Non-alcoholic fatty liver disease is affecting an increasing population worldwide. NAFLD is closely associated with obesity and diabetes. Research has shown that the expression of some important hepatic transporters and enzymes are altered under inflammatory conditions. We examined the effect of NAFLD on the gene expression of several hepatic transporters and enzymes, as well as the impact of exercise in attenuating the effect of NAFLD. We have demonstrated that the mRNA expression of several hepatic transporters and enzymes, as well as FXR were significantly downregulated in liver of rats treated with a HFHCD. We concluded that HFHCD-induced hepatic steatosis, together with the reduced expression of FXR, contributed to the downregulation of expression of hepatic transporters and enzymes. The mRNA expression of TNF-α and IL-1β were unaffected. Interestingly, exercise was found to improve the expression levels of some transporters and enzymes.

Non-alcoholic fatty liver disease (NAFLD) includes simple hepatic steatosis (SS) and non-alcoholic steatohepatitis (NASH). NAFLD is tightly linked to obesity and is thought to be secondary to various noxious signals, some of which may originate from the intestinal microbiota (IM). Despite a growing body of evidence supporting a link between obesity and altered IM, there are no studies assessing the IM of patients with NAFLD. In this cross-sectional study we aimed at comparing fecal levels of total bacteria, Bacteroidetes, C. coccoides, C. leptum, Bifidobacteria, E. coli, and Archaea between healthy controls (HC) and patients with SS or NASH. We found higher C. coccoides levels in NASH compared to SS and lower percentage Bacteroidetes in NASH compared to SS and HC. Controlling for body mass index and fat intake we found an association between presence of NASH and percentage Bacteroidetes. The latter inversely correlated with insulin resistance.

Non-alcoholic fatty liver disease is affecting an increasing population worldwide. NAFLD is closely associated with obesity and diabetes. Research has shown that the expression of some important hepatic transporters and enzymes are altered under inflammatory conditions. We examined the effect of NAFLD on the gene expression of several hepatic transporters and enzymes, as well as the impact of exercise in attenuating the effect of NAFLD. We have demonstrated that the mRNA expression of several hepatic transporters and enzymes, as well as FXR were significantly downregulated in liver of rats treated with a HFHCD. We concluded that HFHCD-induced hepatic steatosis, together with the reduced expression of FXR, contributed to the downregulation of expression of hepatic transporters and enzymes. The mRNA expression of TNF-α and IL-1β were unaffected. Interestingly, exercise was found to improve the expression levels of some transporters and enzymes.

No description available.

El objetivo principal de esta tesis ha sido el desarrollo de nuevos poliuretanos a partir de ácidos grasos como fuentes renovables, utilizando química “click” en la síntesis de los dioles y polioles correspondientes. La primera parte del trabajo describe la preparación de los monómeros “vía” acoplamiento tiol-eno ó tiol-ino, su caracterización y las propiedades de los poliuretanos sintetizados. Como los polímeros a partir de ácidos grasos provienen de macromoléculas biológicas y pueden ser potencialmente biocompatibles, la segunda parte del trabajo está dirigida a incrementar la biocompatibilidad de los poliuretanos a través de diversas estrategias de funcionalización con moléculas bioactivas, para su implementación en ingeniería de tejidos. Tres metodologías fueron investigadas: mezclas con gelatina; inmovilización covalente de colágeno sobre la superficie mediante plasma; e inmovilización iónica de sulfato de condroitina sobre la superficie mediante aminólisis. / The main objective of this thesis has been the development of new polyurethanes from renewable sources such as fatty acids, using "click" chemistry in the synthesis of the corresponding diols and polyols. The first part of this study describes the preparation of monomers "via" thiol-ene or thiol-yne coupling, characterization and properties of the synthesized polyurethanes. As the polymers from fatty acids derived from biological macromolecules and can be potentially biocompatible, the second part of this work is focused on the enhancement of polyurethanes biocompatibility through bioactive molecules functionalization strategies, for tissue engineering purposes. Three approaches have been investigated: blends of polyurethanes and gelatin; covalent surface modification of polyurethanes with collagen by plasma treatment; and ionic surface modification of polyurethanes with chondroitin sulfate by aminolysis treatment.

Polyunsaturated fatty acids (PUFA) affect key cellular and physiological processes in the body ranging from cell signalling to inflammation. Compositional, dietary refinement and bioassay studies have shown strong associations between the PUFA composition of skeletal muscle with various contractile properties as well as the development of obesity and insulin resistance. The incorporation of PUFAs into rat soleus (slow-twitch oxidative), red gastrocnemius (fast-twitch oxidative), and white gastrocnemius (fast-twitch glycolytic) muscle were examined using stable isotope-labelled fatty acids. Two separate tracer studies were conducted. In the first study, four groups of rats were orally dosed with one of three isotopes of 18:2n-6; 13C18-18:2n-6 ethyl ester, 13C18- 18:2n-6 nonesterified fatty acid or 2H5-18:2n-6 ethyl ester and a control group received the vehicle only (olive oil). Animals were sacrificed 8 hours post dosing and soleus, red and white gastrocnemius muscles were collected for lipid analysis. In the second study, rats were orally administered a single dose of a mixture of 4 isotopes (13C18-18:2n-6, 2H5-18:3n-3, 13C16-16:0, and 2H2-18:1n-9) or vehicle only (olive oil) as a control. Groups of animals were sacrificed at 8, 24, and 48 h after dosing and four muscle types (heart, soleus, red and white gastrocnemius) were collected and analyzed for isotopic signal of these fatty acids and their corresponding desaturation and/or elongation products. Soleus accumulated significantly higher concentrations of labelled 18:2n-6, 18:3n-3 and most of n-6 fatty acids derived from 18:2n-6 followed by red gastrocnemius and white gastrocnemius. Heart muscle accumulated 20:5n-3 and 22:6n-3 increasingly over time while skeletal muscle accumulation was variable across muscle types. Labelled 20:5n-3 was detected in red and white gastrocnemius at 8 and 24 h with levels declining by 48 h while no 20:5n-3 was detected in soleus at anytime. Labelled 22:6n-3 was not detected in white gastrocnemius, but 22:6n-3 appeared to be increasing in red gastrocnemius over time. Soleus demonstrated a large accumulation of 22:6n-3 at 8 h with no detectable levels at 48 h. In conclusion we were able to demonstrate that the distribution and metabolism of various PUFAs differ in muscle types with distinct fibre type composition.

Polyunsaturated fatty acids (PUFA) affect key cellular and physiological processes in the body ranging from cell signalling to inflammation. Compositional, dietary refinement and bioassay studies have shown strong associations between the PUFA composition of skeletal muscle with various contractile properties as well as the development of obesity and insulin resistance. The incorporation of PUFAs into rat soleus (slow-twitch oxidative), red gastrocnemius (fast-twitch oxidative), and white gastrocnemius (fast-twitch glycolytic) muscle were examined using stable isotope-labelled fatty acids. Two separate tracer studies were conducted. In the first study, four groups of rats were orally dosed with one of three isotopes of 18:2n-6; 13C18-18:2n-6 ethyl ester, 13C18- 18:2n-6 nonesterified fatty acid or 2H5-18:2n-6 ethyl ester and a control group received the vehicle only (olive oil). Animals were sacrificed 8 hours post dosing and soleus, red and white gastrocnemius muscles were collected for lipid analysis. In the second study, rats were orally administered a single dose of a mixture of 4 isotopes (13C18-18:2n-6, 2H5-18:3n-3, 13C16-16:0, and 2H2-18:1n-9) or vehicle only (olive oil) as a control. Groups of animals were sacrificed at 8, 24, and 48 h after dosing and four muscle types (heart, soleus, red and white gastrocnemius) were collected and analyzed for isotopic signal of these fatty acids and their corresponding desaturation and/or elongation products. Soleus accumulated significantly higher concentrations of labelled 18:2n-6, 18:3n-3 and most of n-6 fatty acids derived from 18:2n-6 followed by red gastrocnemius and white gastrocnemius. Heart muscle accumulated 20:5n-3 and 22:6n-3 increasingly over time while skeletal muscle accumulation was variable across muscle types. Labelled 20:5n-3 was detected in red and white gastrocnemius at 8 and 24 h with levels declining by 48 h while no 20:5n-3 was detected in soleus at anytime. Labelled 22:6n-3 was not detected in white gastrocnemius, but 22:6n-3 appeared to be increasing in red gastrocnemius over time. Soleus demonstrated a large accumulation of 22:6n-3 at 8 h with no detectable levels at 48 h. In conclusion we were able to demonstrate that the distribution and metabolism of various PUFAs differ in muscle types with distinct fibre type composition.

No description available.

We hypothesized that subcutaneous (s.c.) adipose tissue would differ in monounsaturated (MUFA) and saturated fatty acid (SFA) composition among different depots throughout a beef carcass. To test this, 50 carcasses from a variety of breed types and backgrounds were sampled. External fat samples were collected from eight different carcass locations: round, sirloin, loin, rib, chuck, brisket, plate and flank. Samples were used to provide information on slip points, fatty acid composition and MUFA:SFA ratios. Lipids were extracted from s.c. adipose tissue by a modified chloroform:methanol procedure, and fatty acid composition and slip points were measured. The brisket was significantly lower in palmitic (16:0) and stearic (18:0) acid than the other seven sampling sites (P = 0.001). The brisket demonstrated the highest values of MUFA (P = 0.001) with the exception of possessing the lowest value of transvaccenic (18:1t11) acid (P = 0.002). There were also significant differences in the amounts of PUFA among the eight sampling sites. The lowest values were from the brisket with a mean of 25.1. The flank had the highest slip point with a mean of 39.0 (P < or = 0.001). There was a high negative correlation shown between palmitoleic and stearic acid (R2 = 0.827). The brisket displayed the highest values for MUFA:SFA ratios (P = 0.001), whereas the flank was the lowest. Due to the significant differences amongst fat depots within bovine carcasses in their fatty acid composition we conclude that substantial differences exist across fat depots.

Little research has focused on the relationship between lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol metabolism in dogs and cats. To study weight loss and cholesterol metabolism in dogs, four experimental weight-loss diets were fed to 12 obese female beagles for 8 wk in a partial crossover design (n = 6). High- (HGI) or low-glycemic index (LGI) starch and diacylglycerol or triacylglycerol oil were combined to compose diets with similar fatty acid (FA) profiles. Body weight was measured weekly. Fasted blood samples were drawn at wk1, wk4, and wk8 to measure plasma total (TC), unesterified (UC), and esterified cholesterol (EC) concentrations, LCAT activity, and FA composition of the phospholipid (PL) and EC fractions. All groups lost weight. UC increased from wk1 to wk4 (p < 0.05). LCAT activity increased from wk1 to wk4 and remained elevated at wk8 (p < 0.05). Plasma PL FA profiles reflected the diets fed with few diet or time effects. Plasma EC FA profiles reflected the specificity of LCAT for linoleic acid (LA) with minimal diet or time effects. We conclude that weight reduction in dogs occurs in conjunction with increased LCAT activity and altered plasma cholesterol fractions but not changes in plasma PL or EC FA profiles. To measure the activity and demonstrate the FA specificity of LCAT in felines fed varying types of fat, 29 female cats were fed diets enriched with high-oleic sunflower (n = 9), menhaden fish (n = 10), or safflower (n = 10) oil (8g oil/100g kibble) for 4 wk. Fasted blood samples were drawn at d0, d14, and d28 for determination of the blood parameters mentioned previously. LCAT and TC showed no time or diet effects. UC decreased at d28 compared to d0 and d14, while EC increased at d28 compared to d0 and d14 (all p < 0.05). Plasma EC FA profiles reflected the specificity of LCAT for LA with many diet and time effects but contained no docosahexanoic acid (DHA). We conclude that feline LCAT has no measurable affinity for DHA, but both feline and canine LCAT demonstrated specificity for LA regardless of diet fed.