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

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Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-03-26T12:48:59Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) manuela_ortega_marques_rodrigues.pdf: 2356674 bytes, checksum: e576d7cb84dd67e4068acfffffe22e9f (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-03-29T12:57:38Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) manuela_ortega_marques_rodrigues.pdf: 2356674 bytes, checksum: e576d7cb84dd67e4068acfffffe22e9f (MD5) / Made available in DSpace on 2018-03-29T12:57:38Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) manuela_ortega_marques_rodrigues.pdf: 2356674 bytes, checksum: e576d7cb84dd67e4068acfffffe22e9f (MD5) Previous issue date: 2017 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG) / A expans?o do tecido adiposo branco na obesidade leva ? express?o alterada de prote?nas em seus adip?citos, bem como a infiltra??o de c?lulas do sistema imune, especialmente macr?fagos, cujas secre??es levam ao desenvolvimento da inflama??o cr?nica de baixo grau, a qual ? considerada subjacente ao desenvolvimento de in?meras comorbidades. Dentre as formas de tratamento da obesidade, dietas de restri??o cal?rica (RC) nutricionalmente balanceadas induzem a perda de peso e melhorias em marcadores sist?micos da inflama??o, mas os efeitos diretos no tecido adiposo visceral ainda s?o controversos. No entanto, existe uma lacuna sobre qual o impacto dessas dietas na inflama??o local, mesmo em condi??es de sobrecarga lip?dica. Assim, o objetivo deste estudo foi avaliar os efeitos da perda de peso corporal induzida por dieta hipolip?dica ad libitum e pela restri??o cal?rica com dieta hiperlip?dica na inflama??o do tecido adiposo visceral de camundongos obesos. Para tal, inicialmente, camundongos C57BL/6 com 12 semanas de idade, machos, foram divididos em dois grupos: LF ? alimentados com dieta controle hipolip?dica ? do ingl?s low fat (10% das calorias, fonte ?leo de soja, rica em ?cidos graxos poli-insaturados); e HF ? alimentados com dieta controle hiperlip?dica ? do ingl?s high fat (60% calorias, fonte banha de porco, rica em ?cidos graxos saturados) para indu??o da obesidade. Ap?s oito semanas, seis animais de cada grupo foram eutanasiados para verifica??o da adiposidade visceral e estado inflamat?rio (dosagens de prote?na C reativa ? PCR s?rica e hep?tica). Em seguida, os animais HF foram aleatoriamente divididos em tr?s grupos HF ? continuaram recebendo dieta HF; LFAL ? submetidos ao emagrecimento pela substitui??o da dieta HF pela LF e acesso livre (ad libitum) e RHF ? submetidos ao emagrecimento por receberem quantidades restritas em calorias da dieta HF para atingir o mesmo peso corporal dos animais LFAL. A partir deste momento, esses grupos foram alimentados, juntamente com os animais LF, por mais sete semanas. Ao final, foram avaliados o ganho/perda de peso corporal, a adiposidade, as concentra??es s?ricas e hep?ticas de PCR, e as concentra??es de leptina, adiponectina, e das citocinas IL-6, TNF e MCP-1 no tecido adiposo retroperitoneal, al?m da morfologia dos adip?citos e a presen?a de infiltrados inflamat?rios no tecido adiposo retroperitoneal. Ao final da fase de indu??o da obesidade, os animais HF estavam obesos e inflamados. Ao final da fase de indu??o da perda de peso, os grupos LFAL e RHF tiveram pesos corporais semelhantes, menores que o HF e se igualaram ao LF. No entanto, houve maior dificuldade em perder peso pelo grupo RHF em compara??o ao LFAL, dado pelas diferen?as significativas entre os deltas de perda de peso, que foram menores para RHF e pelos coeficientes de efici?ncia energ?tica, que foram maiores para o grupo RHF. Os animais LFAL retornaram a adiposidade e a hipertrofia dos adip?citos viscerais a valores semelhantes ao grupo LF. Isto provavelmente foi o que levou ? menor concentra??o de leptina com concomitante aumento da adiponectina e menor infiltra??o de c?lulas inflamat?rias neste tecido, igualando-se tamb?m ao LF. Em consequ?ncia, houve menor concentra??o tecidual de citocinas pr?-inflamat?rias, al?m de menor concentra??o hep?tica e circulante de PCR. J? para os animais RHF, houve apenas atenua??o da adiposidade e da hipertrofia dos adip?citos retroperitoneais. Isso foi suficiente para restabelecer a concentra??o local de leptina a n?veis semelhantes ao grupo LF, embora n?o tenha elevado a concentra??o de adiponectina. Al?m disso, a infiltra??o de c?lulas inflamat?rias menteve-se tamb?m elevada. N?o houve redu??o da concentra??o de citocinas pr?-inflamat?rias, ? exce??o da IL-6, que reduziu levemente. A concentra??o hep?tica de PCR foi atenuada, o que n?o refletiu na concentra??o s?rica dessa prote?na. Concluiu-se que a restri??o cal?rica com dieta hiperlip?dica foi menos eficiente em promover a perda de peso e de adiposidade e n?o melhorou a inflama??o do tecido adiposo visceral, comparada com a dieta hipolip?dica ad libitum. Inferiuse que a ingest?o de dieta com sobrecarga de lip?deos (60% das calorias) e de ?cidos graxos saturados foi mais determinante da inflama??o local do que a restri??o cal?rica per se. / Disserta??o (Mestrado) ? Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / The expansion of white adipose tissue in obesity leads to altered protein expression in its adipocytes, as well as the infiltration of immune cells, especially macrophages, whose secretions lead to the development of chronic low-grade inflammation, which underlies the development of several comorbidities. Among treatments, caloric restriction (CR) nutritionally balanced diets induce weight loss and ameliorates inflammation systemic markers, but adipose tissue effects are still controversial. Moreover, there is a gap on the impact of these diets on local inflammation, even under lipid overload. Thus, the aim of this study was to evaluate effects of body weight loss induced by a low fat ad libitum diet and a CR in a high fat diet in the visceral adipose tissue inflammation of obese mice. Firstly, 12 weeks of age male C57BL/6 mice were divided into two groups: LF - fed a control low fat diet (10% calories, source soybean oil, high in polyunsaturated fatty acids); and HF - fed a control high fat diet (60% calories, source lard, high in saturated fatty acids) for obesity induction. After eight weeks, six animals from each group were euthanized to verify visceral adiposity and inflammatory status (serum and hepatic C-reactive protein-CRP). Then, HF animals were randomly divided into three groups: HF ? keept at HF diet; LFAL - a weight loss group that was switched from HF to LF and maintained on it ad libitum; RHF - a weight loss group that received restricted amounts of HF to maintain the same body weight as LFAL. Thereafter, these groups were fed, along with the LF animals, for another seven weeks. At end, body weight gain / loss, adiposity, serum and hepatic CRP concentrations, and adipose retroperitoneal tissue concentrations of leptin, adiponectin, IL-6, TNF and MCP-1 were evaluated, as well as adypocite morphology and the presence of inflammatory infiltrates in the retroperitoneal adipose tissue. Obesity was induced, since HF animals had higher weights, adiposity and were inflamed. At the end of the weight loss period, both LFAL and RHF had similar body weight, lower than HF and equal to LF. However, it was more dificcult to loose wheight by the RHF group compared to LFAL, since weight loss deltas were lower for RHF and energy efficiency ratios were higher for RHF group. LFAL animals returned visceral adiposity and retroperitoneal adipocyte hypertrophy similarly to the LF group. Also, there was a lower leptin level with concomitant increase of adiponectin and less infiltration of inflammatory cells in this tissue, also matching to LF. Still, there was a lower tissue concentration of proinflammatory cytokines, and a lower hepatic and serum CRP. For RHF animals, there was only an attenuation in adiposity and visceral adipocyte hypertrophy, although it was sufficient to restore local leptin concentration similarly to LF. However, this regimen was not able to elevate the adiponectin concentration. In addition, the inflammatory cells infiltration was highly elevated. There was no reduction in proinflammatory cytokines concentration, despite IL-6, which was reduced slightly. Hepatic CRP concentration was attenuated, which did not reflect in its serum concentrations. In mice with diet-induced obesity, the weight loss by means a CR in a high fat diet was less effective in promoting wheight and adiposity losses and it did not improve visceral adipose tissue inflammation. It can be inferred that a lipid overload (60% from calories) as well as a saturated fatty acid surplus from the high fat diet were more determinant of local inflammation than caloric restriction per se.

Au cours des dernières décennies, une dégradation de la fertilité des vaches laitières, parallèlement à une augmentation de la production laitière a été observée. Des régions du génome, les QTL, affectent la fertilité femelle. Le but de ce travail de thèse est d’étudier la fertilité et certains paramètres zootechniques chez des vaches Prim'Hosltein en première lactation choisies pour leur haplotype favorable "fertil+" ou défavorable "fertil-" pour un QTL de fertilité situé sur le chromosome 3. Ce phénotypage a montré une meilleure fertilité et un meilleur bilan énergétique dans la première semaine de lactation pour les vaches "fertil+" par rapport aux vaches "fertil-". De plus, les vaches "fertil-" ont un flux d’ingestion plus rapide. Au pic de mobilisation, certains gènes du QTL étaient différentiellement exprimés dans le tissu adipeux des deux haplotypes. Dans les cellules de la granulosa, un de ces gènes, nommé Kirrel, est plus exprimé chez les vaches "fertil+" et sa protéine recombinante inhibe la sécrétion de progestérone in vitro. Notre travail a permis d'affiner les interactions génotype-phénotype liées à un QTL de fertilité et de mettre en avant un des possibles rôles d'un gène de ce QTL dans la fonction de reproduction chez la vache laitière. / In recent decades, the dairy cow fertility has declined, in parallel with an increase in milk production. Some regions of the genome, named QTL, affect female fertility. The purpose of this thesis is to study fertility and some zootechnical parameters in Prim'Hosltein cows in first lactation chosen for their favorable haplotype "fertil+" or unfavorable haplotype "fertil-" for one fertility QTL on chromosome 3. This phenotyping showed better fertility and energy balance in the first week of lactation for "fertil+" than for "fertil-" cows. In addition, "fertil-" cows had a higher eating rate. At the peak of mobilization, the QTL genes are differentially expressed in adipose tissue of "fertil+" and "fertil-" cows. In granulosa cells, one of these genes, named Kirrel, is higher expressed in "fertil+" cows and its recombinant protein inhibits the secretion of progesterone in vitro. Our work has contributed to refine interactions genotype-phenotype linked to one fertility QTL and highlighted one of the possible roles of a gene which belongs to this QTL in the reproductive function in dairy cows.

L’obésité et le diabète sont associés à des complications, notamment une fragilité cutanée. Celle-ci pourrait être associée à une altération du métabolisme du glucose et à une augmentation du tissu adipeux sous-cutané. Il a été montré que l’hypoderme pourrait avoir une fonction spécifique pour la peau. Notre travail a consisté d’une part à caractériser l’adiposité hypodermique et à étudier son influence dans la réactivité du tissu cutané en réponse à des pressions faibles ou fortes chez des souris obèses et d’autre part à étudier le processus de cicatrisation. Les fortes pressions augmentent la fragilité cutanée ce qui peut aboutir à des lésions, notamment des ulcères de pression. Les études ont été réalisées chez des souris C57BL/6J développant une obésité induite par une alimentation riche en lipides et en sucres pendant 4 et 12 semaines. La taille des adipocytes de l’hypoderme a été mesurée ainsi que leur réponse lipolytique en présence ou non d’insuline. La réactivité tissulaire a été évaluée en mesurant les variations du flux sanguin en réponse : 1) à l’application d’une pression locale faible afin de déterminer la vasodilatation induite par la pression (PIV), 2) par iontophorèse d’acétylcholine ou de nitroprussiate de sodium. Afin d’explorer le processus spécifique d’ulcère de pression chez les souris obèses diabétiques, une compression par cycles d’ischémie-reperfusion a été réalisée. Ces études ont été complétées par des explorations métaboliques, histologiques et biochimiques. Par ailleurs nous avons déterminé l’impact de l’augmentation de l’adiposité sur des fibroblastes dermiques in vitro afin de mieux comprendre le processus de cicatrisation.Dans ce travail de thèse, nous avons mis en évidence une augmentation de l’adiposité hypodermique associée à une insulinorésistance tissulaire et systémique. Nous avons également montré un retard de cicatrisation en fonction de l’évolution de l’obésité et des réponses micro vasculaires diminuées post cicatrisation par rapport à une peau non lésée / Obesity and diabetes led to complications, including skin fragility. Skin fragility could be associated to a glucose metabolism alteration and a subcutaneous adipose tissue increase. It has been shown that hypodermis could have a specific function for the skin. Our work consisted on the one hand in characterizing the dermal adiposity and studying its involvement in the skin tissue reactivity in response to low or high pressures in obese mice and, on the other hand, in studying the healing process. High pressures increase cutaneous fragility which can lead to skin wounds, in particular pressure ulcers. This study was realized using C57BL/6J male mice with a diet-induced obesity. C57BL/6J mice were fed a high fat and high sugar diet during 4 or 12 weeks. Hypodermis adipocytes size was measured as well as their lipolytic response in presence or absence of insulin. The skin tissue reactivity was assessed measuring the skin blood flow variations in response to 1) a local pressure application in order to determine the pressure-induced vasodilation (PIV), 2) an acetylcholine or sodium nitroprusside iontophoresis. To examine the specific mechanism of the pressure ulcer in obese diabetic mice, a compression with ischemia-reperfusion cycles was realized. Metabolic assessment, histological and molecular biological studies were carried out to characterize each stage of healing through obesity. Furthermore, we determined the adiposity increase on dermal fibroblasts in vitro to better understand the healing process. In this thesis work, we have highlighted a hypodermis adiposity linked to a tissue and a systemic insulin resistance. We have also showed a delayed healing depending on the evolution of the obesity. The microvascular responses were decreased post healing compared to a non-wounded skin

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

O objetivo do trabalho foi investigar se há ritmicidade dos eventos lipolíticos e lipogênicos no TA peri-epididimal e caracterizar se a pinealectomia interfere nesse processo. O sacrifício dos animais, controles e pinealectomizados, foi realizado de quatro em quatro horas. Em relação a lipogênese observaram-se diferenças significativas entre os horários analisados, no entanto, a comparação entre grupos, não mostrou diferenças significativas, indicando que a pinealectomia não interfere nesse processo metabólico do TAB. O estudo da lipólise mostrou que existem algumas diferenças significativas entre os horários, contudo, a pinealectomia também não interferiu no ritmo desse processo. A utilização do programa COSINOR, para análise da existência de ritmos, evidenciou que existe um ritmo, tanto na lipogênese quanto na lipólise, mas que não ocorre de maneira circadiana, ou seja, não ocorre em intervalos de 24h ±4. Também não foram encontradas diferenças significativas, entre os grupos, quando analisadas: consumo alimentar, ingestão hídrica e evolução do peso corporal. / The objective was to investigate whether there rhythmicity of events in lipolytic and lipogenic TA peri-epididymal and characterize whether pinealectomy interferes with this process. The sacrifice of animals, controls and pinealectomized was performed every four hours. In relation to lipogenesis observed significant differences between the times tested, however, the comparison between groups showed no significant differences, indicating that pinealectomy does not intervene in the metabolic process of WAT. The study of lipolysis showed that there are some significant differences between the times, however, pinealectomy did not affect the rhythms of this process. The use of COSINOR program for analysis of the existence of rhythms, suggest that there is a rhythm in both lipogenesis and lipolysis, but that does not occur in a circadian manner, i.e., does not occur at intervals of 24 ± 4. We also found no significant differences between groups when analyzed food intake, water intake and body weight evolution.

Made available in DSpace on 2016-06-02T19:22:09Z (GMT). No. of bitstreams: 1 5256.pdf: 6965922 bytes, checksum: 5df2e41fa93348b8ef396978016ce615 (MD5) Previous issue date: 2013-06-06 / Universidade Federal de Sao Carlos / Visceral obesity is an important risk factor cardiovascular diseases. After menopause, fat distribution shifts to visceral depots leading to lipid metabolism disorders and chronic lowgrade inflammation. Resistance training (RT) has beneficial effects in postmenopausal women, but its effectiveness in normalizing visceral adipose tissue disorders is not well understood. To address this questions adult female Sprague-Dawley rats were randomly divided into six groups (n=6 per group): sham-sedentary (SHAM), ovariectomized- sedentary (OVX), SHAM-trained (S-T), OVX-T. Sham or ovariectomy procedure was performed with 250 grams. Three weeks after the surgery, trained groups started 10 weeks of climbing in a 1.1-m vertical ladder with progressive load of 65%, 85%, 95% and 100% of rat s previous maximal overload. All animals were killed 92 days after being ovariectomized and trained animals were killed 48 hours after the last training session. Mesenteric, parametrial and subcutaneous adipose tissues were prepared for morphometric analyses in colidina and osmium tetroxide and part of mesenteric adipose tissue was stored for mRNA analyses by quantitative PCR. Resistance training prevented ovariectomy-induced higher body weight, food intake, feeding efficiency and mesenteric and subcutaneous, but not parametrial adipocyte area. In addition, RT avoided OVX-induced upregulation in the lipogenic genes PPAR-&#947;, SREBP-1c and its downstream targets SCD-1 and ACC gene expression. Further, RT increases the gene expression of mitochondrial &#946;-oxidation enzyme CPT-1 in OVX rats. RT also prevented the chronic low-grade inflammation in OVX group, demonstrated by the presence of macrophage markers (F4/80 and CD11b), increase in activated Th1 cells (IFN-&#947;) and the proinflammatory cytokines (TNF-&#945;, IL-1&#946; and IL-6). RT additionally created an antiinflammatory (IL-10) environment. The present results reflect a powerful prophylactic effects of resistance training in preventing pathological effects of estrogen deficiency, both at physiological and molecular levels. Therefore, we suggest that this may be an advantageous low cost-effective treatment at post-menopausal phase, since appropriately prescribed. / A obesidade visceral é um importante fator de risco para doenças cardiovasculares. Após a menopausa, as gorduras passam a ser depositadas preferencialmente em locais viscerais e surgem desordens no metabolismo lipídico e um quadro inflamatório crônico de baixa intensidade. O treinamento resistido (TR) possui efeitos benéficos na pós-menopausa, mas não se sabe se ele é efetivo para normalizar as desordens do tecido adiposo visceral. Para pesquisar estas respostas, ratas Sprague-Dawley adultas foram divididas em 4 grupos (n=6 por grupo): Sham sedentárias (SHAM), ovariectomizadas sedentárias (OVX), sham treinadas (SHAM-TR) e OVX-TR. A cirurgia foi realizada quando as ratas estavam com 250 gramas. Após 3 semanas, os grupos treinados iniciaram um programa de treinamento de 10 semanas (3x por semana) de escalada (4-9 repetições) em uma escada vertical de 1,1 m de altura com sobrecargas progressivas de 65%, 85%, 95% and 100% da carga máxima do rato. As ratas foram sacrificadas 92 dias após a ovariectomia e 48 horas após a última sessão de treino. Os tecidos adiposos mesentérico, parametrial e subcutâneo foram preparados em colidina e tetróxido de ósmio para análises morfométricas e parte do tecido mesentérico foi armazenado para análises de expressão gênica por PCR quantitativa. O treinamento resistido evitou o aumento de massa corporal provocado pela ovariectomia, consumo alimentar, eficiência alimentar e a área dos adipócitos mesentérico e subcutâneo, mas não do parametrial. Além disso, evitou a alta expressão dos genes lipogênicos PPAR-&#947;, SREBP-1c e de seus genes alvos ACC e SCD-1. Adicionalmente, o TR, aumentou a expressão do gene da &#946;-oxidação mitocondrial CPT-1 nas ratas OVX-TR. O TR também evitou a condição inflamatória de baixa intensidade instaurada nas ratas OVX, demonstrado pelo acúmulo de macrófagos (F4/80 e CD11b), aumento de células Th1 ativadas (IFN-&#947;) e de mediadores pó-inflamatórios (TNF-&#945;, IL-1&#946; e IL-6), além de criar um ambiente anti-inflamatório (IL-10). Os resultados deste trabalho refletem um significativo efeito profilático do treinamento resistido sobre parâmetros fisiológicos e moleculares na falta dos hormônios ovarianos. Portanto, podemos sugerir que este pode ser um vantajoso tratamento de baixo custo no período pós-menopausal, se adequadamente prescrito.

Made available in DSpace on 2016-06-02T19:22:55Z (GMT). No. of bitstreams: 1 3956.pdf: 1826733 bytes, checksum: e72222f7d290cf5a26f0db7d34928af6 (MD5) Previous issue date: 2011-10-20 / Financiadora de Estudos e Projetos / The purpose of this study was to investigate the effects of high-fat diet and swimming and resistance training in the adipose tissue, endocannabinoid system and lipid profile in obese rats. Wistar adult male rats were divided into 6 groups (n = 10 per group): sedentary chow diet (SP); sedentary high-fat diet (SH); swimming chow diet (NP); swimming high-fat diet (NH); resistance training chow diet (FP); resistance training high-fat diet (FH). After three weeks feeding on a chow diet or high-fat diet, the animals started the exercise protocols. The NP and NH groups swam 60 minutes/day, five days a week, with a constant overload of 5% body weight during 8 weeks in tanks of 50 cm of height and 30 cm of diameter, for 8 weeks. The groups FP and FH started the resistance training with weights tied to their tails, once every three days for 8 weeks. The animals of SP and HS groups remained sedentary and fed their respective diets. After this period all animals were sacrificed by decapitation and tissues dissected, weighed and immediately stored at -80 º C. High-fat diet increased body weight gain, relative weight of adipose tissues (epididymal, retroperitoneal, visceral and subcutaneous) and adipose tissue area (epididymal, retroperitoneal and visceral). It also increased the fat percentage of all adipose tissues and liver, and increased gene expression of CB1 receptor. The trained groups, both resistance training and swimming, presented lower values of adipocyte area, benefits in lipid profile, lower percentage of fat in the adipose tissue and liver, lower body weight gain, and lower values for gene expression the CB1 receptor. Thus our results indicate the potential benefits of the resistance training and swimming as non pharmacological alternatives to control the deleterious effects of high-fat diet on adipose tissue, lipid profile, lipid content of tissues and control of the endocannabinoid system imbalance caused by high-fat diet. / O objetivo do presente estudo foi investigar os efeitos da dieta hiperlipídica e do treinamento de natação e força sobre o tecido adiposo, perfil lipídico e sistema endocanabinóide de ratos obesos. Para isso, utilizamos sessenta ratos adultos machos divididos em seis grupos: Sedentário Padrão (SP); Sedentário Hiperlipídico (SH); Natação Padrão (NP); Natação Hiperlipídica (NH); Força Padrão (FP); Força Hiperlipídica (FH). Após três semanas recebendo dieta padrão ou hiperlipídica, os animais iniciaram os protocolos de exercício. Os grupos NP e NH nadaram 60 minutos por dia, 5 dias na semana com uma carga de 5% do peso corporal atada ao corpo, em tanques de 50 cm de altura e 30 cm de diâmetro, durante 8 semanas. Os grupos FP e FH realizaram exercício de subida em escada com pesos atados às suas caudas, uma vez a cada três dias, durante 8 semanas. Os animais dos grupos SP e SH continuaram sedentários e alimentados com suas respectivas dietas. Após esse período todos os animais foram sacrificados por decapitação, e os tecidos dissecados, pesados e imediatamente congelado a -80ºC. A dieta hiperlipídica aumentou o ganho de massa corporal, peso relativo dos tecidos adiposos (epididimal, retroperitoneal, visceral e subcutâneo) e área de adipócitos (epididimal, retroperitoneal e visceral). Também aumentou o percentual de gordura de todos os tecidos adiposos e fígado, além de aumentar a expressão gênica do receptor CB1. Os grupos treinados, tanto em força quanto em natação, apresentaram menores valores de área de adipócitos, melhora do perfil lipídico, menores valores no percentual de gordura dos tecidos adiposos e fígado, menores ganhos de massa corporal, além de menores valores de expressão gênica para o receptor CB1. Assim nossos resultados indicam os potenciais benefícios do treinamento força e natação, como alternativas não farmacológicas para controlar os efeitos deletérios da dieta hiperlipídica sobre o tecido adiposo, perfil lipídico, conteúdo lipídico dos tecidos e controle do desequilíbrio do sistema endocanabinóide provocado pela dieta hiperlipídica.

(EN) GH/IGF-1 axis components (GH, growth hormone receptor (GH-R), IGF-1, IGF-1 receptor (IGF-1R), IGF-binding proteins (IGFBPs)) participate in the control of glucose metabolism, inflammatory processes as well as cell proliferation and differentiation, including adipocytes and monocytes. The aim of the present study was to evaluate the role of local mRNA expression of GH/IGF-1 axis components in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) in the development of insulin resistance and differences of adipose tissue mass in following groups of patients: obese females with and without type 2 diabetes mellitus and subjects with active untreated acromegaly. A total number of 66 subjects were included in the study: obese females without type 2 diabetes mellitus (OB), obese females with type 2 diabetes mellitus (T2DM), acromegalic patients (AC) and healthy lean control subjects (C). T2DM underwent 2 weeks of very-low- calorie diet (VLCD - energy content 2500 kJ/day). According to our results we suggest that decreased mRNA expression of IGF-1, IGF-1R, IGFBP-2 and IGFBP-3 in adipose tissue of T2DM subjects may contribute to changes of fat differentiation capacity and the increased IGF-1R mRNA expression in peripheral monocytes in these patients may play a role in the regulation of...