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      Feeding Healthy Beagles Medium-Chain Triglycerides, Fish Oil, and Carnitine Offsets Age-Related Changes in Serum Fatty Acids and Carnitine Metabolites

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      PLoS ONE

      Public Library of Science

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          Abstract

          The purpose of this study was to determine if feeding dogs medium-chain triglycerides (MCT), fish oil, and L-carnitine enriched foods offsets age-associated changes in serum fatty acids (FA) and carnitine metabolites. Forty-one healthy Beagles, mean age 9.9 years (range 3.1 to 14.8), were fed control or one of two treatment foods for 6 months. All foods were complete and balanced and met the nutrient requirements for adult dogs, and had similar concentrations of moisture, protein, and fat (approx. 7.4%, 14.0%, and 18.1%, respectively). The treatment diets both contained added L-carnitine (300 mg/kg) and 0.6% (treatment food 1) or 1.5% (treatment food 2) added fish oil. Treatment food 2 also had increased MCT from coconut oil, added corn oil, and reduced animal fat. Composition of serum FA was determined by gas chromatography of FA methyl esters. Metabolomic profiles of serum samples were determined from extracted supernatants that were split and run on GC/MS and LC/MS/MS platforms, for identification and relative quantification of small metabolites. Body composition was determined by dual energy x-ray absorptiometry. Among dog groups, there was no change in total-lean-body weight, or in serum total protein and serum albumin concentrations, based on time or dietary treatment. Serum concentrations of carnitine metabolites were decreased in geriatric (>7 years) vs. mature adult (≤7 years) dogs, and supplementation with L-carnitine attenuated the effects of aging. The ratio of PUFA to SFA was significantly greater in mature dogs at baseline ( P0.05). Serum concentrations of eicosapentaenoic and docosahexaenoic FA increased in a dose-dependent manner. Dogs consuming treatment food 2 also had increased serum concentrations of lauric and myristic FA, and decreased concentrations of SFA, MUFA, and arachidonate (all P≤0.05) and their PUFA to SFA ratio increased. In summary, dietary MCT, fish oil, and L-carnitine counterbalanced the effects of aging on circulating concentrations of these compounds.

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          Most cited references 27

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          Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale.

          The n-6 fatty acid arachidonic acid (AA; 20:4n-6) gives rise to eicosanoid mediators that have established roles in inflammation and AA metabolism is a long recognised target for commonly used anti-inflammatory therapies. It has generally been assumed that all AA-derived eicosanoids are pro-inflammatory. However this is an over-simplification since some actions of eicosanoids are anti-inflammatory (e.g. prostaglandin (PG) E(2) inhibits production of some inflammatory cytokines) and it has been discovered quite recently that PGE(2) inhibits production of inflammatory leukotrienes and induces production of inflammation resolving lipoxin A(4). The n-3 fatty acids from oily fish and "fish oils", eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), are incorporated into inflammatory cell phospholipids in a time- and dose-dependent manner. They are incorporated partly at the expense of AA, but also of other n-6 fatty acids. EPA and DHA inhibit AA metabolism. Thus production of AA-derived eicosanoids is decreased by these n-3 fatty acids; this occurs in a dose-dependent manner. EPA gives rise to an alternative family of eicosanoids (e.g. PGE(3)), which frequently, but not always, have lower potency than those produced from AA. Recently a new family of EPA- and DHA-derived lipid mediators called resolvins (E- and D-series) has been described. These have potent anti-inflammatory and inflammation resolving properties in model systems. It seems likely that these mediators will explain many of the antiinflammatory actions of n-3 fatty acids that have been described. In addition to modifying the profile of lipid-derived mediators, fatty acids can also influence peptide mediator (i.e. cytokine) production. To a certain extent this action may be due to the altered profile of regulatory eicosanoids, but it seems likely that eicosanoid-independent actions are a more important mechanism. Indeed effects on transcription factors that regulate inflammatory gene expression (e.g. nuclear factor kappaB) seem to be important.
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            Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers.

            Persons with high intake of polyunsaturated fatty acids (PUFAs) have lower cardiovascular morbidity and mortality. The protective effect of PUFAs is mediated by multiple mechanisms, including their antiinflammatory properties. The association of physiological PUFA levels with pro- and antiinflammatory markers has not been established. In 1123 persons (aged 20-98 yr), we examined the relationship between relative concentration of fatty acids in fasting plasma and level of inflammatory markers. Adjusting for age, sex, and major confounders, lower arachidonic and docosahexaenoic acids were associated with significantly higher IL-6 and IL-1ra and significantly lower TGFbeta. Lower alpha-linolenic acid was associated with higher C-reactive protein and IL-1ra, and lower eicosapentaenoic acid was associated with higher IL-6 and lower TGFbeta. Lower docosahexaenoic acid was strongly associated with lower IL-10. Total n-3 fatty acids were associated with lower IL-6 (P = 0.005), IL-1ra (P = 0.004), and TNFalpha (P = 0.040) and higher soluble IL-6r (P < 0.001), IL-10 (P = 0.024), and TGFbeta (P = 0.0012). Lower n-6 fatty acid levels were significantly associated with higher IL-1ra (P = 0.026) and lower TGFbeta (P = 0.014). The n-6 to n-3 ratio was a strong, negative correlate of IL-10. Findings were similar in participants free of cardiovascular diseases and after excluding lipids from covariates. In this community-based sample, PUFAs, and especially total n-3 fatty acids, were independently associated with lower levels of proinflammatory markers (IL-6, IL-1ra, TNFalpha, C-reactive protein) and higher levels of antiinflammatory markers (soluble IL-6r, IL-10, TGFbeta) independent of confounders. Our findings support the notion that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation.
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              The role of carnitine in normal and altered fatty acid metabolism.

              Carnitine is a low-molecular-weight compound obtained from the diet that also is biosynthesized from the essential amino acids lysine and methionine. Carnitine has been identified in a variety of mammalian tissues and has an obligate role in the mitochondrial oxidation of long-chain fatty acids through the action of specialized acyltransferases. Other roles for carnitine include buffering of the acyl coenzyme A (CoA)-CoA ratio, branched-chain amino acid metabolism, removal of excess acyl groups, and peroxisomal fatty acid oxidation. The growing body of evidence about carnitine function has led to increased understanding and identification of disorders associated with altered carnitine metabolism. Disorders of fatty acid oxidation and metabolism typically are associated with primary and secondary forms of carnitine deficiency. These disorders, which include increased lipolysis, increased lipid peroxidation, accumulation of acylcarnitines, and altered membrane permeability, have significant consequences for patients with myocardial diseases and kidney failure. Therapeutic administration of carnitine shows promise in treating selected groups of patients who have altered carnitine homeostasis, resulting in improved cardiac function, increased exercise capacity, reduced muscle cramps, and reduced intradialytic complications.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                7 November 2012
                : 7
                : 11
                Affiliations
                [1 ]Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, United States of America
                [2 ]Pet Nutrition Center, Hill’s Pet Nutrition, Inc, Topeka, Kansas, United States of America
                Auburn University, United States of America
                Author notes

                Competing Interests: The authors have read the journal's policy and have the following conflicts: One of the authors (DEJ) has an affiliation to the commercial funders of this research, as an employee of Hill’s Pet Nutrition. The work presented in this study was funded by and performed at the Pet Nutrition Center, Hill’s Pet Nutrition, Inc., Topeka, KS. http://www.hillspet.com/our-company.html. The funding decision makers had no role in study design, data collection and analysis, or preparation of the manuscript. This does not alter the authors‚ adherence to all the PLOS ONE policies on sharing data and materials. Data is freely available upon request.

                Conceived and designed the experiments: JAH DEJ. Performed the experiments: DEJ. Analyzed the data: JAH DEJ. Contributed reagents/materials/analysis tools: DEJ. Wrote the paper: JAH DEJ.

                Article
                PONE-D-12-16219
                10.1371/journal.pone.0049510
                3492282
                23145181

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 12
                Funding
                The work presented in this study was funded by and performed at the Pet Nutrition Center, Hill’s Pet Nutrition, Inc., Topeka, KS. http://www.hillspet.com/our-company.html. The funding decision makers had no role in study design, data collection and analysis, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Clinical Immunology
                Geriatrics
                Nutrition
                Micronutrient Deficiencies
                Veterinary Science
                Animal Management
                Animal Nutrition
                Animal Types
                Small Animals
                Veterinary Medicine
                Small Animal Care
                Veterinary Immunology

                Uncategorized

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