O Papel dos Níveis Séricos de ANP na Perda de Peso, Risco Cardiometabólico e Composição Corporal de Adolescentes com Obesidade Submetidos a Terapia Interdisciplinar / The Role of ANP Level Response in Interdisciplinary Weight Loss Therapy on Cardiometabolic Risk and Body Composition in Adolescents with Obesity

Resumo Fundamento A ação do peptídeo natriurético atrial (ANP) na natriurese, diurese e vasodilatação, resistência à insulina, fígado, rim e tecido adiposo pode contribuir para o desenvolvimento metabólico e cardiovascular saudável. Embora o nível circulante de ANP seja reduzido em pacientes com obesidade, sua resposta à perda de peso ainda é pouco explorada em populações pediátricas. Objetivo Avaliar os efeitos das variações do ANP em resposta à intervenção interdisciplinar para perda de peso na Síndrome Metabólica (SMet) e nos riscos cardiometabólicos em adolescentes com obesidade. Métodos 73 adolescentes com obesidade participaram de uma terapia interdisciplinar para perda de peso de 20 semanas, incluindo uma abordagem clínica, nutricional, psicológica e de exercícios físicos. A composição corporal, análises bioquímicas e pressão sanguínea foram avaliadas. A SMet foi classificada de acordo com a Federação Internacional de Diabetes (IDF) (2007). Após o tratamento, os voluntários foram divididos de acordo com os níveis de plasma do ANP aumento (n=31) ou ANP redução (n=19). Resultados Ambos os grupos apresentaram redução significativa de peso corporal, índice de massa corporal (IMC) e circunferências de cintura, pescoço e quadril (CC, CP e CQ, respectivamente), e aumento da massa livre de gordura (MLG). É interessante observar que houve uma redução significativa na gordura corporal, na razão de TG/HDL-c e na prevalência de SMet (de 23% para 6%) somente no grupo com ANP aumento. Conclusão Este estudo sugere que o aumento nos níveis séricos de ANP após a terapia para perda de peso pode estar associado a melhorias nos riscos cardiometabólicos e na prevalência reduzida de SMet em adolescentes com obesidade.

Abstract Background The action of atrial natriuretic peptide (ANP) on natriuresis, diuresis and vasodilatation, insulin resistance, liver, kidney, and adipose tissue may contribute to the healthy metabolic and cardiovascular development. Even though the circulating level of ANP is reduced in patients with obesity, its response to weight loss remains poorly explored in pediatric populations. Objective To evaluate the effects of ANP variations in response to interdisciplinary weight loss intervention on metabolic syndrome (MetS) and cardiometabolic risks in adolescents with obesity. Methods 73 adolescents with obesity attended a 20-week clinical interdisciplinary weight loss therapy including clinical, nutritional, psychological and exercise training approach. Body composition, biochemical analyses and blood pressure were evaluated. MetS was classified according to the International Diabetes Federation (IDF) (2007). After the treatment, volunteers were divided according to Increasing (n=31) or Decreasing (n=19) ANP plasma levels. Results Both groups present significant reduction of body weight, Body Mass Index (BMI), waist, neck and hip circumferences (WC, NC and HC, respectively) and increasing fat-free mass (FFM). Interestingly, a significant reduction in body fat, TG/HDL-c ratio and MetS prevalence (from 23% to 6%) was observed in the Increased ANP group only. Conclusion This study suggests that an increase in ANP serum levels after weight loss therapy could be associated with improvements in cardiometabolic risks and the reduced prevalence of MetS in adolescents with obesity.

Antioxidant effect of chamomile tea on the salivary glands of streptozotocin-induced diabetic rats

Abstract: This study aimed to analyze oxidative stress and the activity of antioxidant enzymes in the salivary glands of streptozotocin (STZ)-induced diabetic rats with ad libitum consumption of chamomile tea in substitution of water for 21 days. Rats were divided in two control groups (untreated control and treated control) and two diabetic groups (untreated diabetic and treated diabetic). Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, total antioxidant status (TAS), and malondialdehyde (MDA) concentrations were determined. The chemical composition of the chamomile essential oil revealed 39 compounds, accounting for 93.5% of the total oils. The polyphenolic profile of the tea showed the presence of apigenin, luteolin, umbelliferone, and esculetin. SOD, GPx, CAT, and TAS levels were lower in the parotid (PA) diabetic glands, but treatment increased their concentration in both the submandibular (SM) and PA diabetic salivary glands. Increased MDA levels were observed in the PA diabetic glands, which were decreased by the consumption of chamomile tea with a reduction in hyperglycemia compared to that in untreated diabetic rats. However, the SM diabetic glands showed no difference in the MDA content. The consumption of chamomile tea prevented oxidative stress in the PA glands of diabetic rats, exhibiting hypoglycemic and antioxidant effects. Thus, chamomile tea could be a potential candidate for preventing oral complications in diabetes mellitus.

Effects of an interdisciplinary weight loss program on fibroblast growth factor 21 and inflammatory biomarkers in women with overweight and obesity

ABSTRACT Objective: To investigate the effects of an interdisciplinary intervention on biomarkers of inflammation and their relationship with fibroblast growth factor 21 (FGF21) concentrations in women with overweight and obesity. Subjects and methods: Thirty-one women were enrolled in a 12-week interdisciplinary weight loss program delivered by a team comprising an endocrinologist, nutritionist and exercise physiologist. Body composition; anthropometric measures; metabolic and inflammatory markers including adiponectin, leptin, and atrial natriuretic peptide (ANP) were assessed at baseline and post-therapy. The homeostasis model assessment of insulin resistance (HOMA-IR) and the homeostasis model assessment of adiponectin (HOMA-AD) were calculated. The participants were divided into two groups: those with increased FGF21, and those with decreased FGF21. Results: The sample comprised women aged 32 ± 5 years with a body mass index of 33.64 ± 3.49 kg/m2. Body weight, waist circumference and leptin concentration were decreased in the whole sample after therapy. However, only the group with an increase in FGF21 concentration presented significant improvements in adiponectin concentration and adiponectin/leptin ratio. Moreover, although there was a reduction of leptin in both groups, it was greater in the increased FGF21 groups. There was a reduction in ANP in the decreased FGF21 group. Conclusions: Changes in FGF21 concentrations were different among the women participating in the weight loss program, with some having increased levels and some reduced levels. Furthermore, improvements in adiponectin and the adiponectin/leptin ratio were found only in the group with increased FGF21 concentration.

Higher increase degree of FGF21 post long-term interdisciplinary weight loss therapy preserves the free fat mass and rest metabolic rate in adolescents with obesity

ABSTRACT Objective Fibroblast growth factor 21 (FGF21) is among the activators that can stimulate thermogenesis in the white adipose tissue and brown adipose tissue. People with obesity have elevated blood levels of FGF21, but also develop resistance to its action, impairing its beneficial role. Inversely, clinical treatments to weight loss has been pointed out as an important therapy for increasing and recovering sensitivity to FGF21. The aim was to analyse the effect of long-term weight loss interdisciplinary intervention on FGF21 and body composition. Subjects and methods Eighty-six post-pubertal obese adolescents (14-19 years-old), were submitted to 20 weeks of weight loss therapy (clinical, nutritional, psychological and physical exercise support). Anthropometric measures, body composition and rest metabolic rate (RMR) by bioelectrical impedance, and serum FGF21 sample by ELISA were evaluated. The adolescents were grouped according to FGF21 individual delta variations after therapy: Higher Increase (HI); lower increase (LI); lower decrease (LD); higher decrease (HD). Results All groups present weight loss. Only in FGF21 ≥ 76,5 pg/mL variation the free-fat-mass and rest metabolic rate were preserved and to others group these variables were significantly reduced. Conclusion High increase in FGF21 can contribute to preservation of FFM and RMR after weight loss therapy, could have important implications for energy balance regulation. Future studies are necessary to continue determining the role of magnitude effects of FGF21 levels in obesity to improve clinical practice, especially in paediatrics population.

Serum myristic fatty acid negatively correlates with anti-inflammatory adiponectin/leptin ratio in obese adolescents: effects of long- term therapy / O ácido graxo mirístico sérico correlaciona-se negativamente com a razão adiponectina/leptina anti-inflamatória em adolescentes obesos: efeitos da terapia de longo prazo

Obesity is related to metabolic disorders partially mediated by inflammatory state. In this way, adiponectin/leptin ratio is considered an anti-inflammatory biomarker related to cardiovascular risks. Evidence suggest that decrease in saturated fatty acid intake is an important dietary recommendation to reduce cardiovascular risk factors. Thus, the purpose of the present study was to evaluate if serum myristic fatty acid can modulate metabolic profile and inflammatory process in obese adolescents after weight-loss therapy. Twenty-nine obese post-pubertal obese adolescents, aged 14 to 19 years, were submitted to the long-term interdisciplinary treatment, including physical exercise, clinic, nutritional and psychological intervention. The blood samples were collected to glycaemia, insulin, lipid profile, leptin and adiponectin analysis. Serum fatty acid composition was performed by technical of chromatography in fizzy phase. The therapy promoted significant improvement in body mass, BMI, subcutaneous and visceral fat, insulin, lipid profile, leptin and leptin/adiponectin ratio. Significant decrease in myristic fatty acid was observed. Simple linear regression analysis showed that myristic fatty acid was positively associated with changes in triglycerides and very low density lipoprotein cholesterol, and was negatively associated with adiponectin/leptin ratio. In summary, we observed that long-term weight loss therapy was effective to improve metabolic/inflammatory profile and serum myristic fatty acid. Moreover, our results suggested the relation between changes in serum myristic fatty acids with the anti-inflammatory adiponectin/ leptin ratio, which may modulate metabolic and inflammatory process related to obesity

A obesidade está relacionada a distúrbios metabólicos parcialmente mediados por um estado inflamatório. Desta forma, a razão a diponectina/leptina é considerada um biomarcador anti-inflamatório relacionado aos riscos cardiovasculares. Evidências sugerem que a diminuição na ingestão de ácidos graxos saturados seja uma recomendação dietética importante para reduzir os fatores de risco cardiovascular. Assim, o objetivo do presente estudo foi avaliar se o ácido graxo mirístico sérico pode modular o perfil metabólico e processos inflamatórios em adolescentes obesos após a terapia para perda de peso. Vinte e nove adolescentes pós-púberes e obesos de 14 a 19 anos de idade foram submetidos a um tratamento interdisciplinar de longo prazo, incluindo exercício físico, intervenção clínica, nutricional e psicológica. As amostras de sangue foram coletadas para análise da glicemia, insulina, perfil lipídico, leptina e adiponectina. A composição de ácidos graxos séricos foi realizada por técnicas de cromatografia em fase gasosa. A terapia promoveu uma melhora significativa na massa corporal, IMC, gordura subcutânea e visceral, insulina, perfil lipídico, leptina e a razão leptina/adiponectina. Observou-se uma diminuição significativa na concentração sérica de ácido graxo mirístico. A análise de regressão linear simples mostrou que o ácido graxo mirístico foi positivamente associado a alterações nos triglicerídeos e colesterol de lipoproteínas de muito baixa densidade e foi associado negativamente à proporção de adiponectina/leptina. Em resumo, observamos que a terapia de perda de peso a longo prazo foi efetiva na melhora do perfil metabólico/inflamatório e do ácido graxo mirístico sérico. Além disso, nossos resultados sugerem uma relação entre as alterações no ácido graxo mirístico séricos e a razão adiponectina/leptina antiinflamatória, que podem modular processos metabólicos e inflamatórios relacionados à obesidade

Efeitos de diferentes intensidades de exercício sobre a concentração sérica de interleucinas / Effects of different exercise intensities on serum interleukins levels

O presente estudo teve como objetivo analisar os efeitos agudos e de curta duração de duas intensidades de exercício aeróbio sobre a concentração circulante de IL-6 e IL-10. Quinze homens jovens fisicamente ativos (21,0 ± 1,9 anos) foram submetidos a duas sessões de exercício ("crossover"): alta intensidade de exercício (AIE)- (80% VO2pico), e baixa intensidade de exercício (BIE)- (40% VO2pico), com intervalo de sete dias ("Wash out"). Amostras de sangue foram coletadas em tubos com EDTA, antes do exercício (basal), imediatamente após o exercício (agudo) e após 2 h de recuperação passiva. As concentrações séricas de IL-6 e IL-10 foram determinadas com a utilização de kits comerciais de ELISA. Os resultados demonstraram elevação aguda da IL- 6, em resposta ao AIE em relação ao BIE (p < 0,05), enquanto que a IL-10 apresentou maior redução sistêmica aguda para BIE em comparação a AIE (p < 0,05). Não houve diferença na variação das citocinas após 2 h do término do exercício. Conclui-se que ambas as sessões agudas de exercício são capazes de modular a concentração circulante destas citocinas, e que a magnitude das alterações são dependentes da intensidade do esforço

The aim of this study was to analyze the acute and short-term effects of high and low exercise intensities on IL-6 and IL-10. Fifteen young healthy physically active males (21.0 ± 1.9 yrs) were submitted to 2 experimental trials (cross-over) with a 7-dais wash-out: high exercise intensity (80% VO2peak) and low exercise intensity (40% VO2peak) session. Blood samples were collected before exercise (baseline), immediately after exercise (acute), and two hours after the end of the exercise session (2 h). IL-6 and IL-10 circulating levels were determinate by ELISA. The results demonstrated an acute increase in IL-6 levels after high intensity compared to low intensity exercise (p < 0.05), however, IL-10 presented an acute decrease in response to low intensity exercise (p < 0.05). No effects were observed after 2 h of recovery from the session. Thus we conclude that acute exercise sessions are able to modulate the circulating levels of the studies cytokines, and the magnitudes of these changes are dependent of the exercise intensity

Resistência insulínica pode prejudicar a redução da espessura mediointimal em adolescentes obesos / Insulin resistance can impair reduction on carotid intima-media thickness in obese adolescents

FUNDAMENTO: O processo aterosclerótico no nível endotelial começa em idade precoce e parece estar associado com a obesidade e suas comorbidades como a resistência insulínica. OBJETIVO: O objetivo deste estudo foi verificar a influência da resistência insulínica em marcadores inflamatórios e subclínicos de aterosclerose em adolescentes obesos. MÉTODOS: Sessenta e seis adolescentes obesos pós-púberes foram divididos em dois grupos de acordo com o índice de resistência insulínica estimado pelo Modelo de Avaliação da Homeostase (HOMA-RI): com resistência insulínica (RI) n = 39 e sem resistência insulínica (NRI) n = 27, e foram submetidos a uma intervenção interdisciplinar ao longo de um ano. A espessura mediointimal da artéria carótida comum (EMIC), e o tecido adiposo visceral e subcutâneo foram determinados por ultrassonografia. A composição corporal, pressão arterial, índice HOMA-RI, perfil lipídico e as concentrações de adipocinas [leptina, adiponectina, e inibidor do ativador do plasminogênio-1 (PAI-1)] foram analisados antes e após a terapia. RESULTADOS: Ambos os grupos apresentaram melhoras significativas na composição corporal, estado inflamatório (redução da concentração de leptina e PAI 1; aumento de adiponectina plasmática) e redução da EMIC. Apenas o grupo NRI mostrou correlação positiva entre as alterações na gordura visceral (∆Visceral) e mudanças na EMIC (∆ EMIC) (r = 0,42, p < 0,05). A análise por regressão linear simples revelou o ∆Visceral ser um preditor independente para a redução da EMIC nesse grupo (R2 ajustado = 0,14, p = 0,04). Os valores finais da EIMC permaneceram significativamente maiores no grupo RI, quando comparado com grupo NRI. CONCLUSÃO: A presença de resistência insulínica pode prejudicar mudanças na EMIC levando ao desenvolvimento precoce da aterosclerose em adolescentes obesos submetidos a uma intervenção interdisciplinar.

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Obesidade e adipocinas inflamatórias: implicações práticas para a prescrição de exercício: [revisão] / Obesity and inflammatory adipokines: practical implications for exercise prescription: [review]

A obesidade é uma doença complexa de etiologia multifacetada, com sua própria fisiopatologia, comorbidades e capacidades desabilitantes. Aceitar a obesidade como uma doença é fundamental para o seu tratamento. Atualmente, o tecido adiposo é um dos principais focos das pesquisas em obesidade, devido a uma revolução no entendimento da função biológica desse tecido desde a última década. Já está muito claro que o tecido adiposo branco secreta múltiplos peptídeos bioativos, denominados adipocinas (proteínas sintetizadas e secretadas pelo tecido adiposo). Dessa forma, o objetivo deste trabalho de revisão foi investigar a relação entre obesidade e adipocinas inflamatórias, buscando discutir o papel do exercício físico no tratamento dessa patologia. Os resultados demonstram que uma das mais importantes descobertas das pesquisas recentes em obesidade é o conceito de que ela é caracterizada por uma inflamação crônica. Dentre todas as adipocinas, sem dúvida, a IL-6, o TNF-α, a leptina (pró-inflamatórias) e a adiponectina (anti-inflamatória) vêm recebendo atenção especial da literatura especializada. O aumento da concentração dessas adipocinas promove grande impacto em diversas funções corporais que estão fortemente correlacionadas com doenças cardiovasculares. Uma vez que a obesidade é considerada uma doença inflamatória e o exercício físico modula de forma direta tais processos, é essencial que tenhamos como um dos objetivos principais de nossos programas de exercícios físicos a melhora da resposta inflamatória de obesos.

Obesity is a complex disease with a multifaceted etiology with its own physiopathology, co-morbidities and disabiliting capacities. It is crucial that obesity is acknowledged as a disease in order to treat it. Nowadays, the adipose tissue is the main focus of obesity research due to the improvement in the last decade on biological function of this tissue. It is now clear that white adipose tissue release a large amount of bioactive peptides called adipokines (which are proteins synthesized and released by adipose tissue). Thus, the aim of this review was to investigate the relationship between obesity and inflammatory adipokines, trying to discuss the role of physical exercise in the treatment of this pathology. The results have shown that one of the most important recent discoveries is the concept that obesity is characterized by a chronic inflammation state. Among all adipokines, IL-6, TNF- α, leptin (pro-inflammatory) and adiponectin (anti-inflammatory), have received special attention from the specialized literature. High concentration of these adipokines promotes impact in several body functions, which is strongly linked with cardiovascular diseases. Since obesity is considered an inflammatory disease, and exercise directly modulates this process, it is essential that one of the main aims of exercise therapies is the improvement of the inflammatory response of obese individuals.

Oxintomodulina e obesidade / Oxyntomodulin and obesity

Desde o descobrimento da leptina, avanços consideráveis foram obtidos na caracterização dos mecanismos hipotalâmicos do controle da ingestão alimentar e, atualmente, a oxintomodulina é reconhecida como um regulador da homeostase energética. O presente artigo de revisão enfoca algumas das mais relevantes inter-relações do hormônio oxintomodulina com o apetite, a homeostase energética e aspectos de seu papel na bioquímica e fisiologia nutricional. A oxintomodulina é um peptídeo intestinal anorexígeno produzido pelas células L do intestino. Recentes estudos têm demonstrado que em longo prazo a administração de oxintomodulina reduz a ingestão alimentar e o ganho de peso. Pesquisas em humanos têm verificado que o seu uso reduz o consumo energértico em 25 por cento. Portanto, a oxintomodulina representa uma potente terapia anti-obesidade. Entretanto, o mecanismo de ação da oxintomodulina ainda é desconhecido. Atuais evidências sugerem que tem ação via receptor do peptídeo semelhante ao glucagon 1. Além disso, a literatura mostra que, juntamente com a adoção de hábitos saudáveis e a mudança do estilo de vida, a oxintomodulina pode proporcionar menor avanço da obesidade.

Since the discovery of leptin, great advances occurred in the characterization of hypothalamic mechanisms involved in the control of food intake and oxyntomodulin is currently recognized as a homeostasis energy regulator. This review discusses the most important interrelationships between the hormone oxyntomodulin and appetite, energy homeostasis and aspects of its role in nutritional biochemistry and physiology. Oxyntomodulin is an anorexigenic peptide produced by the L cells of the small intestine. Recent studies have shown that long-term use of oxyntomodulin in rats leads to reduced food intake and weight gain. Studies in humans have demonstrated that its administration reduces food intake by 25 percent. Therefore, oxyntomodulin represents a potent anti-obesity therapy. However, its mechanism of action is unknown. Current evidence suggests that it acts via the peptide receptor similar to glucagon 1. Moreover, the literature shows that together with the adoption of healthy habits and lifestyle changes, oxyntomodulin can reduce weight gain.

Efeitos do exercício crônico sobre a concentração circulante da leptina e grelina em ratos com obesidade induzida por dieta / Effects of the chronic exercise on the circulating concentration of leptin and ghrelin in rats With diet-induced obesity

A obesidade vem se tornando uma das maiores epidemias mundiais, dessa forma, conhecer sua etiologia e mecanismos que regulam seu desenvolvimento é de grande relevância para o seu Tratamento. Portanto, o objetivo do presente estudo foi avaliar os efeitos da obesidade exógena induzida pela dieta de cafeteria e da atividade física crônica em ratos, sobre a adiposidade e a concentração sérica dos hormônios reguladores do balanço energético (leptina e grelina). Foram utilizados 32 ratos Wistar machos, divididos em quatro grupos: Sedentário alimentado com dieta padrão (SN), sedentário alimentado com dieta de cafeteria (SC), treinado alimentado com dieta padrão (TN) e treinado alimentado com dieta de cafeteria (TC). A dieta de cafeteria aumentou significativamente a adiposidade central (RET) e visceral (EPI) (p<0,05), induzindo a obesidade. Por outro lado, o treinamento físico minimizou o efeito da dieta de cafeteria, diminuindo tanto a adiposidade central como a visceral. A atividade física crônica não impediu o desenvolvimento da hiperleptinemia nos ratos normocalóricos e alimentados com dieta de cafeteria. Observou-se ainda que decorrente do treinamento físico e consequente redução de massa, nos animais normocalóricos, houve diminuição na concentração plasmática de grelina. Concluímos com este estudo que a qualidade da dieta e a quantidade de tecido adiposo, apresentaram-se como importantes reguladores da concentração plasmática de hormônios reguladores do balanço energético, reforçando a importância de uma dieta adequada e da atividade física contínua na manutenção do peso corporal no combate aos efeitos deletérios da obesidade.

Obesity is becoming one of the biggest worldwide epidemics. Therefore, knowing its etiology and mechanisms that regulate its development is of great relevance for its treatment. Thus, the aim of the present study was to evaluate the effects of obesity induced by the palatable hyperlipidic diet and of the chronic physical activity in rats, on the adiposity and the serum concentration of regulating hormones of the energy balance (leptin and ghrelin). 32 male Wistar rats were divided in four groups: Sedentary fed with chow diet (SN), sedentary fed with cafeteria diet (SC), trained fed with chow diet (TN) and trained fed with cafeteria diet (TC). The cafeteria diet led to a significant increase of central (RET) and visceral (EPI) adiposity (p<0.05). Conversely,the exercise training minimized the effect of the cafeteria diet, diminishing the central and visceral adiposity. Leptin was also increased in the groups fed with the cafeteria diet, suggesting increase of the resistance to the action of this hormone. Chronic physical activity did not hinder the development of hyperleptinemia. Reduction in the serum ghrelin concentration was observed only in the normocaloric group. Therefore,it has been concluded that the quality of diet and the quantity of adipose tissue mass behaved as important regulators of the serum concentration of leptin and ghrelin, reinforcing the importance of a suitable diet and continuous physical activity in the maintenance of body weight in the combat to the deleterious effects of obesity.

Efeito da ingestäo de álcool durante a lactaçäo e após o desmame sobre o metabolismo hepático e cerebral da cria: um estudo em ratos / Effect of ethanol ingestion during lactation and after weaning on offspring liver and brain metabolism in rats

This study evaluated the effect of ethanol íngestion by lactating and weaned rats on liver and brain metabolismo For this, female Wistar rats, at the first day post partwn, were kept with 4 female and 4 male pups and were divided in two groups: E - received 4 por cento ethanol liquid diet and C - received normal isocaloric liquid diet. On day 24 of life, half of the female (F) and male (M) pups were decapitated. Half of then were divided in four groups: MEC and FEC -received ethanol during lactation and normal diet after weaned; MCE and FCE - received normal diet during lactation and ethanol diet after weaned; MEE and FEE - received ethanol diet during the experimental period; MCC and FCC - received normal diet during experimental period. These animais were killed at 44 days of life. Body weight (g) were measured during all the experimental period. Food consumption was determinei after weaned (kcal/ 100 g of body weight). Ethanol intake, during lactation and/or after weaned, decreased body weight in male and female rats. After weaned food intake was decreased in ethanol treated rats. The relative weight (g/lOOg b. w.) of liver and brain was increased in male rats, with 44 days of life that received ethanol during lactation and/or after weaned. On the other hand, in FEE the liver relative weight was decreased and brain relative weight was increased only in FCE and FEE. Líver protein content was increased in MCE, MEE, FCE and FEE. At 24 days of life ethanol treatment decreased liver ATP citrate lyase activity in male and malic enzyme in male and female. ln female rats that received normal diet after weaned (FEC) the activities of these enzymes were normalized. Although in MEC ATP cit activity increased in liver. Liver lipogenesis rate was increased in MCE, MEE and FEE. Brain relative weight, from male and female ethanol treated rats with 24 days of life, were increased and no changes in enzyme activities were detected. At 44 days of life brain ATP cit activity were decreased in MEE and FEC and malic enzyme ín MEC, FCE and FEC. On the other hand in FEE it was observed an increase in ATP cit and malíc enzyme activities in this tíssue. Brain glucose metabolism and lactate production were studied in male and female rats with 24 or 44 days of life. For these braín slices were incubated at 37ºC ín Krebs-Henseleit buffer under carbogen, in the presence of glucose (5mM) plus l4C-glucose (O.04 mCi) with O-hydroxybutyrate or insulin...(au)