The Journal of nutritional biochemistry
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Whether preformed dietary docosahexaenoic acid (DHA) is required for brain accretion has not been clearly determined. In this study, we investigated in mice the different effects of dietary longer-chain n-3 polyunsaturated fatty acids (PUFAs) and α-linolenic acid (LNA) on brain accretion of DHA and the expression of associated desaturases and transcription factors. C57 BL/6J mice were fed for 3 months with four fish oil n-3 PUFA diets--lower, low, high and higher (0.46%, 0.91%, 1.73% and 4.29% total energy, respectively); a flaxseed oil n-3 PUFA (5.01% total energy) diet; and an n-3 PUFA-deficient diet, respectively. ⋯ Furthermore, the expressions of delta-6 desaturase (D6D) and sterol regulatory element binding protein 1 (SREBP-1) in the liver were down-regulated by all fish oil diets with different amounts of n-3 PUFAs, as well as by the flaxseed oil n-3 PUFA diet, whereas in the brain, D6D, delta-5 desaturase (D5D) and SREBP-1 expressions were down-regulated by the higher fish oil n-3 PUFA diet rather than by other fish oil n-3 PUFA and the flaxseed oil n-3 PUFA diets. These results suggest that preformed dietary DHA, different from those converted by LNA inside the body, is better for brain accretion. Dietary longer-chain n-3 PUFAs affect expressions of D6D, D5D and SREBP-1 in the brain differently from their precursor LNA.
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The heart is unable to synthesize L-carnitine and is strictly dependent on the L-carnitine provided by the blood stream; however, additional studies are needed to better understand the mechanism of L-carnitine supplementation to the heart. The aim of this study was to evaluate the effects of L-carnitine on angiotensin II (Ang II)-induced cardiac fibroblast proliferation and to explore its intracellular mechanism(s). Cultured rat cardiac fibroblasts were pretreated with L-carnitine (1-30 mM) then stimulated with Ang II (100 nM). ⋯ In addition, L-carnitine increased prostacyclin (PGI(2)) generation in cardiac fibroblasts. siRNA transfection of PGI(2) synthase significantly reduced L-carnitine-induced PGI(2) and its anti-proliferation effects on cardiac fibroblasts. Furthermore, blockading potential PGI(2) receptors, including immunoprecipitation (IP) receptors and peroxisome proliferator-activated receptors alpha (PPAR alpha) and delta, revealed that siRNA-mediated blockage of PPAR alpha considerably reduced the anti-proliferation effect of L-carnitine. In summary, these results suggest that L-carnitine attenuates Ang II-induced effects (including NADPH oxidase activation, sphingosine-1-phosphate generation and cell proliferation) in part through PGI(2) and PPAR alpha-signaling pathways.
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Comparative Study
Alpha-, gamma- and delta-tocopherols reduce inflammatory angiogenesis in human microvascular endothelial cells.
Vitamin E, a micronutrient (comprising alpha-, beta-, gamma- and delta-tocopherols, alpha-, beta-, gamma- and delta-tocotrienols), has documented antioxidant and non-antioxidant effects, some of which inhibit inflammation and angiogenesis. We compared the abilities of alpha-, gamma- and delta-tocopherols to regulate human blood cytotoxicity (BEC) and lymphatic endothelial cytotoxicity (LEC), proliferation, invasiveness, permeability, capillary formation and suppression of TNF-alpha-induced VCAM-1 as in vitro models of inflammatory angiogenesis. alpha-, gamma- and delta-tocopherols were not toxic to either cell type up to 40 microM. In BEC, confluent cell density was decreased by all concentrations of delta- and gamma-tocopherol (10-40 microM) but not by alpha-tocopherol. ⋯ In LEC, there was no significant change to TNF-alpha-induced VCAM-1 expression with any concentration of alpha-, gamma- or delta-tocopherol. These data demonstrate that physiological levels (0-40 microM) of alpha-, gamma- and delta-tocopherols are nontoxic and dietary tocopherols, especially delta-tocopherol, can limit several BEC and LEC endothelial behaviors associated with angiogenesis. Tocopherols may therefore represent important nutrient-signals that limit cell behaviors related to inflammation/angiogenesis, which when deficient, may predispose individuals to risks associated with elevated angiogenesis such as inflammation and cancer; further differences seen from the tocopherols may be due to their blood or lymphatic cell origin.
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Overweight and obesity are associated with low grade of inflammation and chronic inflammatory response characterized by abnormal production and activation of some pro-inflammatory signalling pathways. Taking into account that obesity is the direct result of an imbalance between energy intake and energy expenditure, the nutritional factors in the diet, with particular focus on zinc, may play a pivotal role in the development of obesity-associated comorbidities. Considering the potential interactions among zinc nutritional status, inflammation, overweight/obesity and insulin secretion, the aim of the present work was to clarify the influence of zinc dietary intake on some metabolic, inflammatory and zinc status parameters in adult overweight/obese subjects. ⋯ In particular, subjects with a lower zinc dietary intake display a deeper inflammatory status, general impairment of the zinc status, an altered lipid profile and increased insulin production with respect to obese subjects with normal zinc dietary intake. Moreover, in the presence of low dietary zinc intake, the obese subjects are less capable to respond to oxidative stress and to inflammation leading to the development of obesity or to a worsening of already preexisting obesity status. In conclusion, a possible zinc supplementation in obese subjects with a deeper inflammatory status and more altered zinc profile may be suggested in order to limit or reduce the inflammation, taking also into account that zinc supplementation normalizes "inflammaging" as well as zinc profile leading to a correct intra- and extracellular zinc homeostasis.
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Phosphorylated glucosamine (glucosamine-6-phosphate, PGlc) was synthesized using methanesulfonic acid, phosphorus pentoxide (P(2)O(5)), NH(2)NH(2) and DMF. Its inhibitory effect on lipid accumulation in cultured 3T3-L1 adipocytes was investigated by measuring triglyceride contents and Oil Red O staining. In order to understand the mechanism by which lipid accumulation in adipocytes is decreased by PGlc, we examined the expression levels of several genes and proteins associated with adipogenesis and lipolysis using reverse transcription polymerase chain reaction, real-time polymerase chain reaction and Western blot analysis. ⋯ Moreover, treatment with PGlc during adipocyte differentiation induced significant up-regulation of preadipocyte factor 1 mRNA and down-regulation of such adipocyte-specific gene promoters as adipocyte fatty acid binding protein, fatty acid synthase, lipoprotein lipase and leptin. According to the lipolytic response, PGlc up-regulated hormone-sensitive lipase mRNA expression and suppressed the expression levels of tumor necrosis factor-alpha mRNA compared with fully differentiated adipose tissue. These results suggest that the inhibitory effect of PGlc on adipocyte differentiation might be mediated through the down-regulation of adipogenic transcription factors, such as peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein 1 and CCAAT/enhancer binding protein-alpha, which are related to the downstream adipocyte-specific gene promoters.