Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Infecções Respiratórias/prevenção & controle , Betacoronavirus , COVID-19 , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Humanos , Controle de Infecções/métodos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , SARS-CoV-2 , Singapura/epidemiologia , Centros de Atenção TerciáriaAssuntos
Serviços de Saúde Comunitária/normas , Infecções por Coronavirus/terapia , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Pandemias/prevenção & controle , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto , Saúde Pública/normas , Betacoronavirus , COVID-19 , Serviços de Saúde Comunitária/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Previsões , Humanos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Saúde Pública/estatística & dados numéricos , SARS-CoV-2 , Taiwan/epidemiologiaAssuntos
Betacoronavirus , Controle de Doenças Transmissíveis , Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecção Hospitalar/epidemiologia , Hospitais/estatística & dados numéricos , Humanos , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Singapura/epidemiologiaRESUMO
Early weaning (EW) leads to overweight, visceral obesity, hyperleptinemia, and insulin resistance in adulthood. Treatment with Ilex paraguariensis (yerba mate) improves obesity and insulin resistance in these animals. Here, we evaluated the effects of chronic treatment with yerba mate on the redox balance and liver morphology of overweight early-weaned rats. To induce EW, we wrapped the dams with bandages to interrupt milk access during the last 3 days of lactation. Control pups (C) had free access to maternal milk for the full 21 days of lactation. On postnatal day (PN) 150, EW offspring were subdivided into the EW+YM group, which received the aqueous extract of yerba mate (1 g/kg bw by gavage once a day for 30 days) and the EW group, which received water by gavage for the same period. All rats were euthanized on PN180. The EW group showed higher bound carbonyl (a marker of total protein oxidation), higher TBARS levels (a marker of lipid peroxidation), and lower superoxide dismutase (SOD) activity in liver tissue than the C group, as well as higher triglyceride content and microsteatosis. In plasma, the EW offspring showed higher TBARS levels. One month of yerba mate treatment normalized these parameters. Thus, we have shown evidence that yerba mate improved antioxidant defenses and mitigated liver dysfunction in overweight adult rats that were weaned prematurely.
Assuntos
Fígado Gorduroso/prevenção & controle , Ilex paraguariensis/química , Sobrepeso/prevenção & controle , Extratos Vegetais/farmacologia , Triglicerídeos/metabolismo , Desmame , Animais , Fígado Gorduroso/etiologia , Feminino , Resistência à Insulina , Masculino , Sobrepeso/etiologia , Oxirredução/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower ß3-AR, TRα1, and TRß1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.
Assuntos
Tecido Adiposo Marrom/fisiopatologia , Biomarcadores/análise , Sistema Nervoso Simpático/fisiopatologia , Termogênese/fisiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Tecido Adiposo Marrom/metabolismo , Animais , Animais Recém-Nascidos , Western Blotting , Feminino , Imuno-Histoquímica , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Poluição por Fumaça de Tabaco/análiseRESUMO
Ilex paraguariensis (yerba mate) has a beneficial effect in the management of obesity. Here, we studied the effects of yerba mate on hypothalamic changes in leptin and insulin signalling, oxidative stress and liver morphology and metabolism in postnatal early overfeeding (EO) Wistar rats. To induce EO, the litter size was reduced to three pups per dam, and litters with 10 pups per dam were used as a control (10 litters each). On postnatal day (PN) 150, EO offspring were subdivided into EO and EO+mate groups (10 animals each), which were treated with water or mate tea [1 g/kg body weight (BW)/day, by gavage], respectively, for 30 days. The C offspring received water. On PN180, yerba mate treatment prevented BW gain and reduced total body fat, visceral fat and food intake in comparison with the EO group. Leptin and insulin signalling in the hypothalamus measured by Western blotting was reduced only in the EO group. Yerba mate treatment had a greater impact on insulin signalling normalization. In the liver, yerba mate treatment normalized antioxidant enzyme activities and, consequently, decreased lipid peroxidation, determined by malondialdehyde content. In addition, the steatosis level and the liver triglyceride content were also restored. Thus, for the first time, yerba mate was demonstrated to increase antioxidant defences and improve liver metabolism in adult rats that were overfed during lactation, possibly through improvements in the hypothalamic action of insulin. These findings may be important for the treatment of obesity-related disorders.
Assuntos
Hipotálamo/metabolismo , Ilex paraguariensis/química , Insulina/metabolismo , Lactação , Leptina/metabolismo , Hepatopatias/metabolismo , Extratos Vegetais/farmacologia , Animais , Peso Corporal , Aleitamento Materno , Ingestão de Alimentos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Masculino , Hipernutrição/complicações , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
Rats overfed during lactation show higher visceral adipose tissue (VAT) mass and metabolic dysfunctions at adulthood. As both vitamin D and glucocorticoids change adipogenesis, parameters related to metabolism and action of these hormones in the adipocyte can be altered in rats raised in small litters (SL). We also studied the antiobesity effects of high calcium diet since it decreases visceral fat in obesity models. On postnatal day (PN) 3, litter size was adjusted to 3pups/dam (SL) to induce overfeeding. Control litters (NL) remained with 10pups/dam until weaning. From PN120 to PN180, half of the SL rats were fed standard chow (SL) and the other half was fed a calcium-supplemented chow (SL-Ca, 10g CaCO3/kg). Both SL groups were heavier and hyperphagic when compared with the NL group; however, SL-Ca rats ate less than SL. SL-Ca rats had decreased VAT mass and adipocyte size, associated with lower hypothalamic NPY content, VAT fat acid synthase content and leptinemia. At PN120, SL rats had increased plasma 25(OH)D3, Cyp27b1 mRNA and glucocorticoid receptor (GR-α) in the VAT, but lower vitamin D receptor (Vdr) mRNA. At PN180, Cyp27b1 and GR-α remained higher, while Vdr normalized in SL rats. SL-Ca rats had normal VAT Cyp27b1 and GR-α, but lower Vdr Thus, higher body mass and glucocorticoid receptors in the VAT of SL rats are normalized by calcium-enriched diet, and Vdr expression in this tissue is reduced, suggesting a possible role of glucocorticoids and vitamin D in calcium action in the adipocyte.
Assuntos
Cálcio/uso terapêutico , Gordura Intra-Abdominal/efeitos dos fármacos , Obesidade/prevenção & controle , Receptores de Glucocorticoides/metabolismo , Vitamina D/metabolismo , Animais , Cálcio/farmacologia , Suplementos Nutricionais , Modelos Animais de Doenças , Gordura Intra-Abdominal/metabolismo , Masculino , Obesidade/etiologia , Obesidade/metabolismo , Ratos WistarRESUMO
Obesity is related to diabetes, higher oxidative stress and nonalcoholic fatty liver disease, and dietetic therapies, for instance calcium-rich diet, can improve these dysfunctions. Rats raised in small litters (SL) had increased fat depots and insulin resistance at adulthood associated with higher liver oxidative stress and microsteatosis. Thus, we evaluated if dietary calcium can improve these changes. In PN3, litter size was adjusted to 3 pups (SL group) to induce overfeeding, while controls had 10 pups until weaning. At PN120, SL group was randomly divided into: rats fed with standard chow or fed with calcium supplementation (SL-Ca group, 10 g/kg chow) for 60 days. At PN180, dietary calcium normalized food consumption, visceral fat, plasma aspartate aminotransferase (AST) and glycaemia. Concerning oxidative balance, calcium restored both higher hepatic lipid peroxidation and protein carbonylation as well as higher plasma lipid peroxidation. Higher fatty acid synthase (FAS) content, steatosis and lower protein kinase B (Akt) in SL group were normalized by dietary calcium and SL-Ca rats had lower hepatic cholesterol. Thus, calcium supplementation improved the insulin sensitivity, redox balance and steatosis in the liver. Therefore, dietary calcium can be a promising therapy for liver disease in the metabolic syndrome.
Assuntos
Cálcio/administração & dosagem , Fígado Gorduroso/prevenção & controle , Hepatopatias/prevenção & controle , Obesidade/fisiopatologia , Hipernutrição/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Antioxidantes/metabolismo , Western Blotting , Peso Corporal , Cálcio/farmacologia , Dieta , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Feminino , Resistência à Insulina , Lactação , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Ratos , Ratos WistarRESUMO
Rats raised in small litters (SL) are obese and hyperphagic. In the present study, we evaluated whether obesity is associated with changes in the mesocorticolimbic dopaminergic reward system in these animals at adulthood. We also assessed the anti-obesity effects of dietary calcium supplementation. To induce early overfeeding, litters were adjusted to three pups on postnatal day (PN)3 (SL group). Control litters were kept with 10 pups each until weaning (NL group). On PN120, SL animals were subdivided into two groups: SL (standard diet) and SL-Ca [SL with calcium supplementation (10 g calcium carbonate/kg rat chow) for 60 days]. On PN175, animals were subjected to a food challenge: animals could choose between a high-fat (HFD) or a high-sugar diet (HSD). Food intake was recorded after 30 min and 12 h. Euthanasia occurred on PN180. SL rats had higher food intake, body mass and central adiposity. Sixty days of dietary calcium supplementation (SL-Ca) prevented these changes. Only SL animals preferred the HFD at 12 h. Both SL groups had lower tyrosine hydroxylase content in the ventral tegmental area, lower dopaminergic transporter content in the nucleus accumbens, and higher type 2 dopamine receptor (D2R) content in the hypothalamic arcuate nucleus (ARC). They also had higher neuropeptide Y (NPY) and lower pro-opiomelanocortin contents in the ARC. Calcium treatment normalised only D2R and NPY contents. Precocious obesity induces long-term effects in the brain dopaminergic system, which can be associated with an increased preference for fat at adulthood. Calcium treatment prevents this last alteration, partially through its actions on ARC D2R and NPY proteins.
Assuntos
Encéfalo/metabolismo , Cálcio da Dieta/administração & dosagem , Dopamina/metabolismo , Preferências Alimentares , Obesidade/metabolismo , Obesidade/psicologia , Recompensa , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Dieta Hiperlipídica , Ingestão de Alimentos , Ingestão de Energia , Feminino , Masculino , Neuropeptídeo Y/metabolismo , Núcleo Accumbens/metabolismo , Pró-Opiomelanocortina/metabolismo , Ratos Wistar , Receptores de Dopamina D2/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/metabolismoRESUMO
Neonatal overfeeding induced by litter size reduction leads to further obesity and other metabolic disorders, such as liver oxidative stress and microsteatosis at adulthood. We hypothesized that overfeeding causes an early redox imbalance at weaning, which could programme the animals to future liver dysfunction. Thus, we studied lipogenesis, adipogenesis, catecholamine status and oxidative balance in weaned overfed pups. To induce early overfeeding, litters were adjusted to three pups at the 3rd day of lactation (SL group). The control group contained 10 pups per litter until weaning (NL group). Peripheral autonomic nerve function was determined in vivo at 21 days old. Thereafter, pups were killed for further analysis. Differences were considered significant when P < 0.05. The SL pups presented with a higher visceral adipocyte area, higher content of lipogenic enzymes (ACC, FAS) and with a lower content of adipogenic factors (CEBP, PPARγ) in visceral adipose tissue (VAT). Although autonomic nerve activity and adrenal catecholamine production were not significantly altered, catecholamine receptor (ß3ADR) content was lower in VAT. The SL pups also presented with higher triglyceride, PPARγ, PPARα and PGC1α contents in liver. In plasma and liver, the SL pups showed an oxidative imbalance, with higher lipid peroxidation and protein oxidation. The SL group presented with a higher serum alanine aminotransferase (ALT). The early increase in lipogenesis in adipose tissue and liver in weaned overfed rats suggests that the higher oxidative stress and lower catecholamine content in VAT are associated with the early development of liver dysfunction and adipocyte hypertrophy.
Assuntos
Hiperfagia/metabolismo , Fígado/metabolismo , Obesidade/metabolismo , Estresse Oxidativo , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Catecolaminas/metabolismo , Feminino , Lipogênese , Fígado/crescimento & desenvolvimento , Masculino , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ratos , Ratos Wistar , Receptores de Catecolaminas/metabolismo , Fatores de Transcrição/metabolismo , Triglicerídeos/metabolismo , DesmameRESUMO
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.
Assuntos
Fígado Gorduroso/patologia , Fígado/efeitos dos fármacos , Exposição Materna/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Antioxidantes/metabolismo , Bilirrubina/sangue , Catalase/sangue , Relação Dose-Resposta a Droga , Fígado Gorduroso/induzido quimicamente , Feminino , Glutationa Peroxidase/sangue , Insulina/sangue , Proteínas Substratos do Receptor de Insulina/sangue , Resistência à Insulina , Lactação/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Nicotina/efeitos adversos , Carbonilação Proteica , Proteínas Proto-Oncogênicas c-akt/sangue , Ratos , Ratos Wistar , Albumina Sérica/metabolismo , Transdução de Sinais , Superóxido Dismutase/sangue , Triglicerídeos/sangue , Tirosina/análogos & derivados , Tirosina/sangueRESUMO
Childhood obesity is growing in prevalence. Obesity and bone dysfunctions may be related disorders, and therefore our aim was to study the impact of the early overfeeding (EO) in offspring bone health since weaning up to adulthood. To induce EO during lactation, litter size was adjusted to 3 male rats per litter (SL). Litter containing 10 pups per mother was the control (NL). Bone tissue was evaluated by dual-energy X-ray absorptiometry, computed tomography, microcomputed tomography, biomechanical tests, and serum analyses. SL offspring presented higher body weight, fat mass, lean mass from 21 up to 180 days, hyperphagia, and higher visceral fat mass. Bone analysis showed that SL offspring presented higher total bone mineral density (BMD) only at 180 days, and higher total bone mineral content and higher bone area from 21 until 180 days. At 180 days, SL offspring presented higher femur BMD and fourth lumbar vertebra (LV4) BMD, higher femoral head radiodensity and LV4 vertebral body radiodensity, lower trabecular pattern factor and trabecular separation, however with higher trabecular number, higher maximal load, resilience, stiffness and break load, and lower break deformation. SL group had, at 180 days, higher osteocalcin and lower C-terminal cross-linked telopeptide of type I collagen (CTX I). We have shown that the excess of fat mass contributed to an increased bone mass, and hypothesized that this increase could be mediated by the hypothyroidism and previous higher thyroid hormone action and hyperleptinemia at weaning. Furthermore, the increased biomechanical loading due to increased body weight probably help us to understand the protective effects obesity exerts upon bone health.
Assuntos
Comportamento Alimentar , Fêmur/patologia , Fêmur/fisiopatologia , Hipernutrição/patologia , Hipernutrição/fisiopatologia , Absorciometria de Fóton , Animais , Animais Recém-Nascidos , Fenômenos Biomecânicos , Peso Corporal , Densidade Óssea , Colágeno Tipo I/metabolismo , Feminino , Fêmur/diagnóstico por imagem , Gordura Intra-Abdominal/fisiopatologia , Masculino , Tamanho do Órgão , Osteocalcina/metabolismo , Hipernutrição/diagnóstico por imagem , Peptídeos/metabolismo , Ratos Wistar , Desmame , Suporte de Carga , Microtomografia por Raio-XRESUMO
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.
Assuntos
Glândulas Suprarrenais/metabolismo , Catecolaminas/metabolismo , Comportamento Alimentar , Insuficiência Hepática/etiologia , Hiperfagia/fisiopatologia , Fígado/fisiopatologia , Regulação para Cima , Glândulas Suprarrenais/patologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Dopa Descarboxilase/metabolismo , Regulação para Baixo , Hiperfagia/metabolismo , Hiperfagia/patologia , Hipertensão/etiologia , Fígado/metabolismo , Fígado/patologia , Glicogênio Hepático/metabolismo , Masculino , Obesidade/etiologia , Obesidade/fisiopatologia , Ratos , Receptores Adrenérgicos beta 2/metabolismo , Triglicerídeos/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
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.
Assuntos
Proteínas Alimentares/administração & dosagem , Hipotálamo/metabolismo , Leptina/metabolismo , Hipófise/metabolismo , Glândula Tireoide/metabolismo , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/fisiologia , Animais , Western Blotting , Feminino , Técnicas In Vitro , Lactação , Leptina/sangue , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Transdução de Sinais , Estatísticas não Paramétricas , Tireotropina/metabolismo , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
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.
Assuntos
Adipócitos Brancos/metabolismo , Envelhecimento/fisiologia , Lactação/fisiologia , Leptina/biossíntese , Hipernutrição/fisiopatologia , Adipócitos Brancos/citologia , Animais , Animais Recém-Nascidos , Feminino , Ratos , Ratos WistarRESUMO
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.