Chu Ching Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 170-189). / Abstracts in English and Chinese. / Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Classes of Fatty Acids --- p.3 / Chapter 1.2 --- Polyunsaturated Fatty Acids (n-6 & n-3) --- p.4 / Chapter 1.2.1 --- "High Fish Oil Content in Diet, High n-3 PUFAs Intake, Fight against Cardiovascular Risk" --- p.4 / Chapter 1.2.2 --- n-3 Fatty Acids Improve Hypertension --- p.7 / Chapter 1.2.3 --- n-3 Fatty Acids Protect from Atherosclerosis --- p.8 / Chapter 1.2.4 --- PUFAs are Beneficial in Inflammation --- p.11 / Chapter 1.2.5 --- n-3 PUFAs Help to Control Tumour Growth --- p.13 / Chapter 1.3 --- Obesity and Eating Disorder --- p.14 / Chapter 1.3.1 --- "Obesity, a Companion of the Modern World" --- p.14 / Chapter 1.3.2 --- Health Risks Related to Obesity --- p.16 / Chapter 1.3.3 --- Management of Obesity --- p.19 / Chapter 1.3.4 --- Care Must be Taken to Prevent the Development of Eating Disorder or Other Psychological Disturbances during Weight Loss Programme --- p.21 / Chapter 2 --- Weight Cycling with ChowDiet --- p.24 / Chapter 2.1 --- Introduction --- p.24 / Chapter 2.1.1 --- Definition of Weight Cycling --- p.25 / Chapter 2.1.2 --- Incentives Leading to Weight Cycling --- p.26 / Chapter 2.1.3 --- Problems Aroused by Weight Cycling --- p.26 / Chapter 2.1.3.1 --- "Food Preference, Efficiency and Expenditure" --- p.27 / Chapter 2.1.3.2 --- Increased Overall and Central Adiposity --- p.28 / Chapter 2.1.3.3 --- Increased Morbidity and Mortality of Cardiovascular Disease --- p.29 / Chapter 2.1.3.4 --- Psychological Impact and Social Consequences --- p.30 / Chapter 2.2 --- Objective --- p.30 / Chapter 2.3 --- Materials and Methods --- p.31 / Chapter 2.3.1 --- Animal Handling --- p.31 / Chapter 2.3.2 --- Lipid Analysis --- p.35 / Chapter 2.3.2.1 --- Adipose Tissues --- p.35 / Chapter 2.3.2.2 --- Carcass --- p.36 / Chapter 2.3.3 --- Proximate Analysis --- p.37 / Chapter 2.3.3.1 --- Crude Fat --- p.37 / Chapter 2.3.3.2 --- Crude Protein --- p.38 / Chapter 2.3.3.3 --- Moisture --- p.40 / Chapter 2.3.3.4 --- Ash --- p.40 / Chapter 2.3.4 --- Serum Analysis --- p.41 / Chapter 2.3.4.1 --- Serum Triglycerides --- p.41 / Chapter 2.3.4.2 --- Serum Cholesterol --- p.42 / Chapter 2.4 --- Results --- p.44 / Chapter 2.4.1 --- Body Weight --- p.44 / Chapter 2.4.2 --- Food Intake --- p.44 / Chapter 2.4.3 --- Organ Weight --- p.47 / Chapter 2.4.3.1 --- Liver --- p.47 / Chapter 2.4.3.2 --- Adipose Tissues --- p.47 / Chapter 2.4.4 --- Lipid Analysis --- p.52 / Chapter 2.4.4.1 --- Adipose Tissues --- p.52 / Chapter 2.4.4.2 --- Carcass --- p.52 / Chapter 2.4.5 --- Proximate Analysis --- p.60 / Chapter 2.4.5.1 --- Crude Fat --- p.60 / Chapter 2.4.5.2 --- Moisture --- p.60 / Chapter 2.4.5.3 --- Crude Protein and Ash --- p.62 / Chapter 2.4.6 --- Serum Analysis --- p.64 / Chapter 2.4.6.1 --- Serum Triglycerides --- p.64 / Chapter 2.4.6.2 --- Serum Cholesterol --- p.64 / Chapter 2.5 --- Discussion --- p.66 / Chapter 3 --- Degrees of Food Restriction on Bod y Fa tty Acid Composition --- p.71 / Chapter 3.1 --- Introduction --- p.71 / Chapter 3.1.1 --- Skipping Breakfast --- p.71 / Chapter 3.1.2 --- "Nibbling, Grazing vs Gorging" --- p.72 / Chapter 3.1.3 --- Reducing Food Intake in Meals --- p.74 / Chapter 3.1.3.1 --- Anti-Aging Action --- p.74 / Chapter 3.1.3.2 --- Effects on Other Health Issues --- p.75 / Chapter 3.1.3.3 --- Energy Expenditure --- p.77 / Chapter 3.2 --- Objective --- p.78 / Chapter 3.3 --- Materials and Methods --- p.79 / Chapter 3.3.1 --- Animal Handling --- p.79 / Chapter 3.4 --- Results --- p.81 / Chapter 3.4.1 --- Body Weight --- p.81 / Chapter 3.4.2 --- Food Intake --- p.81 / Chapter 3.4.3 --- Organ Weight --- p.83 / Chapter 3.4.3.1 --- Liver --- p.83 / Chapter 3.4.3.2 --- Adipose Tissues --- p.83 / Chapter 3.4.4 --- Lipid Analysis --- p.88 / Chapter 3.4.4.1 --- Adipose Tissues --- p.88 / Chapter 3.4.4.2 --- Carcass --- p.88 / Chapter 3.4.5 --- Proximate Analysis --- p.102 / Chapter 3.4.5.1 --- Crude Fat --- p.102 / Chapter 3.4.5.2 --- Moisture --- p.102 / Chapter 3.4.5.3 --- Crude Protein and Ash --- p.103 / Chapter 3.4.6 --- Serum Analysis --- p.106 / Chapter 3.4.6.1 --- Serum Triglycerides --- p.106 / Chapter 3.4.6.2 --- Serum Cholesterol --- p.106 / Chapter 3.5 --- Discussion --- p.108 / Chapter 4 --- Food Restriction with Diets Containing Various Amount of FAT --- p.112 / Chapter 4.1 --- Introduction --- p.112 / Chapter 4.1.1 --- Adverse Effects of High-Fat Diets --- p.113 / Chapter 4.1.2 --- Adverse Effects of Low-Fat Diets --- p.114 / Chapter 4.2 --- Objective --- p.116 / Chapter 4.3 --- Materials and Methods --- p.117 / Chapter 4.3.1 --- Animal Handling --- p.117 / Chapter 4.4 --- Results --- p.120 / Chapter 4.4.1 --- Body Weight --- p.120 / Chapter 4.4.2 --- Food Intake --- p.120 / Chapter 4.4.3 --- Organ Weight --- p.122 / Chapter 4.4.3.1 --- Liver --- p.122 / Chapter 4.4.3.2 --- Adipose Tissues --- p.122 / Chapter 4.4.4 --- Lipid Analysis --- p.127 / Chapter 4.4.4.1 --- Adipose Tissues --- p.127 / Chapter 4.4.4.2 --- Carcass --- p.127 / Chapter 4.4.5 --- Proximate Analysis --- p.147 / Chapter 4.4.5.1 --- Crude Fat --- p.147 / Chapter 4.4.5.2 --- Moisture --- p.147 / Chapter 4.4.5.3 --- Crude Protein and Ash --- p.148 / Chapter 4.4.6 --- Serum Analysis --- p.151 / Chapter 4.4.6.1 --- Serum Triglycerides --- p.151 / Chapter 4.4.6.2 --- Serum Cholesterol --- p.151 / Chapter 4.5 --- Discussion --- p.153 / Chapter 5 --- Future Prospects --- p.159 / Chapter 5.1 --- Leptin --- p.159 / Chapter 5.2 --- Enzymes --- p.162 / Chapter 6 --- Conclusion --- p.166 / Chapter 7 --- References --- p.170

Orientador: Telma Teresinha Berchielli / Coorientador: Juliana Duarte Messana / Banca: Raul Franzolin Neto / Banca: Renata Helena Branco Arnandes / Banca: Roberta Carrilho Canesin / Resumo: O objetivo deste estudo foi avaliar o efeito de três métodos e quatro tempos de armazenamento da amostra ruminal, sobre a qualidade e rendimento do DNA metagenômico extraído assim como o efeito sobre a composição da comunidade bacteriana ruminal e avaliar o efeito da glicerina bruta (CG) associada ao óleo de soja (OS) na dieta de Novilhos Nelore sobre o consumo, digestibilidade, fermentação, biohidrogenação (BH), microbiota ruminal e fluxo intestinal de ácidos graxos de cadeia longa. No experimento 1 utilizou-se um novilho Nelore equipado com cânula ruminal de silicone como doador de conteúdo ruminal e compreendeu 11 tratamentos: pellet controle (PC), liofilizado controle (LC), P-20: pellet armazenado a -20 ° C por um período de 3, 6 e 12 meses, P-80: pellet armazenado a -80 ° C durante um período de 3, 6 e 12 meses e L-20: amostra liofilizada armazenada a -20 ° C durante um período de 3, 6 e 12 meses. O método L-20 não conseguiu manter o rendimento de DNA durante o armazenamento. O método P-80 apresentou maior rendimento de DNA após 6 meses de armazenamento. Amostras armazenados como pellets (P-20 e P-80) resultaram em menor riqueza Chao 1, ACE e índice Shannon Wiener quando comparado com PC. Enquanto LC e PC apenas foram diferentes na riqueza ACE. O método de armazenamento e tempo de armazenamento influenciou as proporções de 14 ds 17 filos identificado. No método P-20 a proporção de Cianobactérias, Elusimicrobia, Fibrobacteres, Lentisphaerae, Proteobacteria e Espiroquetas ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of this study was to investigate three methods and four storage times for rumen sampling in terms of quality and yield of extracted metagenomic DNA as well as the composition of the rumen bacterial community, and evaluate the effect of soybean oil (SO) and crude glycerin (CG) association on ruminal fermentation, ruminal biohydrogenation (BH) and ruminal microbial population in Nellore steers. In the experiment 1: One Nellore steer fitted with a ruminal silicone-type cannula was used as a donor of ruminal contents. The experiment comprised 11 experimental groups: pellet control (PC), lyophilized control (LC), P-20: pellet stored frozen at -20 °C for a period of 3, 6, and 12 months, P-80: pellet stored frozen at -80 °C for a period of 3, 6, and 12 months, and L-20: lyophilized sample stored frozen at -20 °C for a period of 3, 6, and 12 months. The L-20 method could not maintain the yield of DNA during storage. In addition, the P-80 group showed a greater yield of metagenomic DNA than the other groups after 6 months of storage. Rumen samples stored as pellets (P-20 and P-80) resulted in lower richness Chao 1, ACE, and Shannon Wiener indices when compared to PC, while LC and PC were only different in richness ACE. The storage method and storage time influenced the proportions of 14 of 17 phyla identified by sequencing. In the P-20 group, the proportion of Cyanobacteria, Elusimicrobia, Fibrobacteres, Lentisphaerae, Proteobacteria, and Spirochaetes phyla identified was lower than 1%. In the P-80 group, there was an increase in the proportion of the Bacteroidetes phylum (p = 0.010); however, the proportion of Actinobacteria, Chloroflexi, SR1, Synergistetes, TM7, and WPS.2 phyla were unchanged compared to the PC group (p > 0.05). The class Clostridium was the most abundant in all stored groups and increased in its proportion, (Complete abstract click electronic access below) / Doutor

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Nonalcoholic fatty liver disease (NAFLD) afflicts approximately a quarter of the world’s general population and more than half of the world’s obese population. The disease is characterized by a spectrum of liver pathologies, ranging from simple steatosis or the accumulation of fat within hepatic tissue to steatohepatitis comprised of inflammation and fibrosis, also known as NASH. Simple steatosis is relatively asymptomatic and is considered benign, but NASH poses great risk for advanced forms of liver disease, such as cirrhosis and hepatocellular cancer. Obstructive sleep apnea(OSA) is a respiratory disorder involving the recurrent collapse of the upper airway during sleep. Consequently, the patient experiences constant arousals due to constant blockage followed reopening of the airway. Aside from poor quality and disruption of sleep, chronic intermittent hypoxia (CIH) is also present during OSA. The presence of CIH leaves many vital organs deprived of adequate oxygen to carry out normal physiological function. In response to this hypoxic state, the body upregulates many transcription factors, many of which control inflammatory processes. In recent studies, chronic and recurrent hypoxia generated from OSA has been implicated in the onset and progression of NAFLD. The pathogenesis of NAFLD is believed to be associated with metabolic imbalances, mainly obesity and insulin resistance, both of which also overlap with OSA. These conditions are the main factors in predisposing a patient suffering from OSA to the effects of CIH. Multiple lines of evidence suggest that CIH may accelerate the development of NAFLD through 1) Lipolysis of hepatic adipose tissue and increased hepatic free fatty acids; 2) Upregulation of lipid biosynthetic through CIH; 3) Upregulation of hypoxia-inducible factor 1-alpha by CIH inducing liver inflammation and fibrosis. The primary focus of this thesis will attempt to determine a possible link between OSA and NAFLD. Through citation of prior scientific studies, it will formulate the theory of OSA as a predisposing factor in the heightened risk of NAFLD pathogenesis and development to more severe, terminal stages. Primarily, the review of literature will highlight the metabolic imbalances of obesity and insulin resistance and how each is related to OSA and NAFLD. Ultimately, deposition of fat and inflammation triggered through various chemical factors connected to OSA will depict both the generation and progression of NAFLD.

Background: The role of aspirin (100 mg daily) and omega-3 fatty acids (FA) (1 g daily) for primary prevention of cardiovascular disease in diabetes is being investigated in the 2x2 factorial design ASCEND trial. To support the interpretation of the trial's efficacy findings, it is important to compare self-reported compliance by participants with measures of the biochemical effects of each intervention. The previous data on the effect of supplementation with omega-3 FA on coronary heart disease is uncertain. Methods: The ASCEND trial randomly allocated 15480 people with diabetes (94% type 2 DM) who do not already have diagnosed occlusive arterial disease to receive aspirin or placebo and to omega-3 FA or placebo. Blood and urine samples were collected by mail at baseline and after 3 years follow-up. The effectiveness of aspirin to suppress urinary thromboxane B2 (UTxB2), a marker of platelet activity, and, of omega-3 FA supplements to increase red cell membrane omega-3 index were assessed. A systematic review of previous trials of omega-3 FA was conducted to summarize the prior evidence for the effects of omega-3 FA supplements on major vascular events (MVEs). Results: Aspirin reduced UTxB2 levels by 67% (63-70%) (p < 0.0001) compared with placebo, from 3453 pg/mg (95% CI 3061-3895) at baseline to 1190 pg/mg (1100-1287) on those allocated to aspirin during the trial. During follow-up, the omega-3 index increased by 33% (95% CI 26%-39%) in those allocated omega-3 FA compared to placebo (p < 0.0001). The meta-analysis of previous studies of omega-3 FA showed no effect on MVEs (HR 0.97; [0.93-1.01]) overall or in any pre-specified sub-groups. Conclusions: Low dose aspirin and omega-3 FA are biochemically effective at reducing UTxB2 and increasing the omega-3 index, respectively. Previous trials show that supplementation with omega-3 FA had no significant effect on MVEs. The results of the ASCEND trial, assessing the effects of both aspirin and omega-3 FA on MVEs, will be available in 2018.

Recentemente o câncer de um modo geral, sobretudo o câncer de pulmão tem sido causa de grande preocupação no mundo. O objetivo deste trabalho foi avaliar a atividade antitumoral do óleo (Copaifera reticulata Ducke) in natura e sua fração resina em linhagens celulares não cancerosas (E10) e cancerosas (E9) de pulmão de camundongo. O óleo foi submetido a hidrodestilação para a obtenção da fração resina. As células após o cultivo a 37&deg;C foram tratadas com 8 diferentes concentrações do óleo e da resina, foram mantidas na mesma temperatura por mais 48h na estufa. Depois adicionou-se o reagente Thyazolyl blue tetrazolium bromide para o teste de citotoxicidade e determinação da concentração inibitória de 50% de células viáveis (IC50). Com os resultados, observou-se que ambos os tratamentos agiram como antitumorais e quando comparados entre si percebe-se que o óleo in natura agiu melhor que sua fração resina, sugerindo ser mais citotóxico para as células cancerosas a uma concentração aproximadamente onze vezes menor (E9 [0,0287&micro;L/mL]) do que para as células não cancerosas (E10 [0,3142&micro;L/mL]). A fração resina também inibiu a proliferação celular, na concentração E10 [0,0930&micro;L/mL] e E9 [0,8002&micro;L/mL]. Verificou-se através da técnica de fluorescência com Laranja de Acridina e Brometo de Etídio que os tratamentos induziram a morte das células por apoptose. Conclui-se que o óleo in natura da C. reticulata Ducke agiu melhor como agente antitumoral do que a resina, sugerindo que ocorre um sinergismo entre suas frações e que estudos futuros in vitro e in vivo são necessários para garantir a sua padronização e utilização. / In recent times cancer in general, especially lung cancer has been a cause of great concern in the world. The objective of this work was to evaluate the antitumor activity of the oil (Copaifera reticulata Ducke) in natura and its resin fraction in non-cancerous (E10) and cancerous (E9) lung cells lines of mouse. The oil was subjected to hydrodistillation to obtain the resin fraction. Cells after cultivation at 37&deg;C were treated with 8 different concentrations of oil and resin, and were maintained at the same temperature for another 48h in the oven. The MTT reagent was then added for the cytotoxicity test and determination of the 50% viable cell inhibitory concentration (IC50). The results showed that both treatments acted as antitumor and when the data were compared it was observed that the oil in natura acted better than its resin fraction because it was more cytotoxic to the cancer cells at a concentration almost eleven times smaller (E9 [0,0287&micro;L/mL) than for non-cancer cells (E10 [0,3142&micro;L/mL]). The resin fraction also inhibited cell proliferation, but at a very close concentration for the two cells line (E10 [0,0930&micro;L/mL] and E9 [0,8002 &micro;L/mL]). It was verified by the fluorescence technique with Acridine Orange and Ethidium Bromide that the treatments induced the death of the cells by apoptosis. Its concluded that the in natura oil of C. reticulata Ducke acted better as an antitumor than the resin, suggesting that synergism occurs between its fractions and that future in vitro and in vivo studies are necessary to guarantee its standardization and use.

Vinte e oito bovinos Brangus foram usados para se determinar o efeito da suplementação de cobre e selênio no desempenho, características de carcaça, composição de ácidos graxos no músculo Longissimus dorsi (LD) e na concentração de colesterol sérico e no músculo LD . Os tratamentos foram : 1) C(Controle) - sem a suplementação de cobre e selênio; 2) Se - 2 mg Se/kg de matéria seca na forma de selenito de sódio; 3) Cu- 40 mg Cu/kg de matéria seca na forma de sulfato de cobre; 4) Se/Cu- 2 mg Se/kg de matéria seca na forma de selenito de sódio e 40 mg Cu/kg de matéria seca na forma de sulfato de cobre. O ganho de peso diário aumentou com a suplementação de selênio (P<0,05). A eficiência alimentar foi melhor (P<0,05) nos tratamentos selênio, cobre e selênio/cobre, em relação ao controle. A ingestão de matéria seca não foi alterada pelos tratamentos (P>0,05). A espessura de gordura e composição de ácidos graxos do músculo LD não foram influenciados pelos tratamentos (P>0,05). A concentração sérica de colesterol não foi influenciada pelos tratamentos (P>0,05), entretanto, a concentração de colesterol no LD foi menor nos bovinos suplementados com cobre e selênio (P < 0.05). A glutationa peroxidase e GSSG aumentaram (P<0,05) com a suplementação de cobre , selênio ou selênio/cobre (P <0,05). / Twenty eight Brangus steers were used to determine the effects of copper (Cu) and selenium (Se) supplementation on performance, carcass characteristics, Longissimus dorsi muscle fatty acid composition and serum and Longissimus dorsi muscle cholesterol concentrations. Treatments were: 1) control - no supplemental Cu and Se; 2) Se - 2 mg Se/kg DM as sodium selenite; 3) Cu - 40 mg Cu/kg DM as copper sulfate; 4) Se/Cu - 2 mg Se/kg DM as sodium selenite and 40 mg Cu/kg DM as copper sulfate. Daily weight gain increased with selenium supplementation (P<0,05). Feed efficiency was better in selenium, copper and selenium/copper treatments than in the control group. Dry matter intake was not affected by treatments (P>0.05). Backfat and Longissimus dorsi fatty acid concentrations were not affected by treatments (P > 0.05). Serum cholesterol concentration was not affected by treatments (P>0.05), however, Longissimus dorsi cholesterol concentrations were lower in steers supplemented with Cu and Se (P<0.05). GSSG and GSH Px increased (P<0.05) with Cu, Se and Se/Cu supplementation.

Pancreatic beta-cells regulate blood glucose by secreting insulin in response to nutrients. The development of Type 2 Diabetes (T2D) is characterized by elevated insulin secretion in the fasted state and a failure to adequately respond to nutrient influx, particularly glucose. Current dogma states that insulin resistance is the initiating event in the development of T2D, with compensation by beta-cells necessary to maintain glucose homeostasis. An alternative model, which will be a central theme throughout this thesis, is that hypersecretion of insulin is the initiating and sustaining event in the development of T2D. The underlying cause of insulin hypersecretion is unclear. Determining this is important in order to test this alternative model as a viable target for prevention and treatment of T2D. Because of the association between obesity and hyperinsulinemia, we hypothesized that exposure of the β-cell to high levels of nutrients stimulates insulin hypersecretion. We found that chronic incubation of β-cells in high glucose and/or oleate, which mimics nutrient conditions in obesity, lowered the half-maximal response for glucose to stimulate insulin secretion. The degree of the left-shift correlated with lipid stores. We determined that heightened sensitivity of granule exocytosis to Ca2+ was driving this left-shift. Thus glucose, while not necessarily abnormal in obesity, may cause hypersecretion of insulin due to altered sensitivity of the β-cell to this secretagogue. Iron stores are increased in obesity and are predictive of T2D development. We found that iron acutely stimulated both basal and glucose-stimulated insulin secretion (GSIS) in a reactive oxygen species dependent manner. Interestingly, iron did not increase insulin secretion via Ca2+ influx. Thus, both iron and glucose/oleate induce insulin hypersecretion via an aspect of the triggering pathway that is not Ca2+, the putative triggering signal. Previous work in our laboratory documented that exogenous mono-oleoyl-glycerol, an endogenous lipid signaling molecule and food additive, increases basal insulin secretion. We found that inhibition of monoacylglycerol lipase, which increases cellular monacylglycerol species, reduced GSIS, possibly via a reduction in long-chain CoA. Collectively, our works supports the hypothesis that chronic exposure to high nutrient levels drives insulin hypersecretion in obesity. / 2018-06-15T00:00:00Z

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-17Bitstream added on 2014-06-13T19:27:11Z : No. of bitstreams: 1 lucchesi_an_me_botfm.pdf: 749829 bytes, checksum: 0aa5e082ee905bd7a05a8698d3112ee3 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O diabetes mellitus (DM) é tido como um problema de saúde pública mundial. No Brasil ele atinge mais de 14 milhões de pessoas, sendo acompanhado de altos índices de morbidade e mortalidade. Entretanto, os mecanismos primariamente responsáveis pela agressão dos tecidos e órgãos pelo DM ainda não são completamente conhecidos, o que explica a dificuldade em se estabelecer um tratamento eficaz para prevenir ou controlar a progressão das lesões diabéticas crônicas. O estresse oxidativo celular é tido como um dos mecanismos importantes na gênese do dano tecidual relacionado à hiperglicemia. Através deste mecanismo, o DM poderia aumentar a produção de espécies reativas do oxigênio (EROs) ao nível celular, que pela sua toxicidade, seria capaz de promover o desenvolvimento das lesões diabéticas crônicas. Evidências clínicas sugerem que o fígado de indivíduos diabéticos também poderia sofrer a ação das EROs, no longo prazo, levando a uma seqüência de eventos capaz de determinar a doença gordurosa do fígado de etiologia não-alcoólica (DGFNA), com progressão para esteato-hepatite e cirrose. Todavia, a presença de estresse oxidativo no tecido hepático de portadores de DM, ainda não está bem estabelecida na literatura, o que justifica a realização de novas investigações em modelos-animais de diabetes, no intuito de melhor esclarecer a real participação deste mecanismo na gênese e evolução das lesões hepáticas diabéticas crônicas. Neste estudo foram utilizados 60 ratos machos Lewis, distribuídos em 2 grupos experimentais, com 30 animais cada um, assim designados: GN - Grupo Controle: constituído de ratos normais, não-diabéticos; GD - Grupo Diabético: constituído por animais diabéticos induzidos pela aloxana, sem qualquer tratamento. Cada um dos grupos experimentais foi dividido em 3 subgrupos de ratos, com 10 animais cada um, para serem... / Diabetes mellitus (DM) is considered to be a public-health problem worldwide. In Brazil, it affects 14 million people, and it is accompanied by high morbidity and mortality rates. However, the mechanisms primarily responsible for tissue and organ aggression by DM are not yet fully known, which explains the difficulty in establishing effective treatment to prevent or control the progression of chronic diabetic lesions. Cellular oxidative stress is considered to be one of the important mechanisms in the genesis of hyperglycemia-related tissue damage. Through this mechanism, DM could increase the production of reactive oxygen species (ROS) in the cellular level, which, due to their toxicity, could promote the development of chronic diabetic lesions. Clinical evidence suggests that the liver of diabetic individuals could also suffer the action of ROS in the long term, thus leading to a sequence of events that can determine non-alcoholic fatty liver disease (NAFLD), with progression to steatohepatitis and cirrhosis. However, the presence of oxidative stress in the hepatic tissue of individuals with DM has not been yet well established in the literature, which justifies the performance of new investigations in diabetes animal models with the purpose to clarify the actual participation of such mechanisms in the genesis and development of chronic diabetic hepatic lesions. In this study, 60 males Lewis rats were used. They were distributed into 2 experimental groups, each containing 30 animals and designated as follows: GN – Control Group: consisting of non-diabetic control rats; GD – Diabetic Group: consisting of alloxan-induced diabetic rats without any treatment. Each experimental group was divided into 3 subgroups of rats with 10 animals each to be evaluated and sacrificed respectively at 4 experimental moments, namely: M1– animals from the 3 subgroups, at the initial moment... (Complete abstract click electronic access below)

Dans le contexte actuel d’allongement de l’espérance de vie, la prévalence des maladies liées à l’âge telles que l’ostéoporose est de plus en plus importante. Le coût de la prise en charge de ces pathologies constitue un problème de santé public majeur et la mise en place de stratégies de prévention nutritionnelle adaptées apparaît comme une excellente solution alternative aux traitements habituels. Pourtant, l’étude des activités biologiques des nutriments reste trop marginale pour certains tissus et certaines catégories de molécules, c’est notamment le cas du tissu osseux et des lipides, en particulier les acides gras.Ces derniers sont pourtant capables de moduler le devenir du tissu osseux que ce soit indirectement par des mécanismes systémiques ou directement au niveau de la cellule osseuse. La perte osseuse liée au vieillissement est souvent associée à l’établissement progressif d’une inflammation chronique à bas bruit à l’échelle de l’organisme. Dans ce contexte, les niveaux de cytokines pro-inflammatoires telles que l’interleukine 6 ou le Tumor Necrosis Factor α sont augmentés et ces composés, qui sont connus pour induire la résorption osseuse, pourraient contribuer à la dégradation du squelette. Notre hypothèse de travail était que certains Acides Gras Poly-Insaturés (AGPI) à propriétés anti-inflammatoires pouvaient éventuellement limiter l’inflammation chronique associée au vieillissement et ainsi contribuer à préserver le capital osseux. Dans cette optique, nous avons utilisé la souris SamP8 qui est un modèle de progeria présentant, à douze mois, un phénotype ostéoporotique. Dans ce modèle, l’administration d’un régime délétère à base d’huile de tournesol (ratio acide gras ω6 /ω3 très important) aggrave la perte osseuse en association avec une augmentation des marqueurs inflammatoires systémiques et osseux ainsi qu’une augmentation des marqueurs de la résorption osseuse. La supplémentation de ce régime tournesol avec de l’huile de bourrache ou de l’huile de poisson permet d’apporter des quantités importantes d’AGPI anti-inflammatoires (acide γ-linoléique pour l’huile de bourrache et ω3 pour l’huile de poisson). De manière intéressante, ces deux régimes supplémentés permettent, en plus de réduire les paramètres inflammatoires, de s’opposer à l’augmentation des marqueurs de résorption osseuse et de limiter la diminution de la densité minérale de l’os chez ces souris. Cette étude met donc en évidence le potentiel santé de certains AGPI au regard de la préservation du capital osseux et suggère un rôle déterminant de leurs propriétés anti-inflammatoires systémiques. En parallèle, la description des effets directs des acides gras au niveau cellulaire par l’activation de récepteurs spécifiques occupent une place croissante dans la littérature. Récemment, le récepteur membranaire GPR40 (G Protein coupled Receptor 40) a été mis en évidence pour ses interactions avec les acides gras libres à longues chaînes et nous avons pu montrer son expression dans les précurseurs ostéoclastiques. Nous avons donc émis l’hypothèse que ce récepteur pourrait jouer un rôle dans la médiation des effets des acides gras sur les paramètres du remodelage osseux. Ce travail a permis de mettre en évidence l’existence d’un phénotype ostéoporotique chez la souris invalidée pour le GPR40. L’effet protecteur de ce récepteur semble lié principalement à un effet inhibiteur de son activation sur la différenciation des ostéoclastes. En effet, l’utilisation de l’agoniste spécifique du GPR40 empêche in vitro la différenciation ostéoclastique par RANKL de deux modèles cellulaires de manière GPR40-dépendante. De surcroit, cet agoniste est également capable in vivo de s’opposer à une perte osseuse induite chez la souris. Ces résultats révèlent pour la première fois l’implication du récepteur GPR40 dans la physiologie osseuse et apportent la connaissance d’une nouvelle possibilité de modulation directe des cellules osseuses par les acides gras. / With increasing lifespan, prevalence of age-related complications has grown including skeletal defects such as osteoporosis. Socio-economic consequences of these disorders represent a major public health problem worldwide and in this context, nutritional prevention strategies may be considered as a good option to be associated with usual therapies. However, biological activities of some nutrients have been too poorly deciphered in regards to their bone health potential. This is notably true concerning fatty acids and both their direct and indirect relationships with the skeleton. Age-related bone complications are often associated with a gradual establishment of a systemic low-grade inflammatory condition. This leads to high levels of pro-inflammatory cytokines such as interleukin 6 or tumor necrosis factor α which are known to favour osteoclast-induced bone resorption. Then, these high pro-inflammatory cytokines levels may contribute to age associated bone loss. We hypothesize that in this context, poly-unsaturated fatty acids (PUFA) with known anti-inflammatory properties may counteract both the low-grade inflammation establishment and the associated bone loss. Thus, animals from the progeria mouse model SamP8 were used and were shown to exhibit osteoporosis at twelve months. Feeding these mice with a deletary (very high ω6/ω3 ratio) sunflower oil-based diet results in an exacerbated bone loss, associated with increased systemic and bone inflammation parameters as well as increased bone resorption markers. Either borage or fish oil supplementation of the sunflower oil-based diet result in high amounts of anti-inflammatory PUFAs in the diet (γ-linoleic acid with borage oil and ω3 with fish oil). Interestingly, mice fed with the two “supplemented” diets show reduced inflammatory parameters but also reduced levels of bone resorption markers and preserved bone mineral density. In this work, the bone health potential of some PUFAs was established and was linked to their systemic anti-inflammatory properties. Besides, fatty acids are increasingly studied as signalling molecules, able to modulate cell signalling by their interactions with specific receptors. A few years ago, long chain fatty acids were shown to be ligands of the membrane bound fatty acid receptor GPR40 (G Protein coupled Receptor 40). As we showed GPR40 expression in osteoclast precursors, we hypothesized that it may be involved in fatty acid-induced bone remodelling regulation. In this study, an osteoporotic phenotype was found in GPR40-deficient mice. This GPR40- mediated bone protection seems to involve an anti-osteoclastogenic effect. As a matter of fact, a GPR40 specific agonist led to blunted RANKL-induced osteoclastic differentiation in a GPR40-dependant way. In addition, this agonist was also able in vivo to counteract ovariectomy-induced bone loss in mice. Thus, involvement of GPR40 in bone remodelling was established for the first time in this work, bringing to light a new mechanism in the fatty acid-induced modulation of bone metabolism.