Type II diabetes mellitus (T2DM) has been associated with the onset of diet-induced obesity, which is currently on the rise worldwide. T2DM is typically characterized by insulin resistance in peripheral tissues such as adipose tissue, liver, and skeletal muscle. In skeletal muscle it is widely accepted that the defective insulin action is due to the inability of the cell to sufficiently activate the insulin signalling pathway and promote systemic glucose uptake. The sarcolipin-null (KO) mouse is a potential novel model for diet-induced obesity and diabetes. KO mice become significantly more obese and display a greater glucose intolerance than wildtype (WT) mice following an 8-week high-fat diet (HFD; 42% calories from fat) but the underlying mechanisms are still unknown. In this study the role of defective skeletal muscle insulin signalling in the development of the impaired glucose tolerance in KO mice was investigated. It was hypothesized that the HFD fed KO mice would exhibit greater reductions in IRS1 tyr628 and Akt ser473 phosphorylation (i.e. decreased activation of the insulin signalling pathway) than controls. Furthermore, it was believed that KO mice would display increased phosphorylation of IRS1 ser307, which is commonly associated with insulin resistance. At 16-weeks of age KO mice and littermates were subdivided into two groups and placed on either a HFD (n=30) or chow diet (n=24) for an 8-week period. Changes in body weight, glucose tolerance, and insulin tolerance were assessed pre- and post-diet period. Following the completion of the diet intervention mice were treated with an intraperitoneal injection of insulin (0.75U/kg) or vehicle solution and sacrificed for tissue collection. Epididymal/inguinal and retroperitoneal fat pads were removed for assessment of whole body adiposity. Whole gastrocnemius muscle was excised and homogenized for Western blot analysis of several key proteins of the insulin signalling cascade. Following completion of the HFD KO mice (48.6 ± 1.6 g) weighed significantly more than HFD fed wildtype (WT) mice (41.5 ± 1.6 g), and all chow fed mice (KO: 36.8 ± 1.5 g; WT: 35.2 ± 1.2 g; p<0.001). Glucose tolerance testing showed that KO mice exhibited significantly greater glucose intolerance compared to control mice post-HFD (p<0.001). Insulin tolerance testing, however, revealed no change in insulin sensitivity in KO or WT mice post-HFD (p>0.05). The HFD fed KO mice (0.73 ± 0.06 g) had an elevated retroperitoneal fat pad weight than HFD fed WT (0.49 ± 0.05 g) and all chow fed mice (KO: 0.28 ± 0.04 g; WT: 0.24 ± 0.04 g; p<0.01). Western blot analysis revealed a similar reduction in insulin receptor substrate-1 (IRS1) tyr628 phosphorylation in both KO and WT mice following the HFD (Con WT: 2.82 ± 0.69; Con KO: 3.06 ± 0.73; HFD WT: 1.71 ± 0.28; HFD KO: 1.28 ± 0.11 fold increase over non-insulin stimulated mice; p<0.02). IRS1 ser307 phosphorylation was elevated in both genotypes post-HFD (HFD WT: 2.97 ± 1.19; HFD KO: 2.17 ± 0.59 fold increase over standard chow fed control mice; p<0.03). Insulin treatment did not stimulate phosphorylation of Akt ser473 in KO or WT mice regardless of diet (p>0.05). In summary there was no difference between KO and WT mice in skeletal muscle insulin sensitivity as assessed by the phosphorylation of insulin signalling intermediates. An increase in IRS1 ser307 phosphorylation appears to be the primary mechanism for the reduced activation of IRS1 following the HFD in both KO and WT mice. However, the results from the current investigation did not support the notion that impaired skeletal muscle insulin signalling is responsible for the more pronounced diet-induced glucose intolerance observed in KO mice. Future studies investigating the viability of skeletal muscle GLUT4 translocation and glucose uptake as well as the glucose-induced insulin secretion of pancreatic β-cells following consumption of a HFD would help elucidate the mechanism of glucose intolerance in KO mice.

Obesity is an ever-growing concern in the developed world that carries with it a plethora of health issues. For example, obesity increases an individual’s risk for Type 2 Diabetes and cardiovascular disease. Pregnancy is a vital time for a woman to maintain optimal health, both for her own benefit as well as that of her offspring, and yet almost half of women in the United States who are of age to bear children are overweight or obese. In mice, we found that offspring born to dams fed a high fat diet did not have impaired glucose tolerance, contrary to our hypothesis. In addition, we challenged the offspring with a high fat diet, and found no difference in glucose tolerance as a result of maternal diet. Exercise is at the opposite end of the wellness spectrum – individuals who exercise experience many health benefits. Even overweight or obese individuals who exercise without losing weight have improved insulin sensitivity, for example. Studies have previously used voluntary running and found that offspring born to exercised dams have improved glucose tolerance. With the goal of controlling variable running times and distances, we developed a novel model of controlled exercise and have shown that it is a safe intervention that warrants further study. In addition, many individuals choose to take dietary supplements for various reasons. Branched chain amino acids (BCAAs) are a common dietary supplement that have been shown to increase lean mass, and may be implicated in glucose metabolism. We supplemented female mice with BCAAs for 16 weeks and found that exercise plus BCAAs improved body composition compared to sedentary control-diet fed animals, when exercise alone did not. In summary, we herein explore a number of health behaviors in female mice, both negative treatments such as consumption of a high fat diet and positive interventions such as exercise and BCAA supplementation, and the impact that they may have on the female animal and/or her offspring.

The main aim of this thesis was to increase our understanding of the metabolic responses associated with short-term high-fat overfeeding. To this end, four separate studies are described in this thesis; each of which involved the provision of a high-fat, high-energy diet to young, healthy, lean individuals. The first of these experimental chapters (Chapter 2) determined the effects of a 7-day, high-fat (65%), high-energy (+50%) diet on postprandial metabolic and endocrine responses to a mixed meal challenge. This chapter demonstrates that 7-days of overfeeding impaired glycaemic control in our subject cohort but did not influence the response of selected gut hormones (acylated ghrelin, GLP-1 and GIP). In a mechanistic follow up study utilising stable isotope tracer methodology we then demonstrate that overfeeding-induced impairments in glycaemic control are attributable to subtle alterations in plasma glucose flux, rather than the overt tissue-specific adaptations (e.g. increased EGP, or reduced glucose disposal) that have previously been reported (Chapter 3). In an attempt to delineate the time-course of diet-induced impairments in glycaemic control, we then investigated the effects of 1-day of overfeeding (+80% energy with 73% of total energy coming as fat) (Chapter 4). Results demonstrate that a single day of overfeeding elicits responses which are comparable to 7-days of high-fat overfeeding; highlighting the rapidity with which excessive high-fat food intake can negatively influence glucose metabolism. In chapter 5 we utilised stable isotope tracer and muscle biopsy techniques to demonstrate that 7-days of high-fat overfeeding impairs glycaemic control but does not influence the fed-state mixed muscle protein fractional synthesis rate (FSR). In conclusion, the findings of this thesis demonstrate that while short-term high-fat overfeeding negatively influences whole-body glucose metabolism, skeletal muscle protein metabolism appears to be relatively unaffected in young, lean, healthy humans.

p. 1-86 / Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-09T19:38:13Z No. of bitstreams: 1 Dissertacao Tchana de Oliveira.pdf: 985133 bytes, checksum: 73cb03cf5f89412625c24bc2f8722bed (MD5) / Approved for entry into archive by Rodrigo Meirelles(rodrigomei@ufba.br) on 2013-04-10T14:05:18Z (GMT) No. of bitstreams: 1 Dissertacao Tchana de Oliveira.pdf: 985133 bytes, checksum: 73cb03cf5f89412625c24bc2f8722bed (MD5) / Made available in DSpace on 2013-04-10T14:05:18Z (GMT). No. of bitstreams: 1 Dissertacao Tchana de Oliveira.pdf: 985133 bytes, checksum: 73cb03cf5f89412625c24bc2f8722bed (MD5) Previous issue date: 2010 / A gestação e lactação são períodos caracterizados pelo desenvolvimento e modulação dos sistemas orgânicos. A dieta materna durante este período crítico do desenvolvimento exerce um importante papel na regulação da homeostase dos descendentes e pode trazer conseqüências até a vida adulta. Assim, o presente estudo teve como objetivo investigar os efeitos de uma dieta hiperlipídica durante a gestação e lactação sobre a evolução ponderal, o perfil lipídico, a glicemia, os produtos nitrogenados não protéicos e o consumo alimentar dos descendentes na vida adulta. Fêmeas de ratos Wistar foram alimentadas com dieta hiperlipídica ou dieta padrão durante a gestação e lactação. Os descendentes foram divididos em dois grupos: Descendente Controle (DC, n=10) descendentes de ratas alimentadas com dieta padrão e Descendente Hiperlipídica (DH, n=10) descendentes de ratas alimentadas com a dieta hiperlipídica. Após o desmame ambos os grupos foram alimentados com dieta padrão até a vida adulta. O grupo DH apresentou aumento (p≤0,05), no perfil lipídico, na glicemia e no consumo quando comparado ao grupo controle. Os resultados sugerem que a exposição no período perinatal a dieta hiperlipídica, rica em ácidos graxos saturados pode programar alterações no metabolismo dos descendentes adultos mesmo quando expostos a dieta nutricionalmente equilibrada ao longo da vida. / Salvador

Intervenções ambientais, como a exposição precoce a estressores ou a dietas ricas em calorias, podem alterar a trajetória da maturação neural e influenciar na susceptibilidade a certas patologias a longo-prazo. Neste contexto, o objetivo do presente estudo foi investigar os efeitos de uma exposição ao isolamento social durante o período pré-pubere associado ou não ao consumo precoce e crônico de uma dieta hiperlipídica (HFD) sobre aspectos cognitivos e emocionais, e possíveis mecanismos neuroquímicos associados a essas alterações, no hipocampo, no córtex pré-frontal e no núcleo accumbens de ratos machos na idade adulta. Os resultados mostraram que os dois fatores, estresse e dieta (separadamente), induziram um comportamento do tipo depressivo nos animais na idade adulta. Além disso, os animais isolados apresentaram um déficit cognitivo associado à memória de curta-duração e de trabalho, enquanto que animais com acesso à HFD demonstraram prejuízo somente na memória de curta-duração. Curiosamente, a interação entre os fatores (estresse e dieta) causou uma reversão dos déficits na memória de curta-duração. Em relação às avaliações do comportamento alimentar hedônico, observamos que o grupo com consumo crônico de HFD apresentou uma menor motivação para obter diferentes tipos de alimentos palatáveis doces. Essa redução motivacional não parece ser associada a uma menor palatabilidade e/ou a uma maior saciedade induzida pela HFD. Em relação aos marcadores de plasticidade analisados no córtex pré-frontal, observamos interações entre os fatores estresse e dieta na atividade da enzima Na+K+-ATPase, nos níveis de BNDF e no imunoconteúdo das proteínas AKT e MAPK/ERK, sendo que os fatores quando aplicados isolados diminuem os níveis dos parâmetros analisados, porém quando associados, os níveis retornam ou aumentam em relação aos valores do grupo controle. O hipocampo foi a estrutura mais afetada pelas intervenções ambientais neste trabalho. Observamos que tanto o estresse, como a dieta hiperlipídica (separadamente) causaram uma redução da plasticidade sináptica hipocampal, por meio de diferentes mecanismos: o acesso crônico à HFD afeta proteínas relacionadas ao funcionamento das sinapses, enquanto o isolamento social parece afetar mais particularmente a via de sinalização do BDNF. Com relação aos achados neuroquímicos no núcleo accumbens, observamos uma redução dos receptores dopaminérgico-1 (D1) e canabinóide-1 (CB1) com o consumo de HFD, enquanto que os animais isolados na pré-puberdade apresentaram uma redução do metabolismo dopaminérgico nesta estrutura. Em suma, esta tese demonstra que tanto o isolamento social e como o consumo contínuo de HFD causam comportamento do tipo depressivo e outras alterações comportamentais, e reduzem marcadores de plasticidade importantes no córtex prefrontal e hipocampo. O acesso à HFD também causa uma menor motivação para o comportamento alimentar hedônico. Assim, tais eventos precoces podem afetar a plasticidade neural levando a importantes alterações comportamentais, e assim predispor a diferentes patologias durante a vida. / Environmental interventions, such as early exposure to stressors or high calorie-diets, can alter the trajectory of neural maturation and influence the susceptibility to some pathologies throughout life. In this context, the aim of the present study was to investigate the effects of exposure to social isolation, during the pre-pubertal period, associated or not with early and chronic consumption of a hyperlipid diet (HFD) on cognitive and emotional aspects, and possible mechanisms associated with these changes, in the hippocampus, the prefrontal cortex and the nucleus accumbens of male rats in adulthood. The results showed that both pre-pubertal social isolation and chronic access to a hyperlipidic diet induced a depressive-like behavior in animals during adulthood. In addition, isolated animals had a cognitive deficit associated with short-term and working memory, whereas animals with access to HFD demonstrated impairment only in short-term memory. Interestingly, the interaction between the factors (stress and diet) caused a reversal in relation to short-term memory, remaining similar to the control group. Regarding the evaluations of the hedonic eating behavior, we observed that HFD group presented a lower motivation to obtain different sweet palatable foods. This impaired motivation does not appear to be associated with less palatability and/or satiety induced by the high-fat diet. Concerning plasticity markers in the prefrontal cortex, we observed interactions between stress and diet on Na+ K+-ATPase activity, BNDF levels and AKT and MAPK/ERK immunocontents. These interactions follow a similar profile: when applied alone, the levels of the analyzed parameters decrease, but when associated, the levels return or increase in relation to the values of the control group. The hippocampus was the structure most affected by the environmental interventions. Both stress and HFD caused a reduction of hippocampal synaptic plasticity through different mechanisms: chronic access to HFD affects proteins related to synaptic function, while social isolation affects the BDNF signaling pathway more significantly. Regarding the neurochemical findings in the nucleus accumbens, we observed a reduction in dopaminergic-1 (D1) and cannabinoid-1 (CB1) receptors with chronic HFD intake, whereas isolated animals had a reduction of dopaminergic metabolism in this same structure. In summary, this thesis shows that both social isolation and chronic consumption of HFD lead to depressive-like behavior and to other behavioral changes; they reduce plasticity markers in prefrontal cortex and hippocampus. HFD access also induced a lower motivation for hedonic feeding. Therefore, these early interventions may affect neural plasticity, leading to important behavioral changes, and thus, predispose to different pathologies later in life.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Estudos demonstram que o sobrepeso e a obesidade podem afetar a fertilidade masculina. Além disso, a função tireóidea também esta associada à alteração da função testicular, entretanto, o papel fisiológico dos hormônios tireoideanos na regulação do sistema reprodutor masculino ainda não esta claro. Aos 21 dias de idade, ratos machos receberam uma dieta manipulada contendo diferentes concentrações de óleo de soja até a idade de 30 e 60 dias, os grupos controle (C30, n=6 e C60, n=6), receberam dieta contendo 7% e os grupos hiperlipídicos (HL30, n=6 e HL60, n=6), receberam dieta contendo 19% deste óleo. Ao final de cada período, os animais foram avaliados por DXA (Absorciometria de Raios-x em Duas Energias) e sacrificados por exsanguinação. Para avaliar alterações na estrutura dos tecidos testicular e tireóideo, foram realizados a morfologia e a estereologia. No plasma, para determinar os perfis bioquímico e hormonal, foram avaliados, triglicerídeos, colesterol total, HDL-colesterol, VLDL, glicose e albumina, por métodos colorimétricos e leptina, insulina, T4, T3, TSH e testosterona por radioimunoensaio (RIE). Para evidenciar a expressão de receptor androgênico (AR) em testículos, foi realizado imunomarcação, com anti-AR. Durante todo o período experimental, foram analisados a massa corporal, a ingestão alimentar e o comprimento corporal, os quais permaneceram inalterados. No grupo HL, a massa magra foi menor aos 30 dias, já a gordura corporal total foi maior no mesmo grupo, aos 60 dias nenhuma diferença foi notada entre os grupos. No grupo HL30 não houve diferença quanto à massa dos tecidos, já no grupo HL60, o peso do epidídimo, fígado e gordura visceral mantiveram-se aumentados. No grupo HL30 não houve diferença em relação ao perfil bioquímico, já no grupo HL60, os níveis de glicose, mantiveram-se altos. Quanto às dosagens hormonais no grupo HL30, TSH e leptina estiveram aumentados e T3 reduzido, e no grupo HL60, T3 e leptina estiveram aumentados. Os dados morfométricos e estereológicos de testículo no grupo HL30 mostram aumento no número de túbulos seminíferos e da densidade de comprimento (Lv), já no grupo HL60, há redução no número de túbulos seminíferos e no diâmetro do mesmo. Quanto à expressão de receptor androgênico nas células testiculares, não parece haver diferença entre os grupos independente da idade de consumo da dieta. A dieta hiperlipídica promoveu alterações metabólicas aos 30 dias e modificações na morfologia do tecido tireoidiano e testicular em ambas as idades, o que indica reflexos na função reprodutora. / Studies show that overweight and obesity can affect male fertility. In addition, thyroid function also is associated with the alteration of testicular function, however, the physiological role of thyroid hormones in the regulation of male reproductive system is not yet clear. At 21 days of age, male rats were handled diet containing different concentrations of soy oil until the age of 30 and 60 days, the control group (C30 n=6 , C60 n=6), received a diet containing 7% and the high fat groups (HL30 n=6 , HL60n=6), received diet containing 19 % of this oil. At the end of each period, the animals were assessed by DXA (Absorptiometry X - ray Dual energy) and sacrificed by exsanguination. To assess changes in the structure of the testis and thyroid tissue morphology and stereological were performed. In plasma for determine the hormonal e biochemist profile were evaluated, triglycerides, total cholesterol, HDL cholesterol, VLDL, glucose and albumin by colorimetric assay and leptin, insulin, T4 , T3 , TSH and testosterone by radioimunoassay (RIA) . To demonstrate the expression of androgen receptor (AR) in testis, imunohistochemistry was performed with anti-AR. During the experimental period, body weight, food intake and body length were analyzed, and remained unchanged. Lean mass was lower at 30 days in the HL group, since the body fat total was higher in the same group, after 60 days, no difference was noted between the groups. In HL group at 30 days no difference was noted, and in same group at 60 days, the weight of the epididymis, liver and visceral fat remained higher. The biochemist profile in HL group at 30 days, there are no differences and at the 60 days in same group the level of glucose remained high. For hormonal dosages at 30 days in HL group, TSH and leptin were increased and T3 reduced, at 60 days in the same group, T3 and leptin were increased. Stereological and morphometric in the group Hl at 30 days, data show increases of number of seminiferous tubule and length density (Lv). At 60 days in the same group there are decreased of number of seminiferous tubule and diameter. The expression of androgen receptor (AR), in testis no differences are seems between the groups independent of the ages of consumption of diet. The fat diet promoted metabolic changes at 30 days and changes in the morphology of thyroid and testicular tissue at both ages, indicating an influence on reproductive function.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Dieta materna hiperlipídica (HF) em roedores ocasiona o desenvolvimento de resistência à insulina e o diabetes mellitus tipo 2 na prole adulta. Camundongos fêmeas foram alimentadas com dieta SC (standard chow) ou HF (hiperlipídica) durante oito semanas anteriores ao acasalamento, durante o período gestacional e metade da lactação. Os filhotes machos foram avaliados ao nascimento (0 dia) e aos 10 dias de idade. Nas progenitoras, foram avaliados o ganho de massa corporal (MC), a pressão arterial (PA), a eficiência alimentar (EA) e o teste oral de tolerância à glicose (TOTG). Na prole, foram avaliadas a evolução da massa corporal (MC), a glicemia, a estrutura da ilhota do pâncreas e a massa de célula-beta. Nas progenitoras, a ganho de massa corporal (MC) e a eficiência alimentar (EA) do grupo HF apresentaram um aumento de 50% em relação ao grupo SC durante o período pré-gestacional e um aumento de 70% do ganho de MC e 250% na EA, durante a gestação (P<0,0001). A pressão arterial e os níveis de corticosterona foram maiores no grupo HF quando comparados ao grupo SC (P=0,001). Em relação à massa corporal das proles, não houve diferença ao nascimento, contudo aos 10 dias de idade o grupo HF apresentou um aumento neste parâmetro, assim como um aumento dos níveis de glicemia e aumento do diâmetro da ilhota em relação ao grupo SC (P<0,001). Ao nascimento, a razão da massa de célula-beta/massa do pâncreas (MCB/MP), foi menor no grupo HF quando comparado ao grupo SC (-54%, P<0,0001), no entanto essa diferença não foi observada aos 10 dias de idade. A MCB/MP foi maior no grupo HF aos 10 dias de idade em relação ao grupo SC (+146%, P<0,0001). Desta forma, sugere-se que a administração de dieta materna hiperlipídica durante o período pré-gestacional, durante a gestação e metade da lactação, culmina em alterações precoces no pâncreas da prole, incluindo um remodelamento e uma hipertrofia da célula-beta, a qual apresenta uma recuperação da massa de célula-beta ao final da organogênese, podendo desta forma afetar a sua função na vida adulta.

Submitted by MARCELO CONRADO DE FREITAS null (marceloconrado013@gmail.com) on 2016-03-18T12:57:04Z No. of bitstreams: 1 Tese final MCF.pdf: 1468918 bytes, checksum: 06f97c742fe0f27fb15e0ed7d61c7c09 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-21T19:12:17Z (GMT) No. of bitstreams: 1 freitas_mc_me_prud.pdf: 1468918 bytes, checksum: 06f97c742fe0f27fb15e0ed7d61c7c09 (MD5) / Made available in DSpace on 2016-03-21T19:12:17Z (GMT). No. of bitstreams: 1 freitas_mc_me_prud.pdf: 1468918 bytes, checksum: 06f97c742fe0f27fb15e0ed7d61c7c09 (MD5) Previous issue date: 2016-02-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A ingestão de dieta hiperlipídica pode afetar negativamente o metabolismo celular de diversos tecidos podendo desencadear aumento da inflamação e resistência à insulina no tecido adiposo (TA) e músculo esquelético (ME). A realização do treinamento resistido (TR) pode resultar em adaptações importantes para indivíduos com alterações metabólicas. No entanto, ainda há poucos relatos na literatura sobre os efeitos crônicos do TR na inflamação e expressão de genes envolvidos no metabolismo do TA e ME. Também é pouco conhecido se a cessação do TR poderia causar reversão ou piora dos prováveis beneficios dos efeitos do TR sobre estes parâmetros. Objetivos: Analisar o efeito do TR e do destreinamento de 4 semanas sobre a inflamação e padrão de expressão de genes do metabolismo muscular e do tecido adiposo de ratos alimentados por dieta hiperlipídica. Métodos: Trinta ratos machos Wistar com idade de 2 meses foram subdivididos em três grupos, Dieta Hiperlipídica (DH), Dieta Hiperlipídica Treinado (DHT) e Dieta Hiperlipídica Destreinado (DHD). O treinamento resistido durou 12 semanas, sendo realizado numa plataforma de salto, 3x na semana, cada sessão com 3 séries de 12 repetições, com incremento de carga a cada duas semanas. O grupo DHD interrompeu o treinamento a partir da oitava até a décima segunda semana. Foi analisada a expressão da proteína TNFα, a expressão gênica de AMPK, GLUT-4 e MEF2A no músculo sóleo. Já no TA periepididimal foi analisada a expressão proteica de TNFα e PPARγ, e expressão gênica de TNFα, PPARγ, ACC e HIF-1α, utilizando as técnicas de RT-PCR e Western blotting. Resultados: o TR aumentou a expressão dos genes AMPK em 23%, GLUT-4 em 24% e MEF2A em 20% (p<0,05) e ainda reduziu a expressão proteica em 51% e gênica em 28% de TNFα no ME (p<0,05). Já no TA o grupo DHT apresentou menor expressão gênica de TNFα (40%), ACC (32%) e HIF-1α (31%) (p<0,05) comparado ao grupo DH. O grupo DHT também apresentou expressão proteica de TNFα 40% menor e apresentou aumento de 49% na expressão proteica de PPARγ (p<0,05) comparado ao grupo DH. Com o destreinamento a expressão de TNFα permaneceu reduzida tanto no músculo esquelético como no TA (p<0,05). Além disso, a expressão proteica de PPARγ no TA também permaneceu aumentada (p<0,05). Conclusão: O TR exerce efeitos positivos na redução da inflamação e melhora na expressão de genes relacionados ao metabolismo celular do ME e TA, com manutenção , destas adaptações mesmo após quatro semanas de destreinamento. / High fat diet can adversely affect cellular metabolism of various tissues and trigger increased inflammation and insulin resistance in adipose tissue (AT) and skeletal muscle (SM). The resistive training (RT) may result in positive adaptations for individuals with metabolic disorders. However, there are few reports in the literature showing chronic effects of TR on the inflammation and expression of genes involved in the metabolism of the AT and SM. It is also unknown if the cessation of the resistive training could reverse or could impair the likely benefits of the RT on these gene expression. Objectives: To analyze the effect of TR and 4-week detraining on the inflammation and metabolism gene expression of the SM and AT from rats fed with high fat diet. Methods: Thirty male Wistar rats aged 2 months were divided into three groups, high fat diet (HD), High Fat Diet Trained (DHT) and Detrained High Fat Diet (DHD). Resistive training was performed during 12 weeks, in a jump platform, 3x a week, each session with 3 sets of 12 reps, with load increasing every two weeks. The DHD group interrupted the training from the eighth week until the twelfth week. TNFα protein expression and AMPK, GLUT4 and MEF2A gene expression was evaluated in the soleus muscle. In the periepididymal adipose tissue, PPARγ and TNFα protein expression was evaluated of, as well as TNFα, PPARγ,HIF-1α and ACC gene expression by RT-PCR and Western blotting. of. Results: RT increased the expression of AMPK gene in 23%, GLUT-4 in 24% and MEF2A by 20% (p<0.05), and reduced TNFα protein expression in 51% and 28% in the SM (p<0.05). In the AT, DHT group presented lower (p <0.05) TNFα of (40%), ACC (32%) and HIF-1α (31%) gene expression compared to DH group. DHT group also showed 40% less TNFα protein expression and presented an increase of 49% in the PPARγ protein expression (p<0.05) compared to DH group. With the detraining TNFα expression remained reduced in both SM and AT (p<0.05). Furthermore, the expression of PPARγ protein also remained increased in AT (p<0.05). Conclusion: RT has positive effects in reducing inflammation and improvement in the expression of genes related to cellular metabolism in the SM and AT, which can be maintained even after 4 weeks of the cessation.

abstract: Long term high fat diets (HFD) are correlated with the development of diabetes and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure and function in young male Sprague-Dawley rats. Previous studies have shown that these animals develop indices of diabetes compared to rats fed a standard rodent chow (5% fat) for six weeks. The hypothesis of this study is that six weeks of HFD will lead to early stages of kidney disease as evidenced by morphological and functional changes in the kidney. Alterations in morphology were determined by measuring structural changes in the kidneys (changes in mass, fatty acid infiltration, and structural damage). Alterations in kidney function were measured by analyzing urinary biomarkers of oxidative RNA/DNA damage, renal tissue lipid peroxidation, urinary markers of impaired kidney function (urinary protein, creatinine, and hydrogen peroxide (H2O2)), markers of inflammation (tumor necrosis factor alpha (TNF&#945;) and interleukin 6 (IL-6)), as well as cystatin C, a plasma biomarker of kidney function. The results of these studies determined that short term HFD intake is not sufficient to induce early stage kidney disease. Beyond increases in renal mass, there were no significant differences between the markers of renal structure and function in the HFD and standard rodent chow-fed rats. / Dissertation/Thesis / Masters Thesis Nutrition 2015

abstract: Cardiovascular disease has reached epidemic proportions resulting in its ranking as the number one cause of mortality in the Western world. A key player in the pathophysiology of vascular disease is oxidative stress due to free radical accumulation. This intervention study was conducted to evaluate any potential mediation of oxidative stress using a soil-derived organometallic compound (OMC) with suspected antioxidant properties. A 10-week study was conducted in male Sprague-Dawley rats (n = 42) fed either a high-fat diet (HFD) consisting of 60% kcal from fat or a standard Chow diet containing only 6% kcals from fat. Rats from each diet group were then subdivided into 3 subgroups (n = 6-10 each) that received 0.0 mg/mL, 0.6 mg/mL or 3.0 mg/mL OMC. Neither the diet nor OMC significantly changed protein expression of inducible nitric oxide synthase (iNOS) in isolated aortas. Plasma levels of the inflammatory marker, tumor necrosis factor alpha (TNFα) were below detection after the 10-week trial. Superoxide dismutase (SOD), a scavenger of the free radical, superoxide, was not significantly different following HFD although levels of SOD were significantly higher in Chow rats treated with 0.6 mg/mL OMC compared to HFD rats treated with the same dose (p < 0.05). Lipopolysaccharides (LPS) were significantly increased following 10 weeks of high fat intake (p < 0.05). This increase in endotoxicity was prevented by the high dose of OMC. HFD significantly increased fasting serum glucose levels at both 6 weeks (p < 0.001) and 10 weeks (p < 0.025) compared to Chow controls. The high dose of OMC significantly prevented the hyperglycemic effects of the HFD in rats at 10 weeks (p = 0.021). HFD-fed rats developed hyperinsulinemia after 10 weeks of feeding (p = 0.009), which was not prevented by OMC. The results of this study indicate that OMC may be an effective strategy to help manage diet-induced hyperglycemia and endotoxemia. However, further research is needed to determine the mechanism by which OMC helps prevent hyperglycemia as measures of inflammation (TNFα) and vascular damage (iNOS) were inconclusive. / Dissertation/Thesis / Masters Thesis Nutrition 2018