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Browsing by Subject "Lipid metabolism"

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    Biological assessment and methods to evaluate lipid peroxidation when feeding thermally-oxidized lipids to young pigs.
    (2012-07) Liu, Pai
    Measurements of peroxidation can provide useful information regarding the degree of lipid peroxidation, but limitations of each test should not be overlooked. One objective of this disseration was to evaluate peroxidation in 4 lipids, each with 3 degrees of peroxidation. Lipid sources were: corn oil (CN), canola oil (CA), poultry fat, and tallow. Peroxidation levels were: original lipids (OL), slow-oxidized lipids (SO), and rapid-oxidized lipids (RO). To produce peroxidized lipids, OL were either heated at 95°C for 72 h to produce SO, or heated at 185°C for 7 h for producing RO. Five indicative measurements [peroxide value (PV), p-anisidine value (AnV), thiobarbituric acid reactive substance concentration (TBARS), hexanal concentration, 4-hydroxy nonenal concentration (HNE), and 2,4-decadienal (DDE)] and 2 predictive tests [active oxygen method stability (AOM) and oxidative stability index (OSI)] were performed to quantify the degree of oxidation of the subsequent 12 lipids of varying degrees of peroxidation. Analysis showed that a high PV accurately indicated the high degree of lipid peroxidation, but a moderate or low PV may be misleading due to the unstable characteristics of hydroperoxides as indicated by the unchanged PV of rapidly oxidized CN and CA compared to their original state (OL). However, additional tests which measure secondary peroxidation products such as AnV, TBARS, hexanal, HNE, and DDE may provide a better indication of lipid peroxidation than PV for lipids subjected to a high degree of peroxidation. Similar to PV analysis, these tests may also not provide irrefutable information regarding the extent of peroxidation due to the volatile characteristics of secondary peroxidation products and the ever changing stage of lipid peroxidation. For the predictive tests, AOM accurately reflected the increased lipid peroxidation caused by SO and RO as indicated by the increased AOM value in CN and CA, but not in poultry fat and tallow, which indicates a potential disadvantage of the AOM test. Oxidative stability index successfully showed the increased lipid peroxidation caused by SO and RO in all lipids, but it too may have disadvantages similar to AnV, TBARS, hexanal, DDE, and HNE because OSI directly depends on quantification of the volatile secondary peroxidation products. To accurately analyze the peroxidation damage in lipids, measurements should be determined at appropriate time intervals by more than one test and include different types of peroxidation products simultaneously. Few studies had evaluated the metabolic effects of consuming oxidized lipids in pigs. Another objective of this disseration is to evaluate the effect of feeding thermally-oxidized vegetable oils and animal fats on growth performance, liver gene expression, and liver and serum fatty acid and cholesterol concentration in young pigs. A total of 102 barrows (6.67 ± 0.03 kg BW) were divided into 3 groups and randomly assigned to dietary treatments in a 4 × 3 factorial arrangement. The main factors were lipid source (n = 4: CN, CA, PF, and TL) and lipid peroxidation level (n =3: OL, SO , or RO). Pigs were provided ad libitum access to diets in group pens for 28 d, followed by controlled feed intake in metabolism crates for 10 d. On d 39, all pigs were euthanized for liver samples to determine liver weight, lipid profile, and gene express patterns. Lipid oxidation analysis indicated that compared to the OL, SO and RO had a markedly increased concentrations of primary and secondary peroxidation products, and the increased lipid peroxidation products in CN and CA were higher than those in PF and TL. After a 28-d ad libitum feeding period, pigs fed RO tended to have reduced ADFI (P = 0.09), and ADG (P < 0.05) compared to pigs fed OL, and pigs fed CA had reduced G:F (P < 0.05) compared to pigs fed all other lipids. Pigs fed RO lipids tended to have increased liver weight (P = 0.09) compared to pigs fed OL. Liver triglyceride concentration (LTG) in pigs fed OL was greater (P < 0.05) than in pigs fed RO, and tended to be greater (P < 0.07) than in pigs fed SO. The reduced LTG were consistent with increased (P < 0.05) mRNA expression of PPARα factor target genes (acyl-CoA oxidase, carnitine palmitoyltransferase-1, and mitochondrial 3-hydroxy-3-methylglutary-CoA synthase) in pigs fed SO and RO lipids compared with pigs fed OL. Pigs fed CN or CA tended to have increased LTG (P = 0.09) compared to pigs fed TL. Liver cholesterol concentration in pigs fed CN was less (P < 0.05) than pigs fed PF, and tended to be less (P = 0.06) than pigs fed TL, whereas pigs fed CA had a reduced (P < 0.05) liver cholesterol compared to pigs fed PF or TL. In conclusion, feeding thermally-oxidized lipids negatively affected growth performance and liver triglyceride concentrations of young pigs. In addition, limit is known about the effect of thermally-oxidized lipid on lipid energy value and nutrient digestibility in young pigs. A total of 108 barrows (6.67 ± 0.03 kg BW) were assigned to 12 dietary treatments in a 4 × 3 factorial design, plus a corn-soybean meal control diet to evaluate the effect of lipid source and peroxidation level on DE, ME, and apparent total tract digestibility (ATTD) of DM, GE, ether extract (EE), nitrogen (N), and carbon (C) in young pigs. The main factors were lipid source (n = 4: CN, CA, PF, and TL) and lipid peroxidation level (n =3: OL, SO , or RO). Pigs were provided ad libitum access to diets for 28-d, followed by an 8-d period of controlled feed intake equivalent to 4% BW daily. Diets were formulated based on the ME content of CA with the standardized ileal digestible Lys, Met, Thr, Trp, total Ca, and available P:ME balanced relative to NRC (1998) recommendations. Lipid peroxidation analysis indicated that compared to the OL, SO and RO had a markedly increased concentrations of primary and secondary peroxidation products, and the increase in these peroxidation products in CN and CA were higher than those in PF and TL. Addition of lipids to diets increased (P < 0.05) ATTD of EE and tended to improve (P = 0.06) ATTD of GE compared to pigs fed the control diet. Feeding CN or CA increased (P < 0.05) ATTD of DM, GE, EE, N, and C compared to feeding TL, while feeding PF improved (P < 0.05) ATTD of GE and EE, and tended to increase (P = 0.06) ATTD of C compared to TL. Pigs fed CN had increased (P = 0.05) percentage N retention than pigs fed TL. No peroxidation level effect or interaction between lipid source and peroxidation level on DE and ME was observed. Lipid source tended (P = 0.08) to affect DE, but not ME values of experimental lipids (P > 0.12). Digestible energy values for CA (8,846, 8,682, and 8,668 kcal/kg) and CN (8,867, 8,648, and 8,725 kcal/kg) were about 450 kcal/kg higher than that of TL (8,316, 8,168, and 8,296 kcal/kg), with PF being intermediate (8,519, 8,274, and 8,511 kcal/kg) for OL, SO, and RO, respectively. In conclusion, lipid source affected ATTD of dietary DM, GE, EE, N, and C, and N retention rate; and tended to influence the DE value of the lipid, but did not significantly affect their ME value. Rapid and slow heating of lipids evaluated in this study increased lipid peroxidation products, but had minor effects on nutrient and energy digestibility as well as DE and ME values of the various lipids. Furthermore, no information has been reported regarding the effect of feeding peroxidized lipids on intestinal health or immune function in pigs. Another objective of this dissertation is to evaluate the effect of feeding thermally-oxidized lipids on metabolic oxidative status, gut barrier function, and immune response of young pigs. A total of 108 barrows (6.67 ± 0.03 kg BW) were assigned to 12 dietary treatments in a 4 × 3 factorial design in addition to a corn-soybean meal control diet. The main factors were lipid source (n = 4: CN, CA, PF, and TL) and lipid peroxidation level (n =3: OL, SO , or RO). Pigs were provided ad libitum access to diets for 28 d, followed by controlled feed intake for 10 d. After a 24-h fast on d 38, serum was collected and analyzed for α-tocopherol (α-T), thiobarbituric acid reactive substances (TBARS), endotoxin, haptoglobin, IgA, and IgG. On the same day following serum collection, lactulose and mannitol were fed and subsequently measured in the urine to evaluate gut permeability. There was a source × peroxidation interaction for serum α-T concentration where pigs fed SO or RO had decreased (P < 0.05) serum α-T concentration compared to pigs fed OL in CA and CN diets, but not in pigs fed PF and TL diets. There was no source × peroxidation interaction for serum TBARS, but among all lipid sources, pigs fed SO or RO lipids had increased (P < 0.05) serum TBARS compared with pigs fed OL. In addition, pigs fed CN or CA had higher (P < 0.05) serum TBARS compared to pigs fed PF or TL diets. There was no lipid source × peroxidation level interaction, nor lipid source or peroxidation level effects observed for serum endotoxin, haptoglobin, IgA, or IgG. Pigs fed lipid supplemented diets tended to have increased serum endotoxin (P = 0.06), IgA (P = 0.10), and IgG (P = 0.09) compared to pigs fed the control diet. There was no lipid source × peroxidation level interaction, nor lipid source or peroxidation level effects noted for urinary TBARS and lactulose to mannitol ratio. Compared to pigs fed the control diet, pigs fed diets containing lipids had a lower a lactulose to mannitol ratio (P < 0.01). In conclusion, feeding weaning pigs diets containing 10% thermally-oxidized lipids for 38 d, especially vegetable oils containing high concentration of polyunsaturated fatty acids, appeared to impair oxidative status, but had little influence on gut barrier function or serum immunity parameters.
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    The role of adipose triglyceride lipase in hepatic lipid metabolism, non-alcoholic fatty liver disease and insulin resistance
    (2013-06) Ong, Kuok Teong
    Hepatic triglyceride (TAG) accumulation leads to the development of non-alcoholic fatty liver disease (NAFLD), which is strongly correlated with other metabolic diseases including obesity, insulin resistance and type II diabetes. While the TAG synthetic pathway has been well-researched, our knowledge of the TAG hydrolysis pathway, especially in the liver, is scant. The research project is aimed at understanding the role and mechanisms of hepatic adipose triglyceride lipase (ATGL) and its downstream lipid metabolites in mediating the development of NAFLD and insulin resistance. To elucidate the metabolic functions of hepatic ATGL, we employed adenovirus-mediated knockdown and overexpression in primary hepatocyte cultures and mouse models. We have shown that ATGL is a key TAG hydrolase in the liver that preferentially channels fatty acids (FAs) to mitochondrial β-oxidation, but does not affect VLDL synthesis and secretion. Additionally, ATGL positively regulates PPAR-α and its target gene expression to influence β-oxidation transcriptionally. Liver FA binding protein (LFABP), a major intracellular FA carrier, is not necessary for ATGL-regulated changes in the expression of PPAR-α and its target genes or for the shuttling of hydrolyzed FA to the mitochondria. Moreover, the PPAR-α agonist fenofibrate is unable to normalize the expression of PPAR-α target genes in ATGL knockdown mice, suggesting that ATGL regulates PPAR-α target gene expression in a LFABP- and ligand-independent mechanism. Interestingly, despite enhanced TAG content, mice lacking hepatic ATGL are actually more glucose tolerant without exhibiting impaired insulin signaling. ATGL knockdown also normalizes glucose intolerance in HF diet-induced obese mice. Hepatocytes isolated from mice receiving ATGL knockdown adenovirus display higher glucose oxidation and lower glucose production compared to control cells. Thus, hepatic ATGL knockdown enhances glucose tolerance by increasing hepatic glucose utilization, and uncouples impairments in insulin action from hepatic TAG accumulation. Taken together, hepatic ATGL is a major player in TAG catabolism and FA oxidation. Further investigation is warranted to understand the mechanisms through which ATGL mediates FA oxidation, PPAR-α activity and the uncoupling of hepatic TAG accumulation from impaired insulin signaling and insulin resistance.