RESUMEN
Astrocytes and microglia, the immune competent cells of central nercous system, can be activated in response to metabolic signals such as obesity and hyperleptinaemia. In rats, maternal exposure to nicotine during lactation leads to central obesity, hyperleptinaemia, leptin resistance and alterations in hypothalamic neuropeptides in the offspring during adulthood. In the present study, we studied the activation of astrocytes and microglia, as well as the pattern of inflammatory mediators, in adult offspring of this experimental model. On postnatal day 2 (P2), osmotic minipumps releasing nicotine (NIC) (-6 mg/kg/day) or saline for 14 days were s.c. implanted in dams. Male offspring were killed on P180 and hypothalamic immunohistochemistry, retroperitoneal white adipose tissue (WAT) polymerase chain reaction analysis and multiplex analysis for plasma inflammatory mediators were carried out. At P180, NIC astrocyte cell number was higher in the arcuate nucleus (ARC) (medial: +82%; lateral: +110%), in the paraventricular nucleus (PVN) (+144%) and in the lateral hypothalamus (+121%). NIC glial fibrillary acidic protein fibre density was higher in the lateral ARC (+178%) and in the PVN (+183%). Interleukin-6 was not affected in the hypothalamus. NIC monocyte chemotactic protein 1 was only higher in the periventricular nucleus (+287%). NIC microglia (iba-1-positive) cell number was higher (+68%) only in the PVN, as was the chemokine (C-X3-C motif) receptor 1 density (+93%). NIC interleukin-10 was lower in the WAT (-58%) and plasma (-50%). Thus, offspring of mothers exposed to nicotine during lactation present hypothalamic astrogliosis at adulthood and microgliosis in the PVN.
Asunto(s)
Gliosis/inducido químicamente , Gliosis/complicaciones , Hipotálamo/efectos de los fármacos , Hipotálamo/patología , Exposición Materna/efectos adversos , Nicotina/efectos adversos , Sobrepeso/complicaciones , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Animales Recién Nacidos , Astrocitos/efectos de los fármacos , Astrocitos/fisiología , Recuento de Células , Femenino , Gliosis/metabolismo , Gliosis/patología , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Bombas de Infusión Implantables , Lactancia , Masculino , Microglía/efectos de los fármacos , Microglía/fisiología , Nicotina/administración & dosificación , RatasRESUMEN
Nicotine exposure causes the release of dopamine from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). We have previously shown that maternal exposure to nicotine during lactation causes hyperleptinemia in dams and pups, and leptin is known to decrease dopamine release from the VTA. Here we evaluated whether maternal exposure to nicotine during lactation causes changes in dopamine and leptin signaling pathways at the end of exposure and after 5days of withdrawal in the: VTA, NAc, arcuate nucleus (ARC) and dorsal striatum (DS). On postnatal day (PN) 2, lactating Wistar rats were implanted with minipumps releasing nicotine (NIC; 6mg/kg/day, s.c.) or saline (C) for 14days. Offspring were tested in the elevated plus maze (EPM) and open field on PN14 or PN20, and euthanized on PN15 or PN21. Entries into the open arms and head dips in the EPM were reduced in NIC pups at P20. At weaning (PN21), NIC dams had: lower tyrosine hydroxylase (TH), higher OBRb and SOCS3 contents in VTA; lower TH, higher D1R, D2R and DAT contents in NAc; higher TH content in DS; and higher D2R and SOCS3 contents in ARC. On PN15, NIC offspring had higher D1R, D2R and lower DAT contents in NAc, while on PN21, they had lower DAT in DS, and lower pSTAT3 content in ARC. We evidenced that postnatal nicotine exposure induces relevant changes in the brain reward system of dams and pups, possibly associated with changes in leptinemia and increased offspring anxiety-like behavior.
Asunto(s)
Lactancia , Vías Nerviosas/efectos de los fármacos , Nicotina/farmacología , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Animales , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Femenino , Masculino , Exposición Materna , Aprendizaje por Laberinto/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Ratas , Área Tegmental Ventral/efectos de los fármacos , Área Tegmental Ventral/metabolismoRESUMEN
The mesolimbic reward pathway is activated by drugs of abuse and palatable food, causing a sense of pleasure, which promotes further consumption of these substances. Children whose parents smoke are more vulnerable to present addictive-like behavior to drugs and food.We evaluated the association between maternal nicotine exposure during lactation with changes in feeding, behavior and in the dopaminergic reward system. On postnatal day (PN) 2,Wistar rat dams were implanted with minipumps releasing nicotine (N; 6 mg/kg/day, s.c.) or saline (C) for 14 days. On PN150 and PN160, offspring were divided into 4 groups for a food challenge: N and C that received standard chow(SC); and N and C that could freely self-select (SSD) between high-fat and high-sugar diets (HFD and HSD, respectively). Offspring were tested in the elevated plus maze (EPM) and open field (OF) arena on PN152153. On PN170, offspring were euthanized for central dopaminergic analysis. SSD animals showed an increased food intake compared to SC ones and a preference for HFD. However, N-SSD animals consumed relatively more HSD than C-SSD ones. Regarding behavior, N animals showed an increase in the time spent in the EPM center and a reduction in relative activity in the OF center. N offspring presented lower dopamine receptor (D2R) and transporter (DAT) contents in the nucleus accumbens, and lower D2R in the arcuate nucleus. Postnatal exposure to nicotine increases preference for sugar and anxiety levels in the adult progeny possibly due to a decrease in dopaminergic action in the nucleus accumbens and arcuate nucleus.
Asunto(s)
Ansiedad/metabolismo , Encéfalo/metabolismo , Dopamina/metabolismo , Nicotina/toxicidad , Efectos Tardíos de la Exposición Prenatal , Recompensa , Factores de Edad , Animales , Peso Corporal , Encéfalo/patología , Dieta , Ingestión de Alimentos , Conducta Exploratoria/fisiología , Femenino , Preferencias Alimentarias , Masculino , Aprendizaje por Laberinto/fisiología , Agonistas Nicotínicos/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/patología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratas , Ratas Wistar , Receptores de Dopamina D2/metabolismo , Estadísticas no ParamétricasRESUMEN
Children from pregnant smokers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption. Here, we studied the relationship between tobacco smoke exposure during lactation with feeding, behavior and brain dopaminergic reward system parameters at adulthood. Nursing Wistar rats and their pups were divided into two groups: tobacco smoke-exposed (S: 4times/day, from the 3rd to the 21th day of lactation), and ambient air-exposed (C). On PN175, both offspring groups were subdivided for a food challenge: S and C that received standard chow (SC) or that chose between high-fat (HFD) and high-sucrose diets (HSDs). Food intake was recorded after 30min and 12h. Offspring were tested in the elevated plus maze and open field on PN178-179; they were euthanized for dopaminergic analysis on PN180. SSD (self-selected diet) animals presented a higher food intake compared to SC ones. S-SSD animals ate more than C-SSD ones at 30min and 12h. Both groups preferred the HFD. However, S-SSD animals consumed relatively more HFD than C-SSD at 30min. No behavioral differences were observed between groups. S animals presented lower tyrosine hydroxylase (TH) content in the ventral tegmental area, lower TH, dopaminergic receptor 2, higher dopaminergic receptor 1 contents in the nucleus accumbens and lower OBRb in hypothalamic arcuate nucleus. Tobacco-smoke exposure during lactation increases preference for fat in the adult progeny possibly due to alterations in the dopaminergic system.
Asunto(s)
Encéfalo/metabolismo , Dopamina/metabolismo , Conducta Alimentaria , Exposición Materna/efectos adversos , Recompensa , Contaminación por Humo de Tabaco/efectos adversos , Animales , Animales Recién Nacidos , Condicionamiento Psicológico , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Ingestión de Alimentos , Femenino , Lactancia , Masculino , Actividad Motora , Ratas , Ratas Wistar , Receptores Dopaminérgicos/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Early nicotine exposure causes future obesity and insulin resistance. We evaluated the long-term effect of the maternal nicotine exposure during lactation in liver oxidative status, insulin sensitivity and morphology in adult offspring. Two days after birth, osmotic minipumps were implanted in the dams: nicotine (N), 6 mg/kg/day for 14 days or saline (C). Offspring were killed at 180 days. Protein content of superoxide dismutase, glutathione peroxidase, catalase, nitrotyrosine, 4HNE, IRS1, Akt1 and PPARs were measured. MDA, bound protein carbonyl content, SOD, GPx and catalase activities were determined in liver and plasma. Hepatic morphology and triglycerides content were evaluated. Albumin and bilirubin were determined. In plasma, N offspring had higher catalase activity, and SOD/GPx ratio, albumin and bilirubin levels but lower MDA content. In liver, they presented higher MDA and 4HNE levels, bound protein carbonyl content, SOD activity but lower GPx activity. N offspring presented an increase of lipid droplet, higher triglyceride content and a trend to lower PPARα in liver despite unchanged insulin signaling pathway. Early nicotine exposure causes oxidative stress in liver at adulthood, while protect against oxidative stress at plasma level. In addition, N offspring develop liver microsteatosis, which is related to oxidative stress but not to insulin resistance.
Asunto(s)
Hígado Graso/patología , Hígado/efectos de los fármacos , Exposición Materna/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Animales , Animales Recién Nacidos , Antioxidantes/metabolismo , Bilirrubina/sangre , Catalasa/sangre , Relación Dosis-Respuesta a Droga , Hígado Graso/inducido químicamente , Femenino , Glutatión Peroxidasa/sangre , Insulina/sangre , Proteínas Sustrato del Receptor de Insulina/sangre , Resistencia a la Insulina , Lactancia/efectos de los fármacos , Hígado/fisiopatología , Masculino , Nicotina/efectos adversos , Carbonilación Proteica , Proteínas Proto-Oncogénicas c-akt/sangre , Ratas , Ratas Wistar , Albúmina Sérica/metabolismo , Transducción de Señal , Superóxido Dismutasa/sangre , Triglicéridos/sangre , Tirosina/análogos & derivados , Tirosina/sangreRESUMEN
Postnatal nicotine exposure leads to obesity and hypothyroidism in adulthood. We studied the effects of maternal nicotine exposure during lactation on thyroid hormone (TH) metabolism and function in adult offspring. Lactating rats received implants of osmotic minipumps releasing nicotine (NIC, 6âmg/kg per day s.c.) or saline (control) from postnatal days 2 to 16. Offspring were killed at 180 days. We measured types 1 and 2 deiodinase activity and mRNA, mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD) activity, TH receptor (TR), uncoupling protein 1 (UCP1), hypothalamic TRH, pituitary TSH, and in vitro TRH-stimulated TSH secretion. Expression of deiodinase mRNAs followed the same profile as that of the enzymatic activity. NIC exposure caused lower 5'-D1 and mGPD activities; lower TRß1 content in liver as well as lower 5'-D1 activity in muscle; and higher 5'-D2 activity in brown adipose tissue (BAT), heart, and testis, which are in accordance with hypothyroidism. Although deiodinase activities were not changed in the hypothalamus, pituitary, and thyroid of NIC offspring, UCP1 expression was lower in BAT. Levels of both TRH and TSH were lower in offspring exposed to NIC, which presented higher basal in vitro TSH secretion, which was not increased in response to TRH. Thus, the hypothyroidism in NIC offspring at adulthood was caused, in part, by in vivo TRH-TSH suppression and lower sensitivity to TRH. Despite the hypothyroid status of peripheral tissues, these animals seem to develop an adaptive mechanism to preserve thyroxine to triiodothyronine conversion in central tissues.
Asunto(s)
Exposición Materna , Nicotina/toxicidad , Hormonas Tiroideas/metabolismo , Animales , Animales Lactantes , Femenino , Yoduro Peroxidasa/genética , Yoduro Peroxidasa/metabolismo , Canales Iónicos/metabolismo , Lactancia/efectos de los fármacos , Masculino , Proteínas Mitocondriales/metabolismo , Embarazo , Ratas , Ratas Wistar , Receptores beta de Hormona Tiroidea/metabolismo , Tirotropina/metabolismo , Hormona Liberadora de Tirotropina/metabolismo , Proteína Desacopladora 1RESUMEN
Children from pregnant smokers show more susceptibility to develop obesity in adult life. Previously, we failed to demonstrate a program for obesity in rat offspring only when the mothers were exposed to tobacco smoke during lactation. Here, we studied the short- and long-term effects of smoke exposure (SE) to both dams and their pups during lactation on endocrine and metabolic parameters. For this, we designed an experimental model where nursing rats and their pups were divided into two groups: SE group, exposed to smoke in a cigarette smoking machine (four times/day, from the third to the 21st day of lactation), and group, exposed to filtered air. Pups were killed at 21 and 180 days. At weaning, SE pups showed lower body weight (7%), length (5%), retroperitoneal fat mass (59%), visceral adipocyte area (60%), and higher subcutaneous adipocyte area (95%) with hypoinsulinemia (-29%), hyperthyroxinemia (59%), hypercorticosteronemia (60%), and higher adrenal catecholamine content (+58%). In adulthood, SE offspring showed higher food intake (+10%), body total fat mass (+50%), visceral fat mass (retroperitoneal: 55%; mesenteric: 67%; and epididymal: 55%), and lower subcutaneous adipocyte area (24%) with higher serum glucose (11%), leptin (85%), adiponectin (1.4-fold increase), total triiodothyronine (71%), free thyroxine (57%), TSH (36%), triglycerides (65%), VLDL cholesterol (+66%), and HDL cholesterol (91%) levels and lower corticosteronemia (41%) and adrenal catecholamine content (57%). Our present findings suggest that tobacco SE to both dams and their pups during lactation causes malnutrition in early life that programs for obesity and hormonal and metabolic disturbances in adulthood, only if the pups are submitted to the same smoke environment as the mother.
Asunto(s)
Dislipidemias/etiología , Hiperglucemia/etiología , Lactancia , Desnutrición/etiología , Exposición Materna/efectos adversos , Obesidad/etiología , Contaminación por Humo de Tabaco/efectos adversos , Grasa Abdominal/patología , Adiposidad , Animales , Animales Recién Nacidos , Cámaras de Exposición Atmosférica , Cotinina/sangre , Dislipidemias/sangre , Dislipidemias/patología , Femenino , Hiperglucemia/sangre , Hiperglucemia/patología , Masculino , Desnutrición/sangre , Desnutrición/patología , Desnutrición/fisiopatología , Obesidad/sangre , Obesidad/patología , Distribución Aleatoria , Ratas , Ratas Wistar , Factores de Tiempo , DesteteRESUMEN
Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning)--dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control--dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area (-67.7% and -62%, respectively), body fat mass (-26%), and leptin expression in visceral adipocyte (-64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 (-55%) and TSH (-44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRß3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue (-40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.
Asunto(s)
Enfermedades del Sistema Endocrino/fisiopatología , Crecimiento y Desarrollo , Obesidad/fisiopatología , Destete , Absorciometría de Fotón , Adiposidad , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/patología , Glándulas Suprarrenales/fisiopatología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Enfermedades del Sistema Endocrino/genética , Enfermedades del Sistema Endocrino/patología , Regulación de la Expresión Génica , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/metabolismo , Grasa Intraabdominal/fisiopatología , Leptina/genética , Leptina/metabolismo , Obesidad/genética , Obesidad/patología , Ratas , Ratas Wistar , Receptores Adrenérgicos beta 3/metabolismo , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/metabolismo , Grasa Subcutánea/fisiopatología , Pruebas de Función de la TiroidesRESUMEN
PURPOSE: Rats that are overfed during lactation exhibit neonatal hyperleptinemia and higher visceral adiposity, hypertension, higher liver oxidative stress and insulin resistance in the liver as adults. Previously, we demonstrated that neonatal hyperleptinemia is associated with adrenal medullary hyperfunction, hypertension and liver steatosis in adulthood. Therefore, we hypothesised that adrenal and liver functions are altered in adult obese rats that were overfed during lactation, which would underlie their hypertension and liver alterations. METHODS: The litter size was reduced from ten to three male pups on the third day of lactation until weaning (SL) to induce early overfeeding in Wistar rats. The control group had ten rats per litter (NL). Rats had free access to standard diet, and water after weaning until the rats were 180 days old. RESULTS: The SL group exhibited higher adrenal catecholamine content (absolute: +35% and relative: +40%), tyrosine hydroxylase (+31%) and DOPA decarboxylase (+90%) protein contents and basal catecholamine secretion in vitro (+57%). However, the hormones of the hypothalamic-pituitary-adrenal cortex axis were unchanged. ß3-adrenergic receptor content in visceral adipose tissue was unchanged in SL rats, but the ß2-adrenergic receptor content in the liver was lower in this group (-45%). The SL group exhibited higher glycogen and triglycerides contents in the liver (+79 and +49%, respectively), which suggested microesteatosis. CONCLUSIONS: Neonatal overfeeding led to higher adrenomedullary function, but the liver ß2-adrenergic receptor content was reduced. These results may contribute to the hepatic dysfunction characteristic of liver obesity complications.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Catecolaminas/metabolismo , Conducta Alimentaria , Insuficiencia Hepática/etiología , Hiperfagia/fisiopatología , Hígado/fisiopatología , Regulación hacia Arriba , Glándulas Suprarrenales/patología , Animales , Animales Recién Nacidos , Conducta Animal , Dopa-Decarboxilasa/metabolismo , Regulación hacia Abajo , Hiperfagia/metabolismo , Hiperfagia/patología , Hipertensión/etiología , Hígado/metabolismo , Hígado/patología , Glucógeno Hepático/metabolismo , Masculino , Obesidad/etiología , Obesidad/fisiopatología , Ratas , Receptores Adrenérgicos beta 2/metabolismo , Triglicéridos/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
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.
Asunto(s)
Médula Suprarrenal/metabolismo , Envejecimiento/metabolismo , Catecolaminas/biosíntesis , Lactancia/fisiología , Exposición Materna , Contaminación por Humo de Tabaco/análisis , Animales , Femenino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
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 ß3 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.
Asunto(s)
Glándulas Suprarrenales/crecimiento & desarrollo , Glándulas Suprarrenales/fisiología , Lactancia/efectos de los fármacos , Leptina/biosíntesis , Exposición Materna , Nicotina/farmacología , Caracteres Sexuales , Hormona Adrenocorticotrópica/metabolismo , Animales , Animales Recién Nacidos , Catecolaminas/biosíntesis , Catecolaminas/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Femenino , Masculino , Nicotina/administración & dosificación , Núcleo Hipotalámico Paraventricular/citología , Núcleo Hipotalámico Paraventricular/metabolismo , RatasRESUMEN
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.
Asunto(s)
Composición Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Lactancia/efectos de los fármacos , Pulmón/efectos de los fármacos , Leche/química , Contaminación por Humo de Tabaco/efectos adversos , Adiponectina/sangre , Análisis de Varianza , Animales , Animales Recién Nacidos , Corticosterona/sangre , Ingestión de Alimentos/efectos de los fármacos , Femenino , Insulina/sangre , Leptina/sangre , Prolactina/sangre , Radioinmunoensayo , Ratas , Ratas Wistar , DesteteRESUMEN
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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%). SIGNIFICANCE: 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.
Asunto(s)
Leptina/metabolismo , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Animales Recién Nacidos , Animales Lactantes , Western Blotting , Femenino , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Hipotiroidismo/inducido químicamente , Lactancia , Masculino , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Ratas , Ratas Wistar , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Factores de TiempoRESUMEN
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.
Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Hormonas/sangre , Lactancia/efectos de los fármacos , Exposición Materna , Nicotina/efectos adversos , Animales , Peso Corporal/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Femenino , Masculino , Leche/química , Nicotina/administración & dosificación , Embarazo , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Médula Suprarrenal/anatomía & histología , Médula Suprarrenal/metabolismo , Animales Lactantes/metabolismo , Catecolaminas/metabolismo , Leptina/metabolismo , Animales , Western Blotting , Janus Quinasa 2/metabolismo , Leptina/administración & dosificación , Masculino , Tamaño de los Órganos , Fosforilación/fisiología , Radioinmunoensayo , Ratas , Ratas Wistar , Receptores de Leptina/metabolismo , Análisis de Regresión , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/fisiología , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/metabolismoRESUMEN
The enzyme glucosyltransferase plays an important role in plaque formation and growth. Therefore, chemical inhibition of glucosyltransferase may become an effective method for plaque control. In this investigation we have evaluated the effects of some antiplaque substances (chlorhexidine, cetylpiridinium chloride, iodine, sodium fluoride and sodium dodecyl sulfate) on glucosyltransferase activity. Our results revealed that iodine was the most effective inhibitor. Based on in vitro glucosyltransferase inhibition we may suggest that topical iodine could be an auxiliary method for plaque control.