Stearoyl-coA desaturase-1 (SCD1) activity has been linked to the development of obesity and the metabolic syndrome (MetS) through its central role in lipid metabolism. Understanding how changes in SCD1 activity affect obesity and MetS risk biomarkers and investigating how these changes in activity affect nutrient handling in non-hepatic tissues is also important. This study investigated how acute SCD1 inhibition effected plasma lipids, skeletal muscle nutrient handling and insulin signaling in mice fed a high-carbohydrate very-low fat diet for 10 weeks. This study demonstrated that SCD1 inhibition created acute dyslipidemia, altered nutrient handling protein activity and increased the percentage of saturated fatty acids (SFA) in hepatic and muscle tissue, independent of dietary oleic acid content. However, the molecular controls of protein synthesis in the mTOR pathway were not affected by the loss of SCD1 activity. In conclusion, we observed that inhibiting hepatic SCD1 activity and subsequently changing the monounsaturated fatty acid (MUFA) to SFA ratios in tissues alters normal nutrient handling in skeletal muscle.

Tris(1-chloro-2-propyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) are added to polyurethane foams in a variety of industrial and consumer products to prevent flame ignition. The gradual release of these flame retardants (FRs) from such products leads to contamination of various abiotic and biotic media, including wild birds. Recent studies demonstrated endocrine-disrupting effects of TCPP and TDCPP, including alteration of circulating thyroid hormone (TH) levels. The TH-pathway is essential for normal growth and development in birds. There are limited data on the toxicological effects of TCPP and TDCPP in avian species and, prior to this work, no study has examined their effects in avian embryos. This M.Sc. thesis investigates the developmental, molecular and biochemical effects of TCPP and TDCPP in chicken (Gallus gallus domesticus) embryos via egg injection studies. TCPP delayed pipping at doses ≥9.24 μg/g, both TCPP and TDCPP reduced embryo growth at the highest dose (51.6 μg TCPP/g and 45 μg TDCPP/g), and TDCPP decreased free plasma thyroxine and gallbladder size at 7.64 μg/g and 45 μg/g, respectively. Real-time reverse transcription polymerase chain reaction was used to measure changes in mRNA levels of hepatic genes that were responsive to these FRs in a previous in vitro study. TCPP dysregulated the expression of TH-responsive genes and xenobiotic metabolizing enzymes (cytochrome P450s; CYPs), whereas TDCPP only affected CYPs. Less than 1% of the administered TCPP or TDCPP was detected in egg contents following 19 days of incubation, indicating extensive metabolism of the parent compounds. DNA microarrays were used to perform a global transcriptional analysis on liver samples from embryos that exhibited adverse effects following TDCPP injection. 47 differentially expressed genes were identified at the 45 μg/g dose. Functional analysis revealed that immune function and lipid and steroid metabolism were major targets of TDCPP toxicity and indicated a state of cholestatic liver/biliary fibrosis. Since the TH-pathway is a key regulator of metabolic homeostasis, its disruption early in development is a potential cause of the observed adverse effects. This thesis demonstrates, for the first time, developmental and endocrine-disrupting effects of TCPP and TDCPP in an avian species and attempts to link phenotypic changes to molecular-level disruptions in hopes to improve the understanding of their modes of action.

Stearoyl-coA desaturase-1 (SCD1) activity has been linked to the development of obesity and the metabolic syndrome (MetS) through its central role in lipid metabolism. Understanding how changes in SCD1 activity affect obesity and MetS risk biomarkers and investigating how these changes in activity affect nutrient handling in non-hepatic tissues is also important. This study investigated how acute SCD1 inhibition effected plasma lipids, skeletal muscle nutrient handling and insulin signaling in mice fed a high-carbohydrate very-low fat diet for 10 weeks. This study demonstrated that SCD1 inhibition created acute dyslipidemia, altered nutrient handling protein activity and increased the percentage of saturated fatty acids (SFA) in hepatic and muscle tissue, independent of dietary oleic acid content. However, the molecular controls of protein synthesis in the mTOR pathway were not affected by the loss of SCD1 activity. In conclusion, we observed that inhibiting hepatic SCD1 activity and subsequently changing the monounsaturated fatty acid (MUFA) to SFA ratios in tissues alters normal nutrient handling in skeletal muscle.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.

Thesis (Ph.D. in Molecular Biology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 123-140). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Made available in DSpace on 2014-08-13T14:50:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-22Bitstream added on 2014-08-13T18:00:39Z : No. of bitstreams: 1 000756842.pdf: 789344 bytes, checksum: 061035505a8bd708cd9dbac41aad0d39 (MD5) / A obesidade, doença crônica metabólica caracterizada pelo acúmulo excessivo de tecido adiposo em relação à massa magra tecidual, é considerada uma epidemia global e um importante problema de saúde pública, que afeta tanto países desenvolvidos quanto subdesenvolvidos. O adipócito recebe influência de diversas substâncias e secreta inúmeros peptídeos, como leptina, angiotensina I e II, TGF-β, entre outros, que atuam diretamente ou indiretamente no sistema cardiovascular. Assim, o tecido adiposo não é simplesmente um reservatório de energia, mas um ativo órgão endócrino, parácrino e autócrino com múltiplas funções, capaz de sintetizar e liberar mediadores que participam de diversos processos biológicos, incluindo os que ocorrem no coração. O coração é composto por miócitos, nervos, vasos e matriz extracelular. O principal componente da matriz é o colágeno, com predomínio dos tipos I e III, sendo que, o tipo I é o mais abundante, correspondendo á aproximadamente 80% do colágeno total miocárdico. O colágeno é produzido, principalmente, pelos fibroblastos e degradado pelas metaloproteinases (MMPs). O colágeno, em situação estável, contribui para a manutenção da arquitetura e função cardíaca; entretanto, em resposta a estímulos desencadeados por agentes neuro-hormonais e/ou mecânicos, pode sofrer alterações; esta mudança pode ser resultante do aumento da síntese e/ou diminuição da degradação ou vice-versa. Em pesquisa recente realizada em nosso laboratório foi encontrado diminuição dos níveis protéicos de colágeno tipo I miocárdico em ratos Wistar obesos, por dieta hiperlipídica insaturada por 30 semanas, em relação ao grupo controle. Em razão, dos resultados encontrados em nosso laboratório e da literatura mostrar que a leptina aumenta a atividade das MMP-2 e a síntese da expressão gênica da MMP-9, a proposta deste estudo foi testar a hipótese ... / Obesity is a chronic metabolic disorder characterized by excessive adipose tissue accumulation in relation to lean tissue. Currently, it is a global epidemic and a major public health problem that affects both developed as well as undeveloped countries. The adipocyte receives influence of several substances and secretes numerous peptides, such as leptin, angiotensin I and II, TGF-β, among others, that act directly or indirectly on the cardiovascular system. Thus, adipose tissue is not simply an energy reservoir, but an active endocrine, paracrine and autocrine organ with multiple functions, able to synthesize and release mediators that participate in many biological processes, including those that occur in the heart. The heart is composed of myocytes, nerves, vessels and extracellular matrix. The main component of matrix is collagen, predominantly type I and III, being type I the most abundant, corresponding to approximately 80% of total myocardial collagen. Collagen is mainly produced by fibroblasts and degraded by metalloproteinases (MMPs). Collagen, in a stable condition, contributes to the maintenance of cardiac architecture and function, however, in response to stimuli triggered by neuro-hormonal and/or mechanical agents, it may change, and this change can be due to increased synthesis and/or decreased degradation, or vice versa. In recent research conducted in our laboratory, we found decreased protein levels of myocardial type I collagen in obese Wistar rats by unsaturated high-fat diet for 30 weeks. Due to the results found in our laboratory and because the literature shows that leptin increases MMP-2 activity and MMP-9 gene expression, the purpose of this study was to test the hypothesis that the reduction of myocardial type I collagen is associated with increased MMPs 2 and 9 activities in obese rats by unsaturated high-fat diet. Thirty-day-old male Wistar rats were randomized into to two groups: control ...

Orientadora: Isabel Cristina Boleli / Banca: José Roberto Sartori / Banca: Paulo Sérgio Rosa / Banca: Luciane Helena Gargaglioni Batalhão / Banca: Vera Maria Barbosa de Moraes / Resumo: Dois experimentos foram conduzidos com o objetivo de avaliar os efeitos da ingestão contínua de pectina. No primeiro experimento, foram avaliados a digestibilidade da ração, a viscosidade e o tempo de trânsito intestinal. Para isso, 240 frangos de corte macho Cobb® foram distribuídos em delineamento inteiramente casualizado (DIC), em 4 tratamentos (0, 1, 3 e 5% de pectina) compostos por 6 repetições de 10 aves por unidade experimental. As análises foram realizadas em duas fases: inicial (14 a 18 dias) e crescimento (27 a 31 dias). Os resultados mostraram que com a ingestão de pectina houve melhora da digestibilidade dos nutrientes na fase inicial dos frangos e piora na fase de crescimento, aumento na viscosidade e no tempo de trânsito intestinal e redução na umidade da excreta. No segundo experimento, foram analisados o desempenho e rendimento de cortes aos 35 e 42 dias de idade, o desenvolvimento semanal das aves e o consumo de água, parâmetros bioquímicos plasmáticos, morfometria do tecido adiposo abdominal, morfometria do fígado e teor de lipídio total hepático e dos músculos peitoral maior e gastrocnêmio. Foram utilizados 720 pintos machos Cobb® distribuidos em DIC, composto por 4 tratamentos (0, 1, 3 e 5% de pectina) e 6 repetições de 30 aves por unidade experimental. Na última semana, o consumo de água aumentou com o aumento do nível de pectina na ração. O consumo de até 1% de pectina na ração mantém o desempenho das aves. Aos 42 dias de idade ocorreu redução nos valores de proteína total plasmática com a ingestão de pectina. Os níveis de 3 e 5% reduziram as concentrações de colesterol total e, o nível de 5% reduziram os níveis de HDL. A ingestão de pectina proporcionou diminuição na concentração de lipídio hepático e menor relação entre peso corporal e gordura abdominal com a ingestão de 5% de pectina aos 42 dias. As concentrações... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Two experiments were conducted to evaluate the effects of continuous pectin intake. In the first experiment evaluated the digestibility of feed, the viscosity and intestinal transit time. For this, 240 male Cobb® broilers were distributed in a randomized design in four treatments (0, 1, 3 and 5% pectin) formed by 6 repetitions of 10 birds each. Analyses were performed in two stages: early (14 to18 days) and growth (27 to 31 days). The results showed that the ingestion of pectin had improved the digestibility of nutrients in the initial phase of chickens and worsens during growth, increase in viscosity and intestinal transit time and reduction in moisture of excreta. The second experiment analysed the performance and yield of the 35 and 42 days old, the weekly development of birds and water consumption, biochemical parameters, morphometry of abdominal adipose tissue, liver morphology and hepatic, pectoralis major and gastrocnemius lipid content. We used 720 male Cobb® chicks distributed in a completely randomized design with 4 treatments (0, 1, 3 and 5% pectin) consisting of six replicates of 30 birds each. In the last week, water consumption increased with increase level of pectin in the diet. The consumption up to 1% pectin keeps the performance of broilers.. At 42 days of age there was a reduction in total plasma protein values with the intake of pectin. The levels of 3 and 5% reduced the levels of total cholesterol and the level of 5% reduced levels of HDL. The intake of pectin resulted in decreased hepatic lipid content and lower ratio of body weight and abdominal fat with intake of 5% pectin and 42 days. The lipid concentration in the pectoralis major and gastrocnemius muscles were not influenced by levels of pectin in the same age / Doutor

Orientador: Marcos Jun Watanabe / Resumo: O cavalo atleta necessita de um sistema termorregulatório eficiente para garantir sua homeostasia e funções vitais. O nível de exigência das competições aumenta a cada dia, sendo necessário uma alta conversão energética para produção de trabalho, sem sobrecarga gástrica e com menor produção de calor metabólico. A inclusão de óleos na alimentação equina tem sido realizada neste intuito. Objetivou-se analisar a influência da suplementação com óleo de avocado na termorregulação de equinos submetidos a exercício em esteira, com base nas temperaturas retal e superficial corpórea. Oito equinos machos da raça Árabe, não treinados, foram distribuídos em delineamento randomizado cruzado, sendo um grupo sem suplementação (GC) e outro grupo suplementado com óleo de avocado (GOAv) por um período de seis semanas. Ao fim da sexta semana, os animais foram submetidos a teste padrão de exercício progressivo (TPEP) e após sete dias a teste de baixa intensidade e longa duração (BILD). Após o primeiro ciclo, houve período de descanso “washout” de 30 dias para troca de grupos para o segundo ciclo, que seguiu o protocolo do primeiro. A termorregulação foi avaliada com base na temperatura retal e na temperatura superficial corpórea, obtidas por termografia, de 15 regiões de interesse, sendo 10 na face dorsal distal do membro torácico, quatro na face caudal proximal dos membros pélvicos e uma na face lateral esquerda da cabeça. A temperatura retal e as imagens termográficas foram obtidas antes, um m... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The athletic horse needs an efficient thermoregulatory system to ensure its homeostasis and vital functions. The level of demands of the competitions increases every day, requiring a high energy conversion for work production, without gastric overload and with less metabolic heat production. The inclusion of oils in equine feed has been carried out for this purpose. The objective of this study was to analyze the influence of supplementation with avocado oil on the thermoregulation of horses submitted to treadmill exercise, based on rectal and body surface temperatures. Eight non-trained Arabian male equines were distributed in a randomized crossover design, one control group (CG) without supplementation and another group supplemented (SG) with avocado oil for a period of six weeks. At the end of the sixth week, the animals were submitted to standard exercise test (SET) and after seven days the low intensity test (LIT). After the first cycle, there was a 30-day washout rest period to exchange groups for the second cycle, which followed the protocol of the first one. Thermoregulation was evaluated based on rectal temperature and body surface temperature, obtained by thermography, of 15 regions of interest, ten of the dorsal distal aspect of the thoracic limb, four of the proximal caudal aspect of the pelvic limbs and one of the left lateral aspect of the head. Rectal temperature and thermographic images were obtained before, one minute and 15 minutes after exercise. There was n... (Complete abstract click electronic access below) / Doutor

Alguns estudos experimentais têm sugerido um importante papel do baço no metabolismo lipídico. Poucas análises, entretanto, avaliam o impacto que diferentes fontes de gordura possam exercer sobre os níveis de lipídios plasmáticos. O objetivo deste trabalho foi analisar o efeito de uma dieta nutricionalmente equilibrada (NE) e de uma dieta com gordura suína (GS) como fonte lipídica nos níveis de lipídios plasmáticos em ratos submetidos a esplenectomia total (ET) isolada ou combinada com implante esplênico autógeno (IEA). Foram utilizados 60 ratos Wistar machos adultos, distribuídos em seis grupos, cada um com dez animais: Grupo 1 controle operação simulada, com oferta de ração NE; Grupo 2 controle operação simulada, com oferta de ração GS; Grupo 3 submetidos a ET, com oferta de ração NE; Grupo 4 submetidos a ET, com oferta de ração GS; Grupo 5 submetidos a ET combinada com IEA e com oferta de ração NE; e Grupo 6 submetidos a ET combinada com IEA e com oferta de ração GS. Foram coletadas amostras sangüíneas imediatamente antes da operação (D0), e após 12 semanas de experimento (D+12), para verificação do perfil lipídico, quando os animais foram mortos, com retirada dos implantes esplênicos nos grupos 5 e 6. Houve regeneração morfológica de todos os tecidos esplênicos implantados, não se observando diferença no percentual de regeneração entre os grupos 5 e 6. Não houve diferença no ganho de peso e no consumo de ração entre os grupos de animais, assim como no lipidograma dos animais alimentados com dieta NE quando comparados os níveis plasmáticos em D0 e em D+12, enquanto nos grupos com modificação da fonte lipídica houve elevação das concentrações de colesterol total (CT), lipoproteína de baixa densidade (LDL), lipoproteína de muito baixa densidade (VLDL), triglicerídeos (TGL) e diminuição da concentração de lipoproteína de alta densidade (HDL). Quando comparados os seis grupos de animais, em D+12, apenas os níveis plasmáticos de HDL dos animais dos grupos 2, 4 e 6 apresentaram-se significativamente menores que os do grupo 3. Os resultados deste estudo permitem concluir que a dieta nutricionalmente equilibrada mantém os níveis de lipídios plasmáticos, enquanto a dieta à base de gordura suína provoca alterações no perfil lipídico de ratos alimentados com este tipo de ração, independentemente do procedimento cirúrgico realizado sobre o baço. / An important role of the spleen in lipid metabolism has been suggested by clinical and experimental studies. Few studies, however, have evaluated the impact of different sources of fat in plasma lipid levels. The purpose of the present investigation was to analyze the effect of a nutritionally balanced (NB) diet and a diet containing pork fat (PF) as sources of lipids on the lipid profile of rats submitted to total splenectomy (TS) alone or combined with splenic autotransplantation (SA). Sixty adult male Wistar rats were divided into six groups of 10 animals each: Group 1 sham-operated, fed the NB diet; Group 2 sham-operated, fed the PF diet; Group 3 TS, fed the NB diet; Group 4 TS, fed the PF diet; Group 5 SA, fed the NB diet; and Group 6 SA, fed the PF diet. Blood samples were collected immediately before the operation (D0) and 12 weeks after the beginning of the experiment (D+12) for plasma lipid determination. On D+12, the animals were killed and the splenic implants of groups 5 and 6 were removed. Morphologic regeneration of splenic tissues was observed, with no difference in percent regeneration between these two groups. Weight gain and chow intake were similar among all groups of animals. When D+12 plasma lipid levels were compared to D0, there were no differences in groups 1, 3, and 5, while in groups 2, 4, and 6 total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides (TGL) levels had increased and high density lipoprotein (HDL) levels had decreased. At the end of the experiment, only the HDL levels of groups 2, 4, and 6 were lower than group 3 levels. Our results lead us to conclude that, regardless of the surgical spleen procedure to which the rats were submitted, a nutritionally balanced diet maintained plasma lipid levels, while a diet containing pork fat as a source of lipids led to alterations in lipid profile.