM). We also analyzed serum corticosterone and thyroid hormone levels at postnatal day (PN) 21. Lactating dams were treated with bromocriptine (BRO, 1mg twice a day, inhibiting prolactin) or saline from PN19 to 21 (the last 3 days of lactation). BRO offspring had hypercorticosteronemia and hypothyroidism at PN21. In the RAWM, reductions in latency observed in CON rats were initially more accentuated than in BRO ones. By the end of the testing period, latencies became similar between groups. No difference was observed between groups regarding the number of nose-pokes in the HB. In the EPM, BRO rats stayed less time in and had fewer entries into the open-arms than CON ones. This pattern of results indicates that maternal bromocriptine treatment at the end of the lactating period results in poorer memory/learning performance and in higher levels of anxiety-like behavior in the adult offspring, demonstrating that even a relatively short period of malnutrition during development can have long lasting detrimental effects regarding cognition and emotion.
• 2.86

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  Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure.

  J L Nobre, P C Lisboa, A P Santos-Silva, N S Lima, A C Manhães, J F Nogueira-Neto, A Cabanelas, C C Pazos-Moura, E G Moura, E de Oliveira

  The Journal of endocrinology. 06/2011; 210(3):349-59.

  Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary ca... [more] Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C - standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N - standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D(3) (+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (-37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action.
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  Higher white adipocyte area and lower leptin production in adult rats overfed during lactation.

  E P S Conceição, I H Trevenzoli, E Oliveira, J G Franco, A S Carlos, C C A Nascimento-Saba, E G Moura, P C Lisboa

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 06/2011; 43(7):513-6.

  Litter size reduction during lactation is a good model for childhood obesity since it induces overnutrition and programming for obesity at adulthood. Adult offspring develop higher fat mass content, hyperinsulinemia and insulin resistance, hypertension, lower HDL cholesterol, hyperphagia, and leptin... [more] Litter size reduction during lactation is a good model for childhood obesity since it induces overnutrition and programming for obesity at adulthood. Adult offspring develop higher fat mass content, hyperinsulinemia and insulin resistance, hypertension, lower HDL cholesterol, hyperphagia, and leptin resistance. Leptin resistance is often associated with hyperleptinemia. Although we observed higher SOCS3 and lower STAT3 in the hypothalamus of rats raised in small litters featuring a central leptin resistance, they showed unexpected normoleptinemia at 180 days old. Then, to clarify why early overfed rats did not develop hyperleptinemia when adult, we studied the leptin production by the visceral and subcutaneous adipose tissue and skeletal muscle as well as the morphology in the 2 different fat depots. To induce EO, litter size was reduced to 3 pups/litter (SL group) on the 3 (rd) day of life. In controls (NL group), litter size was adjusted to 10 pups/litter. Rats were killed at 180 days old. The programming of adipose tissue morphology by early overnutrition is specific between the different fat depots with hypertrophy only in the visceral compartment. In addition, the visceral adipocyte showed lower leptin content that may indicate a reduced leptin synthesis. These data suggest that adipocytes from SL rats are dysfunctional, since a higher leptin production in larger adipose cells is expected. In conclusion, postnatal nutrition is determinant for future leptin production by different fat depots as well as adipocyte morphology. These changes seem to be related to the severity of obesity and its metabolic consequences.
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  Blocking leptin action one week after weaning reverts most of the programming caused by neonatal hyperleptinemia in the adult rat.

  P A Trotta, E G Moura, J G Franco, N S Lima, E de Oliveira, A Cordeiro, L L Souza, K J Oliveira, P C Lisboa, C C Pazos Moura, M C F Passos

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 02/2011; 43(3):171-7.

  Hyperleptinemia during lactation programs for higher serum leptin in 30-day-old and adult rats, associated with metabolic changes. Here we evaluated the inhibition of serum leptin at 29 and 30 days on the metabolic phenotype of rats programmed with leptin during lactation. Pups from Wistar rats were... [more] Hyperleptinemia during lactation programs for higher serum leptin in 30-day-old and adult rats, associated with metabolic changes. Here we evaluated the inhibition of serum leptin at 29 and 30 days on the metabolic phenotype of rats programmed with leptin during lactation. Pups from Wistar rats were saline-injected or leptin-injected from postnatal day 1 to day 10. At 29 and 30 days old, animals were injected with anti-leptin antibody (LA and CA) or saline (LS and CS). In adult animals, higher visceral (+53%) and total fat mass (+33%), hyperleptinemia (+67%), hypertriglyceridemia (+47%), and hypoadiponectinemia (-44%) observed in LS group compared to CS were prevented by immunoneutralization of leptin, since LA group had those parameters values similar to CS group. However, immunoblockade of leptin in normal animals led to the same metabolic changes seen in leptin-treated animals, in addition to lower serum adiponectin (-77% vs. CS) and higher insulin resistance index (+37%). Liver sirtuin1 (SIRT1) was higher (+41%) only in LA group, suggesting a role for SIRT1 in the prevention of leptin programming. Hypothalamic OBR was lower and SOCS3 higher in LS group and these changes were normalized in LA group. In conclusion, blocking leptin action one week after weaning seems to revert most of the alterations observed in rats programmed by neonatal hyperleptinemia. Higher liver SIRT1 expression may be one of the mechanisms involved, leading to a better glucose and lipid metabolism. Our data suggest that the lack or the excess of leptin programs an adverse metabolic phenotype in adulthood.
• 2.86

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  Effects of tobacco smoke exposure during lactation on nutritional and hormonal profiles in mothers and offspring.

  A P Santos-Silva, E Oliveira, C R Pinheiro, A L Nunes-Freitas, Y Abreu-Villaça, A C Santana, C C Nascimento-Saba, J F Nogueira-Neto, A M Reis, E G Moura, P C Lisboa

  The Journal of endocrinology. 01/2011; 209(1):75-84.

  Exposure to tobacco smoke is related to changes in energy balance regulation and several endocrine dysfunctions. Previously, we showed that maternal nicotine (the main addictive compound of tobacco) exposure exclusively during lactation affects biochemical profiles in mothers, milk, and pups. As the... [more] Exposure to tobacco smoke is related to changes in energy balance regulation and several endocrine dysfunctions. Previously, we showed that maternal nicotine (the main addictive compound of tobacco) exposure exclusively during lactation affects biochemical profiles in mothers, milk, and pups. As the possible consequences for mothers and offspring of maternal smoking during lactation are still unknown, we evaluated the effects of tobacco smoke exposure on nutritional, biochemical, and hormonal parameters in dams and pups at weaning. After 72 h from birth, lactating rats were divided into two groups: smoke-exposed (S) in a cigarette-smoking machine, 4 × 1 h per day throughout the lactation period without pups; control (C), rats were treated the same as the experimental group but exposed to filtered air. Dams and pups were killed at weaning (21 days of lactation). Body weight and food intake were evaluated. Milk, blood, visceral fat, adrenal, and carcass were collected. S dams showed hyperprolactinemia (+50%), hypoinsulinemia (-40%), hypoleptinemia (-46%), as well as lower triglycerides (-53%) and very low-density lipoprotein cholesterol (-50%). Milk of S dams had higher lactose (+52%) and triglycerides (+78%). S pups presented higher body protein (+17%), lower total (-24%) and subcutaneous fat contents (-25%), hypoglycemia (-11%), hyperinsulinemia (+28%), hypocorticosteronemia (-40%), lower adrenal catecholamine content (-40%), hypertriglyceridemia (+34%), higher high-density lipoprotein cholesterol (+16%), and lower low-density lipoprotein cholesterol (-45%). In conclusion, tobacco smoke exposure leads to changes in nutritional, biochemical, and hormonal parameters in dams and, passively through the milk, may promote several important metabolic disorders in the progeny.
• 2.56

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  Neonatal nicotine exposure alters leptin signaling in the hypothalamus-pituitary-thyroid axis in the late postnatal period and adulthood in rats.

  A P Santos-Silva, E G Moura, C R Pinheiro, A S Rios, Y Abreu-Villaça, M C F Passos, E Oliveira, P C Lisboa

  Life sciences. 07/2010; 87(5-6):187-95.

  Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during la... [more] Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during lactation on the leptin signaling in the hypothalamus-pituitary-thyroid axis of suckling and adult offspring. Two days after delivery, osmotic minipumps were implanted in lactating rats, and nicotine (NIC, 6 mg/kg/day s.c.) or saline (C) was administered for 14days. Offspring were killed at 15 and 180 days-old. Proteins belonging to leptin signaling were analyzed by Western blot. Significant differences had p<0.05. In the hypothalamus, NIC offspring showed higher OB-R and pSTAT-3 content (+58%,+1.34x) at 15 days, and lower OB-R, JAK-2 and pSTAT-3 (-61%, -42%, -56%) at 180 days. In the pituitary gland, NIC offspring showed lower JAK-2 content (-52%) at 15 days, but no differences in adulthood. In the thyroid gland, the NIC group presented lower OB-R, JAK-2 and STAT-3 (-44%, -50%, -47%) and higher pSTAT-3 expression (+80%) at 15 days. At 180 days-old, NIC offspring presented higher thyroid OB-R (+1.54x) and lower pSTAT-3 content (-34%). Neonatal primary hypothyroidism induced by maternal nicotine exposure during lactation may be partially explained by decreased leptin signaling in the thyroid, though the early stimulation of the central leptin pathway did not prevent the thyroid dysfunction. Long-term effects of postnatal nicotine exposure on leptin signaling in the hypothalamus and thyroid appear to involve central and peripheral leptin resistance in adulthood.
• 2.86

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  Neonatal nicotine exposure causes insulin and leptin resistance and inhibits hypothalamic leptin signaling in adult rat offspring.

  Elaine de Oliveira, Egberto G Moura, Ana Paula Santos-Silva, Cíntia R Pinheiro, Natalia S Lima, José Firmino Nogueira-Neto, Andre L Nunes-Freitas, Yael Abreu-Villaça, Magna C F Passos, Patrícia C Lisboa

  The Journal of endocrinology. 07/2010; 206(1):55-63.

  Maternal nicotine (NIC) exposure during lactation leads to overweight, hyperleptinemia, and hypothyroidism in adult rat offspring. In this model, we analyzed adipocyte morphology, glucose homeostasis (serum insulin and adiponectin; liver and muscle glycogen), serum lipid, and the leptin signaling pa... [more] Maternal nicotine (NIC) exposure during lactation leads to overweight, hyperleptinemia, and hypothyroidism in adult rat offspring. In this model, we analyzed adipocyte morphology, glucose homeostasis (serum insulin and adiponectin; liver and muscle glycogen), serum lipid, and the leptin signaling pathway. After birth, osmotic minipumps were implanted in lactating rats, which were divided into the groups NIC (6 mg/kg per day s.c. for 14 days) and control (C, saline). NIC and C offspring were killed at the age of 180 days. Adult NIC rats showed higher total body fat (+10%, P<0.05), visceral fat mass (+12%, P<0.05), and cross-sectional area of adipocytes (epididymal: +12% and inguinal: +43%, P<0.05). Serum lipid profile showed no alteration except for apolipoprotein AI, which was lower. We detected a lower adiponectin:fat mass ratio (-24%, P<0.05) and higher insulinemia (+56%, P<0.05), insulin resistance index (+43%, P<0.05), leptinemia (+113%, P<0.05), and leptin:adiponectin ratio (+98%, P<0.05) in the adult NIC group. These rats presented lower hypothalamic contents of the proteins of the leptin signaling pathway (leptin receptor (OB-R): -61%, janus tyrosine kinase 2: -41%, and p-signal transducer and activator of transcription 3: -56%, P<0.05), but higher suppressor of cytokine signaling 3 (+81%, P<0.05). Therefore, NIC exposure only during lactation programs rats for adipocyte hypertrophy in adult life, as well as for leptin and insulin resistance. Through the effects of NIC, perinatal maternal cigarette smoking may be responsible for the future development of some components of the metabolic syndrome in the offspring.
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  Prolactin inhibition at mid-lactation influences adiposity and thyroid function in adult rats.

  P C Lisboa, L Pires, E de Oliveira, N S Lima, I T Bonomo, A M Reis, M C F Passos, E G Moura

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 05/2010; 42(8):562-9.

  Maternal hypoprolactinemia at the end of lactation (a precocious weaning model) increases milk leptin transfer and results in overweight, leptin resistance, and secondary hypothyroidism at adulthood. We studied the effects of prolactin (PRL) inhibition during mid-lactation (a partial malnutrition mo... [more] Maternal hypoprolactinemia at the end of lactation (a precocious weaning model) increases milk leptin transfer and results in overweight, leptin resistance, and secondary hypothyroidism at adulthood. We studied the effects of prolactin (PRL) inhibition during mid-lactation (a partial malnutrition model) on milk leptin transfer, leptinemia, body composition, and thyroid function. Lactating rats were treated with bromocryptine (BRO, 1 mg/twice daily) or saline on days 7, 8, and 9 of lactation. Offspring were sacrificed 10, 21, and 90 days after birth. After treatment, BRO-treated dams showed hypoprolactinemia and hyperleptinemia, and produced less milk with lower levels of lactose and higher milk triglycerides. Milk leptin levels were lower at weaning. Offspring of BRO-treated dams had lower body weight and length as well as less visceral fat during lactation and adulthood. Total fat was also lower at weaning and adult life, whereas total protein was higher at 90 days-old. BRO offspring presented lower serum T4 and TSH at 10 days-old and weaning, respectively. When adults, these rats exhibited hypoleptinemia, lower levels of thyroid hormones, and higher TSH. Early inhibition of PRL therefore leads to offspring malnutrition and affects subsequent growth. Also, inhibition of PRL during lactation predisposes offspring to hypothyroidism; however, when the inhibition occurs during late lactation, the hypothyroidism is secondary, whereas when it is restricted to mid-lactation, the thyroid hypofunction is primary. The programming effect of milk suppression thus depends on the developmental stage of offspring.
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  Leptin treatment during lactation programs leptin synthesis, intermediate metabolism, and liver microsteatosis in adult rats.

  I H Trevenzoli, A L Rodrigues, E Oliveira, A A Thole, L Carvalho, M S Figueiredo, F P Toste, J F N Neto, M C F Passos, P C Lisboa, E G Moura

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 03/2010; 42(7):483-90.

  Epidemiological and experimental studies have associated development of metabolic syndrome with stressful events (nutritional, hormonal, or environmental) in early life. This phenomenon is known as programing and changes in adipokines levels in early life, especially leptin, seem to be involved with... [more] Epidemiological and experimental studies have associated development of metabolic syndrome with stressful events (nutritional, hormonal, or environmental) in early life. This phenomenon is known as programing and changes in adipokines levels in early life, especially leptin, seem to be involved with its development. We have shown that neonatal hyperleptinemia on lactation programs for leptin resistance, hyperthyroidism, and higher corticosterone and catecholamines levels with cardiovascular consequences. In the present study, we evaluated the effect of hyperleptinemia during lactation on the glucose and lipid metabolism and liver morphology of adult rats, which were saline or leptin-treated (8 microg/100 g of body weight) daily, for the first 10 days of life. Leptin group had lower body mass during treatment, but higher body mass and hyperleptinemia at adulthood, without difference in fat mass. We showed that the probable source of hyperleptinemia is the higher leptin content in the subcutaneous adipose tissue. The programed rats showed hyperinsulinemia and hypoadiponectinemia with higher expression of the hypothalamic Suppressor of Cytokine Signaling 3 (SOCS3), suggesting insulin resistance. Besides, they presented higher liver glycogen and hypertriglyceridemia. We also observed liver microsteatosis in the leptin-programed adult rats. Our data show that neonatal hyperleptinemia alters glucose metabolism, which seems to be partially compensated by the hyperinsulinemia. However, changes in the lipid metabolism are not compensated. It is probable that these changes induced by neonatal hyperleptinemia result from a selective tissue specific resistance both to insulin and leptin at adulthood, and the increase of SOCS3 may play an important role in this process.
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  Nicotine exposure affects mother's and pup's nutritional, biochemical, and hormonal profiles during lactation in rats.

  E Oliveira, C R Pinheiro, A P Santos-Silva, I H Trevenzoli, Y Abreu-Villaça, J F Nogueira Neto, A M Reis, M C F Passos, E G Moura, P C Lisboa

  The Journal of endocrinology. 02/2010; 205(2):159-70.

  We have shown that maternal nicotine exposure during lactation has long-lasting effects on body adiposity and hormonal status of rat offspring. Here, we studied the nutritional and hormonal profiles in this experimental model. Two days after birth, osmotic minipumps were implanted in lactating rats ... [more] We have shown that maternal nicotine exposure during lactation has long-lasting effects on body adiposity and hormonal status of rat offspring. Here, we studied the nutritional and hormonal profiles in this experimental model. Two days after birth, osmotic minipumps were implanted in lactating rats divided into two groups: NIC - continuous s.c. infusions of nicotine (6 mg/kg per day) for 14 days and C - saline. Dams and pups were killed at 15 and 21 days of lactation. Body weight and food intake were evaluated. Milk, blood, visceral fat, carcass, and adrenal gland were collected. All the significant data were P<0.05. At the end of nicotine exposure (15 days), dams presented higher milk production, hyperprolactinemia, and higher serum high-density lipoprotein cholesterol (HDL-C). Milk from NIC dams had higher lactose concentration and energy content. After nicotine withdrawal (21 days), dams showed lower food intake and hyperleptinemia. The 15-day-old NIC pups presented higher total body fat, higher HDL-C, serum leptin, serum corticosterone, and adrenal catecholamine content, but lower tyrosine hydroxylase protein levels. The 21-day-old NIC pups had higher body protein content and serum globulin. Thus, maternal nicotine exposure during lactation results in important changes in nutritional, biochemical, and hormonal parameters in dams and offspring. The pattern of these effects is clearly distinct when comparing the nicotine-exposed group to the withdrawal group, which could be important for the programming effects observed previously.
• 4.40

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  Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway.

  I H Trevenzoli, C R Pinheiro, E P S Conceição, E Oliveira, M C F Passos, P C Lisboa, E G Moura

  American journal of physiology. Endocrinology and metabolism. 02/2010; 298(5):E941-9.

  Leptin serum concentration in early life is an important factor for adequate future development of the offspring. Previously, we demonstrated that hyperleptinemia on lactation programmed for hyperleptinemia, central leptin resistance with lower expression of the long form of leptin receptor at hypot... [more] Leptin serum concentration in early life is an important factor for adequate future development of the offspring. Previously, we demonstrated that hyperleptinemia on lactation programmed for hyperleptinemia, central leptin resistance with lower expression of the long form of leptin receptor at hypothalamus, and higher medullary catecholamine levels with cardiovascular consequences at adulthood. The central objective of this study was to determine the direct effect of leptin on adrenal medullary function of adult rats that were leptin treated during lactation. Adrenal morphology was also accessed. Recombinant murine leptin was injected in the pups during the first 10 days of life (group L, leptin-programmed) or at adulthood during 6 days (group LC). The controls of both experiments received saline (groups C and CC). Both treatments resulted in hyperleptinemia at 150 days old (+78% and 2-fold increase, respectively; P < 0.05). Programmed animals showed hypertrophy of adrenal and higher adrenal catecholamine content at 150 days old (3-fold increase, P < 0.05), and no changes were observed in the LC group. However, LC rats had lower adrenal content of tyrosine hydroxylase (-17%, P < 0.05). Leptin-programmed rats had a lower response to leptin in vitro stimulation (-22%, P < 0.05) and lower expression of key proteins of the leptin signaling pathway, leptin receptor and janus tyrosine kinase 2 in the medullas (-61% and -29%, respectively, P < 0.05). However, they presented higher expression of phosphorylated signal transducer and activator of transcription 3 (+2-fold, P < 0.05). Leptin treatment at adulthood did not affect these parameters. The higher catecholamine synthesis and secretion in the leptin-programmed rats observed in our previous study does not seem to be a consequence of the direct effect of leptin on the medullas. We suggest that the hyperleptinemia of the programmed animals increases adrenal medullary function through sympathetic nervous system activation. In conclusion, high leptin levels on lactation program the activity of the sympathoadrenal system at adulthood that may contribute to the development of adult chronic diseases such as hypertension.
• 2.11

  Impact points

  Maternal flaxseed diet during lactation alters milk composition and programs the offspring body composition, lipid profile and sexual function.

  A A Troina, M S Figueiredo, E G Moura, G T Boaventura, L L Soares, L F M F Cardozo, E Oliveira, P C Lisboa, M A R F Passos, M C F Passos

  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 11/2009;

  We evaluated the effects of maternal dietary flaxseed during lactation on milk composition, body composition and sexual function of the adult female offspring. The dams were fed a control casein diet (C) or flaxseed diet (F, 25%) throughout lactation. F mothers showed higher serum 17beta-estradiol (... [more] We evaluated the effects of maternal dietary flaxseed during lactation on milk composition, body composition and sexual function of the adult female offspring. The dams were fed a control casein diet (C) or flaxseed diet (F, 25%) throughout lactation. F mothers showed higher serum 17beta-estradiol (E(2)) and leptin at weaning. F mother s milk had lower total cholesterol (TC) and higher E(2) and leptin. The offspring of F dams showed lower body mass (BM), body fat mass (BFM), visceral fat mass (VFM), TC and triglycerides (TG) and higher serum leptin and E(2) at 21 days. F offspring showed delayed puberty onset. At 150 days, these offspring presented higher BFM, VFM, TC, TG, E(2) and lower relative uterine weight and lower progesterone. In conclusion, flaxseed during lactation did affect the lipid profile, adipose tissue and sexual function in adulthood, probably due hyperestrogenism and hyperleptinemia at weaning.
• 4.76

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  Maternal prolactin inhibition during lactation programs for metabolic syndrome in adult progeny.

  Egberto G Moura, Isabela T Bonomo, José F Nogueira-Neto, Elaine de Oliveira, Isis H Trevenzoli, Adelina M Reis, Magna C Passos, Patricia Cristina Lisboa

  The Journal of physiology. 09/2009;

  Neonatal malnutrition is associated with metabolic syndrome in adulthood. Maternal hypoprolactinemia at the end of lactation (a precocious weaning model) caused obesity, leptin resistance and hypothyroidism in adult offspring, suggesting an association of PRL and programming of metabolic dysfunction... [more] Neonatal malnutrition is associated with metabolic syndrome in adulthood. Maternal hypoprolactinemia at the end of lactation (a precocious weaning model) caused obesity, leptin resistance and hypothyroidism in adult offspring, suggesting an association of PRL and programming of metabolic dysfunctions. Metabolic syndrome pathogenesis is still unclear, but abdominal obesity, higher triglycerides, lower HDL-c and insulin resistance have been proposed to be important factors involved. Then, we studied the consequences of maternal hypoprolactinemia during lactation on parameters associated with metabolic syndrome. Lactating Wistar rats were treated with bromocriptine (BRO, 1mg/2x/day) or saline on days 19, 20 and 21 of lactation and their offspring were followed from weaning until 180 days-old. Adult BRO offspring had higher body weight (+10%, p<0.05), total body fat (+41%, p<0.05), visceral fat (+20%, p<0.05), subcutaneous fat (+ 3 times, p<0.05) and total body protein (+24%, p<0.05). BRO group presented hyperglycemia (+16%, p<0.05), lower muscle glycogen (-51%, p<0.05), higher cholesterol (+30%, p<0.05), higher LDL-c (+ 1.5 times, p<0.05), higher triglycerides (+49%, p<0.05), lower HDL-c (-28%, p<0.05), hyperleptinemia (+ 2.9 times, p<0.05), hypoadiponectinemia (-16%, p<0.05) and hypoprolactinemia (-54%, p<0.05) as well as higher insulin resistance index (+24%, p<0.05). Regarding adrenal function, BRO rats showed hypercorticosteronemia (+46%, p<0.05) and higher total catecholamine (+37%, p<0.05). In hypothalamus, no change was observed in proteins expression of leptin signalling pathway. Thus, neonatal malnutrition induced by maternal PRL inhibition during late lactation programs for obesity, dyslipidemia and insulin resistance in adult offspring increasing the risk for metabolic syndrome development.
• 2.69

  Impact points

  Temporal Evaluation of Body Composition, Glucose Homeostasis and Lipid Profile of Male Rats Programmed by Maternal Protein Restriction During Lactation.

  A T S Fagundes, E G Moura, M C F Passos, A P Santos-Silva, E de Oliveira, I H Trevenzoli, G Casimiro-Lopes, J F Nogueira-Neto, P C Lisboa

  Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 09/2009;

  Neonatal protein restriction causes lower body weight and hormonal dysfunctions in 6 months-old rats. In this model, we studied the body composition, glycogen content, serum lipid, serum protein, and hormones related to glucose homeostasis in the offspring during development. At birth, lactating rat... [more] Neonatal protein restriction causes lower body weight and hormonal dysfunctions in 6 months-old rats. In this model, we studied the body composition, glycogen content, serum lipid, serum protein, and hormones related to glucose homeostasis in the offspring during development. At birth, lactating rats were divided into: control dams - fed a normal diet (23% protein) and protein restricted dams - fed a diet with 8% protein. After weaning, pups received normal diet. Offspring were killed at 21, 90, and 180 days-old. Protein restricted offspring showed lower visceral fat (90th day: 14%; 180th day: 19%) and lower total fat (90th day: 16%; 180th day: 14%) that explain their lower body weight. They presented lower glycemia (180th day: 17%), lower insulinemia (21st day: 63%; 180th day: 24%), higher adiponectinemia (21st day: 169%), higher liver glycogen (21st day: 104%), and higher muscle glycogen (180th day: 106%), suggesting a higher insulin sensitivity. The higher serum corticosterone (50%), higher adrenal total catecholamines content (98%) as well as in vitro catecholamine secretion (26%) of adult protein restricted offspring, suggest a programming stimulatory effect upon adrenal gland. They also presented several biochemical changes, such as lower serum total protein, albumin and globulin (21st day: 17, 21, 12%, respectively), higher LDL-c (21st day: 69%), lower triglycerides (21st day: 42%; 90th day: 39%), and lower total cholesterol (180th day: 16%). Thus, maternal protein restriction during lactation induces an energy-protein malnutrition, characterized by an impairment of the pup's protein anabolism and, after weaning, the lower adiposity suggests lower lipogenesis and higher lipolytic activity, probably caused by catecholamine and glucocorticoid action.
• 3.22

  Impact points

  Effects of maternal hyperleptinaemia during lactation on short-term memory/learning, anxiety-like and novelty-seeking behavioral traits of adult male rats.

  Mabel C Fraga-Marques, Egberto G Moura, Juliana Oliveira Silva, Sylvio Claudio-Neto, Fernanda Pereira-Toste, Magna C F Passos, Patrícia C Lisboa, Alex C Manhães

  Behavioural brain research. 09/2009;

  The objective of the present study was to evaluate whether maternal hyperleptinaemia programs anxiety-like and novelty-seeking behaviors as well as short-term memory/learning in adult male Wistar rats. During the first 10 days of lactation dams were s.c. injected with either murine leptin (LEP) or s... [more] The objective of the present study was to evaluate whether maternal hyperleptinaemia programs anxiety-like and novelty-seeking behaviors as well as short-term memory/learning in adult male Wistar rats. During the first 10 days of lactation dams were s.c. injected with either murine leptin (LEP) or saline (CON). Adult LEP offspring displayed less anxiety-like behavior and had better memory performance than CON ones, indicating that maternal hyperleptinaemia has specific long lasting behavioral effects at adulthood.