Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Macrophages are phagocytic cells of the innate immune system, which have a central role in immune surveillance, tissue homeostasis and the immune response to bacterial, viral, protozoan and helminth parasites. It is now appreciated that many tissue resident macrophage (resMΦ) populations, including those in the peritoneal and pleural cavity, are derived prenatally prior to the establishment of definitive haematopoiesis in the bone marrow. Once seeded, these resMΦ populations are long-lived and capable of self-renewal via in situ proliferation driven by CSF-1. An inflammatory insult, such as bacterial infection, results in the recruitment of bone marrow derived macrophages (BMDMΦ) and the disappearance of the resMΦ population. BMDMΦ recruited to the site of infection become classically activated upon engagement of pathogen recognition receptors and subsequent STAT1 induction. Classically activated macrophages (CAMΦ) are highly bactericidal through the production of inflammatory cytokines, which direct the TH1 immune response, and upregulation of iNOS to generate high concentrations of intracellular nitric oxide. During resolution of acute inflammation resMΦ undergo a CSF-1 driven proliferative burst to repopulate the tissue. In contrast to bacterial infection, helminth parasites drive a TH2 immune response characterised by CD4+ T cell production of IL-4, which induces proliferation and alternative activation of the resMΦ population, thereby overcoming the need for an inflammatory influx of BMDMΦ. Alternatively activated macrophages (AAMΦ) are generated through signalling from the IL-4Rα subunit and subsequent expression of the molecules RELMα, YM1 and arginase-1. While both BMDMΦ and resMΦ upregulate RELMα, YM1 and Arg-1 in response to IL-4Rα stimulation, microarray analysis revealed an otherwise diverse transcriptional and cell surface phenotype between these populations. It was hypothesised that the diverse modes of macrophage accumulation enlisted by bacterial and helminth parasites, combined with the distinct alternative activation phenotypes employed by BMDMΦ and resMΦ populations would translate into important functional differences as regards anti-parasitic immunity. Chapter 1 and 2 of this thesis addresses the importance of macrophage origin during infection with the filarial nematode Litomosoides sigmodontis, taking advantage of the naturally occurring resistant C57BL/6 and susceptible BALB/c strains. A large disparity in MΦ accumulation was observed throughout the infection time course, with significantly larger numbers present within the pleural cavity of resistant C57BL/6 mice. This difference in MΦ number was a reflection of enhanced F4/80hi resMΦ accumulation. Through Ki67hi staining and the use of CCR2-/- and partial bone marrow chimeric mice, the expanded F4/80hi population in resistant C57BL/6 mice was shown to be a result of proliferation of the local F4/80hiGATA6+CD102+ resMΦ population. A high degree of BMDMΦ incorporation into the resMΦ pool through assumption of an F4/80hiGATA6+CD102+ phenotype was observed in both naïve and infected bone marrow chimeric animals, supporting a recent publication showing gradual incorporation of these cells into the resMΦ niche with age. Importantly, the degree of BMDMΦ incorporation into the F4/80hi population was equivalent between naïve and infected animals, despite a 27-fold difference in cell number, illustrating that expansion is a result of proliferation of local resMΦ, independent of origin. Susceptibility was marked by reduced resMΦ proliferation and enhanced recruitment of bone marrow derived F4/80lo MΦ and monocytes. These recruited BMDMΦ displaced the resMΦ population, failed to integrate the resMΦ niche and were highly positive for PD-L2, a marker specific to BMD AAMΦ. Prevention of monocyte influx and subsequent resMΦ displacement resulted in increased worm killing and a stronger TH2 immune response in susceptible BALB/c mice, thereby confirming a detrimental role for BMD AAMΦ in worm killing. Conversely, in order to confirm a protective role for the expanded resMΦ in resistant C57BL/6 mice we attempted to deplete the resMΦ population through intrapleural delivery of clodronate-loaded liposomes. Due to technical issues we were unable generate statistically significant results when depleting the resMΦ population, however a trend toward decreased worm killing in the absence of resMΦ is evident. Previously generated microarrays in the lab identified the complement cascade as being highly upregulated by AAMΦ induced in response to Brugia malayi infection compared to BMDMΦ (thioglycollate elicited). To investigate the role of complement in resistance to L. sigmodontis, Chapter 3 briefly phenotypes the macrophage compartment of C3-/- C57BL/6 mice during infection. No differences in worm burden or macrophage phenotype could be detected in C3-/- mice compared to WT controls, however this may be explained through differences in strain or MΦ origin. This chapter provides an important foundation for future studies on complement and its role in worm killing during L. sigmodontis infection. The final chapter of the thesis focuses on examining the bactericidal capabilities of BMD and resMΦ populations. An in vitro system was utilised to assess the interaction of bone marrow derived macrophages (thioglycollate elicited) and ResMΦ (from naïve mice) with Salmonella enterica serovar Typhimurium SL3261. I found that in vitro BMDMΦ are infected by/ingest SL3261 to a much greater degree than resMΦ. The resMΦ population is less efficient at both controlling the spread and killing intracellular SL3261 overtime, compared to the BMDMΦ population. In vivo however, there appears to be no difference in the ability of the monocyte derived F4/80lo MΦ and the F4/80hi resident MΦ to be infected by/ ingest SL3261, nor was a difference in bactericidal ability detected. Ultimately my work highlights that the anti-parasitic functions of MΦ populations are not dictated by origin but rather the activation phenotype upon infection and ability to respond to local stimuli.

O gênero Capsicum compreende mais de 200 espécies de pimentas e pimentões e diversas atividades farmacológicas são descritas na literatura. Estudos prévios do nosso grupo de pesquisa têm explorado diferentes atividades biológicas de Capsicum baccatum var. Pendulum (Solanaceae), como antioxidante, antiinflamatória, hipoglicemiante e antidislipidêmica. A prevalência da síndrome metabólica, caracterizada por fatores como obesidade, resistência à insulina, dislipidemia e hipertensão, tem atingido proporções epidêmicas e acomete cerca de 20% da população mundial. Muitas vezes, apenas a mudança no estilo de vida não é eficaz para impedir a progressão da doença, sendo necessário aderir ao tratamento farmacológico. No entanto, não existem fármacos específicos para o tratamento da síndrome, levando à utilização de polifarmácia, que gera dificuldades de adesão ao tratamento e risco de interações medicamentosas. O principal objetivo desse estudo foi avaliar o efeito do extrato butanólico (BUT) e da fração ativa (AF) dos frutos de C. baccatum em um modelo de síndrome metabólica induzido por dieta em camundongos C57BL/6. Inicialmente apresentamos uma revisão de estudos publicados, que utilizam diferentes tipos de dietas hipercalóricas para induzir a síndrome metabólica em roedores. Ao compararmos esses estudos, observamos a forte tendência à utilização de camundongos da linhagem C57BL/6 machos e jovens, respondendo de forma satisfatória à indução da síndrome metabólica. Após, apresentamos o efeito do BUT e AF, nas doses de 200 e 50 mg/kg, respectivamente, sobre os parâmetros glicídicos e lipídicos em modelo de síndrome metabólica em camundongos C57BL/6 submetidos a uma dieta hiperpalatável (HPD) durante 120 dias. Nesse estudo foi visto que o tratamento com C. baccatum via oral, preveniu o ganho de peso, o desenvolvimento de um perfil de intolerância à glicose, o acúmulo de gordura na região abdominal e a elevação nos níveis de insulina e leptina plasmáticas quando comparados ao grupo HPD. Além disso, também preveniu o acúmulo de colesterol e triglicerídeos no fígado e preservou a morfologia do tecido hepático. Assim, C. baccatum se mostrou promissor, prevenindo alterações dos diversos componentes importantes da síndrome metabólica. / The genus Capsicum comprises more than 200 species of peppers and a range of pharmacological activities are described in the literature. Previous studies of our research group have explored several activities for Capsicum baccatum var. pendulum (Solanaceae) species, as antioxidant, anti-inflammatory, hypoglycemic and antidyslipidemic, since the studies with this species are scarce. The prevalence of metabolic syndrome, characterized by the association of factors such as obesity, insulin resistance, dyslipidemia and hypertension, is reaching epidemic proportions worldwide, affecting approximately 20% of world's population. Often, only lifestyle change is not effective in preventing the progression of the disease, being necessary adherence to pharmacological treatment. However, there are no specific drugs for the treatment of the syndrome, leading to the use of polypharmacy, which generates an increase in public spending, difficulties of adherence to treatment, and enhanced risk to drug interactions. The main objective of this study was to evaluate the effect of butanolic extract (BUT) and the active fraction (AF) of C. baccatum on a model of diet-induced metabolic syndrome in C57BL/6 mice. We first present a review of published studies, which use different types of hypercaloric diets to induce metabolic syndrome in rodents. When comparing these studies, we observed a strong trend towards the use of male and young C57BL/6 mice, responding satisfactorily to the metabolic syndrome induction through hypercaloric diets. After, we present the effect of BUT and AF, on glucose and lipid parameters in a model of metabolic syndrome in C57BL/6 mice submitted to a hyperpalatable diet (HPD) for 120 days. In this study, it was seen that oral C. baccatum treatment prevented weight gain, development of a glucose intolerance profile, accumulation of fat in the abdominal area and the increase in plasma insulin and leptin levels when compared to group HPD. Also, it prevented the accumulation of cholesterol and triglycerides in the liver, and preserved the liver tissue morphology. Thus, these results showed the effects of C. baccatum, especially AF, preventing changes in several important components of the metabolic syndrome.

Voluntary wheel running is rewarding and believed to activate the same brain reward system as in alcohol and drug addiction. Brain-derived neurotrophic factor (BDNF), a well-known growth factor widely expressed in the brain, is modulated by both voluntary exercise and alcohol consumption. The aim of this study was to evaluate how voluntary exercise affects the expression levels of BDNF and its receptor TrkB in brain regions involved in positive and negative reinforcement. Additionally we wanted to evaluate the effect it may have on alcohol drinking behaviors in C57BL/6 mice, a mouse model which are naturally prone for engaging in voluntary exercise and voluntary alcohol consumption. We found a small upregulation in DG and CA1 after three weeks of exercise, confirming findings by others, and a significant 3-fold downregulation of BDNF in NAc after both three weeks of exercise and exercise followed by a five week period of either ethanol intake or not. Interestingly, we here show a significant 100-fold increase in BDNF after exercise and a 120-fold increase after both exercise and alcohol consumption in amygdala, a region involved in regulation of anxiety-related behavior and negative reinforcement. Additionally a slightly lower 10-fold increase in BDNF was seen after exercise and a 15-fold increase after exercise followed by ethanol in prefrontal cortex, a structure contributing to reward-related behavior. Behaviorally, we could not either directly following exercise or at five weeks post-exercise detect any significant effect of wheel-running on depression-related behavior. However, we did find that exercise significantly increased the alcohol intake.

O gênero Capsicum compreende mais de 200 espécies de pimentas e pimentões e diversas atividades farmacológicas são descritas na literatura. Estudos prévios do nosso grupo de pesquisa têm explorado diferentes atividades biológicas de Capsicum baccatum var. Pendulum (Solanaceae), como antioxidante, antiinflamatória, hipoglicemiante e antidislipidêmica. A prevalência da síndrome metabólica, caracterizada por fatores como obesidade, resistência à insulina, dislipidemia e hipertensão, tem atingido proporções epidêmicas e acomete cerca de 20% da população mundial. Muitas vezes, apenas a mudança no estilo de vida não é eficaz para impedir a progressão da doença, sendo necessário aderir ao tratamento farmacológico. No entanto, não existem fármacos específicos para o tratamento da síndrome, levando à utilização de polifarmácia, que gera dificuldades de adesão ao tratamento e risco de interações medicamentosas. O principal objetivo desse estudo foi avaliar o efeito do extrato butanólico (BUT) e da fração ativa (AF) dos frutos de C. baccatum em um modelo de síndrome metabólica induzido por dieta em camundongos C57BL/6. Inicialmente apresentamos uma revisão de estudos publicados, que utilizam diferentes tipos de dietas hipercalóricas para induzir a síndrome metabólica em roedores. Ao compararmos esses estudos, observamos a forte tendência à utilização de camundongos da linhagem C57BL/6 machos e jovens, respondendo de forma satisfatória à indução da síndrome metabólica. Após, apresentamos o efeito do BUT e AF, nas doses de 200 e 50 mg/kg, respectivamente, sobre os parâmetros glicídicos e lipídicos em modelo de síndrome metabólica em camundongos C57BL/6 submetidos a uma dieta hiperpalatável (HPD) durante 120 dias. Nesse estudo foi visto que o tratamento com C. baccatum via oral, preveniu o ganho de peso, o desenvolvimento de um perfil de intolerância à glicose, o acúmulo de gordura na região abdominal e a elevação nos níveis de insulina e leptina plasmáticas quando comparados ao grupo HPD. Além disso, também preveniu o acúmulo de colesterol e triglicerídeos no fígado e preservou a morfologia do tecido hepático. Assim, C. baccatum se mostrou promissor, prevenindo alterações dos diversos componentes importantes da síndrome metabólica. / The genus Capsicum comprises more than 200 species of peppers and a range of pharmacological activities are described in the literature. Previous studies of our research group have explored several activities for Capsicum baccatum var. pendulum (Solanaceae) species, as antioxidant, anti-inflammatory, hypoglycemic and antidyslipidemic, since the studies with this species are scarce. The prevalence of metabolic syndrome, characterized by the association of factors such as obesity, insulin resistance, dyslipidemia and hypertension, is reaching epidemic proportions worldwide, affecting approximately 20% of world's population. Often, only lifestyle change is not effective in preventing the progression of the disease, being necessary adherence to pharmacological treatment. However, there are no specific drugs for the treatment of the syndrome, leading to the use of polypharmacy, which generates an increase in public spending, difficulties of adherence to treatment, and enhanced risk to drug interactions. The main objective of this study was to evaluate the effect of butanolic extract (BUT) and the active fraction (AF) of C. baccatum on a model of diet-induced metabolic syndrome in C57BL/6 mice. We first present a review of published studies, which use different types of hypercaloric diets to induce metabolic syndrome in rodents. When comparing these studies, we observed a strong trend towards the use of male and young C57BL/6 mice, responding satisfactorily to the metabolic syndrome induction through hypercaloric diets. After, we present the effect of BUT and AF, on glucose and lipid parameters in a model of metabolic syndrome in C57BL/6 mice submitted to a hyperpalatable diet (HPD) for 120 days. In this study, it was seen that oral C. baccatum treatment prevented weight gain, development of a glucose intolerance profile, accumulation of fat in the abdominal area and the increase in plasma insulin and leptin levels when compared to group HPD. Also, it prevented the accumulation of cholesterol and triglycerides in the liver, and preserved the liver tissue morphology. Thus, these results showed the effects of C. baccatum, especially AF, preventing changes in several important components of the metabolic syndrome.

Submitted by Aline Parisoto Missio null (alinepm@ibb.unesp.br) on 2016-10-07T00:28:57Z No. of bitstreams: 1 DISSERTAÇÃO Aline Missio repositório.pdf: 2424232 bytes, checksum: be4408bb8a9f5dfa38690910cec793fd (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-10-13T14:18:07Z (GMT) No. of bitstreams: 1 missio_ap_m_bot.pdf: 2424232 bytes, checksum: be4408bb8a9f5dfa38690910cec793fd (MD5) / Made available in DSpace on 2016-10-13T14:18:07Z (GMT). No. of bitstreams: 1 missio_ap_m_bot.pdf: 2424232 bytes, checksum: be4408bb8a9f5dfa38690910cec793fd (MD5) Previous issue date: 2016-08-30 / A vitamina D (VitD) ativa possui várias funções importantes incluindo efeitos imunomoduladores na imunidade inata e na específica. A deficiência desta vitamina já alcançou proporções epidêmicas em várias regiões e por isto sua suplementação tem sido sugerida em algumas doenças. Diferentes linhagens de camundongos têm sido utilizadas para avaliar os efeitos imunomoduladores da VitD. O estudo dos efeitos da deficiência e da suplementação com VitD tem sido realizado em seres humanos e também em linhagens isogênicas de camundongos. Neste trabalho comparamos o efeito da suplementação com 0,1 µg de VitD e de paricalcitol nas linhagens murinas C57BL/6 e DBA/1J. Estes animais foram injetados com 0,1 µg de VitD ou paricalcitol durante 15 dias, em dias alternados. O peso corporal foi avaliado diariamente e sangue e baço foram coletados 24 horas após a última dose. Na linhagem C57BL/6 a VitD diminuiu o peso corporal e aumentou a concentração de cálcio sérico. Em relação aos parâmetros imunológicos, houve diminuição da produção de citocinas por células esplênicas e maior expressão de MHC II nas células dendríticas. O paricalcitol não afetou o peso corporal e o nível de cálcio sérico, mas diminuiu a produção de citocinas nesta linhagem. Com exceção do peso corporal que diminuiu, os demais parâmetros não foram afetados pela VitD ou pelo paricalcitol nos camundongos DBA/1J. A suplementação com 0,2 µg de VitD nos animais DBA/1J desencadeou a diminuição de peso corporal, queda na produção de IL-2, IFN-γ e IL-5 por células esplênicas mas não afetou a expressão de moléculas co-estimuladoras. Esta mesma dose elevada de paricalcitol nesta linhagem aumentou a produção de TNF-α, mas não determinou outros efeitos significativos. Analisados de forma conjunta estes resultados mostram que camundongos C57BL/6 e DBA/1J diferem na resposta à suplementação com VitD e paricalcitol, sendo a linhagem DBA/1J mais resistente ao seu efeito. / Active vitamin D (VitD) has a relevant role in many body functions, including effects on innate and adaptive immunity. However, as VitD deficiency already reached epidemic proportions worldwide, its supplementation has been used in various diseases. Different mice strains have been widely employed to investigate VitD immunomodulatory properties. In this work, we compared the effect of VitD and paricalcitol supplementation in C57BL/6 and DBA/1J. The mice were treated with 0.1 µg of VitD or paricalcitol, every other day, during 15 days. Body weight was assessed daily and blood and spleen cells were collected 24 hours after the last dose. In the C57BL/6 strain, VitD decreased body weight and also increased serum calcium concentration. Additionally, VitD decreased cytokine production by the spleen and increased the level of MHC II expression in dendritic cells. Paricalcitol did not affect body weight and serum calcium levels but it decreased cytokine production in this mice strain. Except body weight that was downregulated by VitD, the other parameters were not altered by VitD or paricalcitol in the DBA/1J strain. An increased dose (0.2 µg) of VitD decreased body weight, downregulated IL-2, IFN-γ and IL-5 production by spleen cells but did not affect the other cytokines neither the expression of costimulatory molecules in dendritic cells in DBA/1J mice. This higher dose of paricalcitol significantly increased TNF-α but had no other significant effects. Together, these results show that C57BL/6 and DBA/1J mice strains differ in their response to VitD and paricalcitol supplementation, being DBA/1J more resistant to their effects.

O gênero Capsicum compreende mais de 200 espécies de pimentas e pimentões e diversas atividades farmacológicas são descritas na literatura. Estudos prévios do nosso grupo de pesquisa têm explorado diferentes atividades biológicas de Capsicum baccatum var. Pendulum (Solanaceae), como antioxidante, antiinflamatória, hipoglicemiante e antidislipidêmica. A prevalência da síndrome metabólica, caracterizada por fatores como obesidade, resistência à insulina, dislipidemia e hipertensão, tem atingido proporções epidêmicas e acomete cerca de 20% da população mundial. Muitas vezes, apenas a mudança no estilo de vida não é eficaz para impedir a progressão da doença, sendo necessário aderir ao tratamento farmacológico. No entanto, não existem fármacos específicos para o tratamento da síndrome, levando à utilização de polifarmácia, que gera dificuldades de adesão ao tratamento e risco de interações medicamentosas. O principal objetivo desse estudo foi avaliar o efeito do extrato butanólico (BUT) e da fração ativa (AF) dos frutos de C. baccatum em um modelo de síndrome metabólica induzido por dieta em camundongos C57BL/6. Inicialmente apresentamos uma revisão de estudos publicados, que utilizam diferentes tipos de dietas hipercalóricas para induzir a síndrome metabólica em roedores. Ao compararmos esses estudos, observamos a forte tendência à utilização de camundongos da linhagem C57BL/6 machos e jovens, respondendo de forma satisfatória à indução da síndrome metabólica. Após, apresentamos o efeito do BUT e AF, nas doses de 200 e 50 mg/kg, respectivamente, sobre os parâmetros glicídicos e lipídicos em modelo de síndrome metabólica em camundongos C57BL/6 submetidos a uma dieta hiperpalatável (HPD) durante 120 dias. Nesse estudo foi visto que o tratamento com C. baccatum via oral, preveniu o ganho de peso, o desenvolvimento de um perfil de intolerância à glicose, o acúmulo de gordura na região abdominal e a elevação nos níveis de insulina e leptina plasmáticas quando comparados ao grupo HPD. Além disso, também preveniu o acúmulo de colesterol e triglicerídeos no fígado e preservou a morfologia do tecido hepático. Assim, C. baccatum se mostrou promissor, prevenindo alterações dos diversos componentes importantes da síndrome metabólica. / The genus Capsicum comprises more than 200 species of peppers and a range of pharmacological activities are described in the literature. Previous studies of our research group have explored several activities for Capsicum baccatum var. pendulum (Solanaceae) species, as antioxidant, anti-inflammatory, hypoglycemic and antidyslipidemic, since the studies with this species are scarce. The prevalence of metabolic syndrome, characterized by the association of factors such as obesity, insulin resistance, dyslipidemia and hypertension, is reaching epidemic proportions worldwide, affecting approximately 20% of world's population. Often, only lifestyle change is not effective in preventing the progression of the disease, being necessary adherence to pharmacological treatment. However, there are no specific drugs for the treatment of the syndrome, leading to the use of polypharmacy, which generates an increase in public spending, difficulties of adherence to treatment, and enhanced risk to drug interactions. The main objective of this study was to evaluate the effect of butanolic extract (BUT) and the active fraction (AF) of C. baccatum on a model of diet-induced metabolic syndrome in C57BL/6 mice. We first present a review of published studies, which use different types of hypercaloric diets to induce metabolic syndrome in rodents. When comparing these studies, we observed a strong trend towards the use of male and young C57BL/6 mice, responding satisfactorily to the metabolic syndrome induction through hypercaloric diets. After, we present the effect of BUT and AF, on glucose and lipid parameters in a model of metabolic syndrome in C57BL/6 mice submitted to a hyperpalatable diet (HPD) for 120 days. In this study, it was seen that oral C. baccatum treatment prevented weight gain, development of a glucose intolerance profile, accumulation of fat in the abdominal area and the increase in plasma insulin and leptin levels when compared to group HPD. Also, it prevented the accumulation of cholesterol and triglycerides in the liver, and preserved the liver tissue morphology. Thus, these results showed the effects of C. baccatum, especially AF, preventing changes in several important components of the metabolic syndrome.

No description available.

All five classes of vertebrates use the geomagnetic field for spatial orientation. The geomagnetic field can be used to derive both 'map' and 'compass' information. There is evidence for two different mechanisms used to sense the magnetic field, the radical pair mechanism (RPM) and the magnetite based mechanism (MBM). C57BL/6 laboratory mice can rely on directional information from the magnetic field to position their nests and to solve a water maze task. The primary objective of this research was to characterize the magnetic compass of C57BL/6 laboratory mice in the plus water maze task. These experiments explored sources of variation in magnetic responses and investigated the underlying magnetic compass orientation mechanism in C57BL/6 mice. The results provide evidence that the mouse magnetic compass is sensitive to low-level radiofrequency fields, consistent with the use of the RPM for magnetic orientation. Surprisingly, the results also suggest that C57BL/6 mice have a polarity sensitive compass, consistent with the use of a MBM for magnetic orientation. These experiments confirm that mice have a specialized magnetic compass sense. Furthermore, despite the controlled environment in which these laboratory experiments were conducted, a variety of factors can increase the variability in the response. Future experiments are needed to further characterize the mouse magnetic compass, as there is a possibility of a hybrid magnetic response where both magnetoreception mechanisms could be used for spatial orientation. / Master of Science

A dieta hiperlipídica (high-fat, HF) materna durante a gestação e/ou lactação aumenta a susceptibilidade da prole para o desenvolvimento de doenças crônicas na fase adulta. Verificar a hipótese que a ingestão materna de dieta HF nos períodos críticos de desenvolvimento (gestação e/ou lactação) predispõe à doença não alcoólica do fígado gorduroso e alterações pancreáticas e no tecido adiposo de camundongos machos adultos. Camundongos C57BL/6 fêmeas receberam durante a gestação e/ou lactação dieta padrão (standard chow, SC) ou HF. Filhotes machos foram divididos em cinco grupos: SC provenientes de mães SC; G provenientes de mães HF durante a gestação; L provenientes de mães HF durante a lactação; GL/HF provenientes de mães HF durante a gestação/lactação, mantendo a mesma dieta HF no período pós-natal (do desmame aos 3 meses deidade); GL provenientes de mães HF durante a gestação/lactação trocando a dieta para SC no período pós-natal (do desmame aos 3 meses deidade). Foi analisada ao longo do experimento a massa corporal da prole. No sacrifício (3 meses), o fígado, o pâncreas e a gordura epididimária foram removidos, pesados e processados e o sangue foi coletado para análise bioquímica. Ao nascimento e ao desmame, filhotes GL/HF foram mais pesados (+6% e +44%, p<0,05, respectivamente) que os filhotes SC. Os filhotes G apresentaram resistência à insulina e menor expressão do transportador de glicose no fígado (GLUT-2). A esteatose hepática foi observada nos grupos G, L, GL e principalmente nos filhotes do grupo GL/HF. A expressão hepática da proteína ligante de elementos regulatórios de esteróis (SREBP-1c) estava aumentada nos filhotes G, GL e GL/HF. Os filhotes G, GL e GL/HF apresentaram hipertrofia da ilhota pancreática e dos adipócitos quando comparados com o grupo SC. O consumo de dieta HF durante a gestação mostra-se ser o período mais prejudicial para os filhotes adultos de camundongos. A programação metabólica por dieta HF leva ao remodelamento adverso do fígado, do pâncreas e do tecido adiposo / Maternal high-fat diet (HF) during gestation and/or lactation period increases the susceptibility to development of chronic disease in offspring adult life. This work aimed to verify the hypothesis that maternal intake of high-fat diet in critical periods of pregnancy and/or suckling period predisposes to non alcoholic fatty liver disease, pancreatic and adipose tissue alterations in adulthood mice offspring. C57BL/6 female mice were fed, during gestation and/or lactation phases, with standard chow (SC) or HF diet. Male pups were divided into 5 groups: SC- from SC fed dam; G- from HF fed dam during gestation period; L- from HF fed dam during lactation period; GL- from HF fed dam during gestation and lactation periods and GL/HF- from HF fed dam during gestation and lactation, maintaining HF diet from post-weaning to adulthood. We analyzed body mass in all experiment, and at the euthanasia (3 mo-old), liver, pancreas and adipose tissue were removed, weighted and embedded. Blood was collected to biochemical analyses. At birth and at weaning, GL/HF pups were heavier than SC pups (+6% and +44%, p<0.05, respectively). G offspring showed insulin resistance and lower glucose transporter-2 expression (GLUT-2). Hepatic steatosis was present in G, L, GL and mainly in GL/HF offspring. Sterol regulatory element-binding protein-1c (SREBP-1c) expression was higher in G, GL and GL/HF offspring. It is important to mention that pancreatic islet hypertrophy and adipocyte hypertrophy were affected in G, GL and GL/HF offspring in comparison to SC. HF diet administration during gestation period is worse than lactation period. Furthermore, this type of programming by HF predisposes to adverse remodeling in liver, pancreas and adipose tissue in adult mice offspring