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Sample records for photoaging alter fatty

  1. Skin aging and photoaging alter fatty acids composition, including 11,14,17-eicosatrienoic acid, in the epidermis of human skin.

    PubMed

    Kim, Eun Ju; Kim, Min-Kyoung; Jin, Xing-Ji; Oh, Jang-Hee; Kim, Ji Eun; Chung, Jin Ho

    2010-06-01

    We investigated the alterations of major fatty acid components in epidermis by natural aging and photoaging processes, and by acute ultraviolet (UV) irradiation in human skin. Interestingly, we found that 11,14,17-eicosatrienoic acid (ETA), which is one of the omega-3 polyunsaturated acids, was significantly increased in photoaged human epidermis in vivo and also in the acutely UV-irradiated human skin in vivo, while it was significantly decreased in intrinsically aged human epidermis. The increased ETA content in the epidermis of photoaged human skin and acute UV-irradiated human skin is associated with enhanced expression of human elongase 1 and calcium-independent phosphodiesterase A(2). We demonstrated that ETA inhibited matrix metalloproteinase (MMP)-1 expression after UV-irradiation, and that inhibition of ETA synthesis using EPTC and NA-TCA, which are elongase inhibitors, increased MMP-1 expression. Therefore, our results suggest that the UV increases the ETA levels, which may have a photoprotective effect in the human skin. PMID:20514327

  2. Skin Aging and Photoaging Alter Fatty Acids Composition, Including 11,14,17-eicosatrienoic Acid, in the Epidermis of Human Skin

    PubMed Central

    Kim, Eun Ju; Kim, Min-Kyoung; Jin, Xing-Ji; Oh, Jang-Hee; Kim, Ji Eun

    2010-01-01

    We investigated the alterations of major fatty acid components in epidermis by natural aging and photoaging processes, and by acute ultraviolet (UV) irradiation in human skin. Interestingly, we found that 11,14,17-eicosatrienoic acid (ETA), which is one of the omega-3 polyunsaturated acids, was significantly increased in photoaged human epidermis in vivo and also in the acutely UV-irradiated human skin in vivo, while it was significantly decreased in intrinsically aged human epidermis. The increased ETA content in the epidermis of photoaged human skin and acute UV-irradiated human skin is associated with enhanced expression of human elongase 1 and calcium-independent phophodiesterase A2. We demonstrated that ETA inhibited matrix metalloproteinase (MMP)-1 expression after UV-irradiation, and that inhibition of ETA synthesis using EPTC and NA-TCA, which are elongase inhibitors, increased MMP-1 expression. Therefore, our results suggest that the UV increases the ETA levels, which may have a photoprotective effect in the human skin. PMID:20514327

  3. Dietary Monounsaturated Fatty Acids Intake and Risk of Skin Photoaging

    PubMed Central

    Latreille, Julie; Kesse-Guyot, Emmanuelle; Malvy, Denis; Andreeva, Valentina; Galan, Pilar; Tschachler, Erwin; Hercberg, Serge; Guinot, Christiane; Ezzedine, Khaled

    2012-01-01

    Background Intake of monounsaturated fatty acids has been reported to reduce oxidative stress, insulin resistance and related inflammatory processes and may thus protect from skin photoaging. The objective of this study was to investigate the association between the risk of photoaging, monounsaturated fatty acids intake and the sources of monounsaturated fatty acids. Methodology/Principal Findings A cross sectional study was conducted within the framework of the SUVIMAX cohort. The survey included 1264 women and 1655 men aged between 45 and 60 years old. Dietary monounsaturated fatty acids intakes were estimated by dietary source through at least ten 24-h diet records completed during the first 2.5 years of the follow-up period. Severity of facial skin photoaging was graded by trained investigators at baseline during a clinical examination using a 6-grade scale illustrated by photographs. A lower risk of severe photoaging was associated with higher intakes of monounsaturated fatty acids from olive oil in both sexes. Strikingly, no association was found with intake of monounsaturated fatty acids from animal sources whether from dairy products, meat or processed meat. Conclusion/Significance These findings support the beneficial effect of dietary olive oil or healthy diet habits associated with olive oil consumption on the severity of facial photoaging. PMID:22970231

  4. Mechanisms and treatments of photoaging.

    PubMed

    Poon, Flora; Kang, Sewon; Chien, Anna L

    2015-03-01

    Photoaging is frequently encountered in a dermatologic practice. This systematic literature review aims to explore the etiology of photoaging and address the evidence behind its current management. A comprehensive search of MEDLINE, EMBASE, UpToDate, and the Cochrane Library was conducted. Articles were limited to those relating to photoaging. There are two major approaches in the current management of photoaging. This includes strategies to prevent against ultraviolet damage (e.g. sunscreen) and medications that attempt to reverse existing skin damage (topical retinoids and 5-fluorouracil). There has been a large growth in the variety of treatment options in recent years. While it is important for such growth to continue, prevention via sensible photoprotection methods still remains the best current management option. PMID:25351668

  5. [Photodamage and photoaging--prevention and treatment].

    PubMed

    Grether-Beck, Susanne; Wlaschek, Meinhard; Krutmann, Jean; Scharffetter-Kochanek, Karin

    2005-09-01

    The exposure of human skin to environmental and artificial ultraviolet irradiation has increased significantly. This is not only due to an increased solar UV irradiation as a consequence of the stratospheric ozone depletion, but also the result of an inappropriate social behaviour with the use of tanning parlors being very popular. Besides this, leisure activities and living style with travelling to equatorial regions also add to the individual annual UV load. Since the population in industrialised countries shows an increasing total life span, in parallel the cumulative life time dose of solar and artificial UV-irradiation is dramatically augmented. In addition to the common longterm detrimental effects like immunosuppression and skin cancer, the photooxidative damage due to energy absorption of UV photons in an oxygenized environment leads to alterations of cells, subcellular compartments and macromolecules. The clinical manifestations of UV/ROS induced disturbances result in photoaged skin with wrinkle formation, laxity, leathery appearance as well as fragility, impaired wound healing and higher vulnerability. Strategies to prevent or to minimize photoaging and intrinsic aging of the skin necessarily include protection against UV irradiation and antioxidant homoeostasis. New developments of therapeutic interventions including DNA repair enzymes will be discussed. PMID:16117739

  6. Drug metabolism alterations in nonalcoholic fatty liver disease

    PubMed Central

    Merrell, Matthew D.; Cherrington, Nathan J.

    2013-01-01

    Drug-metabolizing enzymes play a vital role in the elimination of the majority of therapeutic drugs. The major organ involved in drug metabolism is the liver. Chronic liver diseases have been identified as a potential source of significant interindividual variation in metabolism. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting between 60 and 90 million Americans, yet the vast majority of NAFLD patients are undiagnosed. NAFLD encompasses a spectrum of pathologies, ranging from steatosis to nonalcoholic steatohepatitis and fibrosis. Numerous animal studies have investigated the effects of NAFLD on hepatic gene expression, observing significant alterations in mRNA, protein, and activity levels. Information on the effects of NAFLD in human patients is limited, though several significant investigations have recently been published. Significant alterations in the activity of drug-metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions. With the enormous prevalence of NAFLD, it is conceivable that every drug currently on the market is being given to patients with NAFLD. The current review is intended to present the results from both animal models and human patients, summarizing the observed alterations in the expression and activity of the phase I and II drug-metabolizing enzymes. PMID:21612324

  7. New insights in photoaging, UVA induced damage and skin types.

    PubMed

    Battie, Claire; Jitsukawa, Setsuko; Bernerd, Françoise; Del Bino, Sandra; Marionnet, Claire; Verschoore, Michèle

    2014-10-01

    UVA radiation is the most prevalent component of solar UV radiation; it deeply penetrates into the skin and induces profound alterations of the dermal connective tissue. In recent years, the detrimental effects of UVA radiation were more precisely demonstrated at cellular and molecular levels, using adequate methods to identify biological targets of UVA radiation and the resulting cascade impairment of cell functions and tissue degradation. In particular gene expression studies recently revealed that UVA radiation induces modulation of several genes confirming the high sensitivity of dermal fibroblasts to UVA radiation. The major visible damaging effects of UVA radiation only appear after years of exposure: it has been clearly evidenced that they are responsible for more or less early signs of photoageing and photocarcinogenesis. UVA radiation appears to play a key role in pigmented changes occurring with age, the major sign of skin photoaging in Asians. Skin susceptibility to photoaging alterations also depends on constitutive pigmentation. The skin sensitivity to UV light has been demonstrated to be linked to skin color type. PMID:25234829

  8. URBANIZATION ALTERS FATTY ACID CONCENTRATIONS OF STREAM FOOD WEBS IN THE NARRAGANSETT BAY WATERSHED

    EPA Science Inventory

    Urbanization and associated human activities negatively affect stream algal and invertebrate assemblages, likely altering food webs. Our goal was to determine if urbanization affects food web essential fatty acids (EFAs) and if EFAs could be useful ecological indicators in monito...

  9. Non-alcoholic fatty liver disease in HIV infection associated with altered hepatic fatty acid composition.

    PubMed

    Arendt, Bianca M; Mohammed, Saira S; Ma, David W L; Aghdassi, Elaheh; Salit, Irving E; Wong, David K H; Guindi, Maha; Sherman, Morris; Heathcote, E Jenny; Allard, Johane P

    2011-03-01

    Hepatic fatty acid (FA) composition, especially a reduction in n-3 polyunsaturated FA (PUFA) may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is common in HIV-infection.. In a cross-sectional study we compared hepatic FA composition between 20 HIV-infected men with NAFLD (HIV/NAFLD), 21 HIV-negative men with NAFLD (NAFLD), and 7 healthy controls. Within HIV/NAFLD we compared simple steatosis (HIV/SS) to steatohepatitis (HIV/NASH). FA composition in liver and erythrocytes, oxidative stress, diet, and exercise were assessed. Major findings (P<0.05) were: 1) higher hepatic n-6/n-3 ratio in HIV/NAFLD [median (range)] [8.08 (1.08-21.52)] compared to controls [5.83 (3.58-6.93)] and NAFLD [5.97 (1.46-10.40)], with higher n-6 PUFA in HIV/NAFLD compared to NAFLD; 2) lower n-3 PUFA in erythrocytes (mol%), a marker for dietary intake, in HIV/NAFLD [5.26 (1.04-11.75)] compared to controls [8.92 (4.79-12.67)]; 3) the ratios of long-chain PUFA products to essential FA precursors of the n-6 and n-3 series were lower in HIV/NAFLD and NAFLD compared to controls. In contrast, the ratio of oleic/stearic acid was higher in HIV/NAFLD compared to the other groups. These ratios are indirect markers of enzymatic FA desaturation and elongation. Hepatic PUFA, especially biologically active long-chain PUFA, were also lower in HIV/NASH compared to HIV/SS. Oxidative stress was not different among the groups. We conclude that HIV/NAFLD is associated with altered hepatic FA composition. Changes may be due to impaired FA metabolism or suboptimal n-3 PUFA intake. The potential role of n-3 PUFA (e.g. fish oil) to treat or prevent HIV/NAFLD warrants further investigation. PMID:21434863

  10. Beneficial effects of kinin B1 receptor antagonism on plasma fatty acid alterations and obesity in Zucker diabetic fatty rats.

    PubMed

    Talbot, Sébastien; Dias, Jenny Pena; El Midaoui, Adil; Couture, Réjean

    2016-07-01

    Kinins are the endogenous ligands of the constitutive B2 receptor (B2R) and the inducible B1 receptor (B1R). Whereas B2R prevents insulin resistance, B1R is involved in insulin resistance and metabolic syndrome. However, the contribution of B1R in type 2 diabetes associated with obesity remains uncertain. The aim of the present study was to examine the impact of 1-week treatment with a selective B1R antagonist (SSR240612, 10 mg/kg per day, by gavage) on hyperglycemia, hyperinsulinemia, leptinemia, body mass gain, and abnormal plasma fatty acids in obese Zucker diabetic fatty (ZDF) rats. Treatment with SSR240612 abolished the body mass gain and reduced polyphagia, polydipsia, and plasma fatty acid alterations in ZDF rats without affecting hyperglycemia, hyperinsulinemia, and hyperleptinemia. The present study suggests that the upregulated B1R plays a role in body mass gain and circulating fatty acid alterations in ZDF rats. However, mechanisms other than B1R induction would be implicated in glucose metabolism disorder in ZDF rats, based on the finding that SSR240612 did not reverse hyperglycemia and hyperinsulinemia. PMID:27172260

  11. TELOMERE AND TELOMERASE MODULATION BY BERGAMOT POLYPHENOLIC FRACTION IN EXPERIMENTAL PHOTOAGEING IN HUMAN KERATINOCYTES.

    PubMed

    Nisticò, S; Ehrlich, J; Gliozzi, M; Maiuolo, J; Del Duca, E; Muscoli, C; Mollace, V

    2015-01-01

    Photoageing represents the addition of extrinsic chronic ultraviolet radiation-induced damage on intrinsic ageing and accounts for most age-associated changes in skin appearance. In this study, we evaluated the effect of 38% BPF, a highly concentrated extract of the bergamot fruit (Citrus bergamia) on UVB-induced photoageing by examining inflammatory cytokine expression, telomere length/telomerase alterations and cellular viability in human immortalized HaCaT keratinocytes. Our results suggest that 38% BPF protects HaCaT cells against UVB-induced oxidative stress and markers of photoageing in a dose-dependent manner and could be a useful supplement in skin care products. Together with antioxidant properties, BPF, a highly concentrated extract of the bergamot fruit, appears to modulate basic cellular signal transduction pathways leading to anti-proliferative, anti-aging and immune modulating responses. PMID:26403416

  12. Isolation of Arabidopsis mutants with altered seed fatty acid composition

    SciTech Connect

    Lemieux, B.; Browse, J.; Somerville, C. Washington State Univ., Pullman )

    1989-04-01

    By direct screening of Arabidopsis seed fatty acid methyl esters, we have isolated mutants which are deficient in the elongation of 18:1 to 20:1 and the desaturation of 18:2 to 18:3. Both the elongation and the desaturation mutants, designated MB14 and BL1 respectively, have only 10% of the wild-type levels of 20:1 and 18:3 in their seeds. The intermediate levels of 20:1 and 18:3 in F1 seeds of crosses to the wild type indicate that the level of enzyme is regulating the amount of 20:1 and 18:3 in seeds. Consistent with this observation, the mutations were found to segregate 1:2:1 in F2 seeds. We have found that the 18:2 desaturase mutation is clearly expressed in root phosphatidylcholine.

  13. Skin cancer and photoaging in ethnic skin.

    PubMed

    Halder, Rebat M; Ara, Collette J

    2003-10-01

    Skin cancer prevalence in ethnic skin is low. Squamous cell carcinoma, hypopigmented mycosis fungoides, and acral lentiginous melanoma are the most serious types of skin cancer noted in the darker-skinned population. Photoaging occurs less frequently and is less severe in ethnic skin. PMID:14717413

  14. Oral administration of Lactobacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging.

    PubMed

    Kim, Hyun Mee; Lee, Dong Eun; Park, Soo Dong; Kim, Yong-Tae; Kim, Yu Jin; Jeong, Ji Woong; Jang, Sung Sik; Ahn, Young-Tae; Sim, Jae-Hun; Huh, Chul-Sung; Chung, Dae Kyun; Lee, Jung-Hee

    2014-11-28

    Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage, including photoaging. In recent years, probiotics have gained interest due to their beneficial effects on skin health, such as inhibiting atopic dermatitis and improving skin immunity or inflammation. However, little is known about the effects of probiotics on UVBinduced photoaging. In this study, we evaluated the effect of Lactobacillus plantarum HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless mice. The results showed that L. plantarum HY7714 treatment effectively rescued UVB-reduced procollagen expression through the inhibition of UVB-induced matrix metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited the number, depth, and area of wrinkles in hairless mouse skin. Histological data showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal thickness in mice. Western blot and zymography data also revealed that L. plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9 activities in dermal tissue. Collectively, these results provide further insight regarding the skin biological actions of L. plantarum HY7714, a potential skin anti-photoaging agent. PMID:25112318

  15. Fatty acid ethanolamide levels are altered in borderline personality and complex posttraumatic stress disorders.

    PubMed

    Schaefer, Carola; Enning, Frank; Mueller, Juliane K; Bumb, J Malte; Rohleder, Cathrin; Odorfer, Thorsten M; Klosterkötter, Joachim; Hellmich, Martin; Koethe, Dagmar; Schmahl, Christian; Bohus, Martin; Leweke, F Markus

    2014-08-01

    Borderline personality (BPD) and complex posttraumatic stress disorders (PTSD) are both powerfully associated with the experience of interpersonal violence during childhood and adolescence. The disorders frequently co-occur and often result in pervasive problems in, e.g., emotion regulation and altered pain perception, where the endocannabinoid system is deeply involved. We hypothesize an endocannabinoid role in both disorders. We investigated serum levels of the endocannabinoids anandamide and 2-arachidonoylglycerol and related fatty acid ethanolamides (FAEs) in BPD, PTSD, and controls. Significant alterations were found for both endocannabinoids in BPD and for the FAE oleoylethanolamide in PTSD suggesting a respective link to both disorders. PMID:24253425

  16. Altered erythrocyte membrane fatty acid profile in typical Rett syndrome: effects of omega-3 polyunsaturated fatty acid supplementation.

    PubMed

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia; Durand, Thierry; Galano, Jean-Marie; Cortelazzo, Alessio; Zollo, Gloria; Guerranti, Roberto; Gonnelli, Stefano; Caffarelli, Carla; Rossi, Marcello; Pecorelli, Alessandra; Valacchi, Giuseppe; Ciccoli, Lucia; Hayek, Joussef

    2014-11-01

    This study mainly aims at examining the erythrocyte membrane fatty acid (FAs) profile in Rett syndrome (RTT), a genetically determined neurodevelopmental disease. Early reports suggest a beneficial effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on disease severity in RTT. A total of 24 RTT patients were assigned to ω-3 PUFAs-containing fish oil for 12 months in a randomized controlled study (average DHA and EPA doses of 72.9, and 117.1mg/kgb.w./day, respectively). A distinctly altered FAs profile was detectable in RTT, with deficient ω-6 PUFAs, increased saturated FAs and reduced trans 20:4 FAs. FAs changes were found to be related to redox imbalance, subclinical inflammation, and decreased bone density. Supplementation with ω-3 PUFAs led to improved ω-6/ω-3 ratio and serum plasma lipid profile, decreased PUFAs peroxidation end-products, normalization of biochemical markers of inflammation, and reduction of bone hypodensity as compared to the untreated RTT group. Our data indicate that a significant FAs abnormality is detectable in the RTT erythrocyte membranes and is partially rescued by ω-3 PUFAs. PMID:25240461

  17. Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway.

    PubMed

    Prasanth, Mani Iyer; Santoshram, Gunasekaran Santhi; Bhaskar, James Prabhanand; Balamurugan, Krishnaswamy

    2016-02-01

    Ultraviolet radiations (UV) are the primary causative agent for skin aging (photoaging) and cancer, especially UV-A. The mode of action and the molecular mechanism behind the damages caused by UV-A is not well studied, in vivo. The current study was employed to investigate the impact of UV-A exposure using the model organism, Caenorhabditis elegans. Analysis of lifespan, healthspan, and other cognitive behaviors were done which was supported by the molecular mechanism. UV-A exposure on collagen damages the synthesis and functioning which has been monitored kinetically using engineered strain, col-19:: GFP. The study results suggested that UV-A accelerated the aging process in an insulin-like signaling pathway dependent manner. Mutant (daf-2)-based analysis concrete the observations of the current study. The UV-A exposure affected the usual behavior of the worms like pharyngeal movements and brood size. Quantitative PCR profile of the candidate genes during UV-A exposure suggested that continuous exposure has damaged the neural network of the worms, but the mitochondrial signaling and dietary restriction pathway remain unaffected. Western blot analysis of HSF-1 evidenced the alteration in protein homeostasis in UV-A exposed worms. Outcome of the current study supports our view that C. elegans can be used as a model to study photoaging, and the mode of action of UV-A-mediated damages can be elucidated which will pave the way for drug developments against photoaging. PMID:26873884

  18. A randomized and controlled trial about the use of oral isotretinoin for photoaging.

    PubMed

    Bagatin, Ediléia; Parada, Meire O B; Miot, Hélio A; Hassun, Karime M; Michalany, Nilceo; Talarico, Sergio

    2010-02-01

    Topical retinoids are used to treat photoaging; oral isotretinoin is gold standard for acne; "off label" indications, including photoaging, have been reported with insufficient evidence of efficacy. This is a randomized controlled phase II trial with clinical and histological assessment to evaluate efficacy and safety of oral isotretinoin for photoaging. Study population was comprised of 32 menopausal or sterilized women, aged 40-55, divided in 2 groups: A (21) received 20mg isotretinoin, 3 times per week, nightly moisturizer, and daily sunscreen, for three months; B (11) just moisturizer/sunscreen. Main outcome measures were: overall clinical assessment; profilometry, corneometer and elasticity tests in periocular regions and left forearm; before/after biopsies from left forearm in patients of B and in 10 randomly selected of A. Microscopic blinded evaluation of epidermal thickness, dermal elastosis, new collagen, p53 epidermal expression was performed by quantitative digital image analysis. All data were submitted to statistical analysis. Clinical evaluation showed slight improvement; profilometry, corneometer and skin elasticity tests presented significant difference in pre/post values (P = 0.001 to 0.028), but no differences between A/B. Histological findings and p53 expression were comparable between groups before treatment (P > 0.1); microscopic analysis showed no differences between groups for most variables, after treatment. Slight but significant difference between A/B for p53 with major reduction post isotretinoin [0.66+/-0.31 vs. 0.94+/-0.34 respectively (P = 0.04) was observed. There were minor side effects and no significant laboratory test alterations. We concluded that no significant clinical, microscopic changes but p53 epidermal expression reduction were observed. The role of ultra-violet induced p53 mutation in skin carcinogenesis reinforces retinoids chemoprevention. Oral isotretinoin seemed safe but not effective to treat photoaging. Caution

  19. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    SciTech Connect

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  20. The Methoxyflavonoid Isosakuranetin Suppresses UV-B-Induced Matrix Metalloproteinase-1 Expression and Collagen Degradation Relevant for Skin Photoaging.

    PubMed

    Jung, Hana; Lee, Eunjoo H; Lee, Tae Hoon; Cho, Man-Ho

    2016-01-01

    Solar ultraviolet (UV) radiation is a main extrinsic factor for skin aging. Chronic exposure of the skin to UV radiation causes the induction of matrix metalloproteinases (MMPs), such as MMP-1, and consequently results in alterations of the extracellular matrix (ECM) and skin photoaging. Flavonoids are considered as potent anti-photoaging agents due to their UV-absorbing and antioxidant properties and inhibitory activity against UV-mediated MMP induction. To identify anti-photoaging agents, in the present study we examined the preventative effect of methoxyflavonoids, such as sakuranetin, isosakuranetin, homoeriodictyol, genkwanin, chrysoeriol and syringetin, on UV-B-induced skin photo-damage. Of the examined methoxyflavonoids, pretreatment with isosakuranetin strongly suppressed the UV-B-mediated induction of MMP-1 in human keratinocytes in a concentration-dependent manner. Isosakuranetin inhibited UV-B-induced phosphorylation of mitogen-activated protein kinase (MAPK) signaling components, ERK1/2, JNK1/2 and p38 proteins. This result suggests that the ERK1/2 kinase pathways likely contribute to the inhibitory effects of isosakuranetin on UV-induced MMP-1 production in human keratinocytes. Isosakuranetin also prevented UV-B-induced degradation of type-1 collagen in human dermal fibroblast cells. Taken together, our findings suggest that isosakuranetin has the potential for development as a protective agent for skin photoaging through the inhibition of UV-induced MMP-1 production and collagen degradation. PMID:27598131

  1. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease.

    PubMed

    Lake, April D; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D; Lu, Zhenqiang; Lehman-McKeeman, Lois D; Cherrington, Nathan J

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the 'classical' (neutral) and 'alternative' (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. PMID:23391614

  2. Effects of Alterations of Plasma Free Fatty Acid Levels on Pancreatic Glucagon Secretion in Man

    PubMed Central

    Gerich, John E.; Langlois, Maurice; Schneider, Victor; Karam, John H.; Noacco, Claudio

    1974-01-01

    The present investigation was undertaken to ascertain whether alterations in plasma free fatty acids (FFA) affect pancreatic glucagon secretion in man since FFA have been reported to influence pancreatic alpha cell function in other species. Elevation of plasma FFA from a mean (±SE) basal level of 0.478±0.036 mM to 0.712±0.055 mM after heparin administration caused plasma glucagon levels to fall approximately 50%, from a basal value of 122±15 pg/ml to 59±14 pg/ml (P < 0.001). Lowering of plasma FFA from a basal level of 0.520±0.046 mM to 0.252±0.041 mM after nicotinic acid administration raised plasma glucagon from a basal level of 113±18 pg/ml to 168±12 pg/ml (P < 0.005). Infusion of glucose elevated plasma glucose levels to the same degree that heparin raised plasma FFA levels. This resulted in suppression of plasma glucagon despite the fact that plasma FFA levels also were suppressed. Glucagon responses to arginine were diminished after elevation of plasma FFA (P < 0.01) and during infusion of glucose (P < 0.01). Diminution of plasma FFA by nicotinic acid did not augment glucagon responses to arginine. These results thus demonstrate that rather small alterations in plasma FFA within the physiologic range have a significant effect on glucagon secretion in man. Although the effects of glucose appear to predominate over those of FFA, alterations in plasma FFA may nevertheless exert an important physiologic influence over human pancreatic alpha cell function, especially in the postabsorptive state. PMID:4825225

  3. Key Regulatory Role of Dermal Fibroblasts in Pigmentation as Demonstrated Using a Reconstructed Skin Model: Impact of Photo-Aging

    PubMed Central

    Duval, Christine; Cohen, Catherine; Chagnoleau, Corinne; Flouret, Virginie; Bourreau, Emilie; Bernerd, Françoise

    2014-01-01

    To study cutaneous pigmentation in a physiological context, we have previously developed a functional pigmented reconstructed skin model composed of a melanocyte-containing epidermis grown on a dermal equivalent comprising living fibroblasts. The present studies, using the same model, aimed to demonstrate that dermal fibroblasts influence skin pigmentation up to the macroscopic level. The proof of principle was performed with pigmented skins differing only in the fibroblast component. First, the in vitro system was reconstructed with or without fibroblasts in order to test the global influence of the presence of this cell type. We then assessed the impact of the origin of the fibroblast strain on the degree of pigmentation using fetal versus adult fibroblasts. In both experiments, impressive variation in skin pigmentation at the macroscopic level was observed and confirmed by quantitative parameters related to skin color, melanin content and melanocyte numbers. These data confirmed the responsiveness of the model and demonstrated that dermal fibroblasts do indeed impact the degree of skin pigmentation. We then hypothesized that a physiological state associated with pigmentary alterations such as photo-aging could be linked to dermal fibroblasts modifications that accumulate over time. Pigmentation of skin reconstructed using young unexposed fibroblasts (n = 3) was compared to that of tissues containing natural photo-aged fibroblasts (n = 3) which express a senescent phenotype. A stimulation of pigmentation in the presence of the natural photo-aged fibroblasts was revealed by a significant increase in the skin color (decrease in Luminance) and an increase in both epidermal melanin content and melanogenic gene expression, thus confirming our hypothesis. Altogether, these data demonstrate that the level of pigmentation of the skin model is influenced by dermal fibroblasts and that natural photo-aged fibroblasts can contribute to the hyperpigmentation that is

  4. Key regulatory role of dermal fibroblasts in pigmentation as demonstrated using a reconstructed skin model: impact of photo-aging.

    PubMed

    Duval, Christine; Cohen, Catherine; Chagnoleau, Corinne; Flouret, Virginie; Bourreau, Emilie; Bernerd, Françoise

    2014-01-01

    To study cutaneous pigmentation in a physiological context, we have previously developed a functional pigmented reconstructed skin model composed of a melanocyte-containing epidermis grown on a dermal equivalent comprising living fibroblasts. The present studies, using the same model, aimed to demonstrate that dermal fibroblasts influence skin pigmentation up to the macroscopic level. The proof of principle was performed with pigmented skins differing only in the fibroblast component. First, the in vitro system was reconstructed with or without fibroblasts in order to test the global influence of the presence of this cell type. We then assessed the impact of the origin of the fibroblast strain on the degree of pigmentation using fetal versus adult fibroblasts. In both experiments, impressive variation in skin pigmentation at the macroscopic level was observed and confirmed by quantitative parameters related to skin color, melanin content and melanocyte numbers. These data confirmed the responsiveness of the model and demonstrated that dermal fibroblasts do indeed impact the degree of skin pigmentation. We then hypothesized that a physiological state associated with pigmentary alterations such as photo-aging could be linked to dermal fibroblasts modifications that accumulate over time. Pigmentation of skin reconstructed using young unexposed fibroblasts (n = 3) was compared to that of tissues containing natural photo-aged fibroblasts (n = 3) which express a senescent phenotype. A stimulation of pigmentation in the presence of the natural photo-aged fibroblasts was revealed by a significant increase in the skin color (decrease in Luminance) and an increase in both epidermal melanin content and melanogenic gene expression, thus confirming our hypothesis. Altogether, these data demonstrate that the level of pigmentation of the skin model is influenced by dermal fibroblasts and that natural photo-aged fibroblasts can contribute to the hyperpigmentation that is

  5. Ingestion of a single serving of saury alters postprandial levels of plasma n-3 polyunsaturated fatty acids and long-chain monounsaturated fatty acids in healthy human adults

    PubMed Central

    2012-01-01

    Background Saury oil contains considerable amounts of n-3 polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) with long aliphatic tails (>18C atoms). Ingestion of saury oil reduces the risk of developing metabolic syndrome concomitant with increases in n-3 PUFA and long-chain MUFA in plasma and organs of mice. We therefore evaluated changes in postprandial plasma fatty acid levels and plasma parameters in healthy human subjects after ingestion of a single meal of saury. Findings Five healthy human adults ingested 150 g of grilled saury. Blood was collected before the meal and at 2, 6, and 24 hr after the meal, and plasma was prepared. Plasma levels of eicosapentaenoic acid, docosahexaenoic acid, and long-chain MUFA (C20:1 and C22:1 isomers combined) increased significantly throughout the postprandial period compared with the pre-meal baseline. Postprandial plasma insulin concentration increased notably, and plasma levels of glucose and free fatty acids decreased significantly and subsequently returned to the pre-meal levels. Conclusions Our study suggests that a single saury meal may alter the postprandial plasma levels of n-3 PUFA and long-chain MUFA in healthy human subjects. PMID:22846384

  6. Camelina meal increases egg n-3 fatty acid content without altering quality or production in laying hens.

    PubMed

    Kakani, Radhika; Fowler, Justin; Haq, Akram-Ul; Murphy, Eric J; Rosenberger, Thad A; Berhow, Mark; Bailey, Christopher A

    2012-05-01

    Camelina sativa is an oilseed plant rich in n-3 and n-6 fatty acids and extruding the seeds results in high protein meal (*40%) containing high levels of n-3 fatty acids. In this study, we examined the effects of feeding extruded defatted camelina meal to commercial laying hens, measuring egg production, quality, and fatty acid composition. Lohmann White Leghorn hens (29 weeks old) were randomly allocated to three dietary treatment groups (n = 25 per group) and data was collected over a 12 week production period. All the treatment groups were fed a corn soy based experimental diet containing 0% (control), 5, or 10% extruded camelina meal. We found no significant differences in percent hen-day egg production and feed consumed per dozen eggs. Egg shell strength was significantly higher in both camelina groups compared to the controls. Egg total n-3 fatty acid content increased 1.9- and 2.7-fold in 5 and 10% camelina groups respectively relative to the control. A similar increase in DHA content also occurred. Further camelina meal did not alter glucosinolate levels and no detectable glucosinolates or metabolic product isothiocyanates were found in the eggs from either the 5 or 10% camelina groups. These results indicate that camelina meal is a viable dietary source of n-3 fatty acids for poultry and its dietary inclusion results in eggs enriched with n-3 fatty acids. PMID:22302480

  7. Lipid Sources with Different Fatty Acid Profile Alters the Fatty Acid Profile and Quality of Beef from Confined Nellore Steers

    PubMed Central

    Fiorentini, Giovani; Lage, Josiane F.; Carvalho, Isabela P. C.; Messana, Juliana D.; Canesin, Roberta. C.; Reis, Ricardo A.; Berchielli, Telma T.

    2015-01-01

    The present study was conducted to determine the effects of lipid sources with different fatty acids profile on meat fatty acids profile and beef quality traits of Nellore. A total of 45 Nellore animals with an average initial body weight of 419±11 kg (at 15±2 mo) were distributed in a completely randomized design consisting of 5 treatments and 9 replicates. The roughage feed was maize silage (600 g/kg on a dry matter [DM] basis) plus concentrate (400 g/kg on a DM basis). The dietary treatments were as follows: without fat (WF), palm oil (PO), linseed oil (LO), protected fat (PF), and soybean grains (SG). No effects of lipid sources were observed (p>0.05) on beef color, pH, water-holding capacity, and sarcomere length. Beef from cattle fed PO had greater shear-force values (p<0.05) compared to beef from cattle fed WF. Deposition of main unsaturated fatty acids (oleic, linoleic, and linolenic) was greater in treatments WF, SG, and LO, respectively, while the values of conjugated linoleic acid (CLA) were greater when animals were fed LO. The inclusion of LO in the diet enhances the concentration of CLA in longissimus muscle and subcutaneous fat besides improving the atherogenicity index and elongase activity. As such, LO can be used with the aim to improve the quality of beef from confined Nellore cattle. Conversely, the use of PO is not recommended since it may increase the concentration of undesirable unsaturated fatty acids in muscle and subcutaneous fat, shear-force and the atherogenicity index. PMID:26104402

  8. Increased saturated fatty acids in obesity alter resolution of inflammation in part by stimulating prostaglandin production.

    PubMed

    Hellmann, Jason; Zhang, Michael J; Tang, Yunan; Rane, Madhavi; Bhatnagar, Aruni; Spite, Matthew

    2013-08-01

    Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses that lead to chronic, sterile low-grade inflammation, and obese and diabetic humans also have deficits in wound healing and increased susceptibility to infections. Nevertheless, the mechanisms that sustain unresolved inflammation during obesity remain unclear. In this study, we report that saturated free fatty acids that are elevated in obesity alter resolution of acute sterile inflammation by promoting neutrophil survival and decreasing macrophage phagocytosis. Using a targeted mass spectrometry-based lipidomics approach, we found that in db/db mice, PGE2/D2 levels were elevated in inflammatory exudates during the development of acute peritonitis. Moreover, in isolated macrophages, palmitic acid stimulated cyclooxygenase-2 induction and prostanoid production. Defects in macrophage phagocytosis induced by palmitic acid were mimicked by PGE2 and PGD2 and were reversed by cyclooxygenase inhibition or prostanoid receptor antagonism. Macrophages isolated from obese-diabetic mice expressed prostanoid receptors, EP2 and DP1, and contained significantly higher levels of downstream effector, cAMP, compared with wild-type mice. Therapeutic administration of EP2/DP1 dual receptor antagonist, AH6809, decreased neutrophil accumulation in the peritoneum of db/db mice, as well as the accumulation of apoptotic cells in the thymus. Taken together, these studies provide new insights into the mechanisms underlying altered innate immune responses in obesity and suggest that targeting specific prostanoid receptors may represent a novel strategy for resolving inflammation and restoring phagocyte defects in obese and diabetic individuals. PMID:23785121

  9. Agricultural practices altered soybean seed protein, oil, fatty acids, sugars, and minerals in the Midsouth USA

    PubMed Central

    Bellaloui, Nacer; Bruns, H. Arnold; Abbas, Hamed K.; Mengistu, Alemu; Fisher, Daniel K.; Reddy, Krishna N.

    2015-01-01

    Information on the effects of management practices on soybean seed composition is scarce. Therefore, the objective of this research was to investigate the effects of planting date (PD) and seeding rate (SR) on seed composition (protein, oil, fatty acids, and sugars) and seed minerals (B, P, and Fe) in soybean grown in two row-types (RTs) on the Mississippi Delta region of the Midsouth USA. Two field experiments were conducted in 2009 and 2010 on Sharkey clay and Beulah fine sandy loam soil at Stoneville, MS, USA, under irrigated conditions. Soybean were grown in 102 cm single-rows and 25 cm twin-rows in 102 cm centers at SRs of 20, 30, 40, and 50 seeds m-2. The results showed that in May and June planting, protein, glucose, P, and B concentrations increased with increased SR, but at the highest SRs (40 and 50 seeds m-2), the concentrations remained constant or declined. Palmitic, stearic, and linoleic acid concentrations were the least responsive to SR increases. Early planting resulted in higher oil, oleic acid, sucrose, B, and P on both single and twin-rows. Late planting resulted in higher protein and linolenic acid, but lower oleic acid and oil concentrations. The changes in seed constituents could be due to changes in environmental factors (drought and temperature), and nutrient accumulation in seeds and leaves. The increase of stachyose sugar in 2010 may be due to a drier year and high temperature in 2010 compared to 2009; suggesting the possible role of stachyose as an environmental stress compound. Our research demonstrated that PD, SR, and RT altered some seed constituents, but the level of alteration in each year dependent on environmental factors such as drought and temperature. This information benefits growers and breeders for considering agronomic practices to select for soybean seed nutritional qualities under drought and high heat conditions. PMID:25741347

  10. Anti-photoaging and Photoprotective Compounds Derived from Marine Organisms

    PubMed Central

    Pallela, Ramjee; Na-Young, Yoon; Kim, Se-Kwon

    2010-01-01

    Marine organisms form a prominent component of the oceanic population, which significantly contribute in the production of cosmeceutical and pharmaceutical molecules with biologically efficient moieties. In addition to the molecules of various biological activities like anti-bacterial, anti-cancerous, anti-inflammatory and anti-oxidative etc., these organisms also produce potential photoprotective or anti-photoaging agents, which are attracting present day researchers. Continuous exposure to UV irradiation (both UV-A and UV-B) leads to the skin cancer and other photoaging complications, which are typically mediated by the reactive oxygen species (ROS), generated in the oxidative pathways. Many of the anti-oxidative and anti-photoaging compounds have been identified previously, which work efficiently against photodamage of the skin. Recently, marine originated photoprotective or anti-photoaging behavior was observed in the methanol extracts of Corallina pilulifera (CPM). These extracts were found to exert potent antioxidant activity and protective effect on UV-A-induced oxidative stress in human dermal fibroblast (HDF) cells by protecting DNA and also by inhibiting matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to UV-A. The present review depicts various other photoprotective compounds from algae and other marine sources for further elaborative research and their probable use in cosmeceutical and pharmaceutical industries. PMID:20479974

  11. Estrogen receptor beta is a novel therapeutic target for photoaging.

    PubMed

    Chang, Ken C N; Wang, Yihe; Oh, Inn Gyung; Jenkins, Susan; Freedman, Leonard P; Thompson, Catherine C; Chung, Jin Ho; Nagpal, Sunil

    2010-05-01

    One of the many harmful factors faced by the skin is solar UV radiation, which damages skin by inducing chronic low-grade inflammation through increased expression of proinflammatory cytokines, metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). Estrogen receptors (ERs) alpha and beta are ligand-dependent transcription factors that are expressed in skin, and an ERbeta agonist has previously shown efficacy in vivo in models of pain and inflammation. Because ERbeta does not carry the breast and uterine proliferation liabilities of ERalpha, we decided to explore the possibility of using ERbeta as a target for photoaging. We show that ERbeta-selective compounds suppressed the expression of cytokines and MMPs in activated keratinocytes and fibroblast-based in vitro models of photoaging. Furthermore, in activated dermal fibroblasts, ERbeta-selective compounds also inhibited COX-2. These activities of ERbeta ligands in skin cells correlated with the expression levels of ERbeta and showed reversal by treatment with a potent synthetic ER antagonist. Furthermore, the pharmacology of ERbeta-selective compound was observed in wild-type but not in skin cells obtained from ERbeta knockout mice. Finally, we demonstrate that a synthetic ERbeta agonist inhibited UV-induced photodamage and skin wrinkle formation in a murine model of photoaging. Therefore, the potential of an ERbeta ligand to regulate multiple pathways underlying the cause of photoaging suggests ERbeta to be a novel therapeutic target for the prevention and treatment of photoaging. PMID:20110405

  12. Photoaging and chronological aging profile: Understanding oxidation of the skin.

    PubMed

    Peres, P S; Terra, V A; Guarnier, F A; Cecchini, R; Cecchini, A L

    2011-05-01

    The impact of chronological aging and photoaging on the skin is particularly concerning, especially when oxidative stress is involved. This article provides evidence of quantitative and qualitative differences in the oxidative stress generated by chronological aging and photoaging of the skin in HRS/J hairless mice. Analysis of the results revealed an increase in lipid peroxides as the skin gets older and in photoaged skin (10.086 ± 0.70 η MDA/mg and 14.303 ± 1.81 η MDA/mg protein, respectively), although protein oxidation was only verified in chronological aged skin (15.449 ± 0.99 η protein/mg protein). The difference between both skin types is the decay in the capacity of lipid membrane turnover revealed by the dislocation of older skin to the left in the chemiluminescence curve. Imbalance between antioxidant and oxidation processes was verified by the decrease in total antioxidant capacity of chronological and photoaged skins. Although superoxide dismutase remained unchanged, catalase increased in the 18 and 48-week-old skin groups and decreased in irradiated mice, demonstrating that neither enzyme is a good parameter to determine oxidative stress. The differences observed between chronological and photoaging skin represent a potential new approach to understanding the phenomenon of skin aging and a new target for therapeutic intervention. PMID:21356598

  13. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

    PubMed

    Nath, Aritro; Chan, Christina

    2016-01-01

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers. PMID:26725848

  14. Changes in the Enzymes for Fatty Acid Synthesis and Desaturation during Acclimation of Developing Soybean Seeds to Altered Growth Temperature

    PubMed Central

    Cheesbrough, Thomas M.

    1989-01-01

    Temperature-induced changes in the enzymes for fatty acid synthesis and desaturation were studied in developing soybean seeds (Glycine max L. var Williams 82). Changes were induced by culture of the seed pods for 20 hours in liquid media at 20, 25, or 35°C. Linoleoyl and oleoyl desaturases were 94 and 10 times as active, respectively, in seeds cultured at 20°C as those cultured at 25°C. Both desaturases had negligible activity in seeds cultured at 35°C compared to seeds cultured at 20°C. Though less dramatic, other enzymes also showed differences in activity after 20 hours in culture at 20, 25, or 35°C. Stearoyl-acyl carrier protein (ACP) desaturase and CDP-choline:diacylglycerol phosphorylcholine transferase were most active in preparations from 20°C cultures. Activities were twofold lower at 25°C and a further threefold lower in 35°C cultures. Cultures from 25 and 35°C had 60 and 40%, respectively, of the phosphorylcholine:CTP cytidylyl transferase activity present in cultures grown at 20°C. Fatty acid synthetase, malonyl-coenzyme A:ACP transacylase, palmitoyl-ACP elongation, and choline kinase were not significantly altered by culture temperature. These data suggest that the enzymes for fatty acid desaturation and phosphatidylcholine synthesis can be rapidly modulated in response to altered growth temperatures, while the enzymes for fatty acid synthesis and elongation are not. PMID:16666840

  15. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers

    PubMed Central

    Nath, Aritro; Chan, Christina

    2016-01-01

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers. PMID:26725848

  16. Assessing the photoaging process at sun exposed and non-exposed skin using fluorescence lifetime spectroscopy

    NASA Astrophysics Data System (ADS)

    Saito Nogueira, Marcelo; Kurachi, Cristina

    2016-03-01

    Photoaging is the skin premature aging due to exposure to ultraviolet light, which damage the collagen, elastin and can induce alterations on the skin cells DNA, and, then, it may evolve to precancerous lesions, which are widely investigated by fluorescence spectroscopy and lifetime. The fluorescence spectra and fluorescence lifetime analysis has been presented as a technique of great potential for biological tissue characterization at optical diagnostics. The main targeted fluorophores are NADH (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide), which have free and bound states, each one with different average lifetimes. The average lifetimes for free and bound NADH and FAD change according to tissue metabolic alterations and may contribute to a non-invasive clinical investigation of injuries such as skin lesions. These lesions and the possible areas where they may develop can be interrogated using fluorescence lifetime spectroscopy taking into account the variability of skin phototypes and the changes related to melanin, collagen and elastin, endogenous fluorophores which have emissions that spectrally overlap to the NADH and FAD emission. The objective of this study is to assess the variation on fluorescence lifetimes of normal skin at sun exposed and non-exposed areas and associate this variation to the photoaging process.

  17. Altering fatty acid availability does not impair prolonged, continuous running to fatigue: evidence for carbohydrate dependence.

    PubMed

    Leckey, Jill J; Burke, Louise M; Morton, James P; Hawley, John A

    2016-01-15

    We determined the effect of suppressing lipolysis via administration of nicotinic acid (NA) on fuel substrate selection and half-marathon running capacity. In a single-blinded, Latin square design, 12 competitive runners completed four trials involving treadmill running until volitional fatigue at a pace based on 95% of personal best half-marathon time. Trials were completed in a fed or overnight fasted state: 1) carbohydrate (CHO) ingestion before (2 g CHO·kg(-1)·body mass(-1)) and during (44 g/h) [CFED]; 2) CFED plus NA ingestion [CFED-NA]; 3) fasted with placebo ingestion during [FAST]; and 4) FAST plus NA ingestion [FAST-NA]. There was no difference in running distance (CFED, 21.53 ± 1.07; CFED-NA, 21.29 ± 1.69; FAST, 20.60 ± 2.09; FAST-NA, 20.11 ± 1.71 km) or time to fatigue between the four trials. Concentrations of plasma free fatty acids (FFA) and glycerol were suppressed following NA ingestion irrespective of preexercise nutritional intake but were higher throughout exercise in FAST compared with all other trials (P < 0.05). Rates of whole-body CHO oxidation were unaffected by NA ingestion in the CFED and FAST trials, but were lower in the FAST trial compared with the CFED-NA trial (P < 0.05). CHO was the primary substrate for exercise in all conditions, contributing 83-91% to total energy expenditure with only a small contribution from fat-based fuels. Blunting the exercise-induced increase in FFA via NA ingestion did not impair intense running capacity lasting ∼85 min, nor did it alter patterns of substrate oxidation in competitive athletes. Although there was a small but obligatory use of fat-based fuels, the oxidation of CHO-based fuels predominates during half-marathon running. PMID:26586912

  18. Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability*

    PubMed Central

    Bravo, Bruna Souza Felix; Azulay, David Rubem; Luiz, Ronir Raggio; Mandarim-De-Lacerda, Carlos Alberto; Cuzzi, Tullia; Azulay, Mônica Manela

    2015-01-01

    BACKGROUND The off-label use of oral isotretinoin in photoaging is a therapeutic tool that has been used by dermatologists. There are few studies to corroborate its effectiveness and durability. OBJECTIVES To assess, both clinically and histologically, the changes caused by the use of oral isotretinoin in skin photoaging as well as the duration of the effects. METHODS 20 female patients, aged 45-50 years, with phototypes II-VI, none of whom had experienced menopause, were treated with 20mg oral isotretinoin, 3 days a week, for 12 weeks. They underwent clinical analysis and skin biopsies in the pre-auricular region, while histologic cuts enabled assessment of the solar elastosis level and morphologic analysis. RESULTS Clinically, patients, as well as the researching and the assessor physicians, noticed improvement in skin quality. One patient presented severe solar elastosis, 11 manifested the moderate form, while 8 presented the discreet type. According to histological analysis, 65% of the patients revealed alteration in the distribution and thickness of the elastic fibers, which can be interpreted as a histological improvement, while 60% showed an increase in collagen density. We observed an increase in collagen density, from 51.2% to 57.4%, (p=0.004). At the end of the 12-week follow-up period, this density decreased to 54.7% (p=0.050). There was an increase in the density of elastic fibers, from 26.5% to 31.3%, (p=0.02), which had dropped to 27.5% at the end of the 12-week follow-up period. CONCLUSIONS The study confirmed the role of oral isotretinoin in remodeling the extracellular matrix against photoaging, as well as its durability after 12 weeks, especially when we consider collagen fibers. PMID:26375216

  19. Ethanol-Induced Alterations in Fatty Acid-Related Lipids in Serum and Tissues in Mice

    PubMed Central

    Zhao, Zhenwen; Yu, Menggang; Crabb, David; Xu, Yan; Liangpunsakul, Suthat

    2010-01-01

    Background Chronic alcohol consumption is a major factor for several human diseases and alcoholism is associated with a host of societal problems. One of the major alcohol- induced metabolic changes is the increased NADH levels, which reduces glucose synthesis and increases fatty acid (FA) synthesis. Probably more important is the induction of FA synthesizing enzymes under the control of sterol regulatory element binding proteins (SREBP), plus increased malonyl-CoA which blocks FA entry to the mitochondria for oxidation. The changes in FA-related lipids, particularly lysophospholipids (LPLs) and ceramides (Cers), in different tissues in ethanol-fed have not been reported. Methods We systematically determined the levels of FA-related lipids, including FAs, phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI), sphingomyelins (SMs), and ceramides (Cers) in the serum and different tissues by high-performance-liquid-chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The study was performed in C57BL/6J mice fed with Lieber DeCarli diet; in which ethanol was added to account for 27.5% of total calories. The serum and tissues were collected at the time of sacrifice in these mice and the results were compared to pair-fed controls. Results The important observation was that ethanol induced tissue-specific changes, which were related to different FA chains. Several 22:6 FA, 18:0 FA, 18:0 to 18:3 FA-containing lipids were significantly increased in the serum, liver, and skeletal muscle, respectively. In the kidney, all 22:6 FA-containing lipids detected were increased. In addition, alterations of other lipids in tissues, except adipose tissue, were also observed. Conclusions We found tissue-specific alterations in the levels of FA-related lipids after ethanol administration. The implications of these findings

  20. FADS2 Genetic Variance in Combination with Fatty Acid Intake Might Alter Composition of the Fatty Acids in Brain.

    PubMed

    Rizzi, Thais S; van der Sluis, Sophie; Derom, Catherine; Thiery, Evert; van Kesteren, Ronald E; Jacobs, Nele; Van Gestel, Sofie; Vlietinck, Robert; Verhage, Matthijs; Heutink, Peter; Posthuma, Danielle

    2013-01-01

    Multiple lines of evidence suggest that fatty acids (FA) play an important role in cognitive function. However, little is known about the functional genetic pathways involved in cognition. The main goals of this study were to replicate previously reported interaction effects between breast feeding (BF) and FA desaturase (FADS) genetic variation on IQ and to investigate the possible mechanisms by which these variants might moderate BF effect, focusing on brain expression. Using a sample of 534 twins, we observed a trend in the moderation of BF effects on IQ by FADS2 variation. In addition, we made use of publicly available gene expression databases from both humans (193) and mice (93) and showed that FADS2 variants also correlate with FADS1 brain expression (P-value<1.1E-03). Our results provide novel clues for the understanding of the genetic mechanisms regulating FA brain expression and improve the current knowledge of the FADS moderation effect on cognition. PMID:23826354

  1. Altered expression of fatty acid–metabolizing enzymes in aromatase-deficient mice

    PubMed Central

    Nemoto, Yoshihisa; Toda, Katsumi; Ono, Masafumi; Fujikawa-Adachi, Kiyomi; Saibara, Toshiji; Onishi, Saburo; Enzan, Hideaki; Okada, Teruhiko; Shizuta, Yutaka

    2000-01-01

    Hepatic steatosis is a frequent complication in nonobese patients with breast cancer treated with tamoxifen, a potent antagonist of estrogen. In addition, hepatic steatosis became evident spontaneously in the aromatase-deficient (ArKO) mouse, which lacks intrinsic estrogen production. These clinical and laboratory observations suggest that estrogen helps to maintain constitutive lipid metabolism. To clarify this hypothesis, we characterized the expression and activity in ArKO mouse liver of enzymes involved in peroxisomal and mitochondrial fatty acid β-oxidation. Northern analysis showed reduced expression of mRNAs for very long fatty acyl-CoA synthetase, peroxisomal fatty acyl-CoA oxidase, and medium-chain acyl-CoA dehydrogenase, enzymes required in fatty acid β-oxidation. In vitro assays of fatty acid β-oxidation activity using very long (C24:0), long (C16:0), or medium (C12:0) chain fatty acids as the substrates confirmed that the corresponding activities are also diminished. Impaired gene expression and enzyme activities of fatty acid β-oxidation were restored to the wild-type levels, and hepatic steatosis was substantially diminished in animals treated with 17β-estradiol. Wild-type and ArKO mice showed no difference in the binding activities of the hepatic nuclear extracts to a peroxisome proliferator response element. These findings demonstrate the pivotal role of estrogen in supporting constitutive hepatic expression of genes involved in lipid β-oxidation and in maintaining hepatic lipid homeostasis. PMID:10862797

  2. Omega-3 fatty acids alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration.

    PubMed

    Model, Camila S; Gomes, Lara M; Scaini, Giselli; Ferreira, Gabriela K; Gonçalves, Cinara L; Rezin, Gislaine T; Steckert, Amanda V; Valvassori, Samira S; Varela, Roger B; Quevedo, João; Streck, Emilio L

    2014-03-01

    Studies have consistently reported the participation of oxidative stress in bipolar disorder (BD). Evidences indicate that omega-3 (ω3) fatty acids play several important roles in brain development and functioning. Moreover, preclinical and clinical evidence suggests roles for ω3 fatty acids in BD. Considering these evidences, the present study aimed to investigate the effects of ω3 fatty acids on locomotor behavior and oxidative stress parameters (TBARS and protein carbonyl content) in brain of rats subjected to an animal model of mania induced by fenproporex. The fenproporex treatment increased locomotor behavior in saline-treated rats under reversion and prevention model, and ω3 fatty acids prevented fenproporex-related hyperactivity. Moreover, fenproporex increased protein carbonyls in the prefrontal cortex and cerebral cortex, and the administration of ω3 fatty acids reversed this effect. Lipid peroxidation products also are increased in prefrontal cortex, striatum, hippocampus and cerebral after fenproporex administration, but ω3 fatty acids reversed this damage only in the hippocampus. On the other hand, in the prevention model, fenproporex increased carbonyl content only in the cerebral cortex, and administration of ω3 fatty acids prevented this damage. Additionally, the administration of fenproporex resulted in a marked increased of TBARS in the prefrontal cortex, hippocampus, striatum and cerebral cortex, and prevent this damage in the prefrontal cortex, hippocampus and striatum. In conclusion, we are able to demonstrate that fenproporex-induced hyperlocomotion and damage through oxidative stress were prevented by ω3 fatty acids. Thus, the ω3 fatty acids may be important adjuvant therapy of bipolar disorder. PMID:24385143

  3. Omega-3 Fatty Acid Enriched Chevon (Goat Meat) Lowers Plasma Cholesterol Levels and Alters Gene Expressions in Rats

    PubMed Central

    Rajion, Mohamed Ali; Meng, Goh Yong; Soleimani Farjam, Abdoreza

    2014-01-01

    In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n = 10 in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P < 0.05) in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression. PMID:24719886

  4. Alteration in the fatty acid composition of liver, kidney and plasma from diethylhexyl phthalate-treated rats

    SciTech Connect

    Okita, J.R.; Okita, R.T. )

    1990-02-26

    Cytochromes P-450 are induced in rat liver microsomes by a number of compounds which cause peroxisome proliferation. One such compound, diethylhexyl phthalate (DEHP), induces P-450 IVA1 which catalyzes {omega}- and ({omega}-1)-hydroxylation of fatty acids. In liver of rats fed DEHP, there is a 10-fold induction of {omega}-hydroxylation of laurate and ({omega}-1)-hydroxylation of palmitate, as compared to control rat liver. There is a 3-fold induction of other hydroxylations, such as W-hydroxylation of palmitate and {omega}- ({omega}-1)-hydroxylation of syristate. Despite these increases in hydroxylase activity, the authors have not been able to demonstrate increases in hydroxy fatty acids or dicarboxylic acids in liver or plasma of rats fed DEHP. However, alterations in the fatty acid composition of lipids in liver, kidney cortex and plasma were observed. They consistently observed increases in oleate (expressed as mol% of total fatty acid) in liver (11% in control increased to 24% in DEHP-treated), kidney cortex (12% to 16%) and plasma (13% to 24%). This increase in oleate was quite striking when expressed as ug/gm tissue or ug/al plasma. DEHP treatment resulted in increased oleate in mitochondrial, microsomal and cytosolic fractions of liver.

  5. Omega-3 fatty acid enriched chevon (goat meat) lowers plasma cholesterol levels and alters gene expressions in rats.

    PubMed

    Ebrahimi, Mahdi; Rajion, Mohamed Ali; Meng, Goh Yong; Soleimani Farjam, Abdoreza

    2014-01-01

    In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n = 10 in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P < 0.05) in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression. PMID:24719886

  6. Chronological ageing and photoageing of the fibroblasts and the dermal connective tissue.

    PubMed

    Ma, W; Wlaschek, M; Tantcheva-Poór, I; Schneider, L A; Naderi, L; Razi-Wolf, Z; Schüller, J; Scharffetter-Kochanek, K

    2001-10-01

    In recent years, the exposure of human skin to environmental and artificial UV irradiation has increased dramatically. This is due not only to increased solar UV irradiation as a consequence of stratospheric ozone depletion, but also to inappropriate social behaviour with the use of tanning salons still being very popular in the public view. Besides this, leisure activities and a lifestyle that often includes travel to equatorial regions add to the individual annual UV load. In addition to the common long-term detrimental effects such as immunosuppression and skin cancer, the photo-oxidative damage due to energy absorption of UV photons in an oxygenized environment leads to quantitative and qualitative alterations of cells and structural macromolecules of the dermal connective tissue responsible for tensile strength, resilience and stability of the skin. The clinical manifestations of UV/reactive oxygen species (ROS)-induced disturbances result in photoaged skin with wrinkle formation, laxity, leathery appearance as well as fragility, impaired wound healing capacities and higher vulnerability. Strategies to prevent or at least minimize ROS-induced photo-ageing and intrinsic ageing of the skin necessarily include protection against UV irradiation and antioxidant homeostasis. PMID:11696063

  7. Alterations of the lipid content and fatty acid profile of Chlorella protothecoides under different light intensities.

    PubMed

    Krzemińska, Izabela; Piasecka, Agata; Nosalewicz, Artur; Simionato, Diana; Wawrzykowski, Jacek

    2015-11-01

    Chlorella protothecoides is a valuable source of lipids that may be used for biodiesel production. The present work shows analysis of the potential of photoheterotrophic cultivation of C. protothecoides under various light intensities aiming to identify the conditions with maximal biomass and lipid content. An increase in light intensity was associated with an increased specific growth rate and a shortened doubling time. Also, the relative total lipid content increased from 24.8% to 37.5% with increase of light intensity. The composition of fatty acid methyl esters was affected by light intensity with the C16-18 fatty acids increased from 76.97% to 90.24% of total fatty acids. However, the content of linolenic acids decreased with the increase of the culture irradiance. These studies indicate that cultures irradiated with high light intensities achieve the minimal specifications for biodiesel quality on linolenic acids and thus are suitable for biodiesel production. PMID:26231126

  8. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    SciTech Connect

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. |; Giometti, C.S.; Mishler, K.; Slavin, B.G.

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  9. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.

    PubMed

    Peliciari-Garcia, Rodrigo A; Goel, Mehak; Aristorenas, Jonathan A; Shah, Krishna; He, Lan; Yang, Qinglin; Shalev, Anath; Bailey, Shannon M; Prabhu, Sumanth D; Chatham, John C; Gamble, Karen L; Young, Martin E

    2016-10-01

    A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26721420

  10. Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity

    PubMed Central

    Fernandez-Twinn, Denise S.; Martin-Gronert, Malgorzata S.; Musial, Barbara; Fowden, Abigail; Ozanne, Susan E.

    2014-01-01

    Changes in the maternal nutritional environment during fetal development can influence offspring's metabolic risk in later life. Animal models have demonstrated that offspring of diet-induced obese dams develop metabolic complications, including nonalcoholic fatty liver disease. In this study we investigated the mechanisms in young offspring that lead to the development of nonalcoholic fatty liver disease (NAFLD). Female offspring of C57BL/6J dams fed either a control or obesogenic diet were studied at 8 wk of age. We investigated the roles of oxidative stress and lipid metabolism in contributing to fatty liver in offspring. There were no differences in body weight or adiposity at 8 wk of age; however, offspring of obese dams were hyperinsulinemic. Oxidative damage markers were significantly increased in their livers, with reduced levels of the antioxidant enzyme glutathione peroxidase-1. Mitochondrial complex I and II activities were elevated, while levels of mitochondrial cytochrome c were significantly reduced and glutamate dehydrogenase was significantly increased, suggesting mitochondrial dysfunction. Offspring of obese dams also had significantly greater hepatic lipid content, associated with increased levels of PPARγ and reduced triglyceride lipase. Liver glycogen and protein content were concomitantly reduced in offspring of obese dams. In conclusion, offspring of diet-induced obese dams have disrupted liver metabolism and develop NAFLD prior to any differences in body weight or body composition. Oxidative stress may play a mechanistic role in the progression of fatty liver in these offspring. PMID:24789994

  11. Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity.

    PubMed

    Alfaradhi, Maria Z; Fernandez-Twinn, Denise S; Martin-Gronert, Malgorzata S; Musial, Barbara; Fowden, Abigail; Ozanne, Susan E

    2014-07-01

    Changes in the maternal nutritional environment during fetal development can influence offspring's metabolic risk in later life. Animal models have demonstrated that offspring of diet-induced obese dams develop metabolic complications, including nonalcoholic fatty liver disease. In this study we investigated the mechanisms in young offspring that lead to the development of nonalcoholic fatty liver disease (NAFLD). Female offspring of C57BL/6J dams fed either a control or obesogenic diet were studied at 8 wk of age. We investigated the roles of oxidative stress and lipid metabolism in contributing to fatty liver in offspring. There were no differences in body weight or adiposity at 8 wk of age; however, offspring of obese dams were hyperinsulinemic. Oxidative damage markers were significantly increased in their livers, with reduced levels of the antioxidant enzyme glutathione peroxidase-1. Mitochondrial complex I and II activities were elevated, while levels of mitochondrial cytochrome c were significantly reduced and glutamate dehydrogenase was significantly increased, suggesting mitochondrial dysfunction. Offspring of obese dams also had significantly greater hepatic lipid content, associated with increased levels of PPARγ and reduced triglyceride lipase. Liver glycogen and protein content were concomitantly reduced in offspring of obese dams. In conclusion, offspring of diet-induced obese dams have disrupted liver metabolism and develop NAFLD prior to any differences in body weight or body composition. Oxidative stress may play a mechanistic role in the progression of fatty liver in these offspring. PMID:24789994

  12. In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary omega (omega)-3 polyunsaturated fatty acids (PUFA) and omega–6 PUFA are thought to have unique benefits with respect to cardiovascular disease. Macrophages (M phi) differentiated from human monocytic cell line THP-1 were used to assess the effect of omega-3 PUFA (eicosapentaenoic acid [EPA]...

  13. Different Oilseed Supplements Alter Fatty Acid Composition of Different Adipose Tissues of Adult Ewes.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lamb and mutton are important dietary components in human diets in northwest China and throughout the world. Fatty acid composition is an important factor in the definition of meat quality due to its association with meat odor and flavor and nutritional value of fat for human consumption. Twenty-f...

  14. Soybean seed protein, oil, fatty acids, and isoflavones altered by potassium fertilizer rates in the midsouth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research has shown that the effect of potassium fertilizer on soybean ([Glycine max (L.) Merr.] seed composition (protein, oil, fatty acids, and isoflavones) is still largely unknown. Therefore, the objective of this research was to investigate the effects of potassium application on seed p...

  15. Mimp/Mtch2, an Obesity Susceptibility Gene, Induces Alteration of Fatty Acid Metabolism in Transgenic Mice

    PubMed Central

    Tsarfaty, Galia; Kaufman, Dafna; Horev, Judith; Resau, James H.; Tsarfaty, Ilan

    2016-01-01

    Objective Metabolic dysfunctions, such as fatty liver, obesity and insulin resistance, are among the most common contemporary diseases worldwide, and their prevalence is continuously rising. Mimp/Mtch2 is a mitochondrial carrier protein homologue, which localizes to the mitochondria and induces mitochondrial depolarization. Mimp/Mtch2 single-nucleotide polymorphism is associated with obesity in humans and its loss in mice muscle protects from obesity. Our aim was to study the effects of Mimp/Mtch2 overexpression in vivo. Methods Transgenic mice overexpressing Mimp/Mtch2-GFP were characterized and monitored for lipid accumulation, weight and blood glucose levels. Transgenic mice liver and kidneys were used for gene expression analysis. Results Mimp/Mtch2-GFP transgenic mice express high levels of fatty acid synthase and of β-oxidation genes and develop fatty livers and kidneys. Moreover, high-fat diet–fed Mimp/Mtch2 mice exhibit high blood glucose levels. Our results also show that Mimp/Mtch2 is involved in lipid accumulation and uptake in cells and perhaps in human obesity. Conclusions Mimp/Mtch2 alters lipid metabolism and may play a role in the onset of obesity and development of insulin resistance. PMID:27359329

  16. Altered development and function of the placental regions in preeclampsia and its association with long-chain polyunsaturated fatty acids.

    PubMed

    Rani, Alka; Wadhwani, Nisha; Chavan-Gautam, Preeti; Joshi, Sadhana

    2016-09-01

    The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long-chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582-597. doi: 10.1002/wdev.238 For further resources related to this article, please visit the WIREs website. PMID:27239793

  17. Altered Preconception Fatty Acid Intake Is Associated with Improved Pregnancy Rates in Overweight and Obese Women Undertaking in Vitro Fertilisation.

    PubMed

    Moran, Lisa J; Tsagareli, Victoria; Noakes, Manny; Norman, Robert

    2016-01-01

    Maternal preconception diet is proposed to affect fertility. Prior research assessing the effect of altering the fatty acid profile on female fertility is conflicting. The aim of this study was to assess the effect of preconception maternal diet, specifically fatty acid profile, on pregnancies and live births following in vitro fertilisation (IVF). Forty-six overweight and obese women undergoing IVF were randomised to a diet and physical activity intervention (intervention) or standard care (control). Outcome measures included pregnancy, live birth and pre-study dietary intake from food frequency questionnaire. Twenty pregnancies (n = 12/18 vs. n = 8/20, p = 0.12) and 12 live births (n = 7/18 vs. n = 5/20, p = 0.48) occurred following the intervention with no differences between the treatment groups. On analysis adjusted for BMI and smoking status, women who became pregnant had higher levels of polyunsaturated fatty acid (PUFA) intake (p = 0.03), specifically omega-6 PUFA and linoleic acid (LA) (p = 0.045) with a trend for an elevated intake of omega-3 PUFA (p = 0.06). There were no dietary differences for women who did or did not have a live birth. Maternal preconception PUFA, and specifically omega-6 and LA intake, are associated with improved pregnancy rates in overweight and obese women undergoing IVF. This has implications for optimising fertility through preconception nutrition. PMID:26742065

  18. Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals.

    PubMed

    Bosch, Ricardo; Philips, Neena; Suárez-Pérez, Jorge A; Juarranz, Angeles; Devmurari, Avani; Chalensouk-Khaosaat, Jovinna; González, Salvador

    2015-01-01

    Photoaging and photocarcinogenesis are primarily due to solar ultraviolet (UV) radiation, which alters DNA, cellular antioxidant balance, signal transduction pathways, immunology, and the extracellular matrix (ECM). The DNA alterations include UV radiation induced thymine-thymine dimers and loss of tumor suppressor gene p53. UV radiation reduces cellular antioxidant status by generating reactive oxygen species (ROS), and the resultant oxidative stress alters signal transduction pathways such as the mitogen-activated protein kinase (MAPK), the nuclear factor-kappa beta (NF-κB)/p65, the janus kinase (JAK), signal transduction and activation of transcription (STAT) and the nuclear factor erythroid 2-related factor 2 (Nrf2). UV radiation induces pro-inflammatory genes and causes immunosuppression by depleting the number and activity of the epidermal Langerhans cells. Further, UV radiation remodels the ECM by increasing matrixmetalloproteinases (MMP) and reducing structural collagen and elastin. The photoprotective strategies to prevent/treat photoaging and photocarcinogenesis include oral or topical agents that act as sunscreens or counteract the effects of UV radiation on DNA, cellular antioxidant balance, signal transduction pathways, immunology and the ECM. Many of these agents are phytochemical derivatives and include polyphenols and non-polyphenols. The flavonoids are polyphenols and include catechins, isoflavones, proanthocyanidins, and anthocyanins, whereas the non-flavonoids comprise mono phenolic acids and stilbenes. The natural sources of polyphenols include tea, cocoa, grape/wine, soy, pomegranate, and Polypodium leucotomos. The non-phenolic phytochemicals include carotenoids, caffeine and sulphoraphance (SFN). In addition, there are other phytochemical derivatives or whole extracts such as baicalin, flavangenol, raspberry extract, and Photomorphe umbellata with photoprotective activity against UVB radiation, and thereby carcinogenesis. PMID:26783703

  19. Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals

    PubMed Central

    Bosch, Ricardo; Philips, Neena; Suárez-Pérez, Jorge A.; Juarranz, Angeles; Devmurari, Avani; Chalensouk-Khaosaat, Jovinna; González, Salvador

    2015-01-01

    Photoaging and photocarcinogenesis are primarily due to solar ultraviolet (UV) radiation, which alters DNA, cellular antioxidant balance, signal transduction pathways, immunology, and the extracellular matrix (ECM). The DNA alterations include UV radiation induced thymine-thymine dimers and loss of tumor suppressor gene p53. UV radiation reduces cellular antioxidant status by generating reactive oxygen species (ROS), and the resultant oxidative stress alters signal transduction pathways such as the mitogen-activated protein kinase (MAPK), the nuclear factor-kappa beta (NF-κB)/p65, the janus kinase (JAK), signal transduction and activation of transcription (STAT) and the nuclear factor erythroid 2-related factor 2 (Nrf2). UV radiation induces pro-inflammatory genes and causes immunosuppression by depleting the number and activity of the epidermal Langerhans cells. Further, UV radiation remodels the ECM by increasing matrixmetalloproteinases (MMP) and reducing structural collagen and elastin. The photoprotective strategies to prevent/treat photoaging and photocarcinogenesis include oral or topical agents that act as sunscreens or counteract the effects of UV radiation on DNA, cellular antioxidant balance, signal transduction pathways, immunology and the ECM. Many of these agents are phytochemical derivatives and include polyphenols and non-polyphenols. The flavonoids are polyphenols and include catechins, isoflavones, proanthocyanidins, and anthocyanins, whereas the non-flavonoids comprise mono phenolic acids and stilbenes. The natural sources of polyphenols include tea, cocoa, grape/wine, soy, pomegranate, and Polypodium leucotomos. The non-phenolic phytochemicals include carotenoids, caffeine and sulphoraphance (SFN). In addition, there are other phytochemical derivatives or whole extracts such as baicalin, flavangenol, raspberry extract, and Photomorphe umbellata with photoprotective activity against UVB radiation, and thereby carcinogenesis. PMID:26783703

  20. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial.

    PubMed

    Ramsden, Christopher E; Faurot, Keturah R; Zamora, Daisy; Suchindran, Chirayath M; Macintosh, Beth A; Gaylord, Susan; Ringel, Amit; Hibbeln, Joseph R; Feldstein, Ariel E; Mori, Trevor A; Barden, Anne; Lynch, Chanee; Coble, Rebecca; Mas, Emilie; Palsson, Olafur; Barrow, David A; Mann, J Douglas

    2013-11-01

    Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs -2.1; P<0.001) and the number of Headache Days per month (-8.8 vs -4.0; P=0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (-4.6 vs -1.2; P=0.01) and the n-6 in HUFA score (-21.0 vs -4.0%; P<0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P<0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P<0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population. PMID:23886520

  1. Altered UDP-Glucuronosyltransferase and Sulfotransferase Expression and Function during Progressive Stages of Human Nonalcoholic Fatty Liver Disease

    PubMed Central

    Hardwick, Rhiannon N.; Ferreira, Daniel W.; More, Vijay R.; Lake, April D.; Lu, Zhenqiang; Manautou, Jose E.; Slitt, Angela L.

    2013-01-01

    The UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) represent major phase II drug-metabolizing enzymes that are also responsible for maintaining cellular homeostasis by metabolism of several endogenous molecules. Perturbations in the expression or function of these enzymes can lead to metabolic disorders and improper management of xenobiotics and endobiotics. Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver damage ranging from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Because the liver plays a central role in the metabolism of xenobiotics, the purpose of the current study was to determine the effect of human NAFLD progression on the expression and function of UGTs and SULTs in normal, steatosis, NASH (fatty), and NASH (not fatty/cirrhosis) samples. We identified upregulation of UGT1A9, 2B10, and 3A1 and SULT1C4 mRNA in both stages of NASH, whereas UGT2A3, 2B15, and 2B28 and SULT1A1, 2B1, and 4A1 as well as 3′-phosphoadenosine-5′-phosphosulfate synthase 1 were increased in NASH (not fatty/cirrhosis) only. UGT1A9 and 1A6 and SULT1A1 and 2A1 protein levels were decreased in NASH; however, SULT1C4 was increased. Measurement of the glucuronidation and sulfonation of acetaminophen (APAP) revealed no alterations in glucuronidation; however, SULT activity was increased in steatosis compared with normal samples, but then decreased in NASH compared with steatosis. In conclusion, the expression of specific UGT and SULT isoforms appears to be differentially regulated, whereas sulfonation of APAP is disrupted during progression of NAFLD. PMID:23223517

  2. Fatty Acid Esters of Phloridzin Induce Apoptosis of Human Liver Cancer Cells through Altered Gene Expression

    PubMed Central

    Nair, Sandhya V. G.; Ziaullah; Rupasinghe, H. P. Vasantha

    2014-01-01

    Phloridzin (phlorizin or phloretin 2′-O-glucoside) is known for blocking intestinal glucose absorption. We have investigated the anticarcinogenic effect of phloridzin and its novel derivatives using human cancer cell lines. We have synthesised novel acylated derivatives of phloridzin with six different long chain fatty acids by regioselective enzymatic acylation using Candida Antarctica lipase B. The antiproliferative effects of the new compounds were investigated in comparison with the parent compounds, phloridzin, aglycone phloretin, the six free fatty acids and chemotherapeutic drugs (sorafenib, doxorubicin and daunorubicin) using human hepatocellular carcinoma HepG2 cells, human breast adenocarcinoma MDA-MB-231 cells and acute monocytic leukemia THP-1 cells along with normal human and rat hepatocytes. The fatty acid esters of phloridzin inhibited significantly the growth of the two carcinoma and leukemia cells while similar treatment doses were not toxic to normal human or rat hepatocytes. The antiproliferative potency of fatty esters of phloridzin was comparable to the potency of the chemotherapeutic drugs. The fatty acid esters of phloridzin inhibited DNA topoisomerases IIα activity that might induce G0/G1 phase arrest, induced apoptosis via activation of caspase-3, and decreased ATP level and mitochondrial membrane potential in HepG2 cells. Based on the high selectivity on cancer cells, decosahexaenoic acid (DHA) ester of phloridzin was selected for gene expression analysis using RT2PCR human cancer drug target array. Antiproliferative effect of DHA ester of phloridzin could be related to the down regulation of anti-apoptotic gene (BCL2), growth factor receptors (EBFR family, IGF1R/IGF2, PDGFR) and its downstream signalling partners (PI3k/AKT/mTOR, Ras/Raf/MAPK), cell cycle machinery (CDKs, TERT, TOP2A, TOP2B) as well as epigenetics regulators (HDACs). These results suggest that fatty esters of phloridzin have potential chemotherapeutic effects mediated

  3. Photoaging and the clinical utility of fractional laser

    PubMed Central

    Borges, Juliano; Manela-Azulay, Mônica; Cuzzi, Tullia

    2016-01-01

    The description of atomic structure by Niels Bohr set the basis for the emergence of quantum physics. Based on these fundamentals, Einstein published in 1917 a paper on the amplification of energy by Stimulated Emission of Radiation as part of his quantum theories. In 1955, Townes and Gordon turned Einstein’s theories into practice, creating a coherent and amplified microwave device using ammonia gas in an optical medium. But it was at the beginning of the 1980s, that Anderson and Parrish published an article about the selective photothermolysis model which revolutionized clinical practice. The use of laser in photoaging began with CO2 (10,600 nm). In 1989, it was first used for resurfacing of a face with prominent photoaging. Ablative lasers have therefore had great popularity in the 1980s and 1990s, but prolonged postoperative time and significant risk of side effects have lowered the acceptance by patients. In 2004, the description of the fractionated radiation for the treatment of photoaging, by Mainstein, represented a great event. The stimulation of collagen occurred through fractional laser beams, which would reach the selected area while saving islands of sound skin. These islands accelerated the process of cicatrization of the treated tissue and shortened the postprocedure time. Furthermore, the fractionated radiation presented a smaller range of side effects, increasing the safety of the procedure. As mentioned earlier, as fractional lasers incise on the skin, they leave islands of healthy skin that accelerate recovery, while generating necrosis columns. Such necrosis columns remove damaged extracellular matrix material, allowing resettlement of fibroblasts. Such resettled fibroblasts, under the influence of a new tensile strength, restart to produce structures for extracellular matrix, such as collagen, elastin, and proteoglycans, in a more physiological way. Fractional lasers are considered by many dermatologists as the best choice in laser therapy

  4. Photoaging and the clinical utility of fractional laser.

    PubMed

    Borges, Juliano; Manela-Azulay, Mônica; Cuzzi, Tullia

    2016-01-01

    The description of atomic structure by Niels Bohr set the basis for the emergence of quantum physics. Based on these fundamentals, Einstein published in 1917 a paper on the amplification of energy by Stimulated Emission of Radiation as part of his quantum theories. In 1955, Townes and Gordon turned Einstein's theories into practice, creating a coherent and amplified microwave device using ammonia gas in an optical medium. But it was at the beginning of the 1980s, that Anderson and Parrish published an article about the selective photothermolysis model which revolutionized clinical practice. The use of laser in photoaging began with CO2 (10,600 nm). In 1989, it was first used for resurfacing of a face with prominent photoaging. Ablative lasers have therefore had great popularity in the 1980s and 1990s, but prolonged postoperative time and significant risk of side effects have lowered the acceptance by patients. In 2004, the description of the fractionated radiation for the treatment of photoaging, by Mainstein, represented a great event. The stimulation of collagen occurred through fractional laser beams, which would reach the selected area while saving islands of sound skin. These islands accelerated the process of cicatrization of the treated tissue and shortened the postprocedure time. Furthermore, the fractionated radiation presented a smaller range of side effects, increasing the safety of the procedure. As mentioned earlier, as fractional lasers incise on the skin, they leave islands of healthy skin that accelerate recovery, while generating necrosis columns. Such necrosis columns remove damaged extracellular matrix material, allowing resettlement of fibroblasts. Such resettled fibroblasts, under the influence of a new tensile strength, restart to produce structures for extracellular matrix, such as collagen, elastin, and proteoglycans, in a more physiological way. Fractional lasers are considered by many dermatologists as the best choice in laser therapy for

  5. Evaluation of the Quantitative and Qualitative Alterations in the Fatty Acid Contents of the Sebum of Patients with Inflammatory Acne during Treatment with Systemic Lymecycline and/or Oral Fatty Acid Supplementation

    PubMed Central

    Siqueira Talarico, Aline; Parra Duarte, Carla de Oliveira; Silva Pereira, Caroline; de Souza Weimann, Ellem Tatiani; Sabino de Matos, Lissa; Della Coletta, Livia Carolina; Fidelis, Maria Carolina; Vasconcellos, Cidia

    2013-01-01

    Background. Acne is a dermatosis that involves an altered sebum pattern. Objectives. (1) To evaluate if a treatment based on antibiotics (lymecycline) can alter fatty acids contents of the sebum of patients with acne; (2) to evaluate if oral supplementation of fatty acids can interfere with fatty acids contents of the sebum of patients with acne; (3) to evaluate if there is any interaction in fatty acids contents of the sebum of patients with acne when they use both antibiotics and oral supplementation of fatty acids. Methods. Forty-five male volunteers with inflammatory acne vulgaris were treated with 300 mg of lymecycline per day, with 540 mg of γ-linolenic acid, 1,200 mg of linoleic acid, and 510 mg of oleic acid per day, or with both regimens for 90 days. Every 30 days, a sample of sebum from the forehead was collected for fatty acids' chromatographic analysis. Results. Twelve fatty acids studied exhibited some kind of pattern changes during the study: C12:0, C14:0, C15:0, C16:1, C18:0, C18:1n9c+C18:1n9t, C18:2n6t, C18:3n6, C18:3n3, C20:1, C22:0, and C24:0. Conclusions. The daily administration of lymecycline and/or specific fatty acids may slightly influence some fatty acids levels present in the sebum of patients with inflammatory acne vulgaris. PMID:24191156

  6. UV-induced reactive oxygen species in photocarcinogenesis and photoaging.

    PubMed

    Scharffetter-Kochanek, K; Wlaschek, M; Brenneisen, P; Schauen, M; Blaudschun, R; Wenk, J

    1997-11-01

    The increase in UV irradiation on earth due to the stratospheric ozone depletion represents a major environmental threat to the skin increasing its risk of photooxidative damage by UV-induced reactive oxygen species (ROS). Increased ROS load has been implicated in several pathological states including photoaging and photocarcinogenesis of the skin. Large efforts have been made to better define the involvement of distinct ROS in photocarcinogenesis and photoaging. Both pathological processes share common features; however, they reveal unique molecular characteristics which finally determine the fate of the cell and its host. As well as causing permanent genetic changes involving protooncogenes and tumor suppressor genes, ROS activate cytoplasmic signal transduction pathways that are related to growth differentiation, senescence, transformation and tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in biochemical and clinical characteristics of photocarcinogenesis and photoaging. A decrease in the ROS load by efficient sunscreens and/or otherwise protective agents may represent a promising strategy to prevent or at least minimize ROS induced cutaneous pathological states. PMID:9426184

  7. Photoaging versus intrinsic aging: a morphologic assessment of facial skin.

    PubMed

    Bhawan, J; Andersen, W; Lee, J; Labadie, R; Solares, G

    1995-04-01

    Histologic studies have become increasingly important in recognizing morphologic differences in photoaged versus intrinsically aged skin. Earlier histologic studies have attempted to evaluate these changes by examining anatomical sites which are not comparable, such as face and buttocks. As part of a multicenter study, we have quantitatively examined a panel of 16 histologic features in baseline facial skin biopsies from 158 women with moderate to severe photodamage. When compared to the postauricular area (photo protected), biopsies of the crow's feet area (photo exposed) had a twofold increase in melanocytes and a statistically significant increase in melanocytic atypia (p < .0001) and epidermal melanin (p < .0001). Other epidermal changes included reduced epidermal thickness (p < .01), more compact stratum corneum (p < .0001) and increased granular layer thickness (p < .0001) in the crow's feet skin. There was increased solar elastosis (p < .0001), dermal elastic tissue (p < .0001), melanophages (p < .0001), perivascular inflammation (p < .05) and perifollicular fibrosis (p < .01) but no change in the number of mast cells or dermal mucin in the photo exposed skin. Our data document quantitative differences in photoaged versus intrinsically aged facial skin and provides the groundwork for future studies to evaluate the efficacy of new treatments for photoaged skin. PMID:7560349

  8. Alteration of Fatty Acid Oxidation in Tubular Epithelial Cells: From Acute Kidney Injury to Renal Fibrogenesis

    PubMed Central

    Simon, Noémie; Hertig, Alexandre

    2015-01-01

    Renal proximal tubular cells are the most energy-demanding cells in the body. The ATP that they use is mostly produced in their mitochondrial and peroxisomal compartments, by the oxidation of fatty acids. When those cells are placed under a biological stress, such as a transient hypoxia, fatty acid oxidation (FAO) is shut down for a period of time that outlasts injury, and carbohydrate oxidation does not take over. Facing those metabolic constraints, surviving tubular epithelial cells exhibit a phenotypic switch that includes cytoskeletal rearrangement and production of extracellular matrix proteins, most probably contributing to acute kidney injury-induced renal fibrogenesis, thence to the development of chronic kidney disease. Here, we review experimental evidence that dysregulation of FAO profoundly affects the fate of tubular epithelial cells, by promoting epithelial-to-mesenchymal transition, inflammation, and eventually interstitial fibrosis. Restoring physiological production of energy is undoubtedly a possible therapeutic approach to unlock the mesenchymal reprograming of tubular epithelial cells in the kidney. In this respect, the benefit of the use of fibrates is uncertain, but new drugs that could specifically target this metabolic pathway, and, hopefully, attenuate renal fibrosis merit future research. PMID:26301223

  9. Dietary fatty acid composition alters 11β-hydroxysteroid dehydrogenase type 1 gene expression in rat retroperitoneal white adipose tissue.

    PubMed

    Vara Prasad, Sakamuri S S; Jeya Kumar, Shanmugam S; Kumar, Putcha Uday; Qadri, Syed S Y H; Vajreswari, Ayyalasomayajula

    2010-01-01

    The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active forms in vivo. Adipose-specific overexpression of 11β-HSD1 induces metabolic syndrome in mice, whereas 11β-HSD1 null mice are resistant to it. Dietary trans and saturated fatty acids (TFAs and SFAs) are involved in the development of metabolic syndrome, whereas polyunsaturated fatty acids (PUFA) offer protection against this. Here, we report the effects of chronic feeding of different diets containing vanaspati (TFA rich), palm oil (SFA rich) and sunflower oil (PUFA rich) at 10%level on 11β-HSD1 gene expression in rat retroperitoneal adipose tissue. 11β-HSD1 gene expression was significantly higher in TFA rich diet-fed rats compared to SFA rich diet-fed rats, which in turn was significantly higher than PUFA rich diet-fed rats. Similar trend was observed in the expression of CCAAT-enhancer binding protein-α (C/EBP-α), the main transcription factor required for the expression of 11β-HSD1. We propose that TFAs and SFAs increase local amplification of glucocorticoid action in adipose tissue by upregulating 11β-HSD1 by altering C/EBP-α-gene expression. The increased levels of glucocorticoids in adipose tissue may lead to development of obesity and insulin resistance, thereby increasing the risk of developing metabolic syndrome. PMID:20932307

  10. Photoaging Mobile Apps in School-Based Tobacco Prevention: The Mirroring Approach

    PubMed Central

    Seeger, Werner; Buslaff, Fabian

    2016-01-01

    Background Most smokers start smoking during their early adolescence, often with the idea that smoking is glamorous. Adolescent smoking can best be prevented through health education at schools. Interventions that take advantage of the broad availability of mobile phones as well as adolescents’ interest in their appearance may be a novel way to improve prevention. Objective In this first pilot study, we aimed to use mobile phone technology in accordance with the theory of planned behavior to improve school-based tobacco prevention. Methods We used a free photoaging mobile phone app (“Smokerface”) in three German secondary schools via a novel method called mirroring. The students’ altered three-dimensional selfies on mobile phones or tablets were “mirrored” via a projector in front of their whole grade. Using an anonymous questionnaire, we then measured on a 5-point Likert scale the perceptions of the intervention among 125 students of both genders (average age 12.75 years). Results A majority of the students perceived the intervention as fun (77/125, 61.6%), claimed that the intervention motivated them not to smoke (79/125, 63.2%), and stated that they learned new benefits of non-smoking (81/125, 64.8%). Only a minority of students disagreed or fully disagreed that they learned new benefits of non-smoking (16/125, 12.8%) or that they were themselves motivated not to smoke (18/125, 14.4%). Conclusions We have presented a novel method to integrate photoaging in school-based tobacco prevention that affects student peer groups and considers the predictors of smoking in accordance with the theory of planned behavior. PMID:27352819

  11. Morphological change of skin fibroblasts induced by UV Irradiation is involved in photoaging.

    PubMed

    Yamaba, Hiroyuki; Haba, Manami; Kunita, Mayumi; Sakaida, Tsutomu; Tanaka, Hiroshi; Yashiro, Youichi; Nakata, Satoru

    2016-08-01

    Human dermal fibroblasts (HDFs) are typically flattened or extensible shaped and play a critical role in the metabolism of extracellular matrix components. As the properties of fibroblasts in the dermis are considered to be influenced by their morphology, we investigated the morphological changes induced in fibroblasts by ultraviolet (UV) irradiation as well as the relationship between these changes and collagen metabolism. In this study, we showed that UVA exposure induced morphological changes and reduced collagen contents in HDFs. These morphological changes were accompanied a reduction in actin filaments and upregulation of the actin filament polymerization inhibitor, capping protein muscle Z-line ɑ1 (CAPZA1). External actin filament growth inhibitors also affected the shape of HDFs and reduced collagen levels. These results suggest that UVA exposure may inhibit the polymerization of actin filaments and induce morphological changes in skin fibroblasts. These morphological changes in fibroblasts may accelerate reductions in collagen synthesis. This mechanism may be one of the processes responsible for collagen reductions observed in photoaged skin. When natural materials that suppress these morphological changes in HDFs were evaluated, we found that an extract of Lilium 'Casa Blanca' (LCB) suppressed UVA-induced alterations in the shape of HDFs, which are typically followed by inhibition of collagen reduction. An analysis of the active compounds in LCB extract led to the identification of regaloside I, which had a structure of phenylpropanoid glycerol glucoside, as the active compound inhibiting the upregulation of CAPZA1. Therefore, inhibition of UVA-induced morphological changes in HDFs is considered to be promising way for the suppression of collagen reduction in photoaging. PMID:27539902

  12. Time-resolved and steady-state fluorescence spectroscopy for the assessment of skin photoaging process

    NASA Astrophysics Data System (ADS)

    D´Almeida, Camila de Paula; Campos, Carolina; Saito Nogueira, Marcelo; Pratavieira, Sebastião.; Kurachi, Cristina

    2015-06-01

    pathology. The optical properties of these intrinsic fluorophores respond to the microenvironment and the metabolic status, thus making fluorescence spectroscopy a valuable tool to study the conditions of biological tissues. The purpose of this study is to investigate the hairless mice skin metabolic changes during the photoaging process through lifetime and fluorescence measurements targeting NADH and FAD. Two lasers centered at 378 nm and 445 nm, respectively, perform excitation of NADH and FAD. The fluorescence acquisition is carried out at mice dorsal and ventral regions throughout the photoaging protocol and aging process. Differences in fluorescence and lifetime data between young and photoaged mice measurements were observed. The endogenous fluorescence spectrum of photoaged dorsal skin showed an increase compared to young and aged skin. Lifetime of bound NADH and free FAD presented an increase in the first week that continued until the end of the protocol. Aging process is being investigated to complement the information obtained from fluorescence data and lifetime of photoaging process.

  13. Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

    PubMed Central

    Mamikutty, Norshalizah; Thent, Zar Chi; Haji Suhaimi, Farihah

    2015-01-01

    Background. Nonalcoholic fatty liver disease (NAFLD) is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD. Aims. In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis. Methods. The concentration of fructose-drinking water (FDW) used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph. Results. After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density. Conclusion. We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration. PMID:26273656

  14. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Autio, Reija; Borra, Ronald; Ojanen, Xiaowei; Xu, Leiting; Törmäkangas, Timo; Alen, Markku

    2015-01-01

    Background Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD. Methods Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS). Serum samples were analyzed using a nuclear magnetic resonance (NMR) metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot. Results Increased branched-chain amino acid (BCAA), aromatic amino acid (AAA) and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all). Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all), whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all). Conclusions Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis. PMID:26439744

  15. Long chain polyunsaturated fatty acids alter oxytocin signaling and receptor density in cultured pregnant human myometrial smooth muscle cells.

    PubMed

    Kim, Paul Y; Zhong, Miao; Kim, Yoon-Sun; Sanborn, Barbara M; Allen, Kenneth G D

    2012-01-01

    Epidemiological studies and interventional clinical trials indicate that consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as docosahexaenoic acid (DHA) lengthen gestational duration. Although the mechanisms are not well understood, prostaglandins (PG) of the 2-series are known to play a role in the initiation and progress of labor. In animal studies, modest DHA provision has been shown to reduce placental and uterine PGE(2) and PGF(2α), matrix metalloproteinase (MMP)-2 and MMP-9 expression, and placental collagenase activity. However, modulation of PG biosynthesis may not account for all the effects of LC n-3 PUFAs in labor. We investigated one potential PG-independent mechanism of LC PUFA action using cultured pregnant human myometrial smooth muscle cells. Our goal was to characterize the effect of LC PUFA treatment on oxytocin signaling, a potent uterotonic hormone involved in labor. The addition of 10 µM-100 µM DHA or arachidonic acid (AA) to the culture media for 48 h resulted in dose dependent enrichment of these fatty acids in membrane lipid. DHA and AA significantly inhibited phosphatidylinositol turnover and [Ca(2+)](i) mobilization with oxytocin stimulation compared to bovine serum albumin control and equimolar oleic acid. DHA and AA significantly reduced oxytocin receptor membrane concentration without altering binding affinity or rate of receptor internalization. These findings demonstrate a role for LC n-3 PUFAs in regulation of oxytocin signaling and provide new insight into additional mechanisms pertaining to reports of dietary fish and fish oil consumption prolonging gestation. PMID:22848573

  16. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose.

    PubMed

    Goossens, Gijs H; Moors, Chantalle C M; Jocken, Johan W E; van der Zijl, Nynke J; Jans, Anneke; Konings, Ellen; Diamant, Michaela; Blaak, Ellen E

    2016-03-01

    Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-(13)C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects. PMID:26985905

  17. Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disturbances in fatty acid (FA) metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. Therefore, lipid metabolome-wide responses and their relationships with endocrine (cortisol; insulin; adiponectin) responsiveness to acute stress (AS) were assessed in a ...

  18. Dietary (n-6 : n-3) fatty acids alter plasma and tissue fatty acid composition in pregnant Sprague Dawley rats.

    PubMed

    Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

    2012-01-01

    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205

  19. Monitoring photoaging by use of multiphoton fluorescence and second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Lin, Sung-Jan; Jee, Shiou-Hwa; Chan, Jung-Yi; Wu, Ruei-Jr; Lo, Wen; Tan, Hsin-Yuan; Lin, Wei-Chou; Chen, Jau-Shiuh; Young, Tai-Horng; Hsu, Chih-Jung; Dong, Chen-Yuan

    2006-02-01

    It is a field of great interest to develop therapies to rejuvenate photoaged skin. However, the treatment response can not be ideally determined due to lack of a reliable non-invasive method to quantify photoaging. In this study, the photoaging process of skin is investigated by use of a multiphoton fluorescence and second harmonic generation microscopy. We obtain the autofluorescence and second harmonic generation images of superficial dermis from facial skin of individuals of different ages. The results show that autofluorescence signals increase with age while second harmonic generation signals decrease with age. The results are consistent with the histological findings in which collagen is progressively replaced by elastic fibers. In the case of severe photoaging, solar elastosis can be clearly demonstrated by the presence of thick curvy autofluorescent materials in the superficial dermis. We propose a second harmonic generation to autofluorescence aging index of dermis to quantify the photoaging changes. This index is shown to be a good indicator of photoaging. Our results suggest that multiphoton fluorescence and second harmonic generation microscopy can be developed into a non-invasive imaging modelity for the clinical evaluation of photoaging.

  20. A comparative study of baby immature and adult shoots of Aloe vera on UVB-induced skin photoaging in vitro.

    PubMed

    Hwang, Eunson; Kim, Su Hyeon; Lee, Sarah; Lee, Choong Hwan; Do, Seon-Gil; Kim, Jinwan; Kim, Sun Yeou

    2013-12-01

    Ultraviolet (UV) irradiation induces photo-damage of the skin, which in turn causes depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkle formations are associated with collagen synthesis and matrix metalloproteinase (MMP) expression. The production of type I procollagen is regulated by transforming growth factor-β1 (TGF-β1) expression; the activation of MMP is also correlated with an increase of interleukin-6 (IL-6). Aloe barbadensis M. (Aloe vera) is widely used in cosmetic and pharmaceutical products. In this study, we examined whether baby aloe shoot extract (BAE, immature aloe extract), which is from the one-month-old shoots of Aloe vera, and adult aloe shoot extract (AE), which is from the four-month-old shoots of Aloe vera, have a protective effect on UVB-induced skin photoaging in normal human dermal fibroblasts (NHDFs). The effects of BAE and AE on UVB-induced photoaging were tested by measuring the levels of reactive oxygen species, MMP-1, MMP-3, IL-6, type I procollagen, and TGF-β1 after UVB irradiation. We found that NHDF cells treated with BAE after UVB-irradiation suppressed MMP-1, MMP-3, and IL-6 levels compared to the AE-treated cells. Furthermore, BAE treatment elevated type I procollagen and TGF-β1 levels. Our results suggest that BAE may potentially protect the skin from UVB-induced damage more than AE. PMID:23505091

  1. Naringenin targets ERK2 and suppresses UVB-induced photoaging.

    PubMed

    Jung, Sung Keun; Ha, Su Jeong; Jung, Chang Hwa; Kim, Yun Tai; Lee, Hoo-Keun; Kim, Myoung Ok; Lee, Mee-Hyun; Mottamal, Madhusoodanan; Bode, Ann M; Lee, Ki Won; Dong, Zigang

    2016-05-01

    A number of natural phytochemicals have anti-photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase-1 (MMP-1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB-induced MMP-1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3-dimensional (3-D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm(2) ) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB-induced MMP-1 expression and AP-1 activity, and strongly suppressed UVB-induced phosphorylation of Fos-related antigen (FRA)-1 at Ser265. Importantly, UVB irradiation-induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen-activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB-induced extracellular signal-regulated kinase 2 (ERK2) activity and subsequently attenuated UVB-induced phosphorylation of p90(RSK) by competitively binding with ATP. Constitutively active MEK (CA-MEK) increased FRA1 phosphorylation and expression and also induced MMP-1 expression, whereas dominant-negative ERK2 (DN-ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP-1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB-induced wrinkle formation, trans-epidermal water loss and MMP-13 expression. Naringenin exerts potent anti-photoaging effects by suppressing ERK2

  2. Serum phospholipid monounsaturated fatty acid composition and Δ-9-desaturase activity are associated with early alteration of fasting glycemic status.

    PubMed

    Cho, Jae Sun; Baek, Seung Han; Kim, Ji Young; Lee, Jong Ho; Kim, Oh Yoen

    2014-09-01

    Because alterations in blood fatty acid (FA) composition by dietary lipids are associated with insulin resistance and related metabolic disorders, we hypothesized that serum phospholipid FA composition would reflect the early alteration of fasting glycemic status, even in people without metabolic syndrome (MetS). To examine this hypothesis, serum phospholipid FA, desaturase activities, fasting glycemic status, and cardiometabolic parameters were measured in study participants (n = 1022; 30-69 years; male, n = 527; female, n = 495; nondiabetics without disease) who were stratified into normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Total monounsaturated FA (MUFA), oleic acid (OA; 18:1n-9), dihomo-γ-linolenic acid (DGLA; 20:3n-6), Δ-9-desaturase activity (D9D; 18:1n-9/18:0), and DGLA/linoleic acid (20:3n-6/18:2n-6) in serum phospholipids were significantly higher in IFG subjects than NFG controls. Study subjects were subdivided into 4 groups, based on fasting glucose levels and MetS status. Palmitoleic acid (16:1n-7) was highest in IFG-MetS and lowest in NFG-non-MetS subjects. Oleic acid and D9D were higher in IFG-MetS than in the other 3 groups. Dihomo-γ-linolenic acid and DGLA/linoleic acid were higher in MetS than in non-MetS, regardless of fasting glucose levels. The high-sensitivity C-reactive proteins (hs-CRPs) and 8-epi-prostaglandin-F2α were higher in IFG than in NFG, regardless of MetS status. Oxidized low-density lipoproteins were higher in IFG-MetS than in the other 3 groups. Total MUFAs, OA, and D9D were positively correlated with homeostasis model assessment of insulin resistance, fasting glucose, triglyceride, hs-CRP, and 8-epi-prostaglandin-F2α. Palmitoleic acid was positively correlated with triglyceride and hs-CRP. Lastly, total MUFA, OA, palmitoleic acid, and D9D were associated with early alteration of fasting glycemic status, therefore suggesting that these may be useful markers for predicting the risk of type 2

  3. Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling

    PubMed Central

    Clay, Hayley B.; Parl, Angelika K.; Mitchell, Sabrina L.; Singh, Larry; Bell, Lauren N.; Murdock, Deborah G.

    2016-01-01

    Despite the presence of a cytosolic fatty acid synthesis pathway, mitochondria have retained their own means of creating fatty acids via the mitochondrial fatty acid synthesis (mtFASII) pathway. The reason for its conservation has not yet been elucidated. Therefore, to better understand the role of mtFASII in the cell, we used thin layer chromatography to characterize the contribution of the mtFASII pathway to the fatty acid composition of selected mitochondrial lipids. Next, we performed metabolomic analysis on HeLa cells in which the mtFASII pathway was either hypofunctional (through knockdown of mitochondrial acyl carrier protein, ACP) or hyperfunctional (through overexpression of mitochondrial enoyl-CoA reductase, MECR). Our results indicate that the mtFASII pathway contributes little to the fatty acid composition of mitochondrial lipid species examined. Additionally, loss of mtFASII function results in changes in biochemical pathways suggesting alterations in glucose utilization and redox state. Interestingly, levels of bioactive lipids, including lysophospholipids and sphingolipids, directly correlate with mtFASII function, indicating that mtFASII may be involved in the regulation of bioactive lipid levels. Regulation of bioactive lipid levels by mtFASII implicates the pathway as a mediator of intracellular signaling. PMID:26963735

  4. Changing the omega-6 to omega-3 fatty acid ratio in sow diets alters serum, colostrum, and milk fatty acid profiles, but has minimal impact on reproductive performance.

    PubMed

    Eastwood, L; Leterme, P; Beaulieu, A D

    2014-12-01

    This experiment tested the hypothesis that reducing the omega-6 (n-6) to omega-3 (n-3) fatty acid (FA) ratio in sow diets will improve performance, characterized by increased litter size, decreased preweaning mortality, and improved growth performance. Second, we determined if the FA profile in sow and piglet blood, colostrum, and milk are altered when sows are fed diets with varied n-6:n-3 ratios and if the dietary FA ratio impacts circulating concentrations of IgG, IgA, eicosapentaenoic (EPA), or docosahexaenoic (DHA) acid. Sows (n=150) were assigned to 1 of 5 treatments (each divided into gestation and lactation diets) on d 80 of gestation. Period 1 (P1) is defined as d 80 of gestation to weaning and Period 2 (P2) refers to the subsequent breeding to weaning. Diets were wheat and barley based (5% crude fat) and treatments consisted of a control (tallow), 3 diets with plant oil-based n-6:n-3 ratios (9:1P, 5:1P, and 1:1P), and a 5:1 fish oil diet (5:1F). Litter size was unaffected by treatment during P1 and P2 (P>0.10). In P1, birth weight was unaffected by diet (P>0.10); however, weaning weight (P=0.019) and ADG from birth to weaning (P=0.011) were greatest for piglets born to 9:1P and 5:1P sows. During P2, 5:1F sows consumed 10% less feed during lactation (P=0.036), tended to have reduced piglet birth weights (P=0.052), and piglet weaning weight was reduced by 0.8 kg (P=0.040) relative to the other diets. Colostrum and piglet serum IgA and IgG concentrations were unaffected by diet (P>0.10). Serum n-3 FA were greatest in sows (P<0.01) consuming 1:1P and 5:1F diets and in their offspring (P=0.014). Serum α-linolenic acid (ALA) was greatest in 1:1P sows and EPA and DHA were greatest in 5:1F sows (P<0.01). In pre-suckle piglet serum, ALA did not differ among treatment groups (P>0.10). Relative to piglets of sows consuming the control diet, EPA was 2.5-fold greater in the 1:1P group and 4-fold greater in 5:1F group (P<0.01) before suckling. In post-suckle samples

  5. Camelina meal increases egg n-3 fatty acid content without altering egg quality or production in laying hens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Camelina sativa is an oilseed plant rich in n-3 and n-6-fatty acids and extruding defatted seed meal results in high protein meal (~40%) containing residual n-3 fatty acids. We examined the effects of feeding extruded defatted camelina seed meal to commercial laying hens on egg production, quality, ...

  6. Early Growth Response1and Fatty Acid Synthase Expression is Altered in Tumor Adjacent Prostate Tissue and Indicates Field Cancerization

    PubMed Central

    Jones, Anna C.; Trujillo, Kristina A.; Phillips, Genevieve K.; Fleet, Trisha M.; Murton, Jaclyn K.; Severns, Virginia; Shah, Satyan K.; Davis, Michael S.; Smith, Anthony Y.; Griffith, Jeffrey K.; Fischer, Edgar G.; Bisoffi, Marco

    2011-01-01

    BACKGROUND Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer. METHODS Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues. RESULTS EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues. CONCLUSIONS EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention. PMID:22127986

  7. Alterations in MicroRNA Expression Contribute to Fatty Acid–Induced Pancreatic β-Cell Dysfunction

    PubMed Central

    Lovis, Pascal; Roggli, Elodie; Laybutt, D. Ross; Gattesco, Sonia; Yang, Jiang-Yan; Widmann, Christian; Abderrahmani, Amar; Regazzi, Romano

    2008-01-01

    OBJECTIVE—Visceral obesity and elevated plasma free fatty acids are predisposing factors for type 2 diabetes. Chronic exposure to these lipids is detrimental for pancreatic β-cells, resulting in reduced insulin content, defective insulin secretion, and apoptosis. We investigated the involvement in this phenomenon of microRNAs (miRNAs), a class of noncoding RNAs regulating gene expression by sequence-specific inhibition of mRNA translation. RESEARCH DESIGN AND METHODS—We analyzed miRNA expression in insulin-secreting cell lines or pancreatic islets exposed to palmitate for 3 days and in islets from diabetic db/db mice. We studied the signaling pathways triggering the changes in miRNA expression and determined the impact of the miRNAs affected by palmitate on insulin secretion and apoptosis. RESULTS—Prolonged exposure of the β-cell line MIN6B1 and pancreatic islets to palmitate causes a time- and dose-dependent increase of miR34a and miR146. Elevated levels of these miRNAs are also observed in islets of diabetic db/db mice. miR34a rise is linked to activation of p53 and results in sensitization to apoptosis and impaired nutrient-induced secretion. The latter effect is associated with inhibition of the expression of vesicle-associated membrane protein 2, a key player in β-cell exocytosis. Higher miR146 levels do not affect the capacity to release insulin but contribute to increased apoptosis. Treatment with oligonucleotides that block miR34a or miR146 activity partially protects palmitate-treated cells from apoptosis but is insufficient to restore normal secretion. CONCLUSIONS—Our findings suggest that at least part of the detrimental effects of palmitate on β-cells is caused by alterations in the level of specific miRNAs. PMID:18633110

  8. Imaging heterogeneity of membrane and storage lipids in transgenic Camelina sativa seeds with altered fatty acid profiles.

    PubMed

    Horn, Patrick J; Silva, Jillian E; Anderson, Danielle; Fuchs, Johannes; Borisjuk, Ljudmilla; Nazarenus, Tara J; Shulaev, Vladimir; Cahoon, Edgar B; Chapman, Kent D

    2013-10-01

    Engineering compositional changes in oilseeds is typically accomplished by introducing new enzymatic step(s) and/or by blocking or enhancing an existing enzymatic step(s) in a seed-specific manner. However, in practice, the amounts of lipid species that accumulate in seeds are often different from what one would predict from enzyme expression levels, and these incongruences may be rooted in an incomplete understanding of the regulation of seed lipid metabolism at the cellular/tissue level. Here we show by mass spectrometry imaging approaches that triacylglycerols and their phospholipid precursors are distributed differently within cotyledons and the hypocotyl/radicle axis in embryos of the oilseed crop Camelina sativa, indicating tissue-specific heterogeneity in triacylglycerol metabolism. Phosphatidylcholines and triacylglycerols enriched in linoleic acid (C18:2) were preferentially localized to the axis tissues, whereas lipid classes enriched in gadoleic acid (C20:1) were preferentially localized to the cotyledons. Manipulation of seed lipid compositions by heterologous over-expression of an acyl-acyl carrier protein thioesterase, or by suppression of fatty acid desaturases and elongases, resulted in new overall seed storage lipid compositions with altered patterns of distribution of phospholipid and triacylglycerol in transgenic embryos. Our results reveal previously unknown differences in acyl lipid distribution in Camelina embryos, and suggest that this spatial heterogeneity may or may not be able to be changed effectively in transgenic seeds depending upon the targeted enzyme(s)/pathway(s). Further, these studies point to the importance of resolving the location of metabolites in addition to their quantities within plant tissues. PMID:23808562

  9. Branched Chain Fatty Acids Reduce the Incidence of Necrotizing Enterocolitis and Alter Gastrointestinal Microbial Ecology in a Neonatal Rat Model

    PubMed Central

    Ran-Ressler, Rinat R.; Khailova, Ludmila; Arganbright, Kelly M.; Adkins-Rieck, Camille K.; Jouni, Zeina E.; Koren, Omry; Ley, Ruth E.; Brenna, J. Thomas; Dvorak, Bohuslav

    2011-01-01

    Introduction Branched chain fatty acids (BCFA) are found in the normal term human newborn's gut, deposited as major components of vernix caseosa ingested during late fetal life. We tested the hypothesis that premature infants' lack of exposure to gastrointestinal (GI) BCFA is associated with their microbiota and risk for necrotizing enterocolitis (NEC) using a neonatal rat model. Methods Pups were collected one day before scheduled birth. The pups were exposed to asphyxia and cold stress to induce NEC. Pups were assigned to one of three experimental treatments. DF (dam-fed) ; Control, hand-fed rat milk substitute ; BCFA, hand-fed rat milk substitute with 20%w/w BCFA. Total fat was equivalent (11%wt) for both the Control and BCFA groups. Cecal microbiota were characterized by 16S rRNA gene pyrosequencing, and intestinal injury, ileal cytokine and mucin gene expression, interleukin-10 (IL-10) peptide immunohistochemistry, and BCFA uptake in ileum phospholipids, serum and liver were assessed. Results NEC incidence was reduced by over 50% in the BCFA group compared to the Control group as assessed in ileal tissue; microbiota differed among all groups. BCFA-fed pups harbored greater levels of BCFA-associated Bacillus subtilis and Pseudomonas aeruginosa compared to Controls. Bacillus subtilis levels were five-fold greater in healthy pups compared to pups with NEC. BCFA were selectively incorporated into ileal phospholipids, serum and liver tissue. IL-10 expression increased three-fold in the BCFA group versus Controls and no other inflammatory or mucosal mRNA markers changed. Conclusion At constant dietary fat level, BCFA reduce NEC incidence and alter microbiota composition. BCFA are also incorporated into pup ileum where they are associated with enhanced IL-10 and may exert other specific effects. PMID:22194981

  10. Plant fatty acid hydroxylases

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank

    2001-01-01

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  11. Alteration of organic matter during infaunal polychaete gut passage and links to sediment organic geochemistry. Part II: Fatty acids and aldoses

    NASA Astrophysics Data System (ADS)

    Woulds, Clare; Middelburg, Jack J.; Cowie, Greg L.

    2014-07-01

    The activities of sediment-dwelling fauna are known to influence the rates of and pathways through which organic matter is cycled in marine sediments, and thus to influence eventual organic carbon burial or decay. However, due to methodological constraints, the role of faunal gut passage in determining the subsequent composition and thus degradability of organic matter is relatively little studied. Previous studies of organic matter digestion by benthic fauna have been unable to detect uptake and retention of specific biochemicals in faunal tissues, and have been of durations too short to fit digestion into the context of longer-term sedimentary degradation processes. Therefore this study aimed to investigate the aldose and fatty acid compositional alterations occurring to organic matter during gut passage by the abundant and ubiquitous polychaetes Hediste diversicolor and Arenicola marina, and to link these to longer-term changes typically observed during organic matter decay. This aim was approached through microcosm experiments in which selected polychaetes were fed with 13C-labelled algal detritus, and organisms, sediments, and faecal pellets were sampled at three timepoints over ∼6 weeks. Samples were analysed for their 13C-labelled aldose and fatty acid contents using GC-MS and GC-IRMS. Compound-selective net accumulation of biochemicals in polychaete tissues was observed for both aldoses and fatty acids, and the patterns of this were taxon-specific. The dominant patterns included an overall loss of glucose and polyunsaturated fatty acids; and preferential preservation or production of arabinose, microbial compounds (rhamnose, fucose and microbial fatty acids), and animal-synthesised fatty acids. These patterns may have been driven by fatty acid essentiality, preferential metabolism of glucose, and A. marina grazing on bacteria. Fatty acid suites in sediments from faunated microcosms showed greater proportions of saturated fatty acids and bacterial markers

  12. Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Auguet, Teresa; Berlanga, Alba; Guiu-Jurado, Esther; Martinez, Salomé; Porras, José Antonio; Aragonès, Gemma; Sabench, Fátima; Hernandez, Mercé; Aguilar, Carmen; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2014-01-01

    Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis. PMID:25474087

  13. Skin Photoaging and the Role of Antioxidants in Its Prevention

    PubMed Central

    Pandel, Ruža; Poljšak, Borut

    2013-01-01

    Photoaging of the skin depends primarily on the degree of ultraviolet radiation (UVR) and on an amount of melanin in the skin (skin phototype). In addition to direct or indirect DNA damage, UVR activates cell surface receptors of keratinocytes and fibroblasts in the skin, which leads to a breakdown of collagen in the extracellular matrix and a shutdown of new collagen synthesis. It is hypothesized that dermal collagen breakdown is followed by imperfect repair that yields a deficit in the structural integrity of the skin, formation of a solar scar, and ultimately clinically visible skin atrophy and wrinkles. Many studies confirmed that acute exposure of human skin to UVR leads to oxidation of cellular biomolecules that could be prevented by prior antioxidant treatment and to depletion of endogenous antioxidants. Skin has a network of all major endogenous enzymatic and nonenzymatic protective antioxidants, but their role in protecting cells against oxidative damage generated by UV radiation has not been elucidated. It seems that skin's antioxidative defence is also influenced by vitamins and nutritive factors and that combination of different antioxidants simultaneously provides synergistic effect. PMID:24159392

  14. Alteration of seed fatty acid composition by an ethyl methanesulfonate-induced mutation in Arabidopsis thaliana affecting diacylglycerol acyltransferase activity.

    PubMed Central

    Katavic, V; Reed, D W; Taylor, D C; Giblin, E M; Barton, D L; Zou, J; Mackenzie, S L; Covello, P S; Kunst, L

    1995-01-01

    In characterizing the enzymes involved in the formation of very long-chain fatty acids (VLCFAs) in the Brassicaceae, we have generated a series of mutants of Arabidopsis thaliana that have reduced VLCFA content. Here we report the characterization of a seed lipid mutant, AS11, which, in comparison to wild type (WT), has reduced levels of 20:1 and 18:1 and accumulates 18:3 as the major fatty acid in triacylglycerols. Proportions of 18:2 remain similar to WT. Genetic analyses indicate that the fatty acid phenotype is caused by a semidominant mutation in a single nuclear gene, designated TAG1, located on chromosome 2. Biochemical analyses have shown that the AS11 phenotype is not due to a deficiency in the capacity to elongate 18:1 or to an increase in the relative delta 15 or delta 12 desaturase activities. Indeed, the ratio of desaturase/elongase activities measured in vitro is virtually identical in developing WT and AS11 seed homogenates. Rather, the fatty acid phenotype of AS11 is the result of reduced diacylglycerol acyltransferase activity throughout development, such that triacylglycerol biosynthesis is reduced. This leads to a reduction in 20:1 biosynthesis during seed development, leaving more 18:1 available for desaturation. Thus, we have demonstrated that changes to triacylglycerol biosynthesis can result in dramatic changes in fatty acid composition and, in particular, in the accumulation of VLCFAs in seed storage lipids. PMID:7784510

  15. Deletions of the SACPD-C locus elevate seed stearic acid levels but also result in fatty acid and morphological alterations in nitrogen fixing nodules

    PubMed Central

    2014-01-01

    Background Soybean (Glycine max) seeds are the primary source of edible oil in the United States. Despite its widespread utility, soybean oil is oxidatively unstable. Until recently, the majority of soybean oil underwent chemical hydrogenation, a process which also generates trans fats. An alternative to chemical hydrogenation is genetic modification of seed oil through identification and introgression of mutant alleles. One target for improvement is the elevation of a saturated fat with no negative cardiovascular impacts, stearic acid, which typically constitutes a minute portion of seed oil (~3%). Results We examined radiation induced soybean mutants with moderately increased stearic acid (10-15% of seed oil, ~3-5 X the levels in wild-type soybean seeds) via comparative whole genome hybridization and genetic analysis. The deletion of one SACPD isoform encoding gene (SACPD-C) was perfectly correlated with moderate elevation of seed stearic acid content. However, SACPD-C deletion lines were also found to have altered nodule fatty acid composition and grossly altered morphology. Despite these defects, overall nodule accumulation and nitrogen fixation were unaffected, at least under laboratory conditions. Conclusions Although no yield penalty has been reported for moderate elevated seed stearic acid content in soybean seeds, our results demonstrate that genetic alteration of seed traits can have unforeseen pleiotropic consequences. We have identified a role for fatty acid biosynthesis, and SACPD activity in particular, in the establishment and maintenance of symbiotic nitrogen fixation. PMID:24886084

  16. Steroidogenesis in MA-10 Mouse Leydig Cells Is Altered via Fatty Acid Import into the Mitochondria1

    PubMed Central

    Rone, Malena B.; Midzak, Andrew S.; Martinez-Arguelles, Daniel B.; Fan, Jinjiang; Ye, Xiaoying; Blonder, Josip; Papadopoulos, Vassilios

    2014-01-01

    ABSTRACT Mitochondria are home to many cellular processes, including oxidative phosphorylation and fatty acid metabolism, and in steroid-synthesizing cells, they are involved in cholesterol import and metabolism, which is the initiating step in steroidogenesis. The formation of macromolecular protein complexes aids in the regulation and efficiency of these mitochondrial functions, though because of their dynamic nature, they are hard to identify. To overcome this problem, we used Blue-Native PAGE with whole-gel mass spectrometry on isolated mitochondria from control and hormone-treated MA-10 mouse tumor Leydig cells. The presence of multiple mitochondrial protein complexes was shown. Although these were qualitatively similar under control and human chorionic gonadotropin (hCG)-stimulated conditions, quantitative differences in the components of the complexes emerged after hCG treatment. A prominent decrease was observed with proteins involved in fatty acid import into the mitochondria, implying that mitochondrial beta-oxidation is not essential for steroidogenesis. To confirm this observation, we inhibited fatty acid import utilizing the CPT1a inhibitor etomoxir, resulting in increased steroid production. Conversely, stimulation of mitochondrial beta-oxidation with metformin resulted in a dose-dependent reduction in steroidogenesis. These changes were accompanied by changes in mitochondrial respiration and in the lactic acid formed during glycolysis. Taken together, these results suggest that upon hormonal stimulation, mitochondria efficiently import cholesterol for steroid production at the expense of other lipids necessary for energy production, specifically fatty acids required for beta-oxidation. PMID:25210128

  17. Beef Fat Enriched with Polyunsaturated Fatty Acid Biohydrogenation Products Improves Insulin Sensitivity Without Altering Dyslipidemia in Insulin Resistant JCR:LA-cp Rats.

    PubMed

    Diane, Abdoulaye; Borthwick, Faye; Mapiye, Cletos; Vahmani, Payam; David, Rolland C; Vine, Donna F; Dugan, Michael E R; Proctor, Spencer D

    2016-07-01

    The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA-BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti-trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA-BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA-BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri-renal fat (PRF) with differing enrichments of PUFA-BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA-cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS-PRF) or sunflower-seed (SS-PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS-PRF) without altering dyslipidemia. Moreover, FS-PRF but not SS-PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA-BHP in beef PRF with FS feeding may be a useful approach to maximize the health-conferring value of beef-derived fats. PMID:27072368

  18. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome

    PubMed Central

    Ktsoyan, Zhanna A.; Beloborodova, Natalia V.; Sedrakyan, Anahit M.; Osipov, George A.; Khachatryan, Zaruhi A.; Manukyan, Gayane P.; Arakelova, Karine A.; Hovhannisyan, Alvard I.; Arakelyan, Arsen A.; Ghazaryan, Karine A.; Zakaryan, Magdalina K.; Aminov, Rustam I.

    2013-01-01

    In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome. PMID:23373011

  19. Alterations in the fatty acid profile, antioxidant enzymes and protein pattern of Biomphalaria alexandrina snails exposed to the pesticides diazinon and profenfos.

    PubMed

    Bakry, Fayez A; El-Hommossany, Karem; Abd El-Atti, Mahmoud; Ismail, Somaya M

    2016-04-01

    The use of pesticides is widespread in agricultural activities. These pesticides may contaminate the irrigation and drainage systems during agriculture activities and pests' control and then negatively affect the biotic and a biotic component of the polluted water courses. The present study aimed to evaluate the effect of the pesticides diazinon and profenfos on some biological activities of Biomphalaria alexandrina snails such as fatty acid profile, some antioxidant enzymes (thioredoxin reductase (TrxR), sorbitol dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT) as well as glutathione reductase (GR) and lipid peroxidation (LP)) and protein patterns in snails' tissues exposed for 4 weeks to LC10 of diazinon and profenfos. The results showed that the two pesticides caused considerable reduction in survival rates and egg production of treated snails. Identification of fatty acid composition in snail tissues treated with diazinon and profenfos pesticides was carried out using gas-liquid chromatography (GLC). The results declared alteration in fatty acid profile, fluctuation in percentage of long chain and short chain fatty acid contributions either saturated or unsaturated ones, and a decrease in total lipid content in tissues of snails treated with these pesticides. The data demonstrate that there was a significant inhibition in the activities of tissues SOD, CAT, glutathione reductase (GR), TrxR, and SDH in tissues of treated snails, while a significant elevation was detected in LP as compared to the normal control. On the other hand, the electrophoretic pattern of total protein showed differences in number and molecular weights of protein bands due to the treatment of snails. It was concluded that the residues of diazinon and profenfos pesticides in aquatic environments have toxic effects onB. alexandrina snails. PMID:24215063

  20. Perfluorooctanoic acid exposure alters polyunsaturated fatty acid composition, induces oxidative stress and activates the AKT/AMPK pathway in mouse epididymis.

    PubMed

    Lu, Yin; Pan, Yitao; Sheng, Nan; Zhao, Allan Z; Dai, Jiayin

    2016-09-01

    Perfluorooctanoic acid (PFOA) is a degradation-resistant compound with a carbon-fluorine bond. Although PFOA emissions have been reduced since 2000, it remains persistent in the environment. Several studies on laboratory animals indicate that PFOA exposure can impact male fertility. Here, adult male mice received either PFOA (1.25, 5 or 20 mg/kg/d) or an equal volume of water for 28 d consecutively. PFOA accumulated in the epididymis in a dose-dependent manner and resulted in reduced epididymis weight, lower levels of triglycerides (TG), cholesterol (CHO), and free fatty acids (FFA), and activated AKT/AMPK signaling in the epididymis. Altered polyunsaturated fatty acid (PUFA) compositions, such as a higher arachidonic acid:linoleic acid (AA:LA) ratio, concomitant with excessive oxidative stress, as demonstrated by increased malonaldehyde (MDA) and decreased glutathione peroxidase (GSH-Px) in the epididymis, were observed in epididymis tissue following treatment with PFOA. These results indicate that the epididymis is a potential target of PFOA. Oxidative stress and PUFA alteration might help explain the sperm injury and male reproductive dysfunction induced by PFOA exposure. PMID:27262104

  1. Coriander leaf extract exerts antioxidant activity and protects against UVB-induced photoaging of skin by regulation of procollagen type I and MMP-1 expression.

    PubMed

    Hwang, Eunson; Lee, Do-Gyeong; Park, Sin Hee; Oh, Myung Sook; Kim, Sun Yeou

    2014-09-01

    Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging. PMID:25019675

  2. Coriander Leaf Extract Exerts Antioxidant Activity and Protects Against UVB-Induced Photoaging of Skin by Regulation of Procollagen Type I and MMP-1 Expression

    PubMed Central

    Hwang, Eunson; Lee, Do-Gyeong; Park, Sin Hee; Oh, Myung Sook

    2014-01-01

    Abstract Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging. PMID:25019675

  3. Supplementation of essential fatty acids to Holstein calves during late uterine life and first month of life alters hepatic fatty acid profile and gene expression.

    PubMed

    Garcia, M; Greco, L F; Lock, A L; Block, E; Santos, J E P; Thatcher, W W; Staples, C R

    2016-09-01

    Linoleic acid is an essential dietary fatty acid (FA). However, how the supplementation of linoleic acid during uterine and early life may modify the FA profile and transcriptome regulation of the liver, and performance of preweaned dairy calves is unknown. Our objective was to evaluate the effect of supplementation of essential FA to Holstein calves during late uterine and early life on their hepatic FA profile and global gene expression at 30 d of age. During the last 8 wk of pregnancy, Holstein cattle (n=96) were fed either no fat supplement (control), a saturated FA supplement enriched with C18:0, or an unsaturated FA supplement enriched with linoleic acid. Male calves (n=40) born from these dams were fed a milk replacer (MR) with either low (LLA) or high linoleic acid (HLA) concentration as the sole feedstuff during the first 30 d. Liver biopsy was performed at 30 d of age, and microarray analysis was performed on 18 liver samples. Total concentration of FA in liver were greater in calves fed LLA compared with those fed HLA MR (8.2 vs. 7.1%), but plasma concentrations of total FA did not differ due to MR diets. The FA profiles of plasma and liver of calves were affected differently by the prepartum diets. Specifically, the FA profile in liver was affected moderately by the feeding of fat prepartum, but the profiles did not differ due to the type of FA fed prepartum. The type of MR fed during the first 30 d of life had major effects on both plasma and liver FA profiles, resembling the type of fat fed. Plasma and liver of calves fed LLA MR had greater percentage of medium-chain FA (C12:0 and C14:0), whereas plasma and liver from calves fed HLA MR had greater percentages of linoleic and α-linolenic acids. Dams fed fat or a specific type of FA modified the expression of some genes in liver of calves, particularly those genes involved in biological functions and pathways related to upregulation of lipid metabolism and downregulation of inflammatory responses

  4. Aryl Hydrocarbon Receptor–Mediated Induction of Stearoyl-CoA Desaturase 1 Alters Hepatic Fatty Acid Composition in TCDD-Elicited Steatosis

    PubMed Central

    Angrish, Michelle M.; Jones, A.D.; Harkema, Jack R.; Zacharewski, Timothy R.

    2011-01-01

    2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD) induces hepatic dyslipidemia mediated by the aryl hydrocarbon receptor (AhR). Stearoyl-CoA desaturase 1 (Scd1) performs the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis, desaturating 16:0 and 18:0 into 16:1n7 and 18:1n9, respectively. To further examine the role of Scd1 in TCDD-induced hepatotoxicity, comparative studies were performed in Scd1+/+ and Scd1−/− mice treated with 30 μg/kg TCDD. TCDD induced Scd1 activity, protein, and messenger RNA (mRNA) levels approximately twofold. In Scd1+/+ mice, hepatic effects were marked by increased vacuolization and inflammation and a 3.5-fold increase in serum alanine aminotransferase (ALT) levels. Hepatic triglycerides (TRGs) were induced 3.9-fold and lipid profiling by gas chromatography-mass spectroscopy measured a 1.9-fold increase in fatty acid (FA) levels, consistent with the induction of lipid transport genes. Induction of Scd1 altered FA composition by decreasing saturated fatty acid (SFA) molar ratios 8% and increasing MUFA molar ratios 9%. Furthermore, ChIP-chip analysis revealed AhR enrichment (up to 5.7-fold), and computational analysis identified 16 putative functional dioxin response elements (DREs) within Scd1 genomic loci. Band shift assays confirmed AhR binding with select DREs. In Scd1−/− mice, TCDD induced minimal hepatic vacuolization and inflammation, while serum ALT levels remained unchanged. Although Scd1 deficiency attenuated TCDD-induced TRG accumulation, overall FA levels remained unchanged compared with Scd1+/+ mice. In Scd1−/− mice, TCDD induced SFA ratios 8%, reduced MUFA ratios 13%, and induced polyunsaturated fatty acid ratios 5% relative to treated Scd1+/+ mice. Collectively, these results suggest that AhR regulation of Scd1 not only alters lipid composition but also contributes to the hepatotoxicity of TCDD. PMID:21890736

  5. Ethanol extracts of chickpeas alter the total lipid content and expression levels of genes related to fatty acid metabolism in mouse 3T3-L1 adipocytes.

    PubMed

    Shinohara, Shigeo; Gu, Yuanjun; Yang, Ying; Furuta, Yasuo; Tanaka, Masahiko; Yue, Xiaohua; Wang, Weiqing; Kitano, Masaru; Kimura, Hiroshi

    2016-08-01

    Desi-type chickpeas, which have long been used as a natural treatment for diabetes, have been reported to lower visceral adiposity, dyslipidemia and insulin resistance induced by a chronic high-fat diet in rats. In this study, in order to examine the effects of chickpeas of this type in an in vitro system, we used the 3T3-L1 mouse cell line, a subclone of Swiss 3T3 cells, which can differentiate into cells with an adipocyte-like phenotype, and we used ethanol extracts of chickpeas (ECP) instead of chickpeas. Treatment of the 3T3-L1 cells with ECP led to a decrease in the lipid content in the cells. The desaturation index, defined as monounsaturated fatty acids (MUFAs)/saturated fatty acids (SFAs), was also decreased by ECP due to an increase in the cellular content of SFAs and a decrease in the content of MUFAs. The decrease in this index may reflect a decreased reaction from SFA to MUFA, which is essential for fat storage. To confirm this hypothesis, we conducted a western blot analysis, which revealed a reduction in the amount of stearoyl-CoA desaturase 1 (SCD1), a key enzyme catalyzing the reaction from SFA to MUFA. We observed simultaneous inactivations of enzymes participating in lipogenesis, i.e., liver kinase B1 (LKB1), acetyl-CoA carboxylase (ACC) and AMPK, by phosphorylation, which may lead to the suppression of reactions from acetyl-CoA to SFA via malonyl-CoA in lipogenesis. We also investigated whether lipolysis is affected by ECP. The amount of carnitine palmitoyltransferase 1 (CPT1), an enzyme important for the oxidation of fatty acids, was increased by ECP treatment. ECP also led to an increase in uncoupling protein 2 (UCP2), reported as a key protein for the oxidation of fatty acids. All of these results obtained regarding lipogenesis and fatty acid metabolism in our in vitro system are consistent with the results previously shown in rats. We also examined the effects on SCD1 and lipid contents of ethanol extracts of Kabuli

  6. Ethanol extracts of chickpeas alter the total lipid content and expression levels of genes related to fatty acid metabolism in mouse 3T3-L1 adipocytes

    PubMed Central

    Shinohara, Shigeo; Gu, Yuanjun; Yang, Ying; Furuta, Yasuo; Tanaka, Masahiko; Yue, Xiaohua; Wang, Weiqing; Kitano, Masaru; Kimura, Hiroshi

    2016-01-01

    Desi-type chickpeas, which have long been used as a natural treatment for diabetes, have been reported to lower visceral adiposity, dyslipidemia and insulin resistance induced by a chronic high-fat diet in rats. In this study, in order to examine the effects of chickpeas of this type in an in vitro system, we used the 3T3-L1 mouse cell line, a subclone of Swiss 3T3 cells, which can differentiate into cells with an adipocyte-like phenotype, and we used ethanol extracts of chickpeas (ECP) instead of chickpeas. Treatment of the 3T3-L1 cells with ECP led to a decrease in the lipid content in the cells. The desaturation index, defined as monounsaturated fatty acids (MUFAs)/saturated fatty acids (SFAs), was also decreased by ECP due to an increase in the cellular content of SFAs and a decrease in the content of MUFAs. The decrease in this index may reflect a decreased reaction from SFA to MUFA, which is essential for fat storage. To confirm this hypothesis, we conducted a western blot analysis, which revealed a reduction in the amount of stearoyl-CoA desaturase 1 (SCD1), a key enzyme catalyzing the reaction from SFA to MUFA. We observed simultaneous inactivations of enzymes participating in lipogenesis, i.e., liver kinase B1 (LKB1), acetyl-CoA carboxylase (ACC) and AMPK, by phosphorylation, which may lead to the suppression of reactions from acetyl-CoA to SFA via malonyl-CoA in lipogenesis. We also investigated whether lipolysis is affected by ECP. The amount of carnitine palmitoyltransferase 1 (CPT1), an enzyme important for the oxidation of fatty acids, was increased by ECP treatment. ECP also led to an increase in uncoupling protein 2 (UCP2), reported as a key protein for the oxidation of fatty acids. All of these results obtained regarding lipogenesis and fatty acid metabolism in our in vitro system are consistent with the results previously shown in rats. We also examined the effects on SCD1 and lipid contents of ethanol extracts of Kabuli-type chickpeas, which are

  7. Fatty acid-specific alterations in leptin, PPARα, and CPT-1 gene expression in the rainbow trout.

    PubMed

    Coccia, Elena; Varricchio, Ettore; Vito, Pasquale; Turchini, Giovanni Mario; Francis, David Scott; Paolucci, Marina

    2014-10-01

    It is known that fatty acids (FA) regulate lipid metabolism by modulating the expression of numerous genes. In order to gain a better understanding of the effect of individual FA on lipid metabolism related genes in rainbow trout (Oncorhynchus mykiss), an in vitro time-course study was implemented where twelve individual FA (butyric 4:0; caprylic 8:0; palmitic (PAM) 16:0; stearic (STA) 18:0; palmitoleic16:1n-7; oleic 18:1n-9; 11-cis-eicosenoic 20:1n-9; linoleic (LNA) 18:2n-6; α-linolenic (ALA) 18:3n-3; eicosapentenoic (EPA) 20:5n-3; docosahexaenoic (DHA) 22:6n-3; arachidonic (ARA) 20:4n-6) were incubated in rainbow trout liver slices. The effect of FA administration over time was evaluated on the expression of leptin, PPARα and CPT-1 (lipid oxidative related genes). Leptin mRNA expression was down regulated by saturated fatty acids (SFA) and LNA, and was up regulated by monounsaturated fatty acids (MUFA) and long chain PUFA, whilst STA and ALA had no effect. PPARα and CPT-1mRNA expression were up regulated by SFA, MUFA, ALA, ARA and DHA; and down regulated by LNA and EPA. These results suggest that there are individual and specific FA induced modifications of leptin, PPARα and CPT-1 gene expression in rainbow trout, and it is envisaged that such results may provide highly valuable information for future practical applications in fish nutrition. PMID:25108415

  8. Wild chrysanthemum extract prevents UVB radiation-induced acute cell death and photoaging.

    PubMed

    Sun, Sujiao; Jiang, Ping; Su, Weiting; Xiang, Yang; Li, Jian; Zeng, Lin; Yang, Shuangjuan

    2016-03-01

    Wild chrysanthemum (Chrysanthemum indicum L.) is traditionally used in folk medicine as an anti-inflammatory agent. It is also used in the southwest plateau region of China to prevent ultraviolet-induced skin damage. However, the role and mechanism by which wild chrysanthemum prevents UV-induced skin damage and photoaging have never been investigated in vitro. In the present study, we found that aqueous extracts from wild chrysanthemum strongly reduced high-dose UVB-induced acute cell death of human immortalized keratinocytic HaCat cells. Wild chrysanthemum extract was also demonstrated to reduce low-dose UVB-induced expression of the photoaging-related matrix metalloproteinases MMP-2 and MMP-9. The ROS level elevated by UVB irradiation was strongly attenuated by wild chrysanthemum extract. Further study revealed that wild chrysanthemum extract reduced UVB-triggered ERK1/2 and p38 MAPK phosphorylation and their protective role, which is partially dependent on inhibiting p38 activation. These results suggest that wild chrysanthemum extract can protect the skin from UVB-induced acute skin damage and photoaging by reducing the intracellular reactive oxygen species (ROS) level and inhibiting p38 MAPK phosphorylation. The present study confirmed the protective role of wild chrysanthemum against UV-induced skin disorders in vitro and indicated the possible mechanism. Further study to identify the active components in wild chrysanthemum extract would be useful for developing new drugs for preventing and treating skin diseases, including skin cancer and photoaging, induced by UV irradiation. PMID:25052044

  9. Protective effect of porphyra-334 on UVA-induced photoaging in human skin fibroblasts.

    PubMed

    Ryu, Jina; Park, Su-Jin; Kim, In-Hye; Choi, Youn Hee; Nam, Taek-Jeong

    2014-09-01

    The significant increase in life expectancy is closely related to the growing interest in the impact of aging on the function and appearance of the skin. Skin aging is influenced by several factors, and solar ultraviolet (UV) irradiation is considered one of the most important causes of skin photoaging. The aim of this study was to examine the anti-photoaging role of porphyra-334 from Porphyra (P.) yezoensis, a mycosporine-like amino acid (MAA), using high-performance liquid chromatography (HPLC), and electrospray ionization‑mass spectrometry (ESI-MS). In the present study, extracted UV‑absorbing compounds from P. yezoensis included palythine, asterina-330 and porphyra-334. Porphyra-334 was the most abundant MAA in P. yezoensis, and it was therefore used for conducting antiphotoaging experiments. The effect of porphyra-334 on the prevention of photoaging was investigated by measuring reactive oxygen species (ROS) production and matrix metalloproteinase (MMP) levels, as well as extracellular matrix (ECM) components and protein expression in UVA‑irradiated human skin fibroblasts. Porphyra-334 suppressed ROS production and the expression of MMPs following UVA irradiation, while increasing levels of ECM components, such as procollagen, type I collagen, elastin. These results suggest that porphyra-334 has various applications in cosmetics and toiletries because of its anti‑photoaging activities and may serve as a novel anti-aging agent. PMID:24946848

  10. Red light interferes in UVA-induced photoaging of human skin fibroblast cells.

    PubMed

    Niu, Tianhui; Tian, Yan; Ren, Qu; Wei, Lizhao; Li, Xiaoxin; Cai, Qing

    2014-01-01

    The possible regulation mechanism of red light was determined to discover how to retard UVA-induced skin photoaging. Human skin fibroblasts were cultured and irradiated with different doses of UVA, thus creating a photoaging model. Fibroblasts were also exposed to a subtoxic dose of UVA combined with a red light-emitting diode (LED) for five continuous days. Three groups were examined: control, UVA and UVA plus red light. Cumulative exposure doses of UVA were 25 J cm(-2), and the total doses of red light were 0.18 J cm(-2). Various indicators were measured before and after irradiation, including cell morphology, viability, β-galactosidase staining, apoptosis, cycle phase, the length of telomeres and the protein levels of photoaging-related genes. Red light irradiation retarded the cumulative low-dose UVA irradiation-induced skin photoaging, decreased the expression of senescence-associated β-galactosidase, upregulated SIRT1 expression, decreased matrix metalloproteinase MMP-1 and the acetylation of p53 expression, reduced the horizon of cell apoptosis and enhanced cell viability. Furthermore, the telomeres in UVA-treated cells were shortened compared to those of cells in the red light groups. These results suggest that red light plays a key role in the antiphotoaging of human skin fibroblasts by acting on different signaling transduction pathways. PMID:25039464

  11. Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease.

    PubMed

    Wang, Baohong; Jiang, Xiangyang; Cao, Min; Ge, Jianping; Bao, Qiongling; Tang, Lingling; Chen, Yu; Li, Lanjuan

    2016-01-01

    Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G-) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression. PMID:27550547

  12. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation

    PubMed Central

    Patsoukis, Nikolaos; Bardhan, Kankana; Chatterjee, Pranam; Sari, Duygu; Liu, Bianling; Bell, Lauren N.; Karoly, Edward D.; Freeman, Gordon J.; Petkova, Victoria; Seth, Pankaj; Li, Lequn; Boussiotis, Vassiliki A.

    2015-01-01

    During activation, T cells undergo metabolic reprogramming, which imprints distinct functional fates. We determined that on PD-1 ligation, activated T cells are unable to engage in glycolysis or amino acid metabolism but have an increased rate of fatty acid β-oxidation (FAO). PD-1 promotes FAO of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase ATGL, the lipolysis marker glycerol and release of fatty acids. Conversely, CTLA-4 inhibits glycolysis without augmenting FAO, suggesting that CTLA-4 sustains the metabolic profile of non-activated cells. Because T cells utilize glycolysis during differentiation to effectors, our findings reveal a metabolic mechanism responsible for PD-1-mediated blockade of T-effector cell differentiation. The enhancement of FAO provides a mechanistic explanation for the longevity of T cells receiving PD-1 signals in patients with chronic infections and cancer, and for their capacity to be reinvigorated by PD-1 blockade. PMID:25809635

  13. Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease

    PubMed Central

    Wang, Baohong; Jiang, Xiangyang; Cao, Min; Ge, Jianping; Bao, Qiongling; Tang, Lingling; Chen, Yu; Li, Lanjuan

    2016-01-01

    Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G−) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression. PMID:27550547

  14. Protection against Myocardial Ischemia-Reperfusion Injury at Onset of Type 2 Diabetes in Zucker Diabetic Fatty Rats Is Associated with Altered Glucose Oxidation

    PubMed Central

    Povlsen, Jonas Agerlund; Løfgren, Bo; Dalgas, Christian; Birkler, Rune Isak Dupont; Johannsen, Mogens; Støttrup, Nicolaj Brejnholt; Bøtker, Hans Erik

    2013-01-01

    Background Inhibition of glucose oxidation during initial reperfusion confers protection against ischemia-reperfusion (IR) injury in the heart. Mitochondrial metabolism is altered with progression of type 2 diabetes (T2DM). We hypothesized that the metabolic alterations present at onset of T2DM induce cardioprotection by metabolic shutdown during IR, and that chronic alterations seen in late T2DM cause increased IR injury. Methods Isolated perfused hearts from 6 (prediabetic), 12 (onset of T2DM) and 24 (late T2DM) weeks old male Zucker diabetic fatty rats (ZDF) and their age-matched heterozygote controls were subjected to 40 min ischemia/120 min reperfusion. IR injury was assessed by TTC-staining. Myocardial glucose metabolism was evaluated by glucose tracer kinetics (glucose uptake-, glycolysis- and glucose oxidation rates), myocardial microdialysis (metabolomics) and tissue glycogen measurements. Results T2DM altered the development in sensitivity towards IR injury compared to controls. At late diabetes ZDF hearts suffered increased damage, while injury was decreased at onset of T2DM. Coincident with cardioprotection, oxidation of exogenous glucose was decreased during the initial and normalized after 5 minutes of reperfusion. Metabolomic analysis of citric acid cycle intermediates demonstrated that cardioprotection was associated with a reversible shutdown of mitochondrial glucose metabolism during ischemia and early reperfusion at onset of but not at late type 2 diabetes. Conclusions The metabolic alterations of type 2 diabetes are associated with protection against IR injury at onset but detrimental effects in late diabetes mellitus consistent with progressive dysfunction of glucose oxidation. These findings may explain the variable efficacy of cardioprotective interventions in individuals with type 2 diabetes. PMID:23704975

  15. The combined action of omega-3 polyunsaturated fatty acids and grape proanthocyanidins on a rat model of diet-induced metabolic alterations.

    PubMed

    Ramos-Romero, Sara; Molinar-Toribio, Eunice; Pérez-Jiménez, Jara; Taltavull, Núria; Dasilva, Gabriel; Romeu, Marta; Medina, Isabel; Torres, Josep Lluís

    2016-08-10

    It has been suggested that food components such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and (poly)phenols counteract diet-induced metabolic alterations by common or complementary mechanisms. To examine the effects of a combination of ω-3 PUFAs and (poly)phenols on such alterations, adult Wistar-Kyoto rats were fed an obesogenic high-fat high-sucrose diet supplemented, or not, for 24 weeks with: eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) 1 : 1 (16.6 g kg(-1) feed); proanthocyanidin-rich grape seed extract (GSE, 0.8 g kg(-1) feed); or EPA/DHA 1 : 1 + GSE. Body weight, feed intake, and plasma glucose were evaluated every 6 weeks, while adipose tissue weight, insulin, glucagon, ghrelin, leptin, adiponectin, cholesterol, and triglycerides were evaluated at the end of the experiment. ω-3 PUFAs reduced plasma leptin and cholesterol levels, but did not modify diet-induced perigonadal fat or plasma insulin levels; while GSE increased plasma triglyceride levels. The combined action of ω-3 PUFAs and the proanthocyanidins reduced plasma insulin and leptin, as well as partially prevented perigonadal fat accumulation. While separate supplementation with ω-3 PUFAs or grape proanthocyanidins may not counteract all the key metabolic changes induced by a high-energy-dense diet, the combination of both supplements reverts altered insulin, leptin and triglyceride levels to normal. PMID:27418399

  16. Oral ingestion of aloe vera phytosterols alters hepatic gene expression profiles and ameliorates obesity-associated metabolic disorders in zucker diabetic fatty rats.

    PubMed

    Misawa, Eriko; Tanaka, Miyuki; Nomaguchi, Kouji; Nabeshima, Kazumi; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

    2012-03-21

    We investigated the effects of the oral administration of lophenol (Lo) and cycloartanol (Cy), two kinds of antidiabetic phytosterol isolated from Aloe vera , on glucose and lipid metabolism in Zucker diabetic fatty (ZDF) rats. We demonstrated that the administrations of Lo and Cy suppressed random and fasting glucose levels and reduced visceral fat weights significantly. It was also observed that treatments with Lo and Cy decreased serum and hepatic lipid concentrations (triglyceride, nonesterified fatty acid, and total cholesterol). Additionally, Lo and Cy treatments resulted in a tendency for reduction in serum monocyte chemotactic protein-1 (MCP-1) level and an elevation in serum adiponectin level. Furthermore, the expression levels of hepatic genes encoding gluconeogenic enzymes (G6 Pase, PEPCK), lipogenic enzymes (ACC, FAS), and SREBP-1 were decreased significantly by the administrations of aloe sterols. In contrast, Lo and Cy administration increased mRNA levels of glycolysis enzyme (GK) in the liver. It was also observed that the hepatic β-oxidation enzymes (ACO, CPT1) and PPARα expressions tended to increase in the livers of the Lo- and Cy-treated rats compared with those in ZDF-control rats. We therefore conclude that orally ingested aloe sterols altered the expressions of genes related to glucose and lipid metabolism, and ameliorated obesity-associated metabolic disorders in ZDF rats. These findings suggest that aloe sterols could be beneficial in preventing and improving metabolic disorders with obesity and diabetes in rats. PMID:22352711

  17. High Fat Diet Administration during Specific Periods of Pregnancy Alters Maternal Fatty Acid Profiles in the Near-Term Rat

    PubMed Central

    Cerf, Marlon E.; Herrera, Emilio

    2016-01-01

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest high fat diets (HFDs). We therefore determined the maternal fatty acid (FA) profiles in metabolic organs after HFD administration during specific periods of gestation. Rats were fed a HFD for the first (HF1), second (HF2), or third (HF3) week, or for all three weeks (HFG) of gestation. Total maternal plasma non-esterified fatty acid (NEFA) concentrations were monitored throughout pregnancy. At day 20 of gestation, maternal plasma, liver, adipose tissue, and placenta FA profiles were determined. In HF3 mothers, plasma myristic and stearic acid concentrations were elevated, whereas docosahexaenoic acid (DHA) was reduced in both HF3 and HFG mothers. In HF3 and HFG mothers, hepatic stearic and oleic acid proportions were elevated; conversely, DHA and linoleic acid (LA) proportions were reduced. In adipose tissue, myristic acid was elevated, whereas DHA and LA proportions were reduced in all mothers. Further, adipose tissue stearic acid proportions were elevated in HF2, HF3, and HFG mothers; with oleic acid increased in HF1 and HFG mothers. In HF3 and HFG mothers, placental neutral myristic acid proportions were elevated, whereas DHA was reduced. Further, placental phospholipid DHA proportions were reduced in HF3 and HFG mothers. Maintenance on a diet, high in saturated fat, but low in DHA and LA proportions, during late or throughout gestation, perpetuated reduced DHA across metabolic organs that adapt during pregnancy. Therefore a diet, with normal DHA proportions during gestation, may be important for balancing maternal FA status. PMID:26742067

  18. High Fat Diet Administration during Specific Periods of Pregnancy Alters Maternal Fatty Acid Profiles in the Near-Term Rat.

    PubMed

    Cerf, Marlon E; Herrera, Emilio

    2016-01-01

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest high fat diets (HFDs). We therefore determined the maternal fatty acid (FA) profiles in metabolic organs after HFD administration during specific periods of gestation. Rats were fed a HFD for the first (HF1), second (HF2), or third (HF3) week, or for all three weeks (HFG) of gestation. Total maternal plasma non-esterified fatty acid (NEFA) concentrations were monitored throughout pregnancy. At day 20 of gestation, maternal plasma, liver, adipose tissue, and placenta FA profiles were determined. In HF3 mothers, plasma myristic and stearic acid concentrations were elevated, whereas docosahexaenoic acid (DHA) was reduced in both HF3 and HFG mothers. In HF3 and HFG mothers, hepatic stearic and oleic acid proportions were elevated; conversely, DHA and linoleic acid (LA) proportions were reduced. In adipose tissue, myristic acid was elevated, whereas DHA and LA proportions were reduced in all mothers. Further, adipose tissue stearic acid proportions were elevated in HF2, HF3, and HFG mothers; with oleic acid increased in HF1 and HFG mothers. In HF3 and HFG mothers, placental neutral myristic acid proportions were elevated, whereas DHA was reduced. Further, placental phospholipid DHA proportions were reduced in HF3 and HFG mothers. Maintenance on a diet, high in saturated fat, but low in DHA and LA proportions, during late or throughout gestation, perpetuated reduced DHA across metabolic organs that adapt during pregnancy. Therefore a diet, with normal DHA proportions during gestation, may be important for balancing maternal FA status. PMID:26742067

  19. Metabolic programming mediated by an essential fatty acid alters body composition and survival skills of a marine fish.

    PubMed

    Fuiman, Lee A; Perez, Kestrel O

    2015-11-22

    Metabolic programming occurs when variations in nutrition during a specific developmental window result in long-term metabolic effects. It has been studied almost exclusively in humans and other mammals but never in an ecological context. Here, we report metabolic programming and its functional consequences in a marine fish, red drum. We demonstrate that maternal provisioning of eggs with an essential fatty acid, docosahexaenoic acid (DHA), varies with DHA content of the maternal diet. When offspring are reared on a DHA-replete diet, whole-body DHA content of offspring depends upon the amount of DHA that was in the egg. We further demonstrate that whole-body DHA content is correlated with traits related to offspring fitness (escape responses, routine swimming, growth, and survival). DHA content of red drum eggs produced in nature is in the range where the effects of metabolic programming are most pronounced. Our findings indicate that during a brief developmental window, DHA plays a role in establishing the metabolic capacity for its own uptake or storage, with protracted and possibly permanent effects on ecologically important survival skills of individuals and important implications for dynamics of populations and food webs. PMID:26582018

  20. Nitrogen deprivation induces lipid droplet accumulation and alters fatty acid metabolism in symbiotic dinoflagellates isolated from Aiptasia pulchella.

    PubMed

    Weng, Li-Chi; Pasaribu, Buntora; Lin, I-Ping; Tsai, Ching-Hsiu; Chen, Chii-Shiarng; Jiang, Pei-Luen

    2014-01-01

    The stability of cnidarian-dinoflagellate (genus Symbiodinium spp.) endosymbioses depends on the regulation of nutrient transport between Symbiodinium populations and their hosts. Previously, we successfully induced the production of lipid droplets in the free-living cultured Symbiodinium (clade B) under the nitrogen-deprivation condition for 5 days. Therefore, the present study aimed at understanding the disruption of the endosymbiotic relationship between the cnidarians and dinoflagellates by nitrogen deprivation using Aiptasia pulchella as an example. Transmission electron micrographs revealed the formation of lipid droplets induced by nitrogen deprivation, and the lipid analyses further showed that polyunsaturated fatty acids were drastically enriched in Symbiodinium after 30 days of nitrogen deprivation, although these were unaffected after 5 days of nitrogen starvation. The present study also suggested that the host provided nitrogen to the symbiotic cells during short-term environmental stress. However, the relationship started to deteriorate after 30 days. These findings provide a more detailed understanding of the mechanisms of the symbiotic relationship between the symbiotic dinoflagellates in terms of the nitrogen source, which might provide more information for the explanation of the regulatory mechanism underlying endosymbiotic associations. PMID:25047647

  1. Nitrogen Deprivation Induces Lipid Droplet Accumulation and Alters Fatty Acid Metabolism in Symbiotic Dinoflagellates Isolated from Aiptasia pulchella

    NASA Astrophysics Data System (ADS)

    Weng, Li-Chi; Pasaribu, Buntora; -Ping Lin, I.; Tsai, Ching-Hsiu; Chen, Chii-Shiarng; Jiang, Pei-Luen

    2014-07-01

    The stability of cnidarian-dinoflagellate (genus Symbiodinium spp.) endosymbioses depends on the regulation of nutrient transport between Symbiodinium populations and their hosts. Previously, we successfully induced the production of lipid droplets in the free-living cultured Symbiodinium (clade B) under the nitrogen-deprivation condition for 5 days. Therefore, the present study aimed at understanding the disruption of the endosymbiotic relationship between the cnidarians and dinoflagellates by nitrogen deprivation using Aiptasia pulchella as an example. Transmission electron micrographs revealed the formation of lipid droplets induced by nitrogen deprivation, and the lipid analyses further showed that polyunsaturated fatty acids were drastically enriched in Symbiodinium after 30 days of nitrogen deprivation, although these were unaffected after 5 days of nitrogen starvation. The present study also suggested that the host provided nitrogen to the symbiotic cells during short-term environmental stress. However, the relationship started to deteriorate after 30 days. These findings provide a more detailed understanding of the mechanisms of the symbiotic relationship between the symbiotic dinoflagellates in terms of the nitrogen source, which might provide more information for the explanation of the regulatory mechanism underlying endosymbiotic associations.

  2. Polyunsaturated fatty acid supplementation alters proinflammatory gene expression and reduces the incidence of necrotizing enterocolitis in a neonatal rat model.

    PubMed

    Lu, Jing; Jilling, Tamas; Li, Dan; Caplan, Michael S

    2007-04-01

    Although supplementation of preterm formula with polyunsaturated fatty acids (PUFA) has been shown to reduce the incidence of necrotizing enterocolitis (NEC) in animal models and clinical trials, the mechanisms remain elusive. We hypothesized that the protective effect of PUFA on NEC may be due to the ability of PUFA to suppress Toll-like receptor (TLR) 4 and platelet-activating factor receptor (PAFR) gene expression (molecules that are important in the pathogenesis of NEC) in epithelial cells. To investigate the efficacy of different PUFA preparations on NEC in a neonatal rat model, we compared the incidence of NEC among the four PUFA supplemented groups--A: arachidonic acid and docosahexaenoic acid (AA+DHA), B: egg phospholipids (EP), C: DHA, and D: control without PUFA. PUFA supplementation reduced the incidence of NEC and inhibited intestinal PAFR and TLR4 gene expression compared with the controls. To validate the in vivo observations, IEC-6 cells were exposed to PAF after pretreatment with AA or DHA. Both AA and DHA supplementation blocked PAF-induced TLR4 and PAFR mRNA expression in these enterocytes. These results suggest that PUFA modulates gene expression of key factors involved in experimental NEC pathogenesis. These effects might in part explain the protective effect of PUFA on neonatal NEC. PMID:17515866

  3. Nitrogen Deprivation Induces Lipid Droplet Accumulation and Alters Fatty Acid Metabolism in Symbiotic Dinoflagellates Isolated from Aiptasia pulchella

    PubMed Central

    Weng, Li-Chi; Pasaribu, Buntora; -Ping Lin, I.; Tsai, Ching-Hsiu; Chen, Chii-Shiarng; Jiang, Pei-Luen

    2014-01-01

    The stability of cnidarian-dinoflagellate (genus Symbiodinium spp.) endosymbioses depends on the regulation of nutrient transport between Symbiodinium populations and their hosts. Previously, we successfully induced the production of lipid droplets in the free-living cultured Symbiodinium (clade B) under the nitrogen-deprivation condition for 5 days. Therefore, the present study aimed at understanding the disruption of the endosymbiotic relationship between the cnidarians and dinoflagellates by nitrogen deprivation using Aiptasia pulchella as an example. Transmission electron micrographs revealed the formation of lipid droplets induced by nitrogen deprivation, and the lipid analyses further showed that polyunsaturated fatty acids were drastically enriched in Symbiodinium after 30 days of nitrogen deprivation, although these were unaffected after 5 days of nitrogen starvation. The present study also suggested that the host provided nitrogen to the symbiotic cells during short-term environmental stress. However, the relationship started to deteriorate after 30 days. These findings provide a more detailed understanding of the mechanisms of the symbiotic relationship between the symbiotic dinoflagellates in terms of the nitrogen source, which might provide more information for the explanation of the regulatory mechanism underlying endosymbiotic associations. PMID:25047647

  4. Oncogenic ras alters sensitivity of mouse colonocytes to butyrate and fatty acid mediated growth arrest and apoptosis.

    PubMed

    Turner, Nancy D; Zhang, Jianhu; Davidson, Laurie A; Lupton, Joanne R; Chapkin, Robert S

    2002-12-01

    Docosahexaenoic acid (DHA) and butyrate favorably modulate colonocyte proliferation and apoptosis. In order to elucidate how oncogenic Ras modulates responses to these chemopreventive nutrients, we incubated isogenic non-transformed and Ras malignant transformed mouse colon cells with butyrate and DHA or linoleic acid (LA). Combining DHA with 1mM butyrate decreased proliferation relative to LA or no PUFA treatment in both cell lines. At a higher butyrate dose (5mM), caspase 3 activity was elevated to a greater extent in Ras transformed cells. Only non-transformed cells were sensitive to the apoptogenic effects of DHA, indicating that Ras transformation alters sensitivity to dietary chemopreventive agents. PMID:12183072

  5. Nonesterified Fatty Acid-Induced Endoplasmic Reticulum Stress in Cattle Cumulus Oocyte Complexes Alters Cell Metabolism and Developmental Competence.

    PubMed

    Sutton-McDowall, Melanie L; Wu, Linda L Y; Purdey, Malcolm; Abell, Andrew D; Goldys, Ewa M; MacMillan, Keith L; Thompson, Jeremy G; Robker, Rebecca L

    2016-01-01

    Reduced oocyte quality has been associated with poor fertility of high-performance dairy cows during peak lactation, due to negative energy balance. We examined the role of nonesterified fatty acids (NEFAs), known to accumulate within follicular fluid during under- and overnutrition scenarios, in causing endoplasmic reticulum (ER) stress of in vitro maturated cattle cumulus-oocyte complexes (COCs). NEFA concentrations were: palmitic acid (150 μM), oleic acid (200 μM), and steric acid (75 μM). Abattoir-derived COCs were randomly matured for 24 h in the presence of NEFAs and/or an ER stress inhibitor, salubrinal. Total and hatched blastocyst yields were negatively impacted by NEFA treatment compared with controls, but this was reversed by salubrinal. ER stress markers, activating transcription factor 4 (Atf4) and heat shock protein 5 (Hspa5), but not Atf6, were significantly up-regulated by NEFA treatment within whole COCs but reversed by coincubation with salubrinal. Likewise, glucose uptake and lactate production, measured in spent medium samples, showed a similar pattern, suggesting that cumulus cell metabolism is sensitive to NEFAs via an ER stress-mediated process. In contrast, while mitochondrial DNA copy number was recovered in NEFA-treated oocytes, oocyte autofluorescence of the respiratory chain cofactor, FAD, was lower following NEFA treatment of COCs, and this was not reversed by salubrinal, suggesting the negative impact was via reduced mitochondrial function. These results reveal the significance of NEFA-induced ER stress on bovine COC developmental competence, revealing a potential therapeutic target for improving oocyte quality during peak lactation. PMID:26658709

  6. High maternal intake of polyunsaturated fatty acids during pregnancy in mice alters offsprings' aggressive behavior, immobility in the swim test, locomotor activity and brain protein kinase C activity.

    PubMed

    Raygada, M; Cho, E; Hilakivi-Clarke, L

    1998-12-01

    Populations in Western countries consume an excess of polyunsaturated fatty acids (PUFA), even during pregnancy. Since (n-6) PUFA is critical for brain development, we studied whether a high maternal consumption of this fatty acid alters offsprings' affective-like behaviors and (n-6) PUFA-induced protein kinase C (PKC) activity in the brain. Three different strains of pregnant mice were fed isocaloric diets containing either 16% (control) or 43% (high) energy derived from fat high in (n-6) PUFA (corn oil: Balb/c and CD-1 mice, or soybean oil: C3H mice) throughout gestation. From birth onward dams and offspring were fed a nonpurified diet containing 12% energy from a variety of fats. Two- to 12-month-old female and male offspring of dams exposed to a high (n-6) PUFA diet during pregnancy were significantly more active in an open field, more aggressive in the resident-intruder test and spent less time immobile in the swim test than offspring of dams exposed to a control (n-6) PUFA diet. Significantly greater PKC activity in the hypothalamus and moderately less PKC activity in the whole brain (P = 0.10) were seen in the 2-month-old female and male high (n-6) PUFA offspring compared to controls. Our findings indicate that in utero exposure to a high (n-6) PUFA diet subsequently increases locomotor activity and aggression, and reduces immobility in the swim test. The mechanism mediating these effects may be linked to an increased PKC activity in the hypothalamus. PMID:9868200

  7. Intake of a Western diet containing cod instead of pork alters fatty acid composition in tissue phospholipids and attenuates obesity and hepatic lipid accumulation in mice.

    PubMed

    Liisberg, Ulrike; Fauske, Kristin Røen; Kuda, Ondrej; Fjære, Even; Myrmel, Lene Secher; Norberg, Nina; Frøyland, Livar; Graff, Ingvild Eide; Liaset, Bjørn; Kristiansen, Karsten; Kopecky, Jan; Madsen, Lise

    2016-07-01

    The content of the marine n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is far lower in lean than in fatty seafood. Cod filets contain less than 2g fat per kg, whereof approximately 50% is EPA and DHA. However, a large fraction of these n-3 PUFAs is present in the phospholipid (PL) fraction and may have high bioavailability and capacity to change the endocannabinoid profile. Here we investigated whether exchanging meat from a lean terrestrial animal with cod in a background Western diet would alter the endocannabinoid tone in mice and thereby attenuate obesity development and hepatic lipid accumulation. Accordingly, we prepared iso-caloric diets with 15.1 energy (e) % protein, 39.1 e% fat and 45.8 e% carbohydrates using freeze-dried meat from cod filets or pork sirloins, and using a combination of soybean oil, corn oil, margarine, milk fat, and lard as the fat source. Compared with mice receiving diets containing pork, mice fed cod gained less adipose tissue mass and had a lower content of hepatic lipids. This was accompanied by a lower n-6 to n-3 ratio in liver PLs and in red blood cells (RBCs) in the mice. Furthermore, mice receiving the cod-containing diet had lower circulating levels of the two major endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoylglycerol. Together, our data demonstrate that despite the relatively low content of n-3 PUFAs in cod fillets, the cod-containing diet could exert beneficial metabolic effects. PMID:27155918

  8. The protective effect of 18β-Glycyrrhetinic acid against UV irradiation induced photoaging in mice.

    PubMed

    Kong, Song-Zhi; Chen, Hai-Ming; Yu, Xiu-Ting; Zhang, Xie; Feng, Xue-Xuan; Kang, Xin-Huang; Li, Wen-Jie; Huang, Na; Luo, Hui; Su, Zi-Ren

    2015-01-01

    It has been confirmed that repeated exposure of skin to ultraviolet (UV) radiation results in cutaneous oxidative stress and inflammation, which act in concert to cause premature skin aging, well known as photoaging. 18β-Glycyrrhetinic acid (GA), widely used to treat various tissue inflammations, is the main active component of licorice root, and has also been shown to possess favorable anti-oxidative property and modulating immunity function. In the present study, we investigated the potential protective effect of GA on UV-induced skin photoaging in a mouse model. During the experimental period of ten consecutive weeks, the dorsal depilated skin of mice was treated with topical GA for 2 hours prior to UV irradiation. The results showed that GA pretreatment significantly alleviated the macroscopic and histopathological damages in mice skin caused by UV. Meanwhile, the data also indicated that GA markedly up-regulated the activities of the antioxidant enzymes (SOD, GSH-Px), and increased the content of skin collagen, while obviously decreased malonaldehyde level and inhibited high expressions of matrix metalloproteinase-1 (MMP-1) and -3 (MMP-3), as well as down-regulated the expression of inflammatory cytokines such as IL-6, TNF-α and IL-10. Taken together, these findings amply demonstrate that GA observably attenuates UV-induced skin photoaging mainly by virtue of its antioxidative and anti-inflammatory properties, as well as regulating the abnormal expression of MMP-1 and MMP-3. PMID:25498537

  9. Protective effect of gelatin and gelatin hydrolysate from salmon skin on UV irradiation-induced photoaging of mice skin

    NASA Astrophysics Data System (ADS)

    Chen, Tiejun; Hou, Hu; Lu, Jiaohan; Zhang, Kai; Li, Bafang

    2016-05-01

    The objective of this study was to investigate the effect of gelatin (SG) isolated from salmon skin and its hydrolysate (SGH) on photoaging skin, and the mechanism responsible for anti-photoaging. The average molecular weights of SG and SGH were 65 kDa and 873 Da, respectively. The amino acid compositions of SG and SGH were similar. Both of them were abundant in hydrophobic amino acids. Twenty-five peptides were identified from SGH. SG and SGH could improve UV irradiation-induced pathological changes of macroscopical tissue texture and skin morphology. Hydroxyproline content is an indicator of matrix collagen content, SG and SGH could inhibit the decrease of hydroxyproline content in photoaging skin in a dose dependent manner. In addition, SG and SGH could alleviate UV irradiation-induced oxidative damages to skin by increasing the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), increasing the content of glutathione (GSH) and decreasing the content of malonaldehyde (MDA). Moreover, SG and SGH could enhance immune regulation system by increasing the thymus index. Thus, the anti-photoaging mechanisms of SG and SGH were by inhibiting the depletion of antioxidant defense components, involving in the synthesis of collagen and enhancing the function of immune system. Besides, SGH showed a better result in protecting skin from photoaging than SG.

  10. Protective effect of gelatin and gelatin hydrolysate from salmon skin on UV irradiation-induced photoaging of mice skin

    NASA Astrophysics Data System (ADS)

    Chen, Tiejun; Hou, Hu; Lu, Jiaohan; Zhang, Kai; Li, Bafang

    2016-08-01

    The objective of this study was to investigate the effect of gelatin (SG) isolated from salmon skin and its hydrolysate (SGH) on photoaging skin, and the mechanism responsible for anti-photoaging. The average molecular weights of SG and SGH were 65 kDa and 873 Da, respectively. The amino acid compositions of SG and SGH were similar. Both of them were abundant in hydrophobic amino acids. Twenty-five peptides were identified from SGH. SG and SGH could improve UV irradiation-induced pathological changes of macroscopical tissue texture and skin morphology. Hydroxyproline content is an indicator of matrix collagen content, SG and SGH could inhibit the decrease of hydroxyproline content in photoaging skin in a dose dependent manner. In addition, SG and SGH could alleviate UV irradiation-induced oxidative damages to skin by increasing the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), increasing the content of glutathione (GSH) and decreasing the content of malonaldehyde (MDA). Moreover, SG and SGH could enhance immune regulation system by increasing the thymus index. Thus, the anti-photoaging mechanisms of SG and SGH were by inhibiting the depletion of antioxidant defense components, involving in the synthesis of collagen and enhancing the function of immune system. Besides, SGH showed a better result in protecting skin from photoaging than SG.

  11. Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in piglets by differentially altering muscle lipid composition.

    PubMed

    Bergeron, Karen; Julien, Pierre; Davis, Teresa A; Myre, Alexandre; Thivierge, M Carole

    2007-11-01

    This study investigated the role of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) of muscle phospholipids in the regulation of neonatal metabolism. Twenty-eight piglets were weaned at 2 days of age and raised on one of two milk formulas that consisted of either a control formula supplying 0% or a formula containing 3.5% LCn-3PUFAs until 10 or 28 days of age. There was a developmental decline in the insulin sensitivity of amino acid disposal in control pigs during the first month of life, with a slope of -2.24 micromol.kg(-1).h(-1) (P = 0.01) per unit of insulin increment, as assessed using hyperinsulinemic-euglycemic-euaminoacidemic clamps. LCn-3PUFA feeding blunted this developmental decline, resulting in differing insulin sensitivities (P < 0.001). When protein metabolism was assessed under parenteral feeding-induced hyperinsulinemia, LCn-3PUFAs reduced by 16% whole body oxidative losses of amino acids (from 238 to 231 micromol.kg(-1).h(-1); P = 0.06), allowing 41% more amino acids to accrete into body proteins (from 90 to 127 micromol.kg(-1).h(-1); P = 0.06). The fractional synthetic rate of muscle mixed proteins remained unaltered by the LCn-3PUFA feeding. However, LCn-3PUFAs retarded a developmental increase in the essential-to-nonessential amino acid ratio of the muscle intracellular free pool (P = 0.05). Overall, alterations in metabolism were concomitant with a preferential incorporation of LCn-3PUFAs into muscle total membrane phospholipids (P < 0.001), in contrast to intramuscular triglycerides. These results underscore the potential role of LCn-3PUFAs as regulators of different aspects of protein metabolism in the neonate. PMID:17673528

  12. Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in piglets by differentially altering muscle lipid composition

    PubMed Central

    Bergeron, Karen; Julien, Pierre; Davis, Teresa A.; Myre, Alexandre; Thivierge, M. Carole

    2009-01-01

    This study investigated the role of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) of muscle phospholipids in the regulation of neonatal metabolism. Twenty-eight piglets were weaned at 2 days of age and raised on one of two milk formulas that consisted of either a control formula supplying 0% or a formula containing 3.5% LCn-3PUFAs until 10 or 28 days of age. There was a developmental decline in the insulin sensitivity of amino acid disposal in control pigs during the first month of life, with a slope of −2.24 μmol·kg−1·h−1 (P = 0.01) per unit of insulin increment, as assessed using hyperinsulinemic-euglycemic-euaminoacidemic clamps. LCn-3PUFA feeding blunted this developmental decline, resulting in differing insulin sensitivities (P < 0.001). When protein metabolism was assessed under parenteral feeding-induced hyperinsulinemia, LCn-3PUFAs reduced by 16% whole body oxidative losses of amino acids (from 238 to 231 μmol·kg−1·h−1; P = 0.06), allowing 41% more amino acids to accrete into body proteins (from 90 to 127 μmol·kg−1·h−1; P = 0.06). The fractional synthetic rate of muscle mixed proteins remained unaltered by the LCn-3PUFA feeding. However, LCn-3PUFAs retarded a developmental increase in the essential-to-nonessential amino acid ratio of the muscle intracellular free pool (P = 0.05). Overall, alterations in metabolism were concomitant with a preferential incorporation of LCn-3PUFAs into muscle total membrane phospholipids (P < 0.001), in contrast to intramuscular triglycerides. These results underscore the potential role of LCn-3PUFAs as regulators of different aspects of protein metabolism in the neonate. PMID:17673528

  13. Alterations in Glutathione Redox Metabolism, Oxidative Stress, and Mitochondrial Function in the Left Ventricle of Elderly Zucker Diabetic Fatty Rat Heart

    PubMed Central

    Raza, Haider; John, Annie; Howarth, Frank C.

    2012-01-01

    The Zucker diabetic fatty (ZDF) rat is a genetic model in which the homozygous (FA/FA) male animals develop obesity and type 2 diabetes. Morbidity and mortality from cardiovascular complications, due to increased oxidative stress and inflammatory signals, are the hallmarks of type 2 diabetes. The precise molecular mechanism of contractile dysfunction and disease progression remains to be clarified. Therefore, we have investigated molecular and metabolic targets in male ZDF (30–34 weeks old) rat heart compared to age matched Zucker lean (ZL) controls. Hyperglycemia was confirmed by a 4-fold elevation in non-fasting blood glucose (478.43 ± 29.22 mg/dL in ZDF vs. 108.22 ± 2.52 mg/dL in ZL rats). An increase in reactive oxygen species production, lipid peroxidation and oxidative protein carbonylation was observed in ZDF rats. A significant increase in CYP4502E1 activity accompanied by increased protein expression was also observed in diabetic rat heart. Increased expression of other oxidative stress marker proteins, HO-1 and iNOS was also observed. GSH concentration and activities of GSH-dependent enzymes, glutathione S-transferase and GSH reductase, were, however, significantly increased in ZDF heart tissue suggesting a compensatory defense mechanism. The activities of mitochondrial respiratory enzymes, Complex I and Complex IV were significantly reduced in the heart ventricle of ZDF rats in comparison to ZL rats. Western blot analysis has also suggested a decreased expression of IκB-α and phosphorylated-JNK in diabetic heart tissue. Our results have suggested that mitochondrial dysfunction and increased oxidative stress in ZDF rats might be associated, at least in part, with altered NF-κB/JNK dependent redox cell signaling. These results might have implications in the elucidation of the mechanism of disease progression and designing strategies for diabetes prevention. PMID:23203193

  14. The pharmacokinetics of silymarin is altered in patients with hepatitis C virus and nonalcoholic Fatty liver disease and correlates with plasma caspase-3/7 activity.

    PubMed

    Schrieber, Sarah J; Wen, Zhiming; Vourvahis, Manoli; Smith, Philip C; Fried, Michael W; Kashuba, Angela D M; Hawke, Roy L

    2008-09-01

    Silymarin, used by 30 to 40% of liver disease patients, is composed of six major flavonolignans, each of which may contribute to silymarin's hepatoprotective properties. Previous studies have only described the pharmacokinetics for two flavonolignans, silybin A and silybin B, in healthy volunteers. The aim of this study was to determine the pharmacokinetics of the major silymarin flavonolignans in liver disease patients. Healthy volunteers and three patient cohorts were administered a single, 600-mg p.o. dose of milk thistle extract, and 14 blood samples were obtained over 24 h. Silybin A and B accounted for 43% of the exposure to the sum of total silymarin flavonolignans in healthy volunteers and only 31 to 38% in liver disease cohorts as a result of accumulation of silychristin (20-36%). Area under the curve (AUC(0-24h)) for the sum of total silymarin flavonolignans was 2.4-, 3.3-, and 4.7-fold higher for hepatitis C virus (HCV) noncirrhosis, nonalcoholic fatty liver disease (p altered in patients with liver disease. Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans. PMID:18566043

  15. Pancreatic islet function in omega-3 fatty acid-depleted rats: alteration of calcium fluxes and calcium-dependent insulin release.

    PubMed

    Zhang, Y; Oguzhan, B; Louchami, K; Chardigny, J-M; Portois, L; Carpentier, Y A; Malaisse, W J; Herchuelz, A; Sener, A

    2006-09-01

    Considering the insufficient supply of long-chain polyunsaturated omega-3 fatty acids often prevailing in Western populations, this report deals mainly with alterations of Ca(2+) fluxes and Ca(2+)-dependent insulin secretory events in isolated pancreatic islets from omega-3-depleted rats. In terms of (45)Ca(2+) handling, the islets from omega-3-depleted rats, compared with those from normal animals, displayed an unaltered responsiveness to an increase in extracellular K(+) concentration, a lower inflow rate and lower fractional outflow rate of the divalent cation, and higher (45)Ca(2+)-labeled cellular pool(s) at isotopic equilibrium. The latter anomaly was corrected 120 min after intravenous injection of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion, distinct from a control omega-3-poor MCT-olive oil (MCT:OO) emulsion. At 8.3 mM D-glucose, insulin release was higher in islets from omega-3-depleted rats vs. control animals, coinciding with a higher cytosolic Ca(2+) concentration. The relative magnitude of the increase in insulin output attributable to a rise in D-glucose as well as extracellular Ca(2+) or K(+) concentration, to the absence vs. presence of verapamil and to the presence vs. absence of extracellular Ca(2+), theophylline, phorbol 12-myristate 13-acetate, or Ba(2+), was always more pronounced in islets from omega-3-depleted rats injected with the MCT:OO compared with the MCT:FO emulsion. A comparable situation prevailed when comparing islets from noninjected omega-3-depleted and normal rats. In light of these and previous findings, we propose that an impairment of Na(+),K(+)-ATPase activity plays a major, although not an exclusive, role in the perturbation of Ca(2+) fluxes and Ca(2+)-dependent secretory events in the islets from omega-3-depleted rats. PMID:16912059

  16. n-3 polyunsaturated fatty acids suppress CD4(+) T cell proliferation by altering phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] organization.

    PubMed

    Hou, Tim Y; Barhoumi, Rola; Fan, Yang-Yi; Rivera, Gonzalo M; Hannoush, Rami N; McMurray, David N; Chapkin, Robert S

    2016-01-01

    The mechanisms by which n-3 polyunsaturated fatty acids (n-3 PUFA), abundant in fish oil, exert their anti-inflammatory effects have not been rigorously defined. We have previously demonstrated that n-3 PUFA decrease the amount of phosphatidylinositol-(4,5)-bisphosphate, [PI(4,5)P2], in CD4(+) T cells, leading to suppressed actin remodeling upon activation. Since discrete pools of PI(4,5)P2 exist in the plasma membrane, we determined whether n-3 PUFA modulate spatial organization of PI(4,5)P2 relative to raft and non-raft domains. We used Förster resonance energy transfer (FRET) to demonstrate that lipid raft mesodomains in the plasma membrane of CD4(+) T cells enriched in n-3 PUFA display increased co-clustering of Lck(N10) and LAT(ΔCP), markers of lipid rafts. CD4(+) T cells enriched in n-3 PUFA also exhibited a depleted plasma membrane non-raft PI(4,5)P2 pool as detected by decreased co-clustering of Src(N15), a non-raft marker, and PH(PLC-δ), a PI(4,5)P2 reporter. Incubation with exogenous PI(4,5)P2 rescued the effects on the non-raft PI(4,5)P2 pool, and reversed the suppression of T cell proliferation in CD4(+) T cells enriched with n-3 PUFA. Furthermore, CD4(+) T cells isolated from mice fed a 4% docosahexaenoic acid (DHA)-enriched diet exhibited a decrease in the non-raft pool of PI(4,5)P2, and exogenous PI(4,5)P2 reversed the suppression of T cell proliferation. Finally, these effects were not due to changes to post-translational lipidation, since n-3 PUFA did not alter the palmitoylation status of signaling proteins. These data demonstrate that n-3 PUFA suppress T cell proliferation by altering plasma membrane topography and the spatial organization of PI(4,5)P2. PMID:26476105

  17. Photoaging is associated with protein oxidation in human skin in vivo.

    PubMed

    Sander, Christina S; Chang, Hong; Salzmann, Susann; Müller, Cornelia S L; Ekanayake-Mudiyanselage, Swarna; Elsner, Peter; Thiele, Jens J

    2002-04-01

    There is increasing evidence for the generation of reactive oxygen species in skin upon ultraviolet exposure, but little is known about their pathophysiologic relevance in human skin in vivo. We hypothesized that chronic and acute photodamage is mediated by depleted antioxidant enzyme expression and increased oxidative protein modifications. Biopsies from patients with histologically confirmed solar elastosis, from non-ultraviolet-exposed sites of age-matched controls, and from young subjects were analyzed. To evaluate the influence of acute ultraviolet exposures, buttock skin of 12 healthy subjects was irradiated repetitively on 10 d with a solar simulator and compared intraindividually to non-ultraviolet-treated contralateral sites. The antioxidant enzymes catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase were investigated by immunohistochemistry. Protein carbonyls were analyzed by immunohistochemical and immunoblotting techniques in human skin and in cell models. Whereas overall expression of antioxidant enzymes was very high in the epidermis, low baseline levels were found in the dermis. In photoaged skin, a significant depletion of antioxidant enzyme expression was observed within the stratum corneum and in the epidermis. Importantly, an accumulation of oxidatively modified proteins was found specifically within the upper dermis of photoaged skin. Upon acute ultraviolet exposure of healthy subjects, depleted catalase expression and increased protein oxidation were detected. Exposures of keratinocytes and fibroblasts to ultraviolet B, ultraviolet A, and H2O2 led to dose-dependent protein oxidation and thus confirmed in vivo results. In conclusion, the correlation between photodamage and protein oxidation was demonstrated for the first time, which hence may be a relevant pathophysiologic factor in photoaging. PMID:11918707

  18. The effects of continuous application of sunscreen on photoaged skin in Japanese elderly people – the relationship with the usage

    PubMed Central

    Mizuno, Makoto; Kunimoto, Kayo; Naru, Eiji; Kameyama, Koichi; Furukawa, Fukumi; Yamamoto, Yuki

    2016-01-01

    Since photoaging of skin is caused by chronic sun exposure, it is well-recognized that regular sunscreen use can help prevent photoaging of skin in fair-skinned people. Therefore, application of sunscreen is recommended for the prevention of photoaging in many countries. However, the relationship between UV exposure and photoaging has rarely been investigated in clinical studies in Japan. In addition, there have been almost no long-term interventional studies in Japanese people. We have previously conducted a study where Japanese actinic keratosis patients were instructed to continuously apply sunscreen. The results indicated that long-term application of sunscreen is effective in suppressing actinic keratosis progression and generation. In the present study, we investigated the effects of sunscreen on photoaged skin in 14 elderly Japanese people. Skin conditions such as water content, transepidermal water loss, the number of spots, wrinkles, and skin color tone uniformity were measured and compared before and after the study. A statistically significant difference was observed only in skin surface hydration. There were large inter-individual differences in amount of sunscreen used throughout the study. The changes in the number of spots and skin color tone uniformity during the 18 months showed good correlation with amount of sunscreen being used. These results suggest an increase in the number of spots and deterioration in skin color tone uniformity in the 18-month non-sunscreen application period, and that such skin conditions improved with increasing use of sunscreen. In this study, we suggested an inhibitory effect on photoaging symptoms such as spots and skin color tone non-uniformity, by application of the appropriate amount of sunscreen over a long period of time in Japanese people, similar to Caucasians. PMID:27217789

  19. The effects of continuous application of sunscreen on photoaged skin in Japanese elderly people - the relationship with the usage.

    PubMed

    Mizuno, Makoto; Kunimoto, Kayo; Naru, Eiji; Kameyama, Koichi; Furukawa, Fukumi; Yamamoto, Yuki

    2016-01-01

    Since photoaging of skin is caused by chronic sun exposure, it is well-recognized that regular sunscreen use can help prevent photoaging of skin in fair-skinned people. Therefore, application of sunscreen is recommended for the prevention of photoaging in many countries. However, the relationship between UV exposure and photoaging has rarely been investigated in clinical studies in Japan. In addition, there have been almost no long-term interventional studies in Japanese people. We have previously conducted a study where Japanese actinic keratosis patients were instructed to continuously apply sunscreen. The results indicated that long-term application of sunscreen is effective in suppressing actinic keratosis progression and generation. In the present study, we investigated the effects of sunscreen on photoaged skin in 14 elderly Japanese people. Skin conditions such as water content, transepidermal water loss, the number of spots, wrinkles, and skin color tone uniformity were measured and compared before and after the study. A statistically significant difference was observed only in skin surface hydration. There were large inter-individual differences in amount of sunscreen used throughout the study. The changes in the number of spots and skin color tone uniformity during the 18 months showed good correlation with amount of sunscreen being used. These results suggest an increase in the number of spots and deterioration in skin color tone uniformity in the 18-month non-sunscreen application period, and that such skin conditions improved with increasing use of sunscreen. In this study, we suggested an inhibitory effect on photoaging symptoms such as spots and skin color tone non-uniformity, by application of the appropriate amount of sunscreen over a long period of time in Japanese people, similar to Caucasians. PMID:27217789

  20. Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis.

    PubMed

    Pittayapruek, Pavida; Meephansan, Jitlada; Prapapan, Ornicha; Komine, Mayumi; Ohtsuki, Mamitaro

    2016-01-01

    Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Collectively, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins. Based on their structure and substrate specificity, they can be categorized into five main subgroups, namely (1) collagenases (MMP-1, MMP-8 and MMP-13); (2) gelatinases (MMP-2 and MMP-9); (3) stromelysins (MMP-3, MMP-10 and MMP-11); (4) matrilysins (MMP-7 and MMP-26); and (5) membrane-type (MT) MMPs (MMP-14, MMP-15, and MMP-16). The alterations made to the ECM by MMPs might contribute in skin wrinkling, a characteristic of premature skin aging. In photocarcinogenesis, degradation of ECM is the initial step towards tumor cell invasion, to invade both the basement membrane and the surrounding stroma that mainly comprises fibrillar collagens. Additionally, MMPs are involved in angiogenesis, which promotes cancer cell growth and migration. In this review, we focus on the present knowledge about premature skin aging and skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with our main focus on members of the MMP family and their functions. PMID:27271600

  1. Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis

    PubMed Central

    Pittayapruek, Pavida; Meephansan, Jitlada; Prapapan, Ornicha; Komine, Mayumi; Ohtsuki, Mamitaro

    2016-01-01

    Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Collectively, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins. Based on their structure and substrate specificity, they can be categorized into five main subgroups, namely (1) collagenases (MMP-1, MMP-8 and MMP-13); (2) gelatinases (MMP-2 and MMP-9); (3) stromelysins (MMP-3, MMP-10 and MMP-11); (4) matrilysins (MMP-7 and MMP-26); and (5) membrane-type (MT) MMPs (MMP-14, MMP-15, and MMP-16). The alterations made to the ECM by MMPs might contribute in skin wrinkling, a characteristic of premature skin aging. In photocarcinogenesis, degradation of ECM is the initial step towards tumor cell invasion, to invade both the basement membrane and the surrounding stroma that mainly comprises fibrillar collagens. Additionally, MMPs are involved in angiogenesis, which promotes cancer cell growth and migration. In this review, we focus on the present knowledge about premature skin aging and skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with our main focus on members of the MMP family and their functions. PMID:27271600

  2. The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of altered dietary and hormonal conditions

    PubMed Central

    Saggerson, E. D.; Greenbaum, A. L.

    1970-01-01

    1. Epididymal adipose tissues obtained from rats that had been previously starved, starved and refed a high fat diet for 72h, starved and refed bread for 144h or fed a normal diet were incubated in the presence of insulin+glucose or insulin+glucose+acetate. 2. Measurements were made of the whole-tissue concentrations of hexose phosphates, triose phosphates, glycerol 1-phosphate, 3-phosphoglycerate, 6-phosphogluconate, adenine nucleotides, acid-soluble CoA, long-chain fatty acyl-CoA, malate and citrate after 1h of incubation. The release of lactate, pyruvate and glycerol into the incubation medium during this period was also determined. 3. The rates of metabolism of glucose in the hexose monophosphate pathway, the glycolytic pathway, the citric acid cycle and into glyceride glycerol, fatty acids and lactate+pyruvate were also determined over a 2h period in similarly treated tissues. The metabolism of acetate to CO2 and fatty acids in the presence of glucose was also measured. 4. The activities of acetyl-CoA carboxylase, fatty acid synthetase and isocitrate dehydrogenase were determined in adipose tissues from starved, starved and fat-refed, and alloxan-diabetic animals and also in tissues from animals that had been starved and refed bread for up to 96h. Changes in these activities were compared with the ability of similar tissues to incorporate [14C]glucose into fatty acids in vitro. 5. The activities of acetyl-CoA carboxylase and fatty acid synthetase roughly paralleled the ability of tissues to incorporate glucose into fatty acids. 6. Rates of triglyceride synthesis and fatty acid synthesis could not be correlated with tissue concentrations of long-chain fatty acyl-CoA, citrate or glycerol 1-phosphate. In some cases changes in phosphofructokinase flux rates could be correlated with changes in citrate concentration. 7. The main lesion in fatty acid synthesis in tissues from starved, starved and fat-refed, and alloxan-diabetic rats appeared to reside at the level of

  3. Manipulation of culture conditions alters lipid content and fatty acid profiles of a wide variety of known and new oleaginous yeasts species

    PubMed Central

    Sitepu, Irnayuli R.; Sestric, Ryan; Ignatia, Laura; Levin, David; German, J. Bruce; Gillies, Laura A.; Almada, Luis A.G.; Boundy-Mills, Kyria L.

    2013-01-01

    Oleaginous yeasts have been studied for oleochemical production for over 80 years. Only a few species have been studied intensely. To expand the diversity of oleaginous yeasts available for lipid research, we surveyed a broad diversity of yeasts with indicators of oleaginicity including known oleaginous clades, and buoyancy. Sixty-nine strains representing 17 genera and 50 species were screened for lipid production. Yeasts belonged to Ascomycota families, Basidiomycota orders, and the yeast-like algal genus Prototheca. Total intracellular lipids and fatty acid composition were determined under different incubation times and nitrogen availability. Thirteen new oleaginous yeast species were discovered, representing multiple ascomycete and basidiomycete clades. Nitrogen starvation generally increased intracellular lipid content. The fatty acid profiles varied with the growth conditions regardless of taxonomic affiliation. The dominant fatty acids were oleic acid, palmitic acid, linoleic acid, and stearic acid. Yeasts and culture conditions that produced fatty acids appropriate for biodiesel were identified. PMID:23891835

  4. Plasma Acylcarnitine Profiles Suggest Incomplete Fatty Acid ß-Oxidation and Altered Tricarboxylic Cycle Activity in Type 2 Diabetic African-American Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inefficient muscle long-chain fatty acid (LCFA) combustion is associated with insulin resistance, but molecular links between mitochondrial fat catabolism and insulin action remain controversial. We hypothesized that plasma acylcarnitine profiling would identify distinct metabolite patterns reflect...

  5. Long-term ultraviolet A irradiation of the eye induces photoaging of the skin in mice.

    PubMed

    Hiramoto, Keiichi; Yamate, Yurika; Kobayashi, Hiromi; Ishii, Masamitsu

    2012-01-01

    Irradiation by long-term ultraviolet (UV) A initiates the induction of photoaging. However, the mechanisms responsible for the structural changes of skin induced by UVA irradiation of the eye are still unknown. Male hairless mice were used in this study. The eye or dorsal skin was locally exposed to UVA after covering the remaining body surface with aluminum foil at a dose of 110 kJ/m(2) using a FL20SBLB-A lamp for 60 days. The plasma α-melanocyte stimulating hormone (α-MSH), nitrogen oxides (NO(2)/NO(3)), tumor necrosis factor-α (TNF-α), and the prostaglandin E(2) (PGE(2)) content all increased after UVA irradiation. The levels of NO(2)/NO(3), TNF-α, and PGE(2) also increased more after UVA skin irradiation than after UVA eye irradiation. However, the level of α-MSH increased more by eye irradiation than skin irradiation. In addition, UVA irradiation of the eye and dorsal skin increased the number of mast cells and fibroblasts. Furthermore, the expression of the melanocortin-1 receptor (MC1R) was increased on the fibroblast surface by UVA irradiation of the eye. These results indicate that the signal evoked by UVA irradiation of the eye, through the hypothalamo-pituitary proopiomelanocortin system, up-regulated the production of α-MSH. This hormone controls the collagen generation from fibroblasts, thus suggesting that photoaging was induced by UVA irradiation of the eye. PMID:22033528

  6. Singlet molecular oxygen-quenching activity of carotenoids: relevance to protection of the skin from photoaging

    PubMed Central

    Terao, Junji; Minami, Yuko; Bando, Noriko

    2011-01-01

    Carotenoids are known to be potent quenchers of singlet molecular oxygen [O2 (1Δg)]. Solar light-induced photooxidative stress causes skin photoaging by accelerating the generation of reactive oxygen species via photodynamic actions in which O2 (1Δg) can be generated by energy transfer from excited sensitizers. Thus, dietary carotenoids seem to participate in the prevention of photooxidative stress by accumulating as antioxidants in the skin. An in vivo study using hairless mice clarified that a O2 (1Δg) oxygenation-specific peroxidation product of cholesterol, cholesterol 5α-hydroperoxide, accumulates in skin lipids due to ultraviolet-A exposure. Matrix metalloproteinase-9, a metalloproteinase family enzyme responsible for the formation of wrinkles and sagging, was enhanced in the skin of ultraviolet-A -irradiated hairless mice. The activation of metalloproteinase-9 and the accumulation of 5α-hydroperoxide, as well as formation of wrinkles and sagging, were lowered in mice fed a β-carotene diet. These results strongly suggest that dietary β-carotene prevents the expression of metalloproteinase-9 (at least in part), by inhibiting the photodynamic action involving the formation of 5α-hydroperoxide in the skin. Intake of β-Carotene therefore appears to be helpful in slowing down ultraviolet-A -induced photoaging in human skin by acting as a O2 (1Δg) quencher. PMID:21297913

  7. Stereoselective skin anti-photoaging properties of ginsenoside Rg3 in UV-B-irradiated keratinocytes.

    PubMed

    Lim, Chang-Jin; Choi, Woo-Yong; Jung, Hyun-Joo

    2014-01-01

    Ginsenosides are major bioactive constituents that are responsible for the diverse pharmacological activities of ginseng. This work aimed to assess the skin anti-photoaging activities of the two stereoisomeric forms of ginsenoside Rg3, 20(S)-Rg3 and 20(R)-Rg3. When the two Rg3 stereoisomers were added to cultured human keratinocyte HaCaT cells prior to irradiation with 70 mJ/cm(2) UV-B, 20(S)-Rg3, but not 20(R)-Rg3, decreased the UV-B-induced intracellular reactive oxygen species (ROS) levels in a concentration-dependent manner, as detected by both fluorometric and confocal microscopic analyses. Likewise, 20(S)-Rg3, but not 20(R)-Rg3, decreased the UV-B-induced ROS levels in human dermal fibroblast cells. Both stereoisomers were unable to modulate the nitric oxide levels in HaCaT cells under UV-B irradiation, and induced no cytotoxicity in cultured keratinocytes and fibroblasts. 20(S)-Rg3 suppressed the UV-B-induced matrix metalloproteinase (MMP)-2 activities in HaCaT cells. Taken together, these results indicate that 20(S)-Rg3 possesses both ROS-scavenging and MMP-2 inhibitory activities, while 20(R)-Rg3 possesses neither activity. These findings imply that ginsenoside Rg3 stereoselectively demonstrates skin anti-photoaging activities. PMID:25056231

  8. Construction of Nontoxic Polymeric UV-Absorber with Great Resistance to UV-Photoaging

    NASA Astrophysics Data System (ADS)

    Huang, Zhong; Ding, Aishun; Guo, Hao; Lu, Guolin; Huang, Xiaoyu

    2016-05-01

    In this article, we developed a series of new nontoxic polymeric UV-absorbers through covalently attaching a benzophenone derivative onto the main chain of poly(vinyl chloride) (PVC) via mild and quantitative click chemistry. Azide groups were firstly introduced into the backbone of PVC via a nucleophilic reaction without affecting polymeric skeleton. Copper-catalyzed Husigen-Click cycloaddition reaction was performed between the pendant azide groups of PVC and alkynyl of (2-hydroxy-4-(prop-2-ynyloxy)phenyl)(phenyl)methanone at ambient temperature for affording the desired PVC-based UV-absorbers (PVC-UV) with different amounts of benzophenone moieties, which displayed great resistance to photoaging without degradation while exposed to UV irradiation. These polymeric UV-absorbers also showed good solubilities in common organic solvents and no cytotoxicity vs. HaCat cell. Small amounts of PVC-UV were homogeneously mixed with PVC as additive for stabilizing PVC against UV-photoaging without degradation and releasing small molecule even after 200 h while keeping thermal stability. This route of polymeric additive clearly paved an efficient way for solving the puzzle of separation of small molecule additive.

  9. Labisia pumila extract protects skin cells from photoaging caused by UVB irradiation.

    PubMed

    Choi, Hyun-kyung; Kim, Dong-hyun; Kim, Jin Wook; Ngadiran, Sulaiman; Sarmidi, Mohamad Roji; Park, Chang Seo

    2010-03-01

    Labisia pumila (Myrsinaceae), known as "Kacip Fatimah," has been used by many generations of Malay women to induce and facilitate child birth as well as a post partum medicine. However, its topical application on skin has not been reported yet. In this study, we have focused on the anti-photoaging effects of L. pumila. Extract of L. pumila was first analyzed for their antioxidant activities using DPPH (2,2-diphenyl-1-picrylhydrazyl) since UV irradiation is a primary cause of reactive oxygen species (ROS) generation in the skin. The 50% free radical scavenging activity (FSC(50)) of L. pumila extract was determined to be 0.006%, which was equal to that produced by 156 microM ascorbic acid. TNF-alpha and cyclooxygenase (COX-2) play a primary role in the inflammation process upon UV irradiation and are known to be stimulated by UVB. Treatment with L. pumila extract markedly inhibited the TNF-alpha production and the expression of COX-2. Decreased collagen synthesis of human fibroblasts by UVB was restored back to normal level after treatment with L. pumila extract. On the other hand, the enhanced MMP-1 expression upon UVB irradiation was down regulated by L. pumila extract in a dose-dependent manner. Furthermore, treatment of normal keratinocytes with L. pumila extract attenuated UVB-induced MMP-9 expression. These results collectively suggest L. pumila extract has tremendous potential as an anti-photoaging cosmetic ingredient. PMID:20159580

  10. Spent coffee ground extract suppresses ultraviolet B-induced photoaging in hairless mice.

    PubMed

    Choi, Hyeon-Son; Park, Eu Ddeum; Park, Yooheon; Suh, Hyung Joo

    2015-12-01

    The aim of this study is to evaluate the effect of spent coffee ground (SCG) ethanol extract on UVB-induced skin aging in hairless mice. An ethanol extract of SCG (ESCG) was prepared using the residue remaining after extraction of oil from roasted SCG. High performance liquid chromatography (HPLC) analysis showed that the content of caffeine (41.58 ± 0.54 μg/mg) was higher than that of chlorogenic acid isomers (~9.17 μg/mg) in ESCG. ESCG significantly decreased the UVB-induced intracellular reactive oxygen species in HaCaT cells. UVB-induced wrinkle formation in mice dorsal skin was effectively reduced by ESCG administration; high dose of ESCG (5 g/L) caused the reduction of wrinkle area by 30% compared with UVB-treated control (UVBC). This result correlated with the ESCG-mediated decrease in epidermis thickness (25%). In addition, ESCG administration significantly reduced transdermal water loss (20%) and erythema formation (35%) derived from UVB exposure. Collagen type I (COL-1) level in dorsal skin was effectively recovered by ESCG administration. These results were supported by down-regulation of collagen-degrading matrix metalloproteinase 2 (MMP2) and 9 (MMP9) expressions. Our results indicate that ESCG protects mouse skin from UVB-induced photoaging by suppressing the expression of matrix metalloproteinases. Our study suggests that ESCG may be anti-photoaging agent. PMID:26410040

  11. Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation.

    PubMed

    Zhan, Janis Ya-Xian; Wang, Xiu-Fen; Liu, Yu-Hong; Zhang, Zhen-Biao; Wang, Lan; Chen, Jian-Nan; Huang, Song; Zeng, Hui-Fang; Lai, Xiao-Ping

    2016-01-01

    Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent. PMID:26903706

  12. Construction of Nontoxic Polymeric UV-Absorber with Great Resistance to UV-Photoaging

    PubMed Central

    Huang, Zhong; Ding, Aishun; Guo, Hao; Lu, Guolin; Huang, Xiaoyu

    2016-01-01

    In this article, we developed a series of new nontoxic polymeric UV-absorbers through covalently attaching a benzophenone derivative onto the main chain of poly(vinyl chloride) (PVC) via mild and quantitative click chemistry. Azide groups were firstly introduced into the backbone of PVC via a nucleophilic reaction without affecting polymeric skeleton. Copper-catalyzed Husigen-Click cycloaddition reaction was performed between the pendant azide groups of PVC and alkynyl of (2-hydroxy-4-(prop-2-ynyloxy)phenyl)(phenyl)methanone at ambient temperature for affording the desired PVC-based UV-absorbers (PVC-UV) with different amounts of benzophenone moieties, which displayed great resistance to photoaging without degradation while exposed to UV irradiation. These polymeric UV-absorbers also showed good solubilities in common organic solvents and no cytotoxicity vs. HaCat cell. Small amounts of PVC-UV were homogeneously mixed with PVC as additive for stabilizing PVC against UV-photoaging without degradation and releasing small molecule even after 200 h while keeping thermal stability. This route of polymeric additive clearly paved an efficient way for solving the puzzle of separation of small molecule additive. PMID:27138547

  13. Construction of Nontoxic Polymeric UV-Absorber with Great Resistance to UV-Photoaging.

    PubMed

    Huang, Zhong; Ding, Aishun; Guo, Hao; Lu, Guolin; Huang, Xiaoyu

    2016-01-01

    In this article, we developed a series of new nontoxic polymeric UV-absorbers through covalently attaching a benzophenone derivative onto the main chain of poly(vinyl chloride) (PVC) via mild and quantitative click chemistry. Azide groups were firstly introduced into the backbone of PVC via a nucleophilic reaction without affecting polymeric skeleton. Copper-catalyzed Husigen-Click cycloaddition reaction was performed between the pendant azide groups of PVC and alkynyl of (2-hydroxy-4-(prop-2-ynyloxy)phenyl)(phenyl)methanone at ambient temperature for affording the desired PVC-based UV-absorbers (PVC-UV) with different amounts of benzophenone moieties, which displayed great resistance to photoaging without degradation while exposed to UV irradiation. These polymeric UV-absorbers also showed good solubilities in common organic solvents and no cytotoxicity vs. HaCat cell. Small amounts of PVC-UV were homogeneously mixed with PVC as additive for stabilizing PVC against UV-photoaging without degradation and releasing small molecule even after 200 h while keeping thermal stability. This route of polymeric additive clearly paved an efficient way for solving the puzzle of separation of small molecule additive. PMID:27138547

  14. Effect of Microalgal Extracts of Tetraselmis suecica against UVB-Induced Photoaging in Human Skin Fibroblasts.

    PubMed

    Jo, Wol Soon; Yang, Kwang Mo; Park, Hee Sung; Kim, Gi Yong; Nam, Byung Hyouk; Jeong, Min Ho; Choi, Yoo Jin

    2012-12-01

    Exposure of cells to ultraviolet B (UVB) radiation can induce production of free radicals and reactive oxygen species (ROS), which damage cellular components. In addition, these agents can stimulate the expression of matrix metalloproteinase (MMP) and decrease collagen synthesis in human skin cells. In this study, we examined the anti-photoaging effects of extracts of Tetraselmis suecica (W-TS). W-TS showed the strongest scavenging activity against 2,2-difenyl-1-picrylhydrazyl (DPPH) and peroxyl radicals, followed by superoxide anions from the xanthine/xanthine oxidase system. We observed that the levels of both intracellular ROS and lipid peroxidation significantly increased in UVB-irradiated human skin fibroblast cells. Furthermore, the activities of enzymatic antioxidants (e.g., superoxide dismutase) and the levels of non-enzymatic antioxidants (e.g., glutathione) significantly decreased in cells. However, W-TS pretreatment, at the maximum tested concentration, significantly decreased intracellular ROS and malondialdehyde (MDA) levels, and increased superoxide dismutase and glutathione levels in the cells. At this same concentration, W-TS did not show cytotoxicity. Type 1 procollagen and MMP-1 released were quantified using RT-PCR techniques. The results showed that W-TS protected type 1 procollagen against UVBinduced depletion in fibroblast cells in a dose-dependent manner via inhibition of UVB-induced MMP-1. Taken together, the results of the study suggest that W-TS effectively inhibits UVB-induced photoaging in skin fibroblasts by its strong anti-oxidant ability. PMID:24278616

  15. Effects of topical application of patchouli alcohol on the UV-induced skin photoaging in mice.

    PubMed

    Feng, Xue-Xuan; Yu, Xiu-Ting; Li, Wen-Jie; Kong, Song-Zhi; Liu, Yu-Hong; Zhang, Xie; Xian, Yan-Fang; Zhang, Xiao-Jun; Su, Zi-Ren; Lin, Zhi-Xiu

    2014-10-15

    Ultraviolet (UV) irradiation, known to generate reactive oxygen species (ROS) excessively and elicit inflammatory response, is a potent inducer for skin photoaging. Overproduction of ROS in conjunction with the resulting inflammation stimulate the over-expression of matrix metalloproteinases (MMPs), which in turn causes degradation of extracellular matrix, leading finally to coarse wrinkling, dryness, and laxity of the skin. In this study, patchouli alcohol (PA, C15H26O), an active chemical ingredient reputed for free radical scavenging and anti-inflammatory properties, was investigated for its anti-photoaging action using a mouse model whose dorsal skin was depilated. The dorsal skin areas of six-week-old mice were smeared with PA solution or vehicle, followed by UV irradiation for nine consecutive weeks. Protective effects of PA were evaluated macroscopically and histologically, as well as by assaying the antioxidant enzymes (SOD, GSH-Px) activities, the contents of inflammatory factors (IL-10, IL-6, TNF-α), and the levels of MMP-1 and MMP-3. Our findings amply demonstrated that PA significantly accelerated the recovery of the UV-induced skin lesions, evidently through anti-oxidant and anti-inflammatory action, as well as down-regulation of the MMP-1 and MMP-3 expression. PMID:25033712

  16. Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation

    PubMed Central

    Zhan, Janis Ya-Xian; Wang, Xiu-Fen; Liu, Yu-Hong; Zhang, Zhen-Biao; Wang, Lan; Chen, Jian-Nan; Huang, Song; Zeng, Hui-Fang; Lai, Xiao-Ping

    2016-01-01

    Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent. PMID:26903706

  17. N-3 fatty acid intake altered fat content and fatty acid distribution in chicken breast muscle, but did not influence mRNA expression of lipid-related enzymes

    PubMed Central

    2014-01-01

    Background The conversions of the n-3 and n-6 fatty acid of plant origin to the C20 and C22 very long chain fatty acids (LCPUFAs) is regulated by several cellular enzymes such as elongases and desaturases. Methods Sixty-five male one-day old chickens (Ross 308) were randomly divided into four groups and given one of four diets; with or without linseed oil (LO), (the diets contained equal amounts of fat) and with low or high selenium (Se). Final body weight, amount of Se and fat in breast muscle, fatty acid profile, and gene expression for fatty acid desaturases (Fads1, Fads2, Fads9), HMG-CoA reductase, Acyl-CoA oxidase (Acox), carnitine palmitoyl transferase1 (Cpt1), superoxide dismutase (Sod) and glutathione peroxidase4 (Gpx4) were analyzed in all animals, and Gpx activity in whole blood was determined. Results mRNA expression of elongases and desaturases in chicken breast muscle was not affected by feed rich in C18:3n-3. The highly positive correlation between amount of fat in breast muscle and the product/precursor indices of monounsaturated fatty acid synthesis, and the negative correlation between muscle fat and indices of LCPUFA synthesis should be further studied. Conclusion mRNA expression in chicken breast muscle of elongases and desaturases was not affected by feed rich in C18:3n-3. The highly positive correlation between amount of fat in breast muscle and the product/precursor indices of monounsaturated fatty acid synthesis, and the negative correlation between muscle fat and indices of LCPUFA synthesis should be further studied. PMID:24894510

  18. Transcriptome Analysis of Skin Photoaging in Chinese Females Reveals the Involvement of Skin Homeostasis and Metabolic Changes

    PubMed Central

    Yan, Li; Zhang, Feng; Yin, Ning-Bei; Lin, Hong-Bin; Huang, Chen-Yu; Wang, Lei; Yu, Jun; Wang, Duen-Mei; Zhao, Zhen-Min

    2013-01-01

    Background Photoaging is cumulative damage to skin, caused by chronic, repeated solar radiation exposure. Its molecular mechanisms are poorly understood at the level of global gene expression. Objective This study set out to uncover genes and functional modules involved in photoaging at the level of transcription, with the use of skin samples from Chinese women. Methods Using the Illumina microarray platform, we compared the genome-wide expression profiles of 21 pairs of sun-exposed pre-auricular and sun-protected post-auricular skin samples from northern Chinese women. Results With microarray analysis, 1,621 significantly regulated genes due to photoaging were identified from skin samples. These genes were subjected to functional enrichment analyses with both the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation databases. As revealed by the functional analyses, the up-regulated functional modules in sun-exposed pre-auricular skin were related to various cellular activities in regulation of the skin homeostasis (e.g., the KEGG pathways TGF-beta signaling pathway and ECM-receptor interaction), whereas the down-regulated functional modules were mostly metabolic-related. Additionally, five selected genes (HOXA5, LEPR, CLDN5, LAMC3, and CGA) identified as differentially-expressed were further confirmed by quantitative real-time PCR (Q-RT-PCR). Conclusion Our findings suggest that disruption of skin homeostasis and down-regulation of skin metabolism may play important roles in the process of photoaging. PMID:23637934

  19. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  20. Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils

    SciTech Connect

    Woodley, D.T.; Briggaman, R.A. ); Zelickson, A.S. ); Hamilton, T.A.; Weiss, J.S.; Ellis, C.N.; Voorhees, J.J. )

    1990-06-13

    Topical 0.1% tretinoin or vehicle control was applied daily to the forearm skin of six caucasian adults for 4 months. Two-millimeter punch biopsy specimens were obtained from treatment sites at the beginning and end of the study period for electron microscopy. Anchoring fibrils within the epidermal-dermal junction of skin treatment sites were quantitated by blinded, standardized, computer-assisted morphometry. After 4 months of continual daily treatment, skin sites that received topical tretinoin showed double the anchoring fibril density compared with vehicle control sites. The possible mechanism by which topical tretinoin increases anchoring fibrils in skin include the drug's property of inhibiting collagenase, a dermal enzyme that degrades anchoring fibril collagen. The authors speculate that increased numbers of collagenous anchoring fibrils within the papillary dermis of human skin is one of the connective-tissue correlates of the clinical improvement observed in photoaged skin after treatment with topical tretinoin.

  1. Dietary fish oil supplements depress milk fat yield and alter milk fatty acid composition in lactating cows fed grass silage-based diets.

    PubMed

    Kairenius, P; Ärölä, A; Leskinen, H; Toivonen, V; Ahvenjärvi, S; Vanhatalo, A; Huhtanen, P; Hurme, T; Griinari, J M; Shingfield, K J

    2015-08-01

    The potential of dietary fish oil (FO) supplements to increase milk 20:5n-3 and 22:6n-3 concentrations and the associated effects on milk fatty acid (FA) composition, intake, and milk production were examined. Four multiparous lactating cows offered a grass silage-based diet (forage:concentrate ratio 58:42, on a dry matter basis) supplemented with 0, 75, 150, or 300g of FO/d (FO0, FO75, FO150, and FO300, respectively) were used in a 4×4 Latin square with 28-d experimental periods. Milk FA composition was analyzed by complementary silver-ion thin-layer chromatography, gas chromatography-mass spectrometry, and silver-ion HPLC. Supplements of FO decreased linearly dry matter intake, yields of energy-corrected milk, milk fat and protein, and milk fat content. Compared with FO0, milk fat content and yield were decreased by 30.1 and 40.6%, respectively, on the FO300 treatment. Supplements of FO linearly increased milk 20:5n-3 and 22:6n-3 concentrations from 0.07 to 0.18 and 0.03 to 0.10g/100g of FA, respectively. Enrichment of 20:5n-3 and 22:6n-3 was accompanied by decreases in 4- to 18-carbon saturated FA and increases in total conjugated linoleic acid (CLA), trans FA, and polyunsaturated FA concentrations. Fish oil elevated milk fat cis-9,trans-11 CLA content in a quadratic manner, reaching a maximum on FO150 (from 0.61 to 2.15g/100g of FA), whereas further amounts of FO increased trans-10 18:1 with no change in trans-11 18:1 concentration. Supplements of FO also resulted in a dose-dependent appearance of 37 unique 20- and 22-carbon intermediates in milk fat. Concentrations of 16-, 18-, 20-, and 22-carbon trans FA were all increased by FO, with enrichment of trans 18:1 and trans 18:2 being quantitatively the most important. Decreases in milk fat yield to FO were not related to changes in milk trans-10,cis-12 CLA concentration or estimated milk fat melting point. Partial least square regression analysis indicated that FO-induced milk fat depression was associated with

  2. Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in piglets by differentially altering muscle lipid composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated the role of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) of muscle phospholipids in the regulation of neonatal metabolism. Twenty-eight piglets were weaned at 2 days of age and raised on one of two milk formulas that consisted of either a control formula supplying ...

  3. Development and enteral long-chain n-3 fatty acids differentially alters muscle intracellular pools of free amino acids in the neonate piglet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies suggest that feeding long-chain n-3 fatty acids (LCn-3FA) in the diet may blunt the developmental reduction in insulin sensitivity and anabolism in the neonate piglet. To examine the effect of LCn-3FA on protein anabolism, 2-day-old piglets (n=28) were weaned and assigned to one of t...

  4. Contribution of UVA irradiance to the erythema and photoaging effects in solar and sunbed exposures.

    PubMed

    Sola, Yolanda; Lorente, Jerónimo

    2015-02-01

    Even though UVA irradiance had not been considered detrimental to human skin for years, nowadays it is recognized for its role in photoaging and other biological responses. The ratio UVA/UVB is about 17 at a solar zenith angle (SZA) of 20° and it is almost constant up to 60° when it rapidly increases since the UVB wavelengths (280-320nm) are more attenuated than the UVA waveband (320-400nm). For a constant SZA, the ratio increases with the ozone content. The UVA component of the solar erythemal irradiance ranges from 20% at 20° to 30% at 60°, whereas it varies from 50% to 80% in the two different types of measured sunbeds. Moreover, the different spectral distribution of the lamps used for artificial tanning leads frequently to high UVA doses. The biological responses related to skin photoaging (skin sagging and elastosis) could be around fourfold the equivalent solar irradiance at midday in summer midlatitudes and they can be important in unprotected UVA exposures to sunbeds. The UVA dose accumulated during the time required in reaching 1 minimum erythemal dose (MED) increases with the SZA since the exposure durations are longer. Indeed, seasonal differences in the mean UVA dose are observed due to variations in the ozone content that results in longer exposure times without erythema. Although an artificial tanning session is usually shorter than one hour, the UVA dose from sunbeds during the time for 1 MED for skin type II (250Jm(-2)) can be 2-4 times larger than the solar dose, depending on the lamp spectral emission. PMID:25579807

  5. A Review of Clinical Trials Conducted With Oral, Multicomponent Dietary Supplements for Improving Photoaged Skin.

    PubMed

    Birnbaum, Jay; Le Moigne, Anne; Dispensa, Lisa; Buchner, Larry

    2015-12-01

    Although the FDA does not require documentation of efficacy of dietary supplements, prospective clinical studies, including randomized controlled trials, have been conducted with individual micronutrients alone and in combination with other ingredients for promoting skin health. Proposed mechanisms include antioxidation, anti-inflammation, photoprotection, collagen formation, reductions in matrix metalloproteinases, and other effects on photoaging. Literature searches were conducted to identify clinical trials assessing multicomponent dietary supplement formulations on photoaging outcomes. Sixteen studies of various nutrient and non-nutrient ingredients, including essential micronutrients (vitamins, minerals), plant extracts (polyphenols, carotenoids), and marine- or animal-derived ingredients, were identified. Studies were single center, 2-12 months in duration, primarily enrolled women, and evaluated numerous outcomes, including investigator/subject assessments and instrumental/objective measures. Methods to control for potential confounders were implemented in some studies, including limiting sun exposure, cosmetic procedures, and changes in dietary habits/body weight. Given the range of different products, clinical/methodologic heterogeneity, insufficient detail in reporting, and lack of comparable outcome measures, quantitative analysis of results was not possible. Results of individual studies revealed significant improvements from baseline for the dietary supplement group(s) on ≥ 1 endpoint across all studies; significant differences from placebo were observed in 7 of 12 controlled studies (although only 1 study designated a prospectively defined primary endpoint). Most products had only been tested in 1 study; confirmatory studies were rarely conducted per the publicly available literature. Meaningful assessment of dietary supplements, which typically contain nutrients found in the diet, requires unique methodologic considerations and endpoints

  6. Mammalian Fatty Acid Elongases

    PubMed Central

    Jump, Donald B.

    2009-01-01

    Summary Very long chain fatty acids confer functional diversity on cells by variations in their chain length and degree of unsaturation. Microsomal fatty acid elongation represents the major pathway for determining the chain length of saturated, monounsaturated, and polyunsaturated fatty acids in cellular lipids. The overall reaction for fatty acid elongation involves four enzymes and utilizes malonyl CoA, NADPH, and fatty acyl CoA as substrates. While the fundamental pathway and its requirements have been known for many years, recent advances have revealed a family of enzymes involved in the first step of the reaction, i.e., the condensation reaction. Seven fatty acid elongase subtypes (Elovl #1–7) have been identified in the mouse, rat, and human genomes. These enzymes determine the rate of overall fatty acid elongation. Moreover, these enzymes also display differential substrate specificity, tissue distribution, and regulation, making them important regulators of cellular lipid composition as well as specific cellular functions. Herein, methods are described to measure elongase activity, analyze elongation products, and alter cellular elongase expression. PMID:19763486

  7. Large alterations in ganglioside and neutral glycosphingolipid patterns in brains from cases with infantile neuronal ceroid lipofuscinosis/polyunsaturated fatty acid lipidosis.

    PubMed

    Svennerholm, L; Fredman, P; Jungbjer, B; Månsson, J E; Rynmark, B M; Boström, K; Hagberg, B; Norén, L; Santavuori, P

    1987-12-01

    Lipid composition was studied on cerebral tissue from nine children who had died of a progressive encephalopathy called the infantile form of neuronal ceroid lipofuscinosis (INCL) or polyunsaturated fatty acid lipidosis (PFAL). In the terminal stage of the disease, the concentrations of all lipid classes were found to be significantly reduced in the cerebral and cerebellar cortex and white matter. The concentration of gangliosides of the cerebral cortex was 15% and that of cerebrosides (galactosylceramide) in white matter 0.2-5% of the normal values for the children's ages. The reduction of gangliosides mainly affected those of the gangliotetraose series, particularly GD1a. The fatty acids of the linolenic acid series were strongly reduced in ethanolamine and serine phosphoglycerides. A very large increase up to 100-fold of oligoglycosphingolipids of the globo series and two fucose-containing lipids of the neolacto series was found in the forebrain of the three advanced cases examined. The brain tissue also contained very high concentrations of mono-, di-, and trisialogangliosides of the lacto and neolacto series, gangliosides with type 1 chain dominating. The structures of the gangliosides were tentatively identified by gas chromatography-mass spectrometry and monoclonal antibodies with carefully determined epitope specificity. The gangliosides and neutral glycosphingolipids had very similar fatty acid composition, consisting of about 40% stearic acid and 40% C24-acids. PMID:3681296

  8. Bifidobacterium breve with α-Linolenic Acid and Linoleic Acid Alters Fatty Acid Metabolism in the Maternal Separation Model of Irritable Bowel Syndrome

    PubMed Central

    Barrett, Eoin; Fitzgerald, Patrick; Dinan, Timothy G.; Cryan, John F.; Ross, R. Paul; Quigley, Eamonn M.; Shanahan, Fergus; Kiely, Barry; Fitzgerald, Gerald F.; O'Toole, Paul W.; Stanton, Catherine

    2012-01-01

    The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (109 microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats

  9. Fatty acids - trans fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  10. Regenerative and reparative effects of human chorion-derived stem cell conditioned medium on photo-aged epidermal cells.

    PubMed

    Li, Qiankun; Chen, Yan; Ma, Kui; Zhao, Along; Zhang, Cuiping; Fu, Xiaobing

    2016-04-17

    Epidermal cells are an important regenerative source for skin wound healing. Aged epidermal cells have a low ability to renew themselves and repair skin injury. Ultraviolet (UV) radiation, particularly UVB, can cause photo-aging of the skin by suppressing the viability of human epidermal cells. A chorion-derived stem cell conditioned medium (CDSC-CNM) is thought to have regenerative properties. This study aimed to determine the regenerative effects of CDSC-CNM on UVB-induced photo-aged epidermal cells. Epidermal cells were passaged four times and irradiated with quantitative UVB, and non-irradiated cells served as a control group. Cells were then treated with different concentrations of CDSC-CNM. Compared to the non-irradiated group, the proliferation rates and migration rates of UVB-induced photo-aged epidermal cells significantly decreased (p < 0.05) with increasing intracellular radical oxygen species (ROS) generation and DNA damage. After treatment with CDSC-CNM, photo-aged epidermal cells significantly improved their viability, and their ROS generation and DNA damage decreased. The secretory factors in CDSC-CNM, including epidermal growth factor (EGF), transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-8 and the related signaling pathway protein levels, increased compared to the control medium (CM). The potential regenerative and reparative effects of CDSC-CNM indicate that it may be a candidate material for the treatment of prematurely aged skin. The functions of the secretory factors and the mechanisms of CDSC-CNM therapy deserve further attention. PMID:27097375

  11. Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice

    PubMed Central

    Kim, Ha Neui; Gil, Chan Hee; Kim, Yu Ri; Shin, Hwa Kyoung; Choi, Byung Tae

    2016-01-01

    We investigated whether cilostazol, an activator of cyclic adenosine monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as increased staining of collagen fibers and inhibition of reactive oxygen species (ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB was significantly inhibited by cilostazol, whereas the activation of Akt was significantly enhanced by cilostazol. Confirmation of localized protein expression in the skin revealed marked p38 MAPK and NF-κB activation that was mainly detected in the dermis. Marked Akt activation was mainly detected in the epidermis. Our results suggest that cilostazol may have anti-photoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of ROS and related p38 MAPK and NF-κB signaling, and subsequent down-regulation of MMPs. Therefore, cilostazol may protect against photoaging-induced wrinkle formation. PMID:27484958

  12. Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice.

    PubMed

    Kim, Ha Neui; Gil, Chan Hee; Kim, Yu Ri; Shin, Hwa Kyoung; Choi, Byung Tae

    2016-01-01

    We investigated whether cilostazol, an activator of cyclic adenosine monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as increased staining of collagen fibers and inhibition of reactive oxygen species (ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB was significantly inhibited by cilostazol, whereas the activation of Akt was significantly enhanced by cilostazol. Confirmation of localized protein expression in the skin revealed marked p38 MAPK and NF-κB activation that was mainly detected in the dermis. Marked Akt activation was mainly detected in the epidermis. Our results suggest that cilostazol may have anti-photoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of ROS and related p38 MAPK and NF-κB signaling, and subsequent down-regulation of MMPs. Therefore, cilostazol may protect against photoaging-induced wrinkle formation. PMID:27484958

  13. Clinical efficacy of adapalene (differin(®)) 0.3% gel in Chilean women with cutaneous photoaging.

    PubMed

    Herane, María Isabel; Orlandi, Cecilia; Zegpi, Emilia; Valdés, Pilar; Ancić, Ximena

    2012-02-01

    Skin photoaging is a concern for many patients today, and it is important for dermatologists to evaluate new therapeutic approaches. This 6-month open-label study evaluated the effectiveness and safety of adapalene 0.3% gel in 40 Latin American women with signs of facial photoaging. Assessments at baseline, week 12, and week 24 included clinical severity grading, measurement of transepidermal water loss, hydration, and elasticity (Cutometer MPA 850®), evaluation of general skin tone and number of wrinkles (VISIA(®) Complexion Analysis System), and ultrasonography to measure changes in skin thickness. There were significant improvements in clinical grading of wrinkles (p < 0.01) with a reduction in mean severity score of 40% in forehead wrinkles, 52% in periorbital wrinkles, and 29% in perioral wrinkles. Melanin, transepidermal water loss, and hydration were improved, as were general skin tone and the number of wrinkles (p < 0.05). Measurement of skin thickness showed a non-significant improvement in the epidermis and dermis and a significant decrease of the elastosis band (11.6% at week 12 and 15.1% at week 24). Adapalene was well tolerated overall, although three patients discontinued the study due to skin irritation in the first month. We conclude that adapalene 0.3% gel is a new safe and effective approach to photoaging. PMID:22007702

  14. Glycyrrhizic acid (GA), a triterpenoid saponin glycoside alleviates ultraviolet-B irradiation-induced photoaging in human dermal fibroblasts.

    PubMed

    Afnan, Quadri; Adil, Mushtaq Dar; Nissar-Ul, Ashraf; Rafiq, Ahmad Rather; Amir, Hussian Faridi; Kaiser, Peerzada; Gupta, Vijay Kumar; Vishwakarma, Ram; Tasduq, Sheikh Abdullah

    2012-05-15

    Glycyrrhizic acid (GA), a triterpenoid saponin glycoside from the roots and rhizomes of licorice is used in traditional and modern medicine for the treatment of numerous medical conditions including skin diseases and beauty care product. In the present study, we investigated the effect of GA against ultraviolet B (UVB) irradiation-induced photoaging in human dermal fibroblasts (HDFs) and its possible mechanism of action. HDFs were subjected to photoaging by sub-toxic dose of UVB (10 mj/cm(2)) irradiation. Cell viability, matrix metalloproteinase 1 (MMP1), pro-collagen 1, cellular and nuclear morphology, cell cycle, intracellular reactive oxygen species (ROS), caspase 3 and hyaluronidase inhibition assays were performed. Western blotting was used to evaluate the expression of NF-kappa B (NF-κB) and cytochrome-C proteins. GA treatment significantly inhibited photoaging. It achieved this by reducing ROS, NF-κB, cytochrome c, caspase 3 levels and inhibiting hyaluronidase enzyme. The main mechanism seems to be, most likely by blocking MMP1 activation by modulating NF-κB signaling. These findings may be useful for development of natural and safe photoprotective agents against UVB irradiation. PMID:22516896

  15. Oral administration of French maritime pine bark extract (Flavangenol®) improves clinical symptoms in photoaged facial skin

    PubMed Central

    Furumura, Minao; Sato, Noriko; Kusaba, Nobutaka; Takagaki, Kinya; Nakayama, Juichiro

    2012-01-01

    Background French maritime pine bark extract (PBE) has gained popularity as a dietary supplement in the treatment of various diseases due to its polyphenol-rich ingredients. Oligometric proanthocyanidins (OPCs), a class of bioflavonoid complexes, are enriched in French maritime PBE and have antioxidant and anti-inflammatory activity. Previous studies have suggested that French maritime PBE helps reduce ultraviolet radiation damage to the skin and may protect human facial skin from symptoms of photoaging. To evaluate the clinical efficacy of French maritime PBE in the improvement of photodamaged facial skin, we conducted a randomized trial of oral supplementation with PBE. Methods One hundred and twelve women with mild to moderate photoaging of the skin were randomized to either a 12-week open trial regimen of 100 mg PBE supplementation once daily or to a parallel-group trial regimen of 40 mg PBE supplementation once daily. Results A significant decrease in clinical grading of skin photoaging scores was observed in both time courses of 100 mg daily and 40 mg daily PBE supplementation regimens. A significant reduction in the pigmentation of age spots was also demonstrated utilizing skin color measurements. Conclusion Clinically significant improvement in photodamaged skin could be achieved with PBE. Our findings confirm the efficacy and safety of PBE. PMID:22956863

  16. Modulation of fatty acid oxidation alters contact hypersensitivity to urushiols: role of aliphatic chain beta-oxidation in processing and activation of urushiols.

    PubMed

    Kalergis, A M; López, C B; Becker, M I; Díaz, M I; Sein, J; Garbarino, J A; De Ioannes, A E

    1997-01-01

    Lithraea caustica, or litre, a tree of the Anacardiaceae family that is endemic to the central region of Chile, induces a severe contact dermatitis in susceptible human beings. The allergen was previously isolated and characterized as a 3-(pentadecyl-10-enyl) catechol, a molecule belonging to the urushiol group of allergens isolated from poison ivy and poison oak plants. Because urushiols are pro-electrophilic haptens, it is believed that the reactive species are generated intracellularly by skin keratinocytes and Langerhans cells. The active species are presumed to modify self proteins which, after proteolytic processing, would generate immunogenic peptides carrying the hapten. The presence of a 15-carbon-length hydrophobic chain should impair antigen presentation of self-modified peptides by class I MHC molecules, either by steric hindrance or by limiting their sorting to the ER lumen. We have proposed that the shortening of the aliphatic chain by beta-oxidation within peroxisomes and/or mitochondria should be a requirement for the antigen presentation process. To test this hypothesis we investigated the effect of drugs that modify the fatty acid metabolism on urushiol-induced contact dermatitis in mice. Clofibrate, a peroxisomal proliferator in mice, increased the immune response to the urushiols from litre by 50%. Conversely, tetradecyl glycidic acid, an inhibitor of the uptake of fatty acids by mitochondria, decreased the hypersensitivity to the hapten. An increase in the level in glutathione by treatment of the animals with 2-oxotiazolidin-4-carboxilic acid lowered the response. Those findings strongly support a role for the fatty acid oxidative metabolism in the processing and activation of urushiols in vivo. PMID:8980288

  17. Omega-3 Fatty Acid Deficiency Does Not Alter the Effects of Chronic Fluoxetine Treatment on Central Serotonin Turnover or Behavior in the Forced Swim Test in Female Rats

    PubMed Central

    McNamara, Robert K.; Able, Jessica A.; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W.

    2013-01-01

    While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, the neurochemical mechanisms mediating this interaction are not known. Here we investigated the effects of dietary omega-3 (n-3) fatty acid insufficiency on the neurochemical and behavioral effects of chronic fluoxetine (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF, n=40) the n-3 fatty acids during peri-adolescent development (P21-P90), and one half of each group were administered FLX (10 mg/kg/d) for 30 d (P60-P90) prior to testing. In adulthood (P90), regional brain serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers of 5-HT neurotransmission, behavioral responses in the forced swim test (FST), and plasma FLX and norfluoxetine (NFLX) concentrations were investigated. Peri-adolescent n-3 insufficiency led to significant reductions in cortical docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (−25%, p≤0.0001) and DEF+FLX (−28%, p≤0.0001) rats. Untreated DEF rats exhibited significantly lower regional 5-HIAA/5-HT ratios compared with untreated CON rats, but exhibited similar behavioral responses in the FST. In both CON and DEF rats, chronic FLX treatment similarly and significantly decreased 5-HIAA concentrations and the 5-HIAA/5-HT ratio in the hypothalamus, hippocampus, and nucleus accumbens, brainstem tryptophan hydroxylase-2 mRNA expression, and immobility in the FST. While the FLX-induced reduction in 5-HIAA concentrations in the prefrontal cortex was significantly blunted in DEF rats, the reduction in the 5-HIAA/5-HT ratio was similar to CON rats. Although plasma FLX and NFLX levels were not significantly different in DEF and CON rats, the NFLX/FLX ratio was significantly lower in DEF+FLX rats. These preclinical data demonstrate that n-3 fatty acid deficiency does not significantly reduce the effects of chronic

  18. Inhibitory effects of ethanol extracts from nuruk on oxidative stress, melanogenesis, and photo-aging.

    PubMed

    Lee, Sang-Jin; Cho, Sung-Won; Kwon, Yi-Young; Kwon, Hee-Suk; Shin, Woo-Chang

    2012-06-01

    Nuruk contributes to the unique characteristics of Korean alcoholic beverages. In this study, the effects of nuruk extracts (NE) on anti-oxidant characters, melanogenesis, and anti-photoaging activity were investigated. NEs were obtained from the 70% ethanol extracts of six types of nuruk, which have been used in brewing of fermented alcohol beverages in Korea. First, various antioxidant characteristics were identified in terms of 2,2'-azino-bis(3-ethylbenzthiozoline-6-sulphonic acid) (ABTS) radical scavenging activity, superoxide dismutase (SOD) expression, and inhibition of xanthine oxidase activity. NE#4 exhibited potent ABTS radical scavenging activity (IC(50) = 19.51 µg/mL). Compared with NE#4, relatively lower levels of activity were observed for NE#3 and NE#6, with IC(50) values of 90.99 and 76.88 µg/mL, respectively. According to results of western blot analysis for determination of SOD expression in H(2)O(2)-treated HepG2 cells, NE#5 and NE#6 induced a dramatic increase in the expression ratio of SOD, compared to the group treated with H(2)O(2) only. Activity of xanthine oxidase, which converts xanthine into uric acid, generating superoxide ions, was inhibited by NE#4 and NE#6 in a dose-dependent manner. NE#4 induced significant inhibition of mushroom tyrosinase activity. A reduction in cellular melanin contents of 80% was observed in B16F1 melanocytes treated with NE#5 and NE#6; these effects were similar to those of arbutin at 100 µM. In addition, gelatin zymography and reverse transcription-PCR analysis were performed for assessment of anti-photoaging activity of Nuruk. Treatment with NE#6 resulted in dramatically inhibited activities of matrix metalloproteinase (MMP)-2/-9, suppressed expression of MMP-1, and increased expression of type-1 procollagen. Results of gelatin zymography for NE#4 and NE#5 were similar, to a slightly lesser degree. These results suggest the potential of NE#4 and NE#6 as natural ingredients for use in functional foods and

  19. Inhibitory Effects of Ethanol Extracts from Nuruk on Oxidative Stress, Melanogenesis, and Photo-Aging

    PubMed Central

    Lee, Sang-Jin; Cho, Sung-Won; Kwon, Yi-Young; Kwon, Hee-Suk

    2012-01-01

    Nuruk contributes to the unique characteristics of Korean alcoholic beverages. In this study, the effects of nuruk extracts (NE) on anti-oxidant characters, melanogenesis, and anti-photoaging activity were investigated. NEs were obtained from the 70% ethanol extracts of six types of nuruk, which have been used in brewing of fermented alcohol beverages in Korea. First, various antioxidant characteristics were identified in terms of 2,2'-azino-bis(3-ethylbenzthiozoline-6-sulphonic acid) (ABTS) radical scavenging activity, superoxide dismutase (SOD) expression, and inhibition of xanthine oxidase activity. NE#4 exhibited potent ABTS radical scavenging activity (IC50 = 19.51 µg/mL). Compared with NE#4, relatively lower levels of activity were observed for NE#3 and NE#6, with IC50 values of 90.99 and 76.88 µg/mL, respectively. According to results of western blot analysis for determination of SOD expression in H2O2-treated HepG2 cells, NE#5 and NE#6 induced a dramatic increase in the expression ratio of SOD, compared to the group treated with H2O2 only. Activity of xanthine oxidase, which converts xanthine into uric acid, generating superoxide ions, was inhibited by NE#4 and NE#6 in a dose-dependent manner. NE#4 induced significant inhibition of mushroom tyrosinase activity. A reduction in cellular melanin contents of 80% was observed in B16F1 melanocytes treated with NE#5 and NE#6; these effects were similar to those of arbutin at 100 µM. In addition, gelatin zymography and reverse transcription-PCR analysis were performed for assessment of anti-photoaging activity of Nuruk. Treatment with NE#6 resulted in dramatically inhibited activities of matrix metalloproteinase (MMP)-2/-9, suppressed expression of MMP-1, and increased expression of type-1 procollagen. Results of gelatin zymography for NE#4 and NE#5 were similar, to a slightly lesser degree. These results suggest the potential of NE#4 and NE#6 as natural ingredients for use in functional foods and cosmetics

  20. PE11 (Rv1169c) selectively alters fatty acid components of Mycobacterium smegmatis and host cell interleukin-6 level accompanied with cell death

    PubMed Central

    Deng, Wanyan; Zeng, Jie; Xiang, Xiaohong; Li, Ping; Xie, Jianping

    2015-01-01

    PE/PPE family proteins, named after their conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains of N-terminal, are most intriguing aspects of pathologic mycobacterial genome. The roles of most members of this family remain unknown, although selected genes of this family are related to the virulence of Mycobacterium tuberculosis. In order to decipher the role of Rv1169c, the Mycobacterium smegmatis strain heterologous expressed this ORF was constructed and identified that Rv1169c was a cell wall associated protein with a novel function in modifying the cell wall fatty acids. The growth of Rv1169c expressing strain was affected under surface stress, acidic condition and antibiotics treatment. M. smegmatis expressing Rv1169c induced necrotic cell death of macrophage after infection and significantly decreased interlukin-6 production compared to controls. In general, these results underscore a proposing role of Rv1169c in virulence of M. tuberculosis, as it's role in the susceptibility of anti-mycobacteria factors caused by modified cell wall fatty acid, and the induced necrotic cell death by Rv1169c is crucial for M. tuberculosis virulence during infection. PMID:26157429

  1. Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer’s disease as detected by GC-MS

    PubMed Central

    Nasaruddin, Muhammad Luqman; Hölscher, Christian; Kehoe, Patrick; Graham, Stewart Francis; Green, Brian Desmond

    2016-01-01

    Disturbed lipid metabolism is a well-established feature of human Alzheimer’s disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia. PMID:27069549

  2. Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer's disease as detected by GC-MS.

    PubMed

    Nasaruddin, Muhammad Luqman; Hölscher, Christian; Kehoe, Patrick; Graham, Stewart Francis; Green, Brian Desmond

    2016-01-01

    Disturbed lipid metabolism is a well-established feature of human Alzheimer's disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia. PMID:27069549

  3. Bisphenol A Alters n-6 Fatty Acid Composition and Decreases Antioxidant Enzyme Levels in Rat Testes: A LC-QTOF-Based Metabolomics Study

    PubMed Central

    Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

    2012-01-01

    Background Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Methodology/Principal Findings Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. Conclusions/Significance BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity. PMID:23024759

  4. Alterations in levels and ratios of n-3 and n-6 polyunsaturated fatty acids in the temporal cortex and liver of vervet monkeys from birth to early adulthood.

    PubMed

    Miller, Leslie R; Jorgensen, Matthew J; Kaplan, Jay R; Seeds, Michael C; Rahbar, Elaheh; Morgan, Timothy M; Welborn, Andrea; Chilton, Sarah M; Gillis, Julianne; Hester, Austin; Rukstalis, Mae; Sergeant, Susan; Chilton, Floyd H

    2016-03-15

    Deficiencies in omega-3 (n-3) long chain polyunsaturated fatty acids (LC-PUFAs) and increases in the ratio of omega-6 (n-6) to n-3 LC-PUFAs in brain tissues and blood components have been associated with psychiatric and developmental disorders. Most studies have focused on n-3 LC-PUFA accumulation in the brain from birth until 2years of age, well before the symptomatic onset of such disorders. The current study addresses changes that occur in childhood and adolescence. Postmortem brain (cortical gray matter, inferior temporal lobe; n=50) and liver (n=60) from vervet monkeys fed a uniform diet from birth through young adulthood were collected from archived tissues. Lipids were extracted and fatty acid levels determined. There was a marked reduction in the ratio of n-6 LC-PUFAs, arachidonic acid (ARA) and adrenic acid (ADR), relative to the n-3 LC-PUFA, docosahexaenoic acid (DHA), in temporal cortex lipids from birth to puberty and then a more gradual decrease though adulthood. This decrease in ratio resulted from a 3-fold accumulation of DHA levels while concentrations of ARA remained constant. Early childhood through adolescence appears to be a critical period for DHA accretion in the cortex of vervet monkeys and may represent a vulnerable stage where lack of dietary n-3 LC-PUFAs impacts development in humans. PMID:26705667

  5. The Protective Effect of Baicalin against UVB Irradiation Induced Photoaging: An In Vitro and In Vivo Study

    PubMed Central

    Yin, Zhi-qiang; Hu, Yan-yan; Xu, Yang; Wu, Di; Permatasari, Felicia; Luo, Dan; Zhou, Bing-rong

    2014-01-01

    Objective This study was aimed to evaluate the anti-photoaging effects of baicalin on Ultraviolet B (UVB)-induced photoaging in the dorsal skin of hairless mice and premature senescence in human dermal fibroblasts. Methods We established in vivo and in vitro photoaging models by repeated exposures to UVB irradiation. By HE staining, masson staining, immunohistostaing and real-time RT-PCR, we analyzed epidermal thickness, collagen expression and the mRNA and protein levels of type I collagen, type III collagen, interstitial collagenase (MMP-1 and MMP-3) in UVB exposed dorsal mice skin. The aging condition in human dermal fibroblasts was determined by senescence-associated β-galactosidase (SA-β-gal) staining. Cell viability was determined using the Cell Counting Kit-8 (CCK-8). The G1 phase cell growth arrest was analyzed by flow cytometry. The senescence-related protein levels of p16INK-4a, p21WAF-1, and p53 and protein levels of phosphorylated histone H2AX were estimated by Western blotting. Results Topically application of baicalin treatment reduced UVB-induced epidermal thickening of mouse skin and also result in an increase in the production of collagen I and III, and a decrease in the expression of MMP-1 and MMP-3. Compared with the UVB-irradiated group, we found that the irradiated fibroblasts additionally treated with baicalin demonstrated a decrease in the expression of SA-β-gal, a increase in the cell viability, a decrease in the G1 phase cell proportion, a downregulation in the level of senescence-associated and γ-H2AX proteins. However, Baicalin had no difference in the normal fibroblasts without UVB irradiation and long-term Baicalin incubation of UVB-SIPS fibroblasts gave no effects on the cell proliferation. Conclusions Taken together, these results suggest that baicalin significantly antagonizes photoaging induced by UVB in vivo and in vitro, indicating the potential of baicalin application for anti-photoaging treatment. PMID:24949843

  6. The maximal cumulative solar UVB dose allowed to maintain healthy and young skin and prevent premature photoaging.

    PubMed

    Ichihashi, Masamitsu; Ando, Hideya

    2014-10-01

    The young facial skin of children with a smooth healthy appearance changes over time to photoaged skin having mottled pigmentation, solar lentigines, wrinkles, dry and rough skin, leathery texture, and benign and malignant tumors after exposure to chronic, repeated solar radiation. The first sign of photoaging in Japanese subjects is usually solar lentigines appearing around 20 years of age on the face. Fine wrinkles can then appear after 30 years of age, and benign skin tumors, seborrhoeic keratoses, can occur after 35 years of age in sun-exposed skin. We theoretically calculated the maximal daily exposure time to solar radiation, which could prevent the development of photoaged skin until 60 and 80 years of age, based on published data of personal solar UVB doses in sun-exposed skin. One MED (minimal erythema dose) was determined to be 20 mJ/cm(2) , and 200 MED was used as the average yearly dose of Japanese children. Further, we hypothesized that the annual dose of Japanese adults is the same as that of the children. The cumulative UVB dose at 20 years of age was thus calculated to be 4000 MED, and 22 MED was used as the maximal daily UVB dose based on data measured in Kobe, located in the central area of Japan. We used the solar UVB dose from 10:00 a.m. to 14:00 p.m. which occupies 60% of the total daily UV dose, to obtain the maximal UVB per hour in a day, and calculated the maximal daily UV exposure time that would delay the onset of solar lentigines until 60 or 80 years of age. The mean daily sun exposure time to maintain healthy skin until 80 years of age in the summer was calculated to be 2.54 min (0.14 MED) for unprotected skin and 127 min with the use of a sunscreen of SPF (sun protection factor) of 50. In this study, we did not evaluate the photoaging effect of UVA radiation, but findings of the adverse effects of UVA radiation on the skin have accumulated in the last decade. Therefore, it will be important to estimate the maximal dose of solar

  7. Topical tretinoin increases the tropoelastin and fibronectin content of photoaged hairless mouse skin.

    PubMed

    Schwartz, E; Kligman, L H

    1995-04-01

    Topical tretinoin treatment of photoaged hairless mice has been shown in previous studies to stimulate formation of a subepidermal zone of new connective tissue characterized by enhanced collagen synthesis. The aims of this study were to localize and/or quantify elastin, fibronectin, and glycosaminoglycans in the same model. Hairless mice (Skh-1) were irradiated thrice weekly for 10 weeks with gradually increasing doses of ultraviolet (up to 4.5 minimal erythema doses per exposure) from Westinghouse FS-40 bulbs. Mice were then treated five times a week with either 0.05% tretinoin, the ethanol:propylene glycol vehicle, or nothing for another 10 weeks. Controls included mice sacrificed after 10 weeks of ultraviolet treatment and age-matched untreated animals. The distribution of elastin and fibronectin was examined by immunofluorescence microscopy, which revealed fine fibrils in the subepidermal zone in tretinoin-treated skin. A quantitative slot-blot immunobinding assay showed that tretinoin induced a threefold higher amount of tropoelastin compared with controls. Insoluble elastin content (desmosine levels) was similar in all groups. Although fibronectin content was increased by ultraviolet radiation, tretinoin treatment induced the largest increase. In contrast, the amount of glycosaminoglycans, although increased by UVB radiation, was reduced by tretinoin treatment. PMID:7706770

  8. Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging.

    PubMed

    Park, Gaeun; Baek, Sohee; Kim, Jong-Eun; Lim, Tae-gyu; Lee, Charles C; Yang, Hee; Kang, Young-Gyu; Park, Jun Seong; Augustin, Martin; Mrosek, Michael; Lee, Chang Yong; Dong, Zigang; Huber, Robert; Lee, Ki Won

    2015-12-01

    While skin aging is a naturally occurring process by senescence, exposure to ultraviolet (UV) radiation accelerates wrinkle formation and sagging of skin. UV induces skin aging by degrading collagen via activating matrix metalloproteinases (MMPs). In this study, we show that coumestrol, a metabolite of the soybean isoflavone daidzein, has a preventive effect on skin photoaging in three-dimensional human skin equivalent model. Coumestrol inhibited UVB-induced MMP-1 expression and activity. Whole human kinase profiling assay identified FLT3 kinase as a novel target protein of coumestrol in UVB-induced signaling pathway in skin. Coumestrol suppresses FLT3 kinase activity, and subsequently, Ras/MEK/ERK and Akt/p70 ribosomal S6 kinase pathway. This suppresses AP-1 activity and in turn, diminishes MMP-1 gene transcription. Using X-ray crystallography, the binding of coumestrol to FLT3 was defined and implied ATP-competitive inhibition. Residues Lys644 and Phe830 showed local changes to accommodate coumestrol in the ATP-binding pocket. 4-APIA, a pharmacological inhibitor of FLT3, inhibited MMP-1 expression and induced signal transduction changes similar to coumestrol. Taken together, coumestrol inhibits UVB-induced MMP-1 expression by suppressing FLT3 kinase activity. These findings suggest that coumestrol is a novel dietary compound with potential application in preventing and improving UVB-associated skin aging. PMID:26341390

  9. PPARγ activation alters fatty acid composition in adipose triglyceride, in addition to proliferation of small adipocytes, in insulin resistant high-fat fed rats.

    PubMed

    Sato, Daisuke; Oda, Kanako; Kusunoki, Masataka; Nishina, Atsuyoshi; Takahashi, Kazuaki; Feng, Zhonggang; Tsutsumi, Kazuhiko; Nakamura, Takao

    2016-02-15

    It was reported that adipocyte size is potentially correlated in part to amount of long chain polyunsaturated fatty acids (PUFAs) and insulin resistance because several long chain PUFAs can be ligands of peroxisome proliferator-activated receptors (PPARs). In our previous study, marked reduction of PUFAs was observed in insulin-resistant high-fat fed rats, which may indicate that PUFAs are consumed to improve insulin resistance. Although PPARγ agonist, well known as an insulin sensitizer, proliferates small adipocytes, the effects of PPARγ agonist on FA composition in adipose tissue have not been clarified yet. In the present study, we administered pioglitazone, a PPARγ agonist, to high-fat fed rats, and measured their FA composition of triglyceride fraction in adipose tissue and adipocyte diameters in pioglitazone-treated (PIO) and non-treated (control) rats. Insulin sensitivity was obtained with hyperinsulinemic euglycemic clamp. Average adipocyte diameter in the PIO group were smaller than that in the control one without change in tissue weight. In monounsaturated FAs (MUFAs), 14:1n-5, 16:1n-7, and 18:1n-9 contents in the PIO group were lower than those, respectively, in the control group. In contrast, 22:6n-3, 20:3n-6, 20:4n-6, and 22:4n-6 contents in the PIO group were higher than those, respectively, in the control group. Insulin sensitivity was higher in the PIO group than in the control one. These findings suggest that PPARγ activation lowered MUFAs whereas suppressed most of C20 or C22 PUFAs reduction, and that the change of fatty acid composition may be relevant with increase in small adipocytes. PMID:26825545

  10. Targeted mutation of Δ12 and Δ15 desaturase genes in hemp produce major alterations in seed fatty acid composition including a high oleic hemp oil.

    PubMed

    Bielecka, Monika; Kaminski, Filip; Adams, Ian; Poulson, Helen; Sloan, Raymond; Li, Yi; Larson, Tony R; Winzer, Thilo; Graham, Ian A

    2014-06-01

    We used expressed sequence tag library and whole genome sequence mining to identify a suite of putative desaturase genes representing the four main activities required for production of polyunsaturated fatty acids in hemp seed oil. Phylogenetic-based classification and developing seed transcriptome analysis informed selection for further analysis of one of seven Δ12 desaturases and one of three Δ15 desaturases that we designate CSFAD2A and CSFAD3A, respectively. Heterologous expression of corresponding cDNAs in Saccharomyces cerevisiae showed CSFAD2A to have Δx+3 activity, while CSFAD3A activity was exclusively at the Δ15 position. TILLING of an ethyl methane sulphonate mutagenized population identified multiple alleles including non-sense mutations in both genes and fatty acid composition of seed oil confirmed these to be the major Δ12 and Δ15 desaturases in developing hemp seed. Following four backcrosses and sibling crosses to achieve homozygosity, csfad2a-1 was grown in the field and found to produce a 70 molar per cent high oleic acid (18:1(Δ9) ) oil at yields similar to wild type. Cold-pressed high oleic oil produced fewer volatiles and had a sevenfold increase in shelf life compared to wild type. Two low abundance octadecadienoic acids, 18:2(Δ6,9) and 18:2(Δ9,15), were identified in the high oleic oil, and their presence suggests remaining endogenous desaturase activities utilize the increased levels of oleic acid as substrate. Consistent with this, CSFAD3A produces 18:2(Δ9,15) from endogenous 18:1(Δ9) when expressed in S. cerevisiae. This work lays the foundation for the development of additional novel oil varieties in this multipurpose low input crop. PMID:24506492

  11. Production of hydroxylated fatty acids in genetically modified plants

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank; Boddupalli, Sekhar S.

    2005-08-30

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  12. Production of hydroxylated fatty acids in genetically modified plants

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank; Boddupalli, Sekhar S.

    2011-08-23

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  13. A novel polymorphism in the chicken adipocyte fatty acid-binding protein gene (FABP4) that alters ligand-binding and correlates with fatness.

    PubMed

    Wang, Qigui; Guan, Tianzhu; Li, Hui; Bernlohr, David A

    2009-11-01

    Similar to the mammalian FABP4 gene, the chicken (Gallus gallus) FABP4 gene consists of four exons separated by three introns and encodes a 132 amino acid protein termed the adipocyte fatty acid-binding protein (AFABP). In the current study, a novel G/A polymorphism in exon 3 of the chicken FABP4 gene was identified associated with different chicken breeds that leads to either Ser or Asn at amino acid 89 of the AFABP protein. The Baier chicken averages 0.89+/-0.12% abdominal fat and expresses the G allele (Ser 89 isoform) while the Broiler chicken typically has 3.74+/-0.23% abdominal fat and expresses the A allele (Asn 89 isoforms). cDNAs corresponding to the two AFABP isoforms were cloned and expressed in Escherichia coli as GST fusions, purified by using glutathione sepharose 4B chromatography and evaluated for lipid binding using the fluorescent surrogate ligand 1-anilinonaphthalene 8-sulphonic acid (1,8-ANS). The results showed that AFABP Ser89 exhibited a lower ligand-binding affinity with apparent dissociation constants (Kd) of 7.31+/-3.75 microM, while the AFABP Asn89 isoform bound 1,8-ANS with an apparent dissociation constant of 2.99+/-1.00 microM (P=0.02). These results suggest that the Ser89Asn polymorphism may influence chicken AFABP function and ultimately lipid deposition through changing the ligand-binding activity of AFABP. PMID:19595785

  14. Enhanced secretion of glucosyltransferase by changes in potassium ion concentrations is accompanied by an altered pattern of membrane fatty acids in Streptococcus salivarius.

    PubMed Central

    Markevics, L J; Jacques, N A

    1985-01-01

    Growth of Streptococcus salivarius ATCC 25975 in a Na+-based medium containing 1 to 50 mM K+ enhanced extracellular glucosyltransferase production by 3.7-fold over the level of enzyme found in a K+-based medium containing 184 mM K+. Enzyme synthesis and secretion were further enhanced in a nonlinear manner with respect to the concentration of K+ in the medium when cells were cultured from an inoculum grown in the presence of 1 mM K+. This concentration of K+ was the minimum required to maintain a near-maximum growth rate for S. salivarius in medium where K+ was limited. A maximum sevenfold stimulation of glucosyltransferase production occurred at 18 mM K+ under these conditions. Analysis of the total membrane lipids showed that the composition of octadecanoic acid increased with decreasing K+ concentration essentially at the expense of the octadecenoic acid moiety. Extracellular glucosyltransferase production was found to be directly related to the ratio of these two fatty acids. Similar confirmatory results over a greater range of enzyme production were obtained with nonproliferating cell suspensions. PMID:3156125

  15. Aberrant mitochondrial respiration in the livers of rats infected with Fasciola hepatica: the role of elevated non-esterified fatty acids and altered phospholipid composition.

    PubMed Central

    Lenton, L M; Behm, C A; Bygrave, F L

    1995-01-01

    The non-esterified fatty acid (NEFA) content and phospholipid composition of mitochondria isolated from the livers of Wistar rats infected with Fasciola hepatica were examined in relation to the aberrant mitochondrial respiration previously reported [Rule, Behm, and Bygrave (1989) Biochem. J. 260, 517-523]. At 2 weeks post-infection, elevated NEFA levels were associated with uncoupling of mitochondrial respiration that was reversible in vitro by the addition of BSA. State IV respiration rates showed a strong correlation with NEFA content. At 3 weeks post-infection, NEFA content had increased further and uncoupled mitochondria no longer showed any response to BSA. 31P-NMR analyses of cholate extracts of mitochondria from infected livers at 3 weeks post-infection revealed a marked loss of several major phospholipid species with a concomitant increase in catabolic products, particularly glycerophosphocholine and glycerophosphoethanolamine. Similar changes were observed in microsomal extracts. The NEFA content and phospholipid composition of mitochondria isolated from infected, athymic nude rats were not significantly different from uninfected, athymic rats. These findings suggest that uncoupling of liver mitochondria during infection with F. hepatica is the result of phospholipase activation mediated by the immune system of the host. PMID:7733879

  16. Overexpression of the olive acyl carrier protein gene (OeACP1) produces alterations in fatty acid composition of tobacco leaves.

    PubMed

    De Marchis, Francesca; Valeri, Maria Cristina; Pompa, Andrea; Bouveret, Emmanuelle; Alagna, Fiammetta; Grisan, Simone; Stanzione, Vitale; Mariotti, Roberto; Cultrera, Nicolò; Baldoni, Luciana; Bellucci, Michele

    2016-02-01

    Taking into account that fatty acid (FA) biosynthesis plays a crucial role in lipid accumulation in olive (Olea europaea L.) mesocarp, we investigated the effect of olive acyl carrier protein (ACP) on FA composition by overexpressing an olive ACP cDNA in tobacco plants. The OeACP1.1A cDNA was inserted in the nucleus or in the chloroplast DNA of different tobacco plants, resulting in extensive transcription of the transgenes. The transplastomic plants accumulated lower olive ACP levels in comparison to nuclear-transformed plants. Moreover, the phenotype of the former plants was characterized by pale green/white cotyledons with abnormal chloroplasts, delayed germination and reduced growth. We suggest that the transplastomic phenotype was likely caused by inefficient olive ACP mRNA translation in chloroplast stroma. Conversely, total lipids from leaves of nuclear transformants expressing high olive ACP levels showed a significant increase in oleic acid (18:1) and linolenic acid (18:3), and a concomitant significant reduction of hexadecadienoic acid (16:2) and hexadecatrienoic acid (16:3). This implies that in leaves of tobacco transformants, as likely in the mesocarp of olive fruit, olive ACP not only plays a general role in FA synthesis, but seems to be specifically involved in chain length regulation forwarding the elongation to C18 FAs and the subsequent desaturation to 18:1 and 18:3. PMID:26560313

  17. Fatty acids attached to all-trans-astaxanthin alter its cis-trans equilibrium, and consequently its stability, upon light-accelerated autoxidation.

    PubMed

    de Bruijn, Wouter J C; Weesepoel, Yannick; Vincken, Jean-Paul; Gruppen, Harry

    2016-03-01

    Fatty acid esterification, common in naturally occurring astaxanthin, has been suggested to influence both colour stability and degradation of all-trans-astaxanthin. Therefore, astaxanthin stability was studied as influenced by monoesterification and diesterification with palmitate. Increased esterification decelerated degradation of all-trans-astaxanthin (RP-UHPLC-PDA), whereas, it had no influence on colour loss over time (spectrophotometry). This difference might be explained by the observation that palmitate esterification influenced the cis-trans equilibrium. Free astaxanthin produced larger amounts of 9-cis isomer whereas monopalmitate esterification resulted in increased 13-cis isomerization. The molar ratios of 9-cis:13-cis after 60min were 1:1.7 (free), 1:4.8 (monopalmitate) and 1:2.6 (dipalmitate). The formation of 9-cis astaxanthin, with its higher molar extinction coefficient than that of all-trans-astaxanthin, might compensate for colour loss induced by conjugated double bond cleavage. As such, it was concluded that spectrophotometry is not an accurate measure of the degradation of the all-trans-astaxanthin molecule. PMID:26471660

  18. A cosmetic ‘anti-ageing’ product improves photoaged skin: a double-blind, randomized controlled trial

    PubMed Central

    Watson, REB; Ogden, S; Cotterell, LF; Bowden, JJ; Bastrilles, JY; Long, SP; Griffiths, CEM

    2009-01-01

    Background Very few over-the-counter cosmetic ‘anti-ageing’ products have been subjected to a rigorous double-blind, vehicle-controlled trial of efficacy. Previously we have shown that application of a cosmetic ‘anti-ageing’ product to photoaged skin under occlusion for 12 days can stimulate the deposition of fibrillin-1. This observation infers potential to repair and perhaps clinically improve photoaged skin. Objective We examined another similar over-the-counter cosmetic ‘anti-ageing’ product using both the patch test assay and a 6-month double-blind, randomized controlled trial (RCT), with a further 6-month open phase to assess clinical efficacy in photoaged skin. Methods For the patch test, a commercially available test product and its vehicle were applied occluded for 12 days to photoaged forearm skin (n=10) prior to biopsy and immunohistochemical assessment of fibrillin-1; all-trans retinoic acid (RA) was used as a positive control. Sixty photoaged subjects were recruited to the RCT (test product, n = 30 vs. vehicle, n = 30; once daily for 6 months, face and hands) with clinical assessments performed at recruitment and following 1, 3 and 6 months of use. Twenty-eight volunteers had skin biopsies (dorsal wrist) at baseline and at 6 months treatment for immunohistochemical assessment of fibrillin-1 (test product, n=15; vehicle, n=13). All volunteers received the test product for a further 6 months. Final clinical assessments were performed at the end of this open period. Results In the 12-day patch test assay, we observed significant immunohistological deposition of fibrillin-1 in skin treated with the test product and RA compared with the untreated baseline (P=0·005 and 0·015, respectively). In the clinical RCT, at 6 months, the test product produced statistically significant improvement in facial wrinkles as compared to baseline assessment (P = 0·013), whereas vehicle-treated skin was not significantly improved (P = 0·11). After 12 months

  19. Internet-Based Photoaging Within Australian Pharmacies to Promote Smoking Cessation: Randomized Controlled Trial

    PubMed Central

    Carter, Owen; Parsons, Richard; Hendrie, Delia

    2013-01-01

    Background Tobacco smoking leads to death or disability and a drain on national resources. The literature suggests that cigarette smoking continues to be a major modifiable risk factor for a variety of diseases and that smokers aged 18-30 years are relatively resistant to antismoking messages due to their widely held belief that they will not be lifelong smokers. Objective To conduct a randomized controlled trial (RCT) of a computer-generated photoaging intervention to promote smoking cessation among young adult smokers within a community pharmacy setting. Methods A trial was designed with 80% power based on the effect size observed in a published pilot study; 160 subjects were recruited (80 allocated to the control group and 80 to the intervention group) from 8 metropolitan community pharmacies located around Perth city center in Western Australia. All participants received standardized smoking cessation advice. The intervention group participants were also digitally photoaged by using the Internet-based APRIL Face Aging software so they could preview images of themselves as a lifelong smoker and as a nonsmoker. Due to the nature of the intervention, the participants and researcher could not be blinded to the study. The main outcome measure was quit attempts at 6-month follow-up, both self-reported and biochemically validated through testing for carbon monoxide (CO), and nicotine dependence assessed via the Fagerström scale. Results At 6-month follow-up, 5 of 80 control group participants (6.3%) suggested they had quit smoking, but only 1 of 80 control group participants (1.3%) consented to, and was confirmed by, CO validation. In the intervention group, 22 of 80 participants (27.5%) reported quitting, with 11 of 80 participants (13.8%) confirmed by CO testing. This difference in biochemically confirmed quit attempts was statistically significant (χ2 1=9.0, P=.003). A repeated measures analysis suggested the average intervention group smoking dependence score

  20. Protective effect of the standardized green tea seed extract on UVB-induced skin photoaging in hairless mice

    PubMed Central

    Lim, Jae-Youn; Kim, Ok-Kyung; Lee, Jeongmin; Lee, Min-Jae; Kang, Namgil

    2014-01-01

    BACKGROUND/OBJECTIVES Ultraviolet B (UVB) irradiation on skin can induce production of reactive oxygen species (ROS), which cause expression of matrix metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of skin to UVB irradiation leads to histological changes consistent with aging, such as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the protective effect of the standardized green tea seed extract (GSE) on UVB-induced skin photoaging in hairless mice. MATERIALS/METHODS Skin photoaging was induced by UVB irradiation on the back of Skh-1 hairless mice three times per week and UVB irradiation was performed for 10 weeks. Mice were divided into six groups; normal control, UVB irradiated control group, positive control (UVB + dietary supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE 10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200 mg/kg (UVB + dietary supplement of GSE 200 mg/kg). RESULTS The dietary supplement GSE attenuated UVB irradiation-induced wrinkle formation and the decrease in density of dermal collagen fiber. In addition, results of the antioxidant analysis showed that GSE induced a significant increase in antioxidant enzyme activity compared with the UVB irradiation control group. Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and type-1 collagen. CONCLUSIONS Findings of this study suggest that dietary supplement GSE could be useful in attenuation of UVB irradiation-induced skin photoaging and wrinkle formation due to regulation of antioxidant defense systems and MMPs expression. PMID:25110559

  1. Study of the influencing effect of pigments on the photoageing of terpenoid resins used as pictorial media.

    PubMed

    Doménech-Carbó, María Teresa; Kuckova, Stepanka; de la Cruz-Cañizares, Juana; Osete-Cortina, Laura

    2006-07-21

    Terpenoid resins have been mainly used as components of pictorial varnishes and binding media from ancient times. In such latest instances, the resin is mixed with pigments affecting its physical and chemical properties. A new procedure based on gas chromatography-mass spectrometry (GC/MS) has been applied, in this work, in combination with Fourier transform infrared spectroscopy (FTIR), with the aim of determining the changes undergone by di- and triterpenoid resins employed as components of binding media. The GC/MS method is based on the derivatisation of these resins using trimethylsilylimidazol. Characterization of the main components of the di- and triterpenoid fractions and their oxidised products, occurring in the diterpenoid resin colophony and a triterpenoid Mexical copal (Bursera cuneata (Schl) Engl.), has been achieved. Artificially photoaged specimens of pure resin and binary systems pigment+resin prepared as thin films using lead white, ochre yellow, umber raw and verdigris have also been analysed to study the changes undergone by the di- and triterpenoid components of the resins. Oxidation processes taking place on di- and triterpenoids during photoageing are described. Moreover, the results obtained indicate that pigments have a different effect on the two studied resins. Thus, the presence of pigments induces, in general, a catalysing effect on the oxidative polymerisation reactions in the earliest stages of the natural curing of the paint films whereas a loss of the catalysing effectiveness, in particular, for verdigris containing specimens, is observed during photoageing. Complexation of diterpenoid molecules with copper(II) ions in the earliest stages of the curing has also been evidenced by FTIR analysis. PMID:16687153

  2. Ability of sodium copper chlorophyllin complex to repair photoaged skin by stimulation of biomarkers in human extracellular matrix

    PubMed Central

    McCook, John P; Stephens, Thomas J; Jiang, Lily I; Law, Robert M; Gotz, Vincent

    2016-01-01

    Purpose To examine the effect of sodium copper chlorophyllin complex on the expression of biomarkers of photoaged dermal extracellular matrix indicative of skin repair. Patients and methods Following a previously published 12-day clinical assessment model, skin biopsy samples from the forearms of four healthy females with signs of photoaged skin were obtained and samples were analyzed by immunohistochemistry for key biomarkers of aging skin after each subject was treated with a test material consisting of a gel containing a liposomal dispersion of sodium copper chlorophyllin complex 0.05%, a positive control of tretinoin cream 0.025%, and an untreated negative control. Results There was a statistically significantly greater amount of fibrillin/amyloid P and epidermal mucins found for skin treated with the test material containing 0.05% sodium copper chlorophyllin complex and the reference control tretinoin 0.025% cream compared to the negative control (untreated site). Expression of procollagen 1 and dermal mucin also showed a greater presence in the samples treated with the test material and the reference control compared to the negative control, though the differences were not statistically significant. No adverse events were observed or reported by the subjects during the course of the study. Conclusion The results of this human biopsy study suggest that both retinoids and sodium copper chlorophyllin complex have beneficial effects on biomarkers of photoaged skin. Products containing both sodium copper chlorophyllin complex and retinols may provide a dual approach to reversing age-related decreases in hyaluronic acid (HA) in the skin: inhibition of the breakdown of HA via sodium copper chlorophyllin complex by inhibition of hyaluronidase, and stimulation of HA synthases by retinol. PMID:27524916

  3. Characterization and mechanisms of photoageing-related changes in skin. Damages of basement membrane and dermal structures.

    PubMed

    Amano, Satoshi

    2016-08-01

    Sun-exposed skin is characterized by superficial changes such as wrinkles, sagging and pigmentary changes, and also many internal changes in the structure and function of epidermis, basement membrane (BM) and dermis. These changes (so-called photoageing) are predominantly induced by the ultraviolet (UV) component of sunlight. Epidermis of UV-irradiated skin produced several enzymes such as matrix metalloproteinases (MMPs), urinary plasminogen activator (uPA)/plasmin and heparanase, which degrade dermal collagen fibres and elastic fibres in the dermis, and components of epidermal BM. The BM at the dermal-epidermal junction (DEJ) controls dermal-epidermal signalling and plays an important role in the maintenance of a healthy epidermis and dermis. BM is repetitively damaged in sun-exposed skin compared with unexposed skin, leading to epidermal and dermal deterioration and accelerated skin ageing. UV exposure also induces an increase in vascular endothelial growth factor (VEGF), an angiogenic factor, while thrombospondin-1 (TSP-1), an anti-angiogenic factor, is decreased; these changes induce angiogenesis in papillary dermis with increased migration of elastase-positive leucocytes, leading to dermal elastic fibre damage. Elastic fibres, such as oxytalan fibres in papillary dermis, are associated with not only skin resilience, but also skin surface texture, and elastic fibre formation by fibroblasts is facilitated by increased expression of fibulin-5. Thus, induction of fibulin-5 expression is a damage-repair mechanism, and fibulin-5 is an early marker of photoaged skin. UV-induced skin damage is cumulative and leads to premature ageing of skin. However, appropriate daily skincare may ameliorate photoageing by inhibiting processes causing damage and enhancing repair processes. PMID:27539897

  4. Topical application of spent coffee ground extracts protects skin from ultraviolet B-induced photoaging in hairless mice.

    PubMed

    Choi, Hyeon-Son; Park, Eu Ddeum; Park, Yooheon; Han, Sung Hee; Hong, Ki Bae; Suh, Hyung Joo

    2016-06-01

    The aim of this study was to evaluate the protective effect of spent coffee ground (SCG) on ultraviolet (UV) B-induced photoaging in hairless mice. The oil fraction (OSCG) and ethanol extract (ESCG) of SCG were prepared from SCG. OSCG contained a much higher level of caffeine (547.32 ± 1.68 μg mg(-1)) when compared to the sum of its chlorogenic acid derivatives (∼119 μg mg(-1)), and pyrazines were the major aromatic compounds in OSCG. OSCG effectively inhibited the UVB-induced increase in intracellular reactive oxygen species in HaCaT cells. Topical application of OSCG or ESCG significantly reduced the UVB-induced wrinkle formation in mice dorsal skin. The combined application of OSCG and ESCG (OEH) led to a decrease in the wrinkle area by over 35% when compared with the UVB-treated control (UVBC). Epidermal thickness was also reduced by 40%. This result was connected to the significant reduction in transdermal water loss (27%) and erythema formation (48%) that result from UVB irradiation. Polarization-sensitive optical coherence tomography (PS-OCT) and antibody-based histological analyses showed that OSCG and ESCG effectively suppressed the UVB-induced decrease in collagen content. The level of type 1 collagen (COL1) in the OEH group was enhanced by around 40% compared with the UVB control group (UVBC). This was attributed to the down-regulation of matrix metalloproteinases (MMP2, 9, and 13), which are known to be responsible for collagen destruction. Our results indicate that topical treatment with OSCG/ESCG protects mouse skin from UVB-induced photoaging by down-regulating MMPs; therefore, suggesting the potential of SCG extracts as a topical anti-photoaging agent. PMID:27195822

  5. The development of hyperbaric oxygen therapy for skin rejuvenation and treatment of photoaging.

    PubMed

    Asadamongkol, Bralipisut; Zhang, John H

    2014-01-01

    Hyperbaric oxygen therapy (HBOT), a therapy that have patients breath in pure oxygen in a pressurized chamber, has been long used as a treatment for conditions such as decompression sickness and carbon monoxide poisoning. Oxygen recently has been found to be an important component in skin rejuvenation, treatment of photoaging skin, and improvement in skin complexions. The interest in the use of HBOT for this purpose is continually growing and becoming more widespread. In addition to aging and genetic makeup, chronic UV radiation due to everyday exposure, especially UV-B, can greatly increase the rate of wrinkle formation through increasing skin angiogenesis and degradation of extracellular matrix molecules. The use of HBOT and hyperoxia conditions has been found to attenuate the formation of wrinkles from UV irradiation. It accomplishes the task by possibly inhibiting various processes and pathways involved such as the HIF1-α, VEGF, neutrophil infiltrations, and MMP-2 & MMP-9, which are directly involved with promoting skin angiogenesis in its active state. There are currently medical aesthetic clinics that are using oxygen therapy under high pressure applied directly to skin to reduce visible wrinkles but this procedure is not widespread yet due to more research that needs to be done on this topic. However, this treatment for wrinkles is definitely growing due to recent studies done showing the effectiveness of oxygen therapy on wrinkles. This review article will explore and summarize researches done on possible mechanisms dealing with the use of oxygen therapy for reduction of UVB-caused wrinkles, its side effects, and its possible future improvement and use in medicine. PMID:24690202

  6. "Multi Light and Drugs": a new technique to treat face photoaging. Comparative study with photorejuvenation.

    PubMed

    Mezzana, Paolo

    2008-04-01

    Nonablative skin rejuvenation using laser, intense pulsed lights (IPLs), or radiofrequency techniques are becoming increasingly popular. In this paper, a novel protocol that integrates IPL sessions, low intense light and vitamin C, low-weight hyaluronic acid, betaglucan dermal injection versus IPL photorejuvenation as monotherapy is compared. A group of 100 patients, all women, with ages ranging from 35 to 65 years old (median age 56.3) with different degrees of photodamage was considered. A blinded control study was done. The patients were divided not randomly into two groups. These groups are similar for ages, skin types, and degrees of photoaging distribution. A first group of 40 patients had monotherapy consisting of seven sessions of IPL only. A second group of 60 patients had triple therapy consisting of seven sessions of IPL as well as nine sessions of low intense diode light and also biostimulation by drugs. Considering only the improvement in hyperpigmentations and teleangectasias, the monotherapy and the triple therapy show good results with no significant statistical difference between the two groups. Considering the improvement in skin texture and firmness in the group treated only with monotherapy, 30% (12 patients) had positive results, and 70% (28 patients) had poor results. In the group treated with triple therapy, 70% (42 patients) had positive results, and 30% (18 patients) had poor results, with the main differences in skin silicone negative imprints. On the basis of the data presented, the new technique of IPL, low intensity diode light, and multidrugs biostimulation seems to be a safe and effective method for skin rejuvenation and upgrades the effects of IPL in the fibroblasts' stimulation. PMID:17492340

  7. The development of hyperbaric oxygen therapy for skin rejuvenation and treatment of photoaging

    PubMed Central

    2014-01-01

    Hyperbaric oxygen therapy (HBOT), a therapy that have patients breath in pure oxygen in a pressurized chamber, has been long used as a treatment for conditions such as decompression sickness and carbon monoxide poisoning. Oxygen recently has been found to be an important component in skin rejuvenation, treatment of photoaging skin, and improvement in skin complexions. The interest in the use of HBOT for this purpose is continually growing and becoming more widespread. In addition to aging and genetic makeup, chronic UV radiation due to everyday exposure, especially UV-B, can greatly increase the rate of wrinkle formation through increasing skin angiogenesis and degradation of extracellular matrix molecules. The use of HBOT and hyperoxia conditions has been found to attenuate the formation of wrinkles from UV irradiation. It accomplishes the task by possibly inhibiting various processes and pathways involved such as the HIF1-α, VEGF, neutrophil infiltrations, and MMP-2 & MMP-9, which are directly involved with promoting skin angiogenesis in its active state. There are currently medical aesthetic clinics that are using oxygen therapy under high pressure applied directly to skin to reduce visible wrinkles but this procedure is not widespread yet due to more research that needs to be done on this topic. However, this treatment for wrinkles is definitely growing due to recent studies done showing the effectiveness of oxygen therapy on wrinkles. This review article will explore and summarize researches done on possible mechanisms dealing with the use of oxygen therapy for reduction of UVB-caused wrinkles, its side effects, and its possible future improvement and use in medicine. PMID:24690202

  8. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context

    PubMed Central

    Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco J.; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3+ or BrdU+ cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3+), astroglia (GFAP+), and microglia (Iba1+ cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3+ and BrdU+ subgranular cells as well as GFAP+, Iba1+ and cleaved caspase-3+ cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3+, GFAP+ and 3-weeks-old BrdU+ cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context. PMID:25870539

  9. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.

    PubMed

    Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco J; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context. PMID:25870539

  10. Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols.

    PubMed

    Maki, K C; Geohas, J G; Dicklin, M R; Huebner, M; Udani, J K

    2015-08-01

    This randomized, double-blind, placebo-controlled multi-center trial investigated the lipid-altering effects of a medical food (PDL-0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae-derived carotenoid; and 100 mg/d tocopherol-free gamma/delta tocotrienols enriched with geranylgeraniol, extracted from annatto, on triacylglycerols (TAG), other lipoprotein lipids, and oxidized low-density lipoprotein (LDL) in 102 subjects with TAG 150-499 mg/dL (1.69-5.63 mmol/L) and LDL cholesterol (LDL-C) ≥70 mg/dL (1.81 mmol/L). Compared to placebo, after eight weeks of treatment, PDL-0101 significantly reduced median TAG (-9.5% vs. 10.6%, p<0.001), while not significantly altering mean LDL-C (-3.0% vs. -8.0% for PDL-0101 and placebo, respectively, p=0.071), mean high-density lipoprotein cholesterol (~3% decrease in both groups, p=0.732), or median oxidized LDL concentrations (5% vs. -5% for PDL-0101 and placebo, respectively, p=0.112). These results demonstrate that PDL-0101 is an effective medical food for the management of elevated TAG. PMID:26076828

  11. Fractional Erbium laser in the treatment of photoaging: randomized comparative, clinical and histopathological study of ablative (2940nm) vs. non-ablative (1540nm) methods after 3 months*

    PubMed Central

    Borges, Juliano; Cuzzi, Tullia; Mandarim-de-Lacerda, Carlos Alberto; Manela-Azulay, Mônica

    2014-01-01

    BACKGROUND Fractional non-ablative lasers keep the epidermis intact, while fractional ablative lasers remove it, making them theoretically more effective. OBJECTIVES To evaluate the clinical and histological alterations induced by fractional photothermolysis for treating photoaging, comparing the possible equivalence of multiple sessions of 1540nm Erbium, to one session of 2940nm Erbium. METHODS Eighteen patients (mean age 55.9) completed the treatment with three sessions of 1540nm fractional Erbium laser on one side of the face (50 mJ/mB, 15ms, 2 passes), and one session of 2940nm on the other side (5mJ/mB, 0.25ms, 2 passes). Biopsies were performed before and 3 months after treatment. Clinical, histological and morphometric evaluations were carried out. RESULTS All patients presented clinical improvement with no statistically significant difference (p> 0.05) between the treated sides. Histopathology revealed a new organization of collagen and elastic fibers, accompanied by edema, which was more evident with the 2940nm laser. This finding was confirmed by morphometry, which showed a decrease in collagen density for both treatments, with a statistical significance for the 2940nm laser (p > 0.001). CONCLUSIONS Three 1540nm sessions were clinically equivalent to one 2940nm session. The edema probably contributed to the positive results after three months, togheter with the new collagen and elastic fibers organization. The greater edema after the 2940nm session indicates that dermal remodeling takes longer than with 1540nm. It is possible that this histological superiority relates to a more prolonged effect, but a cohort longer than three months is needed to confirm that supposition. PMID:24770501

  12. Molecular mechanisms and in vivo mouse models of skin aging associated with dermal matrix alterations.

    PubMed

    Hwang, Kyung-A; Yi, Bo-Rim; Choi, Kyung-Chul

    2011-03-01

    Skin is the most superficial body organ and plays an important role in protecting the body from environmental damage and in forming social relations. With the increase of the aging population in our society, dermatological and cosmetic concerns of skin aging are rapidly increasing. Skin aging is a complex process combined with intrinsic and extrinsic factors. Intrinsic or chronological skin aging results from the passage of time and is influenced by genetic factors. Extrinsic skin aging is mainly determined by UV irradiation, also called photoaging. These two types of aging processes are superimposed on sun-exposed skin, and have a common feature of causing dermal matrix alterations that mostly contribute to the formation of wrinkles, laxity, and fragility of aged skin. The dermal matrix contains extracellular matrix proteins such as collagen, elastin, and proteoglycans that confer the strength and resiliency of skin. Skin aging associated with dermal matrix alterations and atrophy can be caused by cellular senescence of dermal cells like fibroblasts, and decreased synthesis and accelerated degradation of dermal matrix components, especially collagen fibers. Both intrinsic aging and photoaging exert influence during each step of dermal matrix alteration via different mechanisms. Mouse models of skin aging have been extensively developed to elucidate intrinsic aging and photoaging processes, to validate in vitro biochemical data, and to test the effects of pharmacological tools for retarding skin aging because they have the advantages of being genetically similar to humans and are easily available. PMID:21826153

  13. Skin anti-photoaging properties of ginsenoside Rh2 epimers in UV-B-irradiated human keratinocyte cells.

    PubMed

    Oh, Sun-Joo; Lee, Sihyeong; Choi, Woo-Yong; Lim, Chang-Jin

    2014-09-01

    Ginseng, one of the most widely used herbal medicines, has a wide range of therapeutic and pharmacological applications. Ginsenosides are the major bioactive ingredients of ginseng, which are responsible for various pharmacological activities of ginseng. Ginsenoside Rh2, known as an antitumour ginsenoside, exists as two different stereoisomeric forms, 20(S)-ginsenoside Rh2 [20(S)-Rh2] and 20(R)-ginsenoside Rh2 [20(R)-Rh2]. This work aimed to assess and compare skin anti-photoaging activities of 20(S)-Rh2 and 20(R)-Rh2 in UV-B-irradiated HaCat cells. 20(S)-Rh2, but not 20(R)-Rh2, was able to suppress UV-B-induced ROS production in HaCat cells. Both stereoisomeric forms could not modulate cellular survival and NO level in UV-B-irradiated HaCat cells. Both 20(S)-Rh2 and 20(R)-Rh2 exhibited suppressive effects on UV-B-induced MMP-2 activity and expression in HaCat cells. In brief, the two stereoisomers of ginsenoside Rh2, 20(S)-Rh2 and 20(R)-Rh2, possess skin anti-photoaging effects but possibly in different fashions. PMID:25116621

  14. Cynaropicrin from Cynara scolymus L. suppresses photoaging of skin by inhibiting the transcription activity of nuclear factor-kappa B.

    PubMed

    Tanaka, Yuka Tsuda; Tanaka, Kiyotaka; Kojima, Hiroyuki; Hamada, Tomoji; Masutani, Teruaki; Tsuboi, Makoto; Akao, Yukihiro

    2013-01-15

    Aging of skin is characterized by skin wrinkling, laxity, and pigmentation induced by several environmental stress factors. Histological changes during the photoaging of skin include hyperproliferation of keratinocytes and melanocytes causing skin wrinkles and pigmentation. Nuclear factor kappa B (NF-κB) is one of the representative transcription factors active in conjunction with inflammation. NF-κB is activated by stimulation such as ultraviolet rays and inflammatory cytokines and induces the expression of various genes such as those of basic fibroblast growth factor (bFGF) and matrix metalloprotease-1 (MMP-1). We screened several plant extracts for their possible inhibitory effect on the transcriptional activity of NF-κB. One of them, an extract from Cynara scolymus L., showed a greatest effect on the suppression of NF-κB transactivation. As a result, we found that cynaropicrin, which is a sesquiterpene lactone, inhibited the NF-κB-mediated transactivation of bFGF and MMP-1. Furthermore, it was confirmed that in an in vivo mouse model cynaropicrin prevented skin photoaging processes leading to the hyperproliferation of keratinocytes and melanocytes. These findings taken together indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation. PMID:23232059

  15. Anti-photoaging activity and inhibition of matrix metalloproteinase (MMP) by marine red alga, Corallina pilulifera methanol extract

    NASA Astrophysics Data System (ADS)

    Ryu, BoMi; Qian, Zhong-Ji; Kim, Moon-Moo; Nam, Ki Wan; Kim, Se-Kwon

    2009-02-01

    Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by UV-irradiation-associated generation of reactive oxygen species (ROS). In this study, the alga Corallina pilulifera methanol (CPM) extract has been shown to exert a potent antioxidant activity and protective effect on UVA-induced oxidative stress of human dermal fibroblast (HDF) cell. Antioxidant evaluated by various antioxidant assays. These include reducing power, total antioxidant, DPPH radical scavenging, hydroxyl radical scavenging and protective effect on DNA damage caused by hydroxyl radicals generated. Further, the ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS on HT-1080 cells. Those various antioxidant activities were compared to standard antioxidants such as α-tocopherol. In addition, the in vitro activities of MMP-2 and MMP-9 in HDF cell were inhibited by C. pilulifera methanol extract dose dependently by using gelatin zymography method. The results obtained in the present study suggested that the C. pilulifera methanol extract may be a potential source of natural anti-photoaging.

  16. Fernblock, a Nutriceutical with Photoprotective Properties and Potential Preventive Agent for Skin Photoaging and Photoinduced Skin Cancers

    PubMed Central

    Gonzalez, Salvador; Gilaberte, Yolanda; Philips, Neena; Juarranz, Angeles

    2011-01-01

    Many phytochemicals are endowed with photoprotective properties, i.e., the capability to prevent the harmful effects of excessive exposure to ultraviolet (UV) light. These effects include photoaging and skin cancer, and immunosuppression. Photoprotection is endowed through two major modes of action: UV absorption or reflection/scattering; and tissue repair post-exposure. We and others have uncovered the photoprotective properties of an extract of the fern Polypodium leucotomos (commercial name Fernblock). Fernblock is an all-natural antioxidant extract, administered both topically (on the skin) or orally. It inhibits generation of reactive oxygen species (ROS) production induced by UV including superoxide anion. It also prevents damage to the DNA, inhibits UV-induced AP1 and NF-κB, and protects endogenous skin natural antioxidant systems, i.e., CAT, GSH, and GSSR. Its photoprotective effects at a cellular level include a marked decrease of UV-mediated cellular apoptosis and necrosis and a profound inhibition of extracellular matrix remodeling. These molecular and cellular effects translate into long-term inhibition of photoaging and carcinogenesis that, together with its lack of toxicity, postulate its use as a novel-generation photoprotective nutriceutical of phytochemical origin. PMID:22272084

  17. Fatty acid induced metabolic memory involves alterations in renal histone H3K36me2 and H3K27me3.

    PubMed

    Kumar, Sandeep; Pamulapati, Himani; Tikoo, Kulbhushan

    2016-02-15

    Accumulating evidence suggest that diabetic complications persist even after the maintenance of normal glucose levels. However, the molecular mechanisms involved are still unclear. In the present study, we have investigated the molecular mechanism behind the presence of insulin resistance (IR) condition even after normalization of circulating lipids levels both in vivo and in vitro. Persistent inhibition of insulin signalling in absence of elevated circulating lipids level confirms the presence of metabolic memory in our model of IR. IR in human urine derived podocyte-like epithelial cells (HUPECs) was developed by incubating cells with palmitate (750 μM) for 24 h and in SD rats by feeding high fat diet for 16 weeks. Inhibition of insulin induced FOXO1 (regulator of gluconeogenic genes) degradation persisted even after 48 h of palmitate removal from the culture media. Metabolic memory by palmitate was found to be associated with increased FOXO1 activity as evident from increased expression of FOXO1 target genes such as PDK4, p21, G6Pc and IGFBP1. To understand the reason for prolonged activation of FOXO1 and its target genes, chromatin immuno-precipitation (ChIP) was performed with histone H3K36me2 and H3K27me3 antibodies. ChIP assay shows persistent increase in abundance of histone H3K36me2 on promoter region of FOXO1. We also show decreased abundance of histone H3K27me3 on promoter region of FOXO1, in the kidneys of HFD fed rats, which persisted even after 8 weeks of diet reversal. Taken together, we provide first evidence that circulating lipids generate metabolic memory possibly by altering the abundance of histone H3K36me2 and H3K27me3 on FOXO1 promoter. PMID:26747726

  18. Altered Colonic Mucosal Polyunsaturated Fatty Acid (PUFA) Derived Lipid Mediators in Ulcerative Colitis: New Insight into Relationship with Disease Activity and Pathophysiology

    PubMed Central

    Eiden, Michael; Shute, Janis K.; Brown, James F.; Calder, Philip C.; Trebble, Timothy M.

    2013-01-01

    Objectives Ulcerative colitis (UC) is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA)) are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX) inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids) within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC. Design Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically. Results Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems. Conclusions Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile. PMID:24204637

  19. 5-Aminolevulinic Acid-based Photodynamic Intense Pulsed Light Therapy Shows Better Effects in the Treatment of Skin Photoaging in Asian Skin

    PubMed Central

    Xiang, Leihong Flora; Gold, Michael H.

    2010-01-01

    Objective: To investigate the effects of photodynamic intense pulsed light therapy on skin photoaging in Asian skin. Methods: This was a prospective, single-blinded, controlled, clinical trial with 40 patients enrolled. The enrolled patients applied 5% 5-aminolevulinic acid on the left side of the face while a placebo was applied on the right side of the face. After a one-hour incubation, the patients received intense pulsed light therapy. After four treatment cycles, the pH values, transepidermal water loss of the dermis of the forehead and canthus skin, as well as the moisture capacity of stratum corneum and the global score of photoaging were assessed. Results: The pH value of forehead and canthus skin, moisture capacity of stratum corneum, and the dermis of forehead and canthus skin of the photodynamic intense pulsed light therapy treated sides were significantly higher than those of the control sides in all of the patients. The photoaging score decreased after the therapy on both sides, with the photodynamic intense pulsed light therapy treated sides decreasing more than the control sides (P<0.01). Conclusion: 5-aminolevulinic acid photodynamic intense pulsed light therapy showed better effects in the treatment of skin photoaging compared to intense pulsed light therapy alone. PMID:20725543

  20. Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo.

    PubMed

    Humbert, Philippe G; Haftek, Marek; Creidi, Pierre; Lapière, Charles; Nusgens, Betty; Richard, Alain; Schmitt, Daniel; Rougier, André; Zahouani, Hassan

    2003-06-01

    Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing. PMID:12823436

  1. [Therapeutic effects of larger doses of arachidonic acid added to DHA on social impairment and its relation to alterations of polyunsaturated fatty acids in individuals with autism spectrum disorders].

    PubMed

    Yui, Kunio; Koshiba, Mamiko; Nakamura, Shun; Onishi, Masako

    2011-06-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA) and docosahexaenoic acid (DHA) may play key roles in brain network maturation. ARA plays an important role in signal transduction related to neuronal maturation. This study aims to evaluate the efficacy of supplementing with larger doses of ARA added to DHA in a double-blind, placebo-controlled 16-week trial. To confirm findings observed in the placebo-controlled trial, an additional 16-week open-label study was further conducted. To examine the relationship between the efficacy of the supplementation regimen and alterations in PUFAs levels, we examined plasma levels of PUFAs. We used the Social Responsiveness Scale (SRS) and the Aberrant Behavior Checklist-Community (ABC) to estimate psychotic symptoms. Repeated measures ANOVA revealed that this supplementation significantly improved SRS-measured communication as well as ABC-measured social withdrawal during the placebo-controlled trial. The treatment effect sizes were more favorable for the treatment group compared with the placebo group (communication: 0.87 vs. 0.44; social withdrawal: 0.88 vs. 0.54). At the end of the placebo-controlled trial, there was a significant difference in the change in plasma ARA levels from the baseline and a trend towards a significant difference in plasma ARA levels between the two groups. The open-label study was not powered to detect significant improvements in the outcome measures or significant differences in plasma ARA levels. The present clinical trials suggest that supplementation with larger ARA doses added to DHA improves social impairment in individuals with ASD via ARA-induced upregulation of neuronal functioning. PMID:21800702

  2. Rosuvastatin Decreases Intestinal Fatty Acid Binding Protein (I-FABP), but Does Not Alter Zonulin or Lipopolysaccharide Binding Protein (LBP) Levels, in HIV-Infected Subjects on Antiretroviral Therapy

    PubMed Central

    Funderburg, Nicholas T.; Boucher, Morgan; Sattar, Abdus; Kulkarni, Manjusha; Labbato, Danielle; Kinley, Bruce I.; McComsey, Grace A.

    2016-01-01

    Introduction Altered gastrointestinal (GI) barrier integrity and subsequent microbial translocation may contribute to immune activation in HIV infection. We have reported that rosuvastatin improved several markers of immune activation in HIV+ participants, but the effect of statin treatment on markers of GI barrier dysfunction is unknown. Methods SATURN-HIV is a randomized, double-blind, placebo-controlled trial assessing the effect of rosuvastatin (10mg/daily) on markers of cardiovascular disease, inflammation, and immune activation in ART-treated patients. Gut-barrier integrity was assessed by the surrogate markers intestinal fatty acid binding protein (I-FABP), a marker of enterocyte death, and zonulin-1, a marker of gut epithelial cell function. Levels of lipopolysaccharide binding protein (LBP) were measured as a marker of microbial translocation. Results Rosuvastatin significantly reduced levels of I-FABP during the treatment period compared to the placebo. There was no effect of rosuvastatin treatment on levels of zonulin or LBP. Baseline levels of LBP were directly related to several markers of immune activation in samples from all participants, including soluble CD163, IP-10, VCAM-1, TNFR-II, and the proportion of CD4+ and CD8+ T cells expressing CD38 and HLA-DR. Many of these relationships, however, were not seen in the statin arm alone at baseline or over time, as inflammatory markers often decreased and LBP levels were unchanged. Conclusions Forty-eight weeks of rosuvastatin treatment reduced levels of I-FABP, but did not affect levels of zonulin or LBP. The reduction in levels of inflammatory markers that we have reported with rosuvastatin treatment is likely mediated through other mechanisms not related to gut integrity or microbial translocation.

  3. Facial primer provides immediate and long-term improvements in mild-to-moderate facial hyperpigmentation and fine lines associated with photoaging

    PubMed Central

    Roberts, Wendy E; Jiang, Lily I; Herndon, James H

    2015-01-01

    Background Photoaged skin results from various environmental factors, most importantly chronic sun exposure. Dyschromia and fine lines/wrinkles are common clinical manifestations of photodamaged skin. Purpose This single-center clinical trial was conducted to assess the efficacy and tolerability of a new multifunctional facial primer (camouflage, broad-spectrum SPF 50, and a treatment for hyperpigmentation) when used by females with mild-to-moderate facial hyperpigmentation and fine lines due to photoaging over a course of 12 weeks. Patients and methods Subjects were provided test material (Even Up-Clinical Pigment Perfector) and supporting products to use on their face and neck. Products were used according to specific application instructions. Clinical grading for efficacy and tolerability assessments were performed by an expert grader at baseline, baseline (post-application primer), week 4, week 8, week 12, and week 12 (post-application primer). Standardized digital photographs were taken, and self-assessment questionnaires were conducted. Results Twenty-eight female subjects completed the 12-week trial. The facial primer improved scores for the appearance of hyperpigmentation and other photoaging parameters immediately after the first application. The treatment also showed a progressive improvement in the clinical assessment of hyperpigmentation and other photoaging parameters over the 12-week trial. These long-term benefits can be attributed to an improvement in the underlying skin condition. The facial primer was well tolerated. Subject questionnaires showed that the product was highly rated at all visits. Conclusion The facial primer was shown to be effective and well tolerated for immediate and long-term improvement in the appearance of mild-to-moderate hyperpigmentation and fine lines associated with photodamage when used over a 12-week period. PMID:26366102

  4. Ixora parviflora Protects against UVB-Induced Photoaging by Inhibiting the Expression of MMPs, MAP Kinases, and COX-2 and by Promoting Type I Procollagen Synthesis

    PubMed Central

    Wen, Kuo-Ching; Fan, Pei-Ching; Tsai, Shang-Yuan; Shih, I-Chen; Chiang, Hsiu-Mei

    2012-01-01

    Ixora parviflora with high polyphenol content exhibited antioxidant activity and reducing UVB-induced intracellular reactive oxygen species production. In this study, results of the photoaging screening experiments revealed that IPE at 1000 μg/mL reduced the activity of bacterial collagenase by 92.7 ± 4.2% and reduced the activity of elastase by 32.6 ± 1.4%. Therefore, we investigated the mechanisms by which IPE exerts its anti-photoaging activity. IPE at 1 μg/mL led to an increase in type I procollagen expression and increased total collagen synthesis in fibroblasts at 5 μg/mL. We found that IPE inhibited MMP-1, MMP-3, and MMP-9 expression at doses of 1, 5, and 10 μg/mL, respectively, in fibroblasts exposed to UV irradiation (40 mJ/cm2). Gelatin zymography assay showed that IPE at 50 μg/mL inhibited MMP-9 secretion/activity in cultured fibroblasts after UVB exposure. In addition, IPE inhibited the phosphorylation of p38, ERK, and JNK induced by UVB. Furthermore, IPE inhibited the UVB-induced expression of Smad7. In addition, IPE at 1 μg/mL inhibited NO production and COX-2 expression in UV-exposed fibroblasts. These findings show that IPE exhibits anti-inflammatory and anti-photoaging activities, indicating that IPE could be a potential anti-aging agent. PMID:22203872

  5. Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids.

    PubMed

    Beld, Joris; Abbriano, Raffaela; Finzel, Kara; Hildebrand, Mark; Burkart, Michael D

    2016-04-22

    In both eukaryotes and prokaryotes, fatty acid synthases are responsible for the biosynthesis of fatty acids in an iterative process, extending the fatty acid by two carbon units every cycle. Thus, odd numbered fatty acids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fatty acids as substrates for their fatty acid synthases and their downstream enzymes. We fed various odd and short chain fatty acids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fatty acids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fatty acid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fatty acids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fatty acids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fatty acids was only observed in Synechocystis and C. reinhardtii. We further probed fatty acid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fatty acid desaturases. In particular, supplementation with thia fatty acids can alter fatty acid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fatty acids can reveal major differences between fatty acid metabolism in various organisms. Often unnatural fatty acids have antibacterial or even therapeutic properties. Feeding of short

  6. High levels of vegetable oils in plant protein-rich diets fed to gilthead sea bream ( Sparus aurata L.): growth performance, muscle fatty acid profiles and histological alterations of target tissues.

    PubMed

    Benedito-Palos, Laura; Navarro, Juan C; Sitjà-Bobadilla, Ariadna; Bell, J Gordon; Kaushik, Sadasivam; Pérez-Sánchez, Jaume

    2008-11-01

    The feasibility of fish oil (FO) replacement by vegetable oils (VO) was investigated in gilthead sea bream (Sparus aurata L.) in a growth trial conducted for the duration of 8 months. Four isolipidic and isoproteic diets rich in plant proteins were supplemented with L-lysine (0.55 %) and soya lecithin (1 %). Added oil was either FO (control) or a blend of VO, replacing 33 % (33VO diet), 66 % (66VO diet) and 100 % (VO diet) of FO. No detrimental effects on growth performance were found with the partial FO replacement, but feed intake and growth rates were reduced by about 10 % in fish fed the VO diet. The replacement strategy did not damage the intestinal epithelium, and massive accumulation of lipid droplets was not found within enterocytes. All fish showed fatty livers, but signs of lipoid liver disease were only found in fish fed the VO diet. Muscle fatty acid profiles of total lipids reflected the diet composition with a selective incorporation of unsaturated fatty acids in polar lipids. The robustness of the phospholipid fatty acid profile when essential fatty acid requirements were theoretically covered by the diet was evidenced by multivariate principal components analysis in fish fed control, 33VO and 66VO diets. PMID:18377678

  7. Nonalcoholic fatty liver disease.

    PubMed

    Brunt, Elizabeth M; Wong, Vincent W-S; Nobili, Valerio; Day, Christopher P; Sookoian, Silvia; Maher, Jacquelyn J; Bugianesi, Elisabetta; Sirlin, Claude B; Neuschwander-Tetri, Brent A; Rinella, Mary E

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring. PMID:27188459

  8. Photoaging of retinal pigment epithelial melanosomes: The effect of photobleaching on morphology and reactivity of the pigment granules.

    PubMed

    Zadlo, Andrzej; Szewczyk, Grzegorz; Sarna, Michal; Kozinska, Anna; Pilat, Anna; Kaczara, Patrycja; Sarna, Tadeusz

    2016-08-01

    To elucidate the mechanism of age-related changes in antioxidant and photoprotective properties of human retinal pigment epithelium (RPE) melanosomes, the effect of in vitro photoaging of bovine RPE melanosomes was examined employing an array of complementary spectroscopic and analytical methods. Electron paramagnetic resonance (EPR) spectroscopy, saturation recovery EPR, atomic force microscopy (AFM) and dynamic light scattering (DLS) were used to determine melanin content of control and photobleached melanosomes, and to monitor changes in their morphology. Methylene blue (MB), TEMPO choline, dysprosium(III) ions and singlet oxygen were employed as molecular probes to characterize the efficiency of control and photobleached melanosomes to interact with different reagents. EPR oximetry, UV-vis absorption spectroscopy, iodometric assay of lipid hydroperoxides and time-resolved singlet oxygen phosphorescence were used to analyze the efficiency of photobleached and untreated melanosomes to inhibit MB-photosensitized oxidation of liposomal lipids. The obtained results revealed that, compared to untreated melanosomes, moderately photobleached melanosomes protected unsaturated lipids less efficiently against photosensitized peroxidiation, while weakly photobleached melanosomes were actually better antioxidant and photoprotective agents. The observed changes could be attributed to two effects - modification of the melanosome morphology and oxidative degradation of the melanin functional groups induced by different degree of photobleaching. While the former increases the accessibility of melanin nanoaggregates to reagents, the latter reduces the efficiency of melanin to interact with chemical and physical agents. PMID:27338854

  9. Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxygenated fatty acids are useful as specialty chemicals, plasticizers, and biomedicals. Microbial enzymes convert fatty acids to mono-, di-, and trihydroxy fatty acid products. Among them, Bacillus megaterium ALA2 converted n-6 and n-3 PUFAs to many new oxygenated fatty acids. Linoleic acid was ...

  10. Solar Ultraviolet Irradiation Reduces Collagen in Photoaged Human Skin by Blocking Transforming Growth Factor-β Type II Receptor/Smad Signaling

    PubMed Central

    Quan, Taihao; He, Tianyuan; Kang, Sewon; Voorhees, John J.; Fisher, Gary J.

    2004-01-01

    Ultraviolet (UV) irradiation from the sun reduces production of type I procollagen (COLI), the major structural protein in human skin. This reduction is a key feature of the pathophysiology of premature skin aging (photoaging). Photoaging is the most common form of skin damage and is associated with skin carcinoma. TGF-β/Smad pathway is the major regulator of type I procollagen synthesis in human skin. We have previously reported that UV irradiation impairs transforming growth factor-β (TGF-β)/Smad signaling in mink lung epithelial cells. We have investigated the mechanism of UV irradiation impairment of the TGF-β/Smad pathway and the impact of this impairment on type I procollagen production in human skin fibroblasts, the major collagen-producing cells in skin. We report here that UV irradiation impairs TGF-β/Smad pathway in human skin by down-regulation of TGF-β type II receptor (TβRII). This loss of TβRII occurs within 8 hours after UV irradiation and precedes down-regulation of type I procollagen expression in human skin in vivo. In human skin fibroblasts, UV-induced TβRII down-regulation is mediated by transcriptional repression and results in 90% reduction of specific, cell-surface binding of TGF-β. This loss of TβRII prevents downstream activation of Smad2/3 by TGF-β, thereby reducing expression of type I procollagen. Preventing loss of TβRII by overexpression protects against UV inhibition of type I procollagen gene expression in human skin fibroblasts. UV-induced down-regulation of TβRII, with attendant reduction of type I procollagen production, is a critical molecular mechanism in the pathophysiology of photoaging. PMID:15331399

  11. Omega-3 Fatty Acids

    MedlinePlus

    Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount ... the blood in people with very high triglycerides. Omega-3 fatty acids are in a class of medications ...

  12. Omega-6 Fatty Acids

    MedlinePlus

    Omega-6 fatty acids are types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other types of omega-6 fatty acids are found in black currant seed, borage seed, ...

  13. Omega-6 Fatty Acids

    MedlinePlus

    ... types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean ... from studying specific omega-6 fatty acids or plant oils containing omega-6 fatty acids. See the separate ...

  14. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  15. The effect of systemic cyclosporin A on a hairless mouse model of photoaging.

    PubMed

    Moloney, S J; Learn, D B

    1992-10-01

    The mechanisms that cause skin wrinkling in response to chronic exposure to sunlight are unknown. We investigated the possibility that wrinkling of Skh-1 hairless mice is associated with an ultraviolet (UV) radiation-induced immunologic alteration. Exposing Skh-1 hairless mice to a regimen of nonerythemal UV-B (290-320 nm) radiation induced skin wrinkles after 6-7 weeks. Concomitant treatment with cyclosporin A decreased the time to the onset of wrinkles to approximately 4 weeks. Exposing HRS/J hairless mice or athymic nude mice to a similar nonerythemal UV-B radiation regimen for 10 weeks failed to induce skin wrinkles. Concomitant administration of cyclosporin A and UV-B radiation for 7 weeks to HRS/J hairless mice induced no skin wrinkles. Ultraviolet-B or UV-B plus cyclosporin A exposure caused increased immunohistochemical staining for Ia and F4/80 antigens in the upper dermis of tissue from Skh-1 mice, as compared to controls. Treating Skh-1 mice with UV-B radiation plus cyclosporin A was also associated with a large increase in the number of CD3+ cells in the dermis. These staining patterns were absent in similarly treated HRS/J hairless mice. Dermal mast cell numbers in Skh-1 mice were 2-3-fold higher than in HRS/J, athymic nude or NSA mice. Treatment with cyclosporin A increased Skh-1 dermal mast cell numbers approximately 2-fold but had no effect on the dermal mast cell numbers in HRS/J or NSA mice. Based on these findings we postulate that UV-B light and cyclosporin A exacerbate an immunological condition in Skh-1 mice, one consequence of which is manifested as skin wrinkles. Thus, the induction of skin wrinkles in this mouse strain may have no relevance to the wrinkles observed in human skin after chronic exposure to sunlight. PMID:1454879

  16. Valencene from the Rhizomes of Cyperus rotundus Inhibits Skin Photoaging-Related Ion Channels and UV-Induced Melanogenesis in B16F10 Melanoma Cells.

    PubMed

    Nam, Joo Hyun; Nam, Da-Yeong; Lee, Dong-Ung

    2016-04-22

    Ultraviolet (UV) radiation deeply penetrates skin and causes inflammation and pigmentary changes and triggers immune responses. Furthermore, accumulating evidence suggests that calcium ion channels, such as TRPV1 and ORAI1, mediate diverse dermatological processes including melanogenesis, skin wrinkling, and inflammation. The rhizomes of Cyperus rotundus have been used to treat inflammatory diseases including dermatitis. However, their effects on UV-induced photoaging-related ion channels remain unknown. Therefore, this study was undertaken to evaluate the antagonistic effects of C. rotundus extract and their constituents on TRPV1 and ORAI1 channels. Electrophysiological analysis revealed that valencene (1) isolated from the hexane fraction potently inhibited capsaicin-induced TRPV1 and ORAI1 currents at 90 μM (69 ± 15% and 97 ± 2% at -60 and -120 mV, respectively). The inhibitory effect of 1 on cytoplasmic Ca(2+) concentrations in response to ORAI1 activation (85 ± 2% at 50 μM) was also confirmed. Furthermore, 1 concentration-dependently decreased the melanin content after UVB irradiation in murine B16F10 melanoma cells by 82.66 ± 2.14% at 15 μg/mL. These results suggest that C. rotundus rhizomes have potential therapeutic effects on UV-induced photoaging and indicate that the therapeutic and cosmetic applications of 1 are worth further investigation. PMID:26967731

  17. Protective effect of Disporum sessile D.Don extract against UVB-induced photoaging via suppressing MMP-1 expression and collagen degradation in human skin cells.

    PubMed

    Mohamed, Mohamed Antar Aziz; Jung, Mira; Lee, Sang Min; Lee, Tae Hoon; Kim, Jiyoung

    2014-04-01

    In the present study, we report that Disporum sessile D.Don herbal extract (DDE) possesses anti-skin photoaging effect through inhibition of MMP-1 mRNA and protein expression levels and increase collagen production in UVB-irradiated human dermal fibroblast cells (NHDF). To delineate the molecular mechanism by which DDE inhibited MMP-1 expression, immortal human keratinocytes cells (HaCaT) have been used. We have found that DDE inhibited UVB-induced MMP-1 mRNA and protein expression levels in HaCaT cells through inhibition of UVB-induced activation of NF-κB in HaCaT cells. Inhibitors of NF-κB (Bay11-7082), and mitogen-activated protein kinases such as extracellular regulated kinase (PD98059), c-Jun N-terminal kinase (SP600125), and p38 (SB203580) suppressed expression of MMP-1, and phosphorylation of these signaling molecules were attenuated by DDE. DDE also inhibited phosphorylation of IKKα and IκBα, and reduced nuclear translocation of NF-κB. Our results also demonstrated that DDE inhibited NF-κB driven expression of luciferase reporter gene and the DNA binding of NF-κB to its cognate binding site in UV-irradiated cells. Therefore, these results strongly suggest that DDE can be utilized as a potential agent for prevention and treatment of skin photoaging. PMID:24705373

  18. Fernblock (Polypodium leucotomos Extract): Molecular Mechanisms and Pleiotropic Effects in Light-Related Skin Conditions, Photoaging and Skin Cancers, a Review

    PubMed Central

    Parrado, Concepcion; Mascaraque, Marta; Gilaberte, Yolanda; Juarranz, Angeles; Gonzalez, Salvador

    2016-01-01

    Healthier life styles include increased outdoors time practicing sports and walking. This means increased exposure to the sun, leading to higher risk of sunburn, photoaging and skin cancer. In addition to topical barrier products, oral supplementations of various botanicals endowed with antioxidant activity are emerging as novel method of photoprotection. Polypodium leucotomos extract (PL, commercial name Fernblock®, IFC Group, Spain) is a powerful antioxidant due to its high content of phenolic compounds. PL is administered orally, with proven safety, and it can also be used topically. Its mechanisms include inhibition of the generation and release of reactive oxygen species (ROS) by ultraviolet (UV) light. It also prevents UV- and ROS-induced DNA damage with inhibition of AP1 and NF-κB and protection of natural antioxidant enzyme systems. At the cellular level, PL decreases cellular apoptosis and necrosis mediated UV and inhibits abnormal extracellular matrix remodeling. PL reduces inflammation, prevents immunosuppression, activates tumor suppressor p53 and inhibits UV-induced cyclooxygenase-2 (COX-2) enzyme expression. In agreement with increased p53 activity, PL decreased UV radiation-induced cell proliferation. PL also prevents common deletions mitochondrial DNA damage induced by UVA, and MMP-1 expression induced Visible Light and Infrared Radiation. These cellular and molecular effects are reflected in inhibitions of carcinogenesis and photoaging. PMID:27367679

  19. Fernblock (Polypodium leucotomos Extract): Molecular Mechanisms and Pleiotropic Effects in Light-Related Skin Conditions, Photoaging and Skin Cancers, a Review.

    PubMed

    Parrado, Concepcion; Mascaraque, Marta; Gilaberte, Yolanda; Juarranz, Angeles; Gonzalez, Salvador

    2016-01-01

    Healthier life styles include increased outdoors time practicing sports and walking. This means increased exposure to the sun, leading to higher risk of sunburn, photoaging and skin cancer. In addition to topical barrier products, oral supplementations of various botanicals endowed with antioxidant activity are emerging as novel method of photoprotection. Polypodium leucotomos extract (PL, commercial name Fernblock(®), IFC Group, Spain) is a powerful antioxidant due to its high content of phenolic compounds. PL is administered orally, with proven safety, and it can also be used topically. Its mechanisms include inhibition of the generation and release of reactive oxygen species (ROS) by ultraviolet (UV) light. It also prevents UV- and ROS-induced DNA damage with inhibition of AP1 and NF-κB and protection of natural antioxidant enzyme systems. At the cellular level, PL decreases cellular apoptosis and necrosis mediated UV and inhibits abnormal extracellular matrix remodeling. PL reduces inflammation, prevents immunosuppression, activates tumor suppressor p53 and inhibits UV-induced cyclooxygenase-2 (COX-2) enzyme expression. In agreement with increased p53 activity, PL decreased UV radiation-induced cell proliferation. PL also prevents common deletions mitochondrial DNA damage induced by UVA, and MMP-1 expression induced Visible Light and Infrared Radiation. These cellular and molecular effects are reflected in inhibitions of carcinogenesis and photoaging. PMID:27367679

  20. Targeted alterations in dietary n-3 and n-6 fatty acids improve life functioning and reduce psychological distress among patients with chronic headache: a secondary analysis of a randomized trial.

    PubMed

    Ramsden, Christopher E; Faurot, Keturah R; Zamora, Daisy; Palsson, Olafur S; MacIntosh, Beth A; Gaylord, Susan; Taha, Ameer Y; Rapoport, Stanley I; Hibbeln, Joseph R; Davis, John M; Mann, J Douglas

    2015-04-01

    Omega-3 and omega-6 fatty acids are precursors of bioactive lipid mediators posited to modulate both physical pain and psychological distress. In a randomized trial of 67 subjects with severe headaches, we recently demonstrated that targeted dietary manipulation-increasing omega-3 fatty acids with concurrent reduction in omega-6 linoleic acid (the H3-L6 intervention)-produced major reductions in headache compared with an omega-6 lowering (L6) intervention. Because chronic pain is often accompanied by psychological distress and impaired health-related quality of life (HRQOL), we used data from this trial to examine whether the H3-L6 intervention favorably impacted these domains. Additionally, we examined the effect of the interventions on the number of cases with substantial physical or mental impairments as defined by cutoff values in the Brief Symptom Inventory (BSI-18), Medical Outcomes Study Short Forms 12 (SF-12), Headache Impact Test (HIT-6), and the number of headache days per month. In the intention-to-treat analysis, participants in the H3-L6 group experienced statistically significant reductions in psychological distress (BSI-18 mean difference: -6.56; 95% confidence interval [CI]: -11.43 to -1.69) and improvements in SF-12 mental (mean difference: 6.01; 95% CI: 0.57 to 11.45) and physical (mean difference: 6.65; 95% CI: 2.14 to 11.16) health summary scores. At 12 weeks, the proportion of subjects experiencing substantial impairment according to cutoff values in the BSI-18, SF-12 physical, HIT-6, and headache days per month was significantly lower in the H3-L6 group. Dietary manipulation of n-3 and n-6 fatty acids, previously shown to produce major improvements in headache, was found to also reduce psychological distress and improve HRQOL and function. PMID:25790451

  1. THP-1 macrophage lipid accumulation unaffected by fatty acid double bond geometric or positional configuration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary fatty acid type alters atherosclerotic lesion progression and macrophage lipid accumulation. Incompletely elucidated are the mechanisms by which fatty acids differing in double-bond geometric or positional configuration alter arterial lipid accumulation. The objective of this study was to ev...

  2. Opposite regulation of CD36 ubiquitination by fatty acids and insulin: effects on fatty acid uptake.

    PubMed

    Smith, Jill; Su, Xiong; El-Maghrabi, Raafat; Stahl, Philip D; Abumrad, Nada A

    2008-05-16

    FAT/CD36 is a membrane scavenger receptor that facilitates long chain fatty acid uptake by muscle. Acute increases in membrane CD36 and fatty acid uptake have been reported in response to insulin and contraction. In this study we have explored protein ubiquitination as one potential mechanism for the regulation of CD36 level. CD36 expressed in Chinese hamster ovary (CHO) or HEK 293 cells was found to be polyubiquitinated via a process involving both lysines 48 and 63 of ubiquitin. Using CHO cells expressing the insulin receptor (CHO/hIR) and CD36, it is shown that addition of insulin (100 nm, 10 and 30 min) significantly reduced CD36 ubiquitination. In contrast, ubiquitination was strongly enhanced by fatty acids (200 microm palmitate or oleate, 2 h). Similarly, endogenous CD36 in C2C12 myotubes was ubiquitinated, and this was enhanced by oleic acid treatment, which also reduced total CD36 protein in cell lysates. Insulin reduced CD36 ubiquitination, increased CD36 protein, and inhibited the opposite effects of fatty acids on both parameters. These changes were paralleled by changes in fatty acid uptake, which could be blocked by the CD36 inhibitor sulfosuccinimidyl oleate. Mutation of the two lysine residues in the carboxyl-terminal tail of CD36 markedly attenuated ubiquitination of the protein expressed in CHO cells and was associated with increased CD36 level and enhanced oleate uptake and incorporation into triglycerides. In conclusion, fatty acids and insulin induce opposite alterations in CD36 ubiquitination, modulating CD36 level and fatty acid uptake. Altered CD36 turnover may contribute to abnormal fatty acid uptake in the insulin-resistant muscle. PMID:18353783

  3. Metabolite profiling of enzymatically hydrolyzed and fermented forms of Opuntia ficus-indica and their effect on UVB-induced skin photoaging.

    PubMed

    Cho, Dong-Woon; Kim, Dae-Eung; Lee, Dae-Hee; Jung, Kyung-Hoon; Hurh, Byung-Serk; Kwon, Oh Wook; Kim, Sun Yeou

    2014-01-01

    Fermentation of natural products is emerging as an important processing method and is attracting a lot of attention because it may have the advantage of having a new biological function. In this study, fruits of Opuntia ficus-indica were enzymatically hydrolyzed and then fermented with two species of yeast. We identified novel prominent markers in enzymatically hydrolyzed O. ficus-indica (EO) and fermented O. ficus-indica (FO) samples by using an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. We also evaluated the effect of EO and FO on photoaging of skin cells exposed to ultraviolet radiation. We identified the major fermented metabolite in the FO as ferulic acid. Our in vitro study indicated that FO significantly enhanced the concentration of pro-collagen type 1 than the EO, by increasing the TGF-β1 production. PMID:24446110

  4. Anti-photoaging potential of Botulinum Toxin Type A in UVB-induced premature senescence of human dermal fibroblasts in vitro through decreasing senescence-related proteins.

    PubMed

    Permatasari, Felicia; Hu, Yan-yan; Zhang, Jia-an; Zhou, Bing-rong; Luo, Dan

    2014-04-01

    This study was aimed to evaluate the anti-photoaging effects of Botulinum Toxin Type A (BoNTA) in Ultraviolet B-induced premature senescence (UVB-SIPS) of human dermal fibroblasts (HDFs) in vitro and the underlying mechanism. We established a stress-induced premature senescence model by repeated subcytotoxic exposures to Ultraviolet B (UVB) irradiation. The aging condition was determined by cytochemical staining of senescence-associated β-galactosidase (SA-β-gal). The tumor suppressor and senescence-associated protein levels of p16(INK-4a), p21(WAF-1), and p53 were estimated by Western blotting. The G1 phase cell growth arrest was analyzed by flow cytometry. The mRNA expressions of p16, p21, p53, COL1a1, COL3a1, MMP1, and MMP3 were determined by real-time PCR. The level of Col-1, Col-3, MMP-1, and MMP-3 were determined by ELISA. Compared with the UVB-irradiated group, we found that the irradiated fibroblasts additionally treated with BoNTA demonstrated a decrease in the expression of SA-β-gal, a decrease in the level of tumor suppressor and senescence-associated proteins, a decrease in the G1 phase cell proportion, an increase in the production of Col-1 and Col-3, and a decrease in the secretion of MMP-1 and MMP-3, in a dose-dependent manner. Taken together, these results indicate that BoNTA significantly antagonizes premature senescence induced by UVB in HDFs in vitro, therefore potential of intradermal BoNTA injection as anti-photoaging treatment still remains a question. PMID:24727404

  5. Novel applications of diagnostic x-rays in activating photo-agents through x-ray induced visible luminescence from rare-earth particles: an in vitro study

    NASA Astrophysics Data System (ADS)

    Abliz, Erkinay; Collins, Joshua E.; Friedberg, Joseph S.; Kumar, Ajith; Bell, Howard; Waynant, Ronald W.; Tata, Darrell B.

    2010-02-01

    Photodynamic agents such as Photofrin II (Photo II) utilized in photodynamic therapy (PDT) possess a remarkable property to become preferentially retained within the tumor's micro-environment. Upon the photo-agent's activation through visible light photon absorption, the agents exert their cellular cytotoxicity through type II and type I mechanistic pathways through extensive generation of reactive oxygen species (ROS): singlet oxygen 1O2, superoxide anion O2 -, and hydrogen peroxide H2O2, within the intratumoral environment. Unfortunately, due to shallow visible light penetration depth (~2mm to 5mm) in tissues, the PDT strategy currently has largely been restricted to the treatments of surface tumors, such as the melanomas. Additional invasive strategies through optical fibers are currently utilized in getting the visible light into the intended deep seated targets within the body for PDT. In this communication, we report on a novel strategy in utilizing "soft" energy diagnostic X-rays to indirectly activate Photo II through X-ray induced luminescence from Gadolinium oxysulfide (20 micron dimension) particles doped with Terbium: Gd2O2S:Tb. X-ray induced visible luminescence from Gd2O2S:Tb particles was spectroscopically characterized and the ROS production levels from clinically relevant concentration (10 μg/ml) of Photo II was quantified through changes in the Vitamin C absorbance. ROS kinetics through X-ray induced luminescence was found to be similar to the ROS kinetics from red He-Ne laser exposures used in the clinics. Taken together, in-vitro findings herein provide the basis for future studies in determining the safety and efficacy of this non-invasive X-ray induced luminescence strategy in activating photo-agent in deep seated tumors.

  6. Quantitation of myocardial fatty acid metabolism using PET

    SciTech Connect

    Bergmann, S.R.; Weinheimer, C.J.; Markham, J.; Herrero, P.

    1996-10-01

    Abnormalities of fatty acid metabolism in the heart presage contractile dysfunction and arrhythmias. This study was performed to determine whether myocardial fatty acid metabolism could be quantified noninvasively using PET and 1-{sup 11}C-palmitate. Anesthetized dogs were studied during control conditions; during administration of dobutamine; after oxfenicine; and during infusion of glucose. Dynamic PET data after administration of 1-{sup 11}C-palmitate were fitted to a four-compartment mathematical model. Modeled rates of palmitate utilization correlated closely with directly measured myocardial palmitate and total long-chain fatty acid utilization (r = 0.93 and 0.96, respectively, p < 0.001 for each) over a wide range of arterial fatty acid levels and altered patterns of myocardial substrate use (fatty acid extraction fraction ranging from 1% to 56%, glucose extraction fraction from 1% to 16% and myocardial fatty acid utilization from 1 to 484 nmole/g/min). The percent of fatty acid undergoing oxidation could also be measured. The results demonstrate the ability to quantify myocardial fatty acid utilization with PET. The approach is readily applicable for the determination of fatty acid metabolism noninvasively in patients. 37 refs., 5 figs., 4 tabs.

  7. Fats and fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The absolute fat requirement of the human species is the amount of essential fatty acids needed to maintain optimal fatty acid composition of all tissues and normal eicosanoid synthesis. At most, this requirement is no more than about 5% of an adequate energy intake. However, fat accounts for appro...

  8. Omega-3 Fatty Acids

    MedlinePlus

    Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of triglycerides (a fat-like ... people with very high triglycerides. Omega-3 fatty acids are in a class of medications called antilipemic ...

  9. Dietary omega-3 fatty acids for women.

    PubMed

    Bourre, Jean-Marie

    2007-01-01

    This review details the specific needs of women for omega-3 fatty acids, including alpha linoleic acid (ALA) and the very long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fatty acids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fatty acid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood. ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fatty acids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fatty acids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes. The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola), walnuts and so-called "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs. PMID:17254747

  10. A Rosemary Extract Rich in Carnosic Acid Selectively Modulates Caecum Microbiota and Inhibits β-Glucosidase Activity, Altering Fiber and Short Chain Fatty Acids Fecal Excretion in Lean and Obese Female Rats

    PubMed Central

    Larrosa, Mar; Obiol, María; García-Villalba, Rocío; González-Barrio, Rocío; Issaly, Nicolas; Flanagan, John; Roller, Marc; Tomás-Barberán, Francisco A.; García-Conesa, María-Teresa

    2014-01-01

    Background Carnosic acid (CA) and rosemary extracts (RE) show body-weight, energy metabolism and inflammation regulatory properties in animal models but the mechanisms are not yet understood. Gut microbiota plays an important role in the host metabolism and inflammatory status and is modulated by the diet. The aim of this research was to investigate whether a RE enriched in CA affected caecum microbiota composition and activity in a rat model of genetic obesity. Methods and Principal Findings A RE (40% CA) was administered with the diet (0.5% w/w) to lean (fa/+) and obese (fa/fa) female Zucker rats for 64 days. Changes in the microbiota composition and β-glucosidase activity in the caecum and in the levels of macronutrients and short chain fatty acids (SCFA) in feces were examined. The RE increased the Blautia coccoides and Bacteroides/Prevotella groups and reduced the Lactobacillus/Leuconostoc/Pediococccus group in both types of animals. Clostridium leptum was significantly decreased and Bifidobacterium increased only in the lean rats. β-Glucosidase activity was significantly reduced and fecal fiber excretion increased in the two genotypes. The RE also increased the main SCFA excreted in the feces of the obese rats but decreased them in the lean rats reflecting important differences in the uptake and metabolism of these molecules between the two genotypes. Conclusions Our results indicate that the consumption of a RE enriched in CA modifies microbiota composition and decreases β-glucosidase activity in the caecum of female Zucker rats while it increases fiber fecal elimination. These results may contribute to explain the body weight gain reducing effects of the RE. The mutated leptin receptor of the obese animals significantly affects the microbiota composition, the SCFA fecal excretion and the host response to the RE intake. PMID:24733124

  11. Trans Fatty Acids

    NASA Astrophysics Data System (ADS)

    Doyle, Ellin

    1997-09-01

    Fats and their various fatty acid components seem to be a perennial concern of nutritionists and persons concerned with healthful diets. Advice on the consumption of saturated, polyunsaturated, monounsaturated, and total fat bombards us from magazines and newspapers. One of the newer players in this field is the group of trans fatty acids found predominantly in partially hydrogenated fats such as margarines and cooking fats. The controversy concerning dietary trans fatty acids was recently addressed in an American Heart Association (AHA) science advisory (1) and in a position paper from the American Society of Clinical Nutrition/American Institute of Nutrition (ASCN/AIN) (2). Both reports emphasize that the best preventive strategy for reducing risk for cardiovascular disease and some types of cancer is a reduction in total and saturated fats in the diet, but a reduction in the intake of trans fatty acids was also recommended. Although the actual health effects of trans fatty acids remain uncertain, experimental evidence indicates that consumption of trans fatty acids adversely affects serum lipid levels. Since elevated levels of serum cholesterol and triacylglycerols are associated with increased risk of cardiovascular disease, it follows that intake of trans fatty acids should be minimized.

  12. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  13. It is all about fluidity: Fatty acids and macrophage phagocytosis.

    PubMed

    Schumann, Julia

    2016-08-15

    Phagocytosis is an early and fundamental step for the effective clearance of disease causing agents. The ability to engulf and kill pathogens is considered as a major effector function of macrophages. In their phagocytic role macrophages are part of the first line of innate immune defense. A number of studies investigating fatty acid effects on macrophage phagocytosis have been conducted over many years. In vitro-data consistently report that alterations in macrophage membrane fatty acid composition are linked to an altered phagocytic capacity, i.e. an increase in membrane unsaturated fatty acid content is associated with an increase in engulfment and killing rate. The mode of action of fatty acids seems to be the modulation of the physical nature of the macrophage plasma membrane. It appears that the saturated-to-unsaturated fatty acid ratio of macrophage membrane phospholipids is of importance in determining macrophage phagocytic capacity. Available in vivo-data are less clear. At present, there is a lack of systematic studies elucidating key factors such as fatty acid efficacy, effective dose or dosing intervals. Without this knowledge the targeted modulation of macrophage phagocytosis in vivo by fatty acids is still a distant possibility. PMID:25987422

  14. Ghrelin reduces hepatic mitochondrial fatty acid beta oxidation.

    PubMed

    Rigault, C; Le Borgne, F; Georges, B; Demarquoy, J

    2007-04-01

    Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiologically induces food intake and seems to alter lipid and glucid metabolism in several tissues such as adipose tissue and liver. Liver has a key position in lipid metabolism as it allows the metabolic orientation of fatty acids between oxidation and esterification. We investigated the effects of peripheral ghrelin administration on 2 crucial parameters of fatty acid oxidation: the levocarnitine (L-carnitine)-dependent entry of the fatty acids in the mitochondria and the mitochondrial fatty acid oxidation. Ghrelin was either given to rats prior to the hepatocyte preparation and culture or used to treat hepatocytes prepared from control animals. Direct incubation of ghrelin to raw hepatocytes did not induce any change in the studied parameters. In hepatocytes prepared from 3 nmol ghrelin-treated rats, a 44% reduction of the mitochondrial fatty acid oxidation while no alteration of the L-carnitine-related parameters were observed. These results suggested (a) that ghrelin has no direct effect on liver, and (b) that when administrated to a whole organism, ghrelin may alter the lipid metabolism and the energy balance through a marked decrease in liver fatty acid oxidation. PMID:17556859

  15. Fatty liver - nonalcoholic

    MedlinePlus

    ... American Gastroenterological Association. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and ...

  16. Role of bioactive fatty acids in nonalcoholic fatty liver disease.

    PubMed

    Juárez-Hernández, Eva; Chávez-Tapia, Norberto C; Uribe, Misael; Barbero-Becerra, Varenka J

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fatty acids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fatty acids have a dual role in various human and murine models. In contrast, polyunsaturated fatty acids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fatty acids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fatty acids possible biomarkers for NAFLD. Bioactive fatty acids provide health benefits through modification of fatty acid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fatty acids in nutritional and clinical treatment strategies for patients with NAFLD. PMID:27485440

  17. Time-Course of Alterations in Myocardial Glucose Utilization in the Zucker Diabetic Fatty (ZDF) Rat with Correlation to Gene Expression of Glucose Transporters: A Small Animal PET Investigation

    PubMed Central

    Shoghi, Kooresh I.; Gropler, Robert J.; Sharp, Terry; Herrero, Pilar; Fettig, Nicole; Su, Yi; Mitra, Mayurranjan S.; Kovacs, Attila; Finck, Brian N.; Welch, Michael J.

    2010-01-01

    Objective Diabetic cardiomyopathy is associated with abnormalities in glucose metabolism. We evaluated myocardial glucose metabolism in a rodent model of Type 2 Diabetes (T2D), namely the Zucker Diabetic Rat (ZDF), and validated PET measures of glucose uptake against gene and protein expression of glucose transporters. Methods Six lean and ZDF rat underwent small animal PET imaging at the age of 14 weeks and at the age of 19 weeks. The imaging protocol consisted of a 60-minute dynamic acquisition with 18FDG (0.5–0.8mCi). Dynamic images were reconstructed using filtered back projection (FBP) with a 2.5 zoom on the heart and 40 frames per imaging session. PET measures of myocardial glucose uptake rate (MGUp) and utilization were determined with an input function derived by the Hybrid Image- Blood Sampling (HIBS) algorithm on recovery-corrected anterolateral myocardial regions of interest. Following the PET imaging session at week 19, hearts were extracted for gene and protein expression analysis of GLUT1 and GLUT4. The dependence of MGUp on gene expression of GLUT1 and GLUT4 was characterized by multiple-regression analysis. Results Compared to lean littermate control rats, MGUp was significantly depressed in ZDF rats at both week 14 and week 19 (P<0.006). Moreover, lean rats at week 19 displayed significantly higher MGUp than week 14 (P=0.007). Consistent with diminished MGUp, gene expression of GLUT4 was significantly (P=0.004) lower in ZDF rats. Finally, MGUp significantly (P=0.0003) correlated with gene expression of GLUT4. Conclusions Using small animal PET, we confirmed alterations in myocardial glucose utilization and validated PET measure of MGUp against gene and protein expression of glucose transporters in the diabetic heart of an animal model of T2D. PMID:18632819

  18. n-3 Fatty acids and asthma.

    PubMed

    Kumar, Aishwarya; Mastana, Sarabjit S; Lindley, Martin R

    2016-06-01

    Asthma is one of the most common and prevalent problems worldwide affecting over 300 million individuals. There is some evidence from observational and intervention studies to suggest a beneficial effect of n-3 PUFA in inflammatory diseases, specifically asthma. Marine-based n-3 PUFA have therefore been proposed as a possible complementary/alternative therapy for asthma. The proposed anti-inflammatory effects of n-3 fatty acids may be linked to a change in cell membrane composition. This altered membrane composition following n-3 fatty acid supplementation (primarily EPA and DHA) can modify lipid mediator generation via the production of eicosanoids with a reduced inflammatory potential/impact. A recently identified group of lipid mediators derived from EPA including E-series resolvins are proposed to be important in the resolution of inflammation. Reduced inflammation attenuates the severity of asthma including symptoms (dyspnoea) and exerts a bronchodilatory effect. There have been no major health side effects reported with the dietary supplementation of n-3 fatty acids or their mediators; consequently supplementing with n-3 fatty acids is an attractive non-pharmacological intervention which may benefit asthma. PMID:26809946

  19. Fatty Acid Oxidation and Cardiovascular Risk during Menopause: A Mitochondrial Connection?

    PubMed Central

    Oliveira, Paulo J.; Carvalho, Rui A.; Portincasa, Piero; Bonfrate, Leonilde; Sardao, Vilma A.

    2012-01-01

    Menopause is a consequence of the normal aging process in women. This fact implies that the physiological and biochemical alterations resulting from menopause often blur with those from the aging process. It is thought that menopause in women presents a higher risk for cardiovascular disease although the precise mechanism is still under discussion. The postmenopause lipid profile is clearly altered, which can present a risk factor for cardiovascular disease. Due to the role of mitochondria in fatty acid oxidation, alterations of the lipid profile in the menopausal women will also influence mitochondrial fatty acid oxidation fluxes in several organs. In this paper, we propose that alterations of mitochondrial bioenergetics in the heart, consequence from normal aging and/or from the menopausal process, result in decreased fatty acid oxidation and accumulation of fatty acid intermediates in the cardiomyocyte cytosol, resulting in lipotoxicity and increasing the cardiovascular risk in the menopausal women. PMID:22496981

  20. Lipoproteini lipase-derived fatty acids: physiology and dysfunction.

    PubMed

    Lee, Jee; Goldberg, Ira J

    2007-12-01

    Under normal circumstances, most energy substrate used for heart contraction derives from fatty acids in the form of nonesterified fatty acids bound to albumin or fatty acids derived from lipolysis of lipoprotein-bound triglyceride by lipoprotein lipase (LpL). By creating LpL knockout mice (hLpL0), we learned that loss of cardiac LpL leads to myocardial dysfunction; therefore, neither nonesterified fatty acids nor increased glucose metabolism can replace LpL actions. hLpL0 mice do not survive abdominal aortic constriction and they develop more heart failure with hypertension. Conversely, we created a mouse overexpressing cardiomyocyte-anchored LpL. This transgene produced cardiac lipotoxicity and dilated cardiomyopathy. Methods to alter this phenotype and the causes of other models of lipotoxicity are currently being studied and will provide further insight into the physiology of lipid metabolism in the heart. PMID:18367009

  1. Long chain fatty acids and dietary fats in fetal nutrition

    PubMed Central

    Cetin, Irene; Alvino, Gioia; Cardellicchio, Manuela

    2009-01-01

    Long chain polyunsaturated fatty acids are essential nutrients for a healthy diet. The different kinds consumed by the mother during gestation and lactation may influence pregnancy, fetal and also neonatal outcome. The amount of fatty acids transferred from mother to fetus depends not only on maternal metabolism but also on placental function, i.e. by the uptake, metabolism and then transfer of fatty acids to the fetus. The third trimester of gestation is characterized by an increase of long chain polyunsaturated fatty acids in the fetal circulation, in particular docosahexaenoic acid, especially to support brain growth and visual development. These mechanisms may be altered in pathological conditions, such as intrauterine growth restriction and diabetes, when maternal and fetal plasma levels of long chain polyunsaturated fatty acids undergo significant changes. The aim of this review is to describe the maternal and placental factors involved in determining fetal fatty acid availability and metabolism, focusing on the specific role of long chain polyunsaturated fatty acids in normal and pathological pregnancies. PMID:19528253

  2. Omega-3 fatty acids (image)

    MedlinePlus

    Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. ...

  3. Discovery of essential fatty acids

    PubMed Central

    Spector, Arthur A.; Kim, Hee-Yong

    2015-01-01

    Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fatty acids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fatty acid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fatty acids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fatty acid. The Burrs surmised that other unsaturated fatty acids were essential and subsequently demonstrated that linolenic acid, the omega-3 fatty acid analog of linoleic acid, is also an essential fatty acid. The discovery of essential fatty acids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684

  4. The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

    PubMed

    Bertin, Matthew J; Voronca, Delia C; Chapman, Robert W; Moeller, Peter D R

    2014-01-01

    Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. PMID:24240104

  5. Maternal Effects on Fatty Acid Composition of Soybean Seed Oil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acid composition of soybean (Glycine max (L.) Merr.) seed oil affects its nutritional value and physical and chemical characteristics. The success of developing soybean lines with genetically altered seed oil is greatly determined by the rate of genetic gain through selection. Maternal effec...

  6. Fatty Acids of Thiobacillus thiooxidans

    PubMed Central

    Levin, Richard A.

    1971-01-01

    Fatty acid spectra were made on Thiobacillus thiooxidans cultures both in the presence and absence of organic compounds. Small additions of glucose or acetate had no significant effect either on growth or fatty acid content. The addition of biotin had no stimulatory effect but did result in slight quantitative changes in the fatty acid spectrum. The predominant fatty acid was a C19 cyclopropane acid. PMID:4945206

  7. DNA ALTERATIONS

    EPA Science Inventory

    The exposure of an organism to genotoxic chemicals may induce a cascade of genetic events. nitially, structural alterations to DNA are formed. ext, the DNA damage is processed and subsequently expressed in mutant gene products. inally, diseases result from the genetic damage. he ...

  8. New bioactive fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  9. New Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to new compounds, 7,10-dihydroxy-8(E)-octadecen...

  10. Rosiglitazone increases fatty acid oxidation and fatty acid translocase (FAT/CD36) but not carnitine palmitoyltransferase I in rat muscle mitochondria

    PubMed Central

    Benton, Carley R; Holloway, Graham P; Campbell, S E; Yoshida, Yuko; Tandon, Narendra N; Glatz, Jan F C; Luiken, Joost J J F P; Spriet, Lawrence L; Bonen, Arend

    2008-01-01

    Peroxisome proliferator-activated receptors (PPARs) alter the expression of genes involved in regulating lipid metabolism. Rosiglitazone, a PPARγ agonist, induces tissue-specific effects on lipid metabolism; however, its mode of action in skeletal muscle remains unclear. Since fatty acid translocase (FAT/CD36) was recently identified as a possible regulator of skeletal muscle fatty acid transport and mitochondrial fatty acid oxidation, we examined in this tissue the effects of rosiglitazone infusion (7 days, 1 mg day−1) on FAT/CD36 mRNA and protein, its plasmalemmal content and fatty acid transport. In addition, in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria we examined rates of fatty acid oxidation, FAT/CD36 and carnitine palmitoyltransferase I (CPTI) protein, and CPTI and β-hydroxyacyl CoA dehydrogenase (β-HAD) activities. Rosiglitazone did not alter FAT/CD36 mRNA or protein expression, FAT/CD36 plasmalemmal content, or the rate of fatty acid transport into muscle (P > 0.05). In contrast, rosiglitazone increased the rates of fatty acid oxidation in both SS (+21%) and IMF mitochondria (+36%). This was accompanied by concomitant increases in FAT/CD36 in subsarcolemmal (SS) (+43%) and intermyofibrillar (IMF) mitochondria (+46%), while SS and IMF CPTI protein content, and CPTI submaximal and maximal activities (P > 0.05) were not altered. Similarly, citrate synthase (CS) and β-HAD activities were also not altered by rosiglitazone in SS and IMF mitochondria (P > 0.05). These studies provide another example whereby changes in mitochondrial fatty oxidation are associated with concomitant changes in mitochondrial FAT/CD36 independent of any changes in CPTI. Moreover, these studies identify for the first time a mechanism by which rosiglitazone stimulates fatty acid oxidation in skeletal muscle, namely the chronic, subcellular relocation of FAT/CD36 to mitochondria. PMID:18238811

  11. Microbial production of fatty alcohols.

    PubMed

    Fillet, Sandy; Adrio, José L

    2016-09-01

    Fatty alcohols have numerous commercial applications, including their use as lubricants, surfactants, solvents, emulsifiers, plasticizers, emollients, thickeners, and even fuels. Fatty alcohols are currently produced by catalytic hydrogenation of fatty acids from plant oils or animal fats. Microbial production of fatty alcohols may be a more direct and environmentally-friendly strategy since production is carried out by heterologous enzymes, called fatty acyl-CoA reductases, able to reduce different acyl-CoA molecules to their corresponding primary alcohols. Successful examples of metabolic engineering have been reported in Saccharomyces cerevisiae and Escherichia coli in which the production of fatty alcohols ranged from 1.2 to 1.9 g/L, respectively. Due to their metabolic advantages, oleaginous yeasts are considered the best hosts for production of fatty acid-derived chemicals. Some of these species can naturally produce, under specific growth conditions, lipids at high titers (>50 g/L) and therefore provide large amounts of fatty acyl-CoAs or fatty acids as precursors. Very recently, taking advantage of such features, over 8 g/L of C16-C18 fatty alcohols have been produced in Rhodosporidium toruloides. In this review we summarize the different metabolic engineering strategies, hosts and cultivation conditions used to date. We also point out some future trends and challenges for the microbial production of fatty alcohols. PMID:27465852

  12. Mutant fatty acid desaturase and methods for directed mutagenesis

    DOEpatents

    Shanklin, John; Whittle, Edward J.

    2008-01-29

    The present invention relates to methods for producing fatty acid desaturase mutants having a substantially increased activity towards substrates with fewer than 18 carbon atom chains relative to an unmutagenized precursor desaturase having an 18 carbon chain length specificity, the sequences encoding the desaturases and to the desaturases that are produced by the methods. The present invention further relates to a method for altering a function of a protein, including a fatty acid desaturase, through directed mutagenesis involving identifying candidate amino acid residues, producing a library of mutants of the protein by simultaneously randomizing all amino acid candidates, and selecting for mutants which exhibit the desired alteration of function. Candidate amino acids are identified by a combination of methods. Enzymatic, binding, structural and other functions of proteins can be altered by the method.

  13. (Radioiodinated free fatty acids)

    SciTech Connect

    Knapp, Jr., F. F.

    1987-12-11

    The traveler participated in the Second International Workshop on Radioiodinated Free Fatty Acids in Amsterdam, The Netherlands where he presented an invited paper describing the pioneering work at the Oak Ridge National Laboratory (ORNL) involving the design, development and testing of new radioiodinated methyl-branched fatty acids for evaluation of heart disease. He also chaired a technical session on the testing of new agents in various in vitro and in vivo systems. He also visited the Institute for Clinical and Experimental Nuclear Medicine in Bonn, West Germany, to review, discuss, plan and coordinate collaborative investigations with that institution. In addition, he visited the Cyclotron Research Center in Liege, Belgium, to discuss continuing collaborative studies with the Osmium-191/Iridium-191m radionuclide generator system, and to complete manuscripts and plan future studies.

  14. A method for measuring fatty acid oxidation in C. elegans.

    PubMed

    Elle, Ida Coordt; Rødkær, Steven Vestergaard; Fredens, Julius; Færgeman, Nils Joakim

    2012-01-01

    The nematode C. elegans has during the past decade proven to be a valuable model organism to identify and examine molecular mechanisms regulating lipid storage and metabolism. While the primary approach has been to identify genes and pathways conferring alterations in lipid accumulation, only a few recent studies have recognized the central role of fatty acid degradation in cellular lipid homeostasis. In the present study, we show how complete oxidation of fatty acids can be determined in live C. elegans by examining oxidation of tritium-labeled fatty acids to tritiated H2O that can be measured by scintillation counting. Treating animals with sodium azide, an inhibitor of the electron transport chain, reduced (3)H2O production to approximately 15%, while boiling of animals prior to assay completely blocked the production of labeled water. We demonstrate that worms fed different bacterial strains exhibit different fatty acid oxidation rates. We show that starvation results in increased fatty acid oxidation, which is independent of the transcription factor NHR-49. On the contrary, fatty acid oxidation is reduced to approximately 70% in animals lacking the worm homolog of the insulin receptor, DAF-2. Hence, the present methodology can be used to delineate the role of specific genes and pathways in the regulation of β-oxidation in C. elegans. PMID:24058820

  15. Using Caenorhabditis elegans to Uncover Conserved Functions of Omega-3 and Omega-6 Fatty Acids

    PubMed Central

    Watts, Jennifer L.

    2016-01-01

    The nematode Caenorhabditis elegans is a powerful model organism to study functions of polyunsaturated fatty acids. The ability to alter fatty acid composition with genetic manipulation and dietary supplementation permits the dissection of the roles of omega-3 and omega-6 fatty acids in many biological process including reproduction, aging and neurobiology. Studies in C. elegans to date have mostly identified overlapping functions of 20-carbon omega-6 and omega-3 fatty acids in reproduction and in neurons, however, specific roles for either omega-3 or omega-6 fatty acids are beginning to emerge. Recent findings with importance to human health include the identification of a conserved Cox-independent prostaglandin synthesis pathway, critical functions for cytochrome P450 derivatives of polyunsaturated fatty acids, the requirements for omega-6 and omega-3 fatty acids in sensory neurons, and the importance of fatty acid desaturation for long lifespan. Furthermore, the ability of C. elegans to interconvert omega-6 to omega-3 fatty acids using the FAT-1 omega-3 desaturase has been exploited in mammalian studies and biotechnology approaches to generate mammals capable of exogenous generation of omega-3 fatty acids. PMID:26848697

  16. Nonalcoholic Fatty Liver Disease and the Gut Microbiome.

    PubMed

    Boursier, Jerome; Diehl, Anna Mae

    2016-05-01

    Recent progress has allowed a more comprehensive study of the gut microbiota. Gut microbiota helps in health maintenance and gut dysbiosis associates with chronic metabolic diseases. Modulation of short-chain fatty acids and choline bioavailability, lipoprotein lipase induction, alteration of bile acid profile, endogenous alcohol production, or liver inflammation secondary to endotoxemia result from gut dysbiosis. Modulation of the gut microbiota by pre/probiotics gives promising results in animal, but needs to be evaluated in human before use in clinical practice. Gut microbiota adds complexity to the pathophysiology of nonalcoholic fatty liver disease but represents an opportunity to discover new therapeutic targets. PMID:27063268

  17. IMPACT OF SOYBEAN OILS VARYING IN FATTY ACID PROFILE ON T CELL PROLIFERATION OF MODERATELY HYPERLIPIDEMIC SUBJECTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Linoleic acid and alpha linolenic acid are essential fatty acids, which play an important role in modulation of T cell proliferation. We studied the effects of feeding selectively bred and genetically modified soybean oils distinguished by altered fatty acid profiles, resulting in varied linoleic/li...

  18. Total dietary fat and omega-3 fatty acids have modest effects on urinary sex hormones in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Total fat and omega-3 fatty acids in the diet may affect breast cancer risk by altering estrogen metabolism. The purpose of this study was to elucidate the effects of differing total fat and omega-3 fatty acid content of diets on a panel of urinary estrogens and metabolites. A controlled, cross-ove...

  19. Carotenoids and non-alcoholic fatty liver disease

    PubMed Central

    Yilmaz, Bahiddin; Sahin, Kazim; Bilen, Hande; Bahcecioglu, Ibrahim H.; Bilir, Birdal; Ashraf, Sara; Halazun, Karim J.

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a growing health problem around the world, especially in developed countries. NAFLD includes all cases of fatty liver disease from simple steatosis to cirrhosis, without excessive alcohol intake, use of steatogenic medication or hereditary disorders. Pathogenesis is associated with dietary high fat intake, decreased free fatty acid (FFA) oxidation, increased hepatic lipogenesis and lipolysis from the adipose tissue. These metabolic alterations contribute to the hepatic fat accumulation. Consequently, stimulated oxidative stress and inflammation play a major role in hepatocellular damage. Therefore, antioxidant and anti-inflammatory agents may have a role in the prevention of this disease. Carotenoids are potent antioxidant and anti-inflammatory micronutrients, which have been investigated in the prevention and treatment of NAFLD. The main sources of the carotenoids are fruits and vegetables. In this article we review the potential role and possible molecular mechanism of carotenoids in NAFLD. PMID:26151056

  20. Acute fatty liver of pregnancy: an update on mechanisms

    PubMed Central

    Natarajan, Sathish Kumar; Thangaraj, Kavitha R; Goel, Ashish; Eapen, C E; Balasubramanian, K A; Ramachandran, Anup

    2011-01-01

    Acute fatty liver of pregnancy (AFLP), characterized by hepatic microvesicular steatosis, is a sudden catastrophic illness occurring almost exclusively in the third trimester of pregnancy. Defective fatty acid oxidation in the fetus has been shown to be associated with this disease. Since the placenta has the same genetic makeup as the fetus and as AFLP patients generally recover following delivery, we hypothesized that the placenta might be involved in pathogenesis of this disease. In an animal model of hepatic microvesicular steatosis (using sodium valproate), we found that microvesicular steatosis results in mitochondrial structural alterations and oxidative stress in subcellular organelles of the liver. In placentas from patients with AFLP, we observed placental mitochondrial dysfunction and oxidative stress in subcellular organelles. In addition, defective placental fatty acid oxidation results in accumulation of toxic mediators such as arachidonic acid. Escape of these mediators into the maternal circulation might affect the maternal liver resulting in microvesicular steatosis.

  1. Treatment of Fatty Acid Oxidation Disorders

    MedlinePlus

    ... of fatty acid oxidation disorders Treatment of fatty acid oxidation disorders E-mail to a friend Please ... page It's been added to your dashboard . Fatty acid oxidation disorders are rare health conditions that affect ...

  2. Dietary n-3 polyunsaturated fatty acids modify fatty acid composition in hepatic and abdominal adipose tissue of sucrose-induced obese rats.

    PubMed

    Alexander-Aguilera, Alfonso; Berruezo, Silvia; Hernández-Diaz, Guillermo; Angulo, Ofelia; Oliart-Ros, Rosamaria

    2011-12-01

    The fatty acid profile of hepatocytes and adipocytes is determined by the composition of the dietary lipids. It remains unclear which fatty acid components contribute to the development or reduction of insulin resistance. The present work examined the fatty acid composition of both tissues in sucrose-induced obese rats receiving fish oil to determine whether the effect of dietary (n-3) polyunsaturated fatty acids (PUFAs) on the reversion of metabolic syndrome in these rats is associated to changes in the fatty acid composition of hepatocyte and adipocyte membrane lipids. Animals with metabolic syndrome were divided into a corn-canola oil diet group and a fish oil diet group, and tissues fatty acids composition were analyzed after 6 weeks of dietary treatment. Fatty acid profiles of the total membrane lipids were modified by the fatty acid composition of the diets fed to rats. N-3 PUFAs levels in animals receiving the fish oil diet plus sucrose in drinking water were significantly higher than in animals under corn-canola oil diets. It is concluded that in sucrose-induced obese rats, consumption of dietary fish oil had beneficial effects on the metabolic syndrome and that such effects would be conditioned by the changes in the n-3 PUFAs composition in hepatic and adipose tissues because they alter membrane properties and modify the type of substrates available for the production of active lipid metabolites acting on insulin resistance and obesity. PMID:21695545

  3. The scope for manipulating the polyunsaturated fatty acid content of beef: a review.

    PubMed

    Vahmani, Payam; Mapiye, Cletos; Prieto, Nuria; Rolland, David C; McAllister, Tim A; Aalhus, Jennifer L; Dugan, Michael E R

    2015-01-01

    Since 1950, links between intake of saturated fatty acids and heart disease have led to recommendations to limit consumption of saturated fatty acid-rich foods, including beef. Over this time, changes in food consumption patterns in several countries including Canada and the USA have not led to improvements in health. Instead, the incidence of obesity, type II diabetes and associated diseases have reached epidemic proportions owing in part to replacement of dietary fat with refined carbohydrates. Despite the content of saturated fatty acids in beef, it is also rich in heart healthy cis-monounsaturated fatty acids, and can be an important source of long-chain omega-3 (n-3) fatty acids in populations where little or no oily fish is consumed. Beef also contains polyunsaturated fatty acid biohydrogenation products, including vaccenic and rumenic acids, which have been shown to have anticarcinogenic and hypolipidemic properties in cell culture and animal models. Beef can be enriched with these beneficial fatty acids through manipulation of beef cattle diets, which is now more important than ever because of increasing public understanding of the relationships between diet and health. The present review examines recommendations for beef in human diets, the need to recognize the complex nature of beef fat, how cattle diets and management can alter the fatty acid composition of beef, and to what extent content claims are currently possible for beef fatty acids. PMID:26199725

  4. Omega-3 Fatty Acids and Skeletal Muscle Health

    PubMed Central

    Jeromson, Stewart; Gallagher, Iain J.; Galloway, Stuart D. R.; Hamilton, D. Lee

    2015-01-01

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle. PMID:26610527

  5. Omega-3 Fatty Acids and Skeletal Muscle Health.

    PubMed

    Jeromson, Stewart; Gallagher, Iain J; Galloway, Stuart D R; Hamilton, D Lee

    2015-11-01

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle. PMID:26610527

  6. Designer laying hen diets to improve egg fatty acid profile and maintain sensory quality

    PubMed Central

    Goldberg, Erin M; Ryland, Donna; Gibson, Robert A; Aliani, Michel; House, James D

    2013-01-01

    The fatty acid composition of eggs is highly reflective of the diet of the laying hen; therefore, nutritionally important fatty acids can be increased in eggs in order to benefit human health. To explore the factors affecting the hen's metabolism and deposition of fatty acids of interest, the current research was divided into two studies. In Study 1, the fatty acid profile of eggs from Bovan White hens fed either 8%, 14%, 20%, or 28% of the omega-6 fatty acid, linoleic acid (LA) (expressed as a percentage of total fatty acids), and an additional treatment of 14% LA containing double the amount of saturated fat (SFA) was determined. Omega-6 fatty acids and docosapentaenoic acid (DPA) in the yolk were significantly (P < 0.05) increased, and oleic acid (OA) and eicosapentaenoic acid (EPA) were significantly decreased with an increasing dietary LA content. In Study 2, the fatty acid and sensory profiles were determined in eggs from Shaver White hens fed either (1) 15% or 30% of the omega-3 fatty acid, alpha-linolenic acid (ALA) (of total fatty acids), and (2) low (0.5), medium (1), or high (2) ratios of SFA: LA+OA. Increasing this ratio resulted in marked increases in lauric acid, ALA, EPA, DPA, and docosahexaenoic acid (DHA), with decreases in LA and arachidonic acid. Increasing the dietary ALA content from 15% to 30% (of total fatty acids) did not overcome the DHA plateau observed in the yolk. No significant differences (P ≥ 0.05) in aroma or flavor between cooked eggs from the different dietary treatments were observed among trained panelists (n = 8). The results showed that increasing the ratio of SFA: LA+OA in layer diets has a more favorable effect on the yolk fatty acid profile compared to altering the LA content at the expense of OA, all while maintaining sensory quality. PMID:24804037

  7. Real time non invasive imaging of fatty acid uptake in vivo

    PubMed Central

    Henkin, Amy H.; Cohen, Allison S.; Dubikovskaya, Elena A.; Park, Hyo Min; Nikitin, Gennady F.; Auzias, Mathieu G.; Kazantzis, Melissa; Bertozzi, Carolyn R.; Stahl, Andreas

    2012-01-01

    Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin-sensitivity. To enable non-invasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). We show that this probe faithfully recapitulates cellular fatty acid uptake and can be used in animal systems as a valuable tool to localize and quantitate in real-time lipid fluxes such as intestinal fatty acid absorption and brown adipose tissue activation. This imaging approach should further our understanding of basic metabolic processes and pathological alterations in multiple disease models. PMID:22928772

  8. Plant fatty acid hydroxylase

    DOEpatents

    Somerville, Chris; van de Loo, Frank

    2000-01-01

    The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.

  9. Obesity and cancer progression: is there a role of fatty acid metabolism?

    PubMed

    Balaban, Seher; Lee, Lisa S; Schreuder, Mark; Hoy, Andrew J

    2015-01-01

    Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression. PMID:25866768

  10. Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

    PubMed Central

    Balaban, Seher; Lee, Lisa S.; Schreuder, Mark; Hoy, Andrew J.

    2015-01-01

    Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression. PMID:25866768

  11. Fatty acid-producing hosts

    SciTech Connect

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  12. Visible light treatment of photoaging.

    PubMed

    Dierickx, Christine C; Anderson, R Rox

    2005-01-01

    Recently, a number of new devices have been developed specifically to improve the visible signs of aging in a noninvasive way. These include visible or near-infrared lasers, intense pulsed light sources (IPL), light-emitting diode (LED), and radiofrequency devices. This paper reviews the use of visible light sources and examines the attributes of specific systems for noninvasive skin rejuvenation. PMID:16229721

  13. Gut microbiome and nonalcoholic fatty liver diseases.

    PubMed

    Zhu, Lixin; Baker, Robert D; Baker, Susan S

    2015-01-01

    We review recent findings and hypotheses on the roles of gut microbiome in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD). Microbial metabolites and cell components contribute to the development of hepatic steatosis and inflammation, key components of nonalcoholic steatohepatitis (NASH), the severe form of NAFLD. Altered gut microbiome can independently cause obesity, the most important risk factor for NAFLD. This capability is attributed to short-chain fatty acids (SCFAs), major gut microbial fermentation products. SCFAs account for a large portion of caloric intake of the host, and they enhance intestinal absorption by activating GLP-2 signaling. However, elevated SCFAs may be an adaptive measure to suppress colitis, which could be a higher priority than imbalanced calorie intake. The microbiome of NASH patients features an elevated capacity for alcohol production. The pathomechanisms for alcoholic steatohepatitis may apply to NASH. NAFLD/NASH is associated with elevated Gram-negative microbiome and endotoxemia. However, many NASH patients exhibited normal serum endotoxin indicating that endotoxemia is not required for the pathogenesis of NASH. These observations suggest that microbial intervention may benefit NAFLD/NASH patients. However, very limited effects were observed using traditional probiotic species. Novel probiotic therapy based on NAFLD/NASH specific microbial composition represents a promising future direction. PMID:25310763

  14. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances.

    PubMed

    Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism. PMID:26742061

  15. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances

    PubMed Central

    Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism. PMID:26742061

  16. Alcohol Deranges Hepatic Lipid Metabolism via Altered Transcriptional Regulation.

    PubMed Central

    Crabb, David W.

    2004-01-01

    Alcohol has classically been thought to cause fatty liver by way of altered redox potential in the liver, which inhibits fatty acid oxidation. Additional effects appear to play a role both in impairing fat oxidation and stimulating lipogenesis. Alcohol reduces the DNA binding and transcription-activating properties of peroxisome proliferator-activated receptor alpha (PPARalpha), both in cultured cells and in mice fed alcohol. Treatment of alcohol-fed mice with a PPARalpha agonist reverses fatty liver despite continued alcohol consumption. Alcohol also activates sterol response element- binding protein 1 (SREBP-1), inducing a battery of lipogenic enzymes. This effect may be due in part to inhibition of AMP-dependent protein kinase. This understanding of alcohol effects provides new therapeutic targets to reverse alcoholic fatty liver. Images Fig. 4 Fig. 6 PMID:17060973

  17. Effect of dietary Fatty acids on human lipoprotein metabolism: a comprehensive update.

    PubMed

    Ooi, Esther M M; Watts, Gerald F; Ng, Theodore W K; Barrett, P Hugh R

    2015-06-01

    Dyslipidemia is a major risk factor for cardiovascular disease (CVD). Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high n-3 polyunsaturated fatty-acids (PUFA) consumption diminished hepatic triglyceride-rich lipoprotein (TRL) secretion and enhanced TRL to low-density lipoprotein (LDL) conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased very low-density lipoprotein (VLDL) cholesterol and triglyceride concentrations by up-regulating VLDL lipolysis and uptake. In a study of healthy subjects, the intake of saturated fatty-acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia. Low medium-chain triglyceride may not appreciably alter TRL metabolism. Replacing carbohydrate with monounsaturated fatty-acids increased TRL catabolism. Trans-fatty-acid decreased LDL and enhanced high-density lipoprotein catabolism. Interactions between APOE genotype and n-3 PUFA in regulating lipid responses were also described. The major advances in understanding the effect of dietary fatty-acids on lipoprotein metabolism has centered on n-3 PUFA. This knowledge emphasizes the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potentially CVD risk. Additional studies are required to better characterize the cardiometabolic effects of other dietary fatty-acids. PMID:26043038

  18. Abiotic synthesis of fatty acids

    NASA Technical Reports Server (NTRS)

    Leach, W. W.; Nooner, D. W.; Oro, J.

    1978-01-01

    The formation of fatty acids by Fischer-Tropsch-type synthesis was investigated with ferric oxide, ammonium carbonate, potassium carbonate, powdered Pueblito de Allende carbonaceous chondrite, and filings from the Canyon Diablo meteorite used as catalysts. Products were separated and identified by gas chromatography and mass spectrometry. Iron oxide, Pueblito de Allende chondrite, and Canyon Diablo filings in an oxidized catalyst form yielded no fatty acids. Canyon Diablo filings heated overnight at 500 C while undergoing slow purging by deuterium produced fatty acids only when potassium carbonate was admixed; potassium carbonate alone also produced these compounds. The active catalytic combinations gave relatively high yields of aliphatic and aromatic hydrocarbons; substantial amounts of n-alkenes were almost invariably observed when fatty acids were produced; the latter were in the range C6 to C18, with maximum yield in C9 or 10.

  19. Nitrogen dioxide induced changes in level of free fatty acids, triglyceride, esterified fatty acid, ganglioside and lipase activity in the guinea pig brain

    SciTech Connect

    Farahani, H.; Hasan, M. )

    1992-02-01

    The biochemical response to controlled inhalation of nitrogen dioxide (NO2) was studied in 18 male guinea pigs. Animals were exposed to 2.5, 5.0, and 10 ppm NO2 for 2h daily for 35 consecutive days, and the results compared with six control animals exposed to filtered air for 2h daily for same period. Five biochemical parameters, including triglyceride, free fatty acids, esterified fatty acid, ganglioside and lipase activity were measured immediately after the last day of exposure. At 2.5 ppm NO2 inhalation no significant changes occurred in any region of the central nervous system (CNS). While as the dose concentration was increased to 5 and 10 ppm nitrogen dioxide, significant dose-related alteration were observed in the levels of triglyceride, free fatty acid, esterified fatty acid, ganglioside and lipase activity in the different regions of the guinea pig CNS.

  20. Defining a relationship between dietary fatty acids and the cytochrome P450 system in a mouse model of fatty liver disease

    PubMed Central

    Gonzalez, Monika; Sealls, Whitney; Jesch, Elliot D.; Brosnan, M. Julia; Ladunga, Istvan; Ding, Xinxin; Black, Paul N.

    2011-01-01

    Liver-specific ablation of cytochrome P450 reductase in mice (LCN) results in hepatic steatosis that can progress to steatohepatitis characterized by inflammation and fibrosis. The specific cause of the fatty liver phenotype is poorly understood but is hypothesized to result from elevated expression of genes encoding fatty acid synthetic genes. Since expression of these genes is known to be suppressed by polyunsaturated fatty acids, we performed physiological and genomics studies to evaluate the effects of dietary linoleic and linolenic fatty acids (PUFA) or arachidonic and decosahexaenoic acids (HUFA) on the hepatic phenotypes of control and LCN mice by comparison with a diet enriched in saturated fatty acids. The dietary interventions with HUFA reduced the fatty liver phenotype in livers of LCN mice and altered the gene expression patterns in these livers to more closely resemble those of control mice. Importantly, the expression of genes encoding lipid pathway enzymes were not different between controls and LCN livers, indicating a strong influence of diet over POR genotype. These analyses highlighted the impact of POR ablation on expression of genes encoding P450 enzymes and proteins involved in stress and inflammation. We also found that livers from animals of both genotypes fed diets enriched in PUFA had gene expression patterns more closely resembling those fed diets enriched in saturated fatty acids. These results strongly suggest only HUFA supplied from an exogenous source can suppress hepatic lipogenesis. PMID:21098682

  1. MASS SPECTROMETRY OF FATTY ALDEHYDES

    PubMed Central

    Berdyshev, Evgeny V.

    2011-01-01

    Fatty aldehydes are important components of the cellular lipidome. Significant interest has been developed towards the analysis of the short chain α,β-unsaturated and hydroxylated aldehydes formed as a result of oxidation of polyunsaturated fatty acids. Multiple gas chromatography-mass spectrometry (GC/MS) and subsequently liquid chromatography-mass spectrometry (LC/MS) approaches have been developed to identify and quantify short-chain as well as long-chain fatty aldehydes. Due to the ability to non-enzymaticaly form Schiff bases with amino groups of proteins, lipids, and with DNA guanidine, free aldehydes are viewed as a marker or metric of fatty acid oxidation and not the part of intracellular signaling pathways which has significantly limited the overall attention this group of molecules have received. This review provides an overview of current GC/MS and LC/MS approaches of fatty aldehyde analysis as well as discusses technical challenges standing in the way of free fatty aldehyde quantitation. PMID:21930240

  2. A Thioesterase Bypasses the Requirement for Exogenous Fatty Acids in the plsX Deletion of Streptococcus pneumoniae

    PubMed Central

    Parsons, Joshua B.; Frank, Matthew W.; Eleveld, Marc J.; Schalkwijk, Joost; Broussard, Tyler C.; de Jonge, Marien I.; Rock, Charles O.

    2015-01-01

    Summary PlsX is an acyl-acyl carrier protein (ACP):phosphate transacylase that interconverts the two acyl donors in Gram-positive bacterial phospholipid synthesis. The deletion of plsX in Staphylococcus aureus results in a requirement for both exogenous fatty acids and de novo type II fatty acid biosynthesis. Deletion of plsX (SP0037) in Streptococcus pneumoniae did not result in an auxotrophic phenotype. The ΔplsX S. pneumoniae strain was refractory to myristic acid-dependent growth arrest, and unlike the wild-type strain, was susceptible to fatty acid synthesis inhibitors in the presence of exogenous oleate. The ΔplsX strain contained longer-chain saturated fatty acids imparting a distinctly altered phospholipid molecular species profile. An elevated pool of 18- and 20-carbon saturated fatty acids was detected in the ΔplsX strain. A S. pneumoniae thioesterase (TesS, SP1408) hydrolyzed acyl-ACP in vitro, and the ΔtesS ΔplsX double knockout strain was a fatty acid auxotroph. Thus, the TesS thioesterase hydrolyzed the accumulating acyl-ACP in the ΔplsX strain to liberate fatty acids that were activated by fatty acid kinase to bypass a requirement for extracellular fatty acid. This work identifies tesS as the gene responsible for the difference in exogenous fatty acid growth requirement of the ΔplsX strains of S. aureus and S. pneumoniae. PMID:25534847

  3. Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes.

    PubMed

    Fukushima, Arata; Lopaschuk, Gary D

    2016-10-01

    Obesity and diabetes are major public health problems, and are linked to the development of heart failure. Emerging data highlight the importance of alterations in cardiac energy metabolism as a major contributor to cardiac dysfunction related to obesity and diabetes. Increased rates of fatty acid oxidation and decreased rates of glucose utilization are two prominent changes in cardiac energy metabolism that occur in obesity and diabetes. This metabolic profile is probably both a cause and consequence of a prominent cardiac insulin resistance, which is accompanied by a decrease in both cardiac function and efficiency, and by the accumulation of potentially toxic lipid metabolites in the heart that can further exaggerate insulin resistance and cardiac dysfunction. The high cardiac fatty acid oxidation rates seen in obesity and diabetes are attributable to several factors, including: 1) increased fatty acid supply and uptake into the cardiomyocyte, 2) increased transcription of fatty acid metabolic enzymes, 3) decreased allosteric control of mitochondrial fatty acid uptake and fatty acid oxidation, and 4) increased post-translational acetylation control of various fatty acid oxidative enzymes. Emerging evidence suggests that therapeutic approaches aimed at switching the balance of cardiac energy substrate preference from fatty acid oxidation to glucose use can prevent cardiac dysfunction associated with obesity and diabetes. Modulating acetylation control of fatty acid oxidative enzymes is also a potentially attractive strategy, although presently this is limited to precursors of nicotinamide adenine or nonspecific activators of deacetylation such as resveratrol. This review will focus on the metabolic alterations in the heart that occur in obesity and diabetes, as well as on the molecular mechanisms controlling these metabolic changes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26996746

  4. BRAIN-SPECIFIC CARNITINE PALMITOYLTRANSFERASE-1C: ROLE IN CNS FATTY ACID METABOLISM, FOOD INTAKE AND BODY WEIGHT

    PubMed Central

    Wolfgang, Michael J.; Cha, Seung Hun; Millington, David S.; Cline, Gary; Shulman, Gerald I; Suwa, Akira; Asaumi, Makoto; Kurama, Takeshi; Shimokawa, Teruhiko; Lane, M. Daniel

    2014-01-01

    While the brain does not utilize fatty acids as a primary energy source, recent evidence shows that intermediates of fatty acid metabolism serve as hypothalamic sensors of energy status. Increased hypothalamic malonyl-CoA, an intermediate in fatty acid synthesis, is indicative of energy surplus and leads to the suppression of food intake and increased energy expenditure. Malonyl-CoA functions as an inhibitor of CPT1, a mitochondrial outer membrane enzyme that initiates translocation of fatty acids into mitochondria for oxidation. The mammalian brain expresses a unique homologous CPT1, CPT1c, that binds malonyl-CoA tightly but does not support fatty acid oxidation in vivo, in hypothalamic explants or in heterologous cell culture systems. CPT1c KO mice under fasted or refed conditions do not exhibit an altered CNS transcriptome of genes known to be involved in fatty acid metabolism. CPT1c KO mice exhibit normal levels of metabolites and of hypothalamic malonyl-CoA and fatty acyl-CoA levels either in the fasted or refed states. However, CPT1c KO mice exhibit decreased food intake and lower body weight than WT littermates. In contrast, CPT1c KO mice gain excessive body weight and body fat when fed a high-fat diet while maintaining lower or equivalent food intake. Heterozygous mice display an intermediate phenotype. These findings provide further evidence that CPT1c plays a role in maintaining energy homeostasis, but not through altered fatty acid oxidation. PMID:18248603

  5. Influence of dietary partially hydrogenated fat high in trans fatty acids on lipid composition and function of intestinal brush border membrane in rats.

    PubMed

    Ghafoorunissa, S A.I.

    2001-02-01

    The effect of dietary hydrogenated fat (Indian vanaspati) high in trans fatty acids (6 en%) on lipid composition, fluidity and function of rat intestinal brush border membrane was studied at 2 and 8 en% of linoleic acid. Three groups of weanling rats were fed rice-pulse based diet containing 10% fat over a ten week period: Group I (groundnut oil), Group II (vanaspati), Group III (vanaspati + safflower oil). The functionality of the brush border membrane was assessed by the activity of membrane bound enzymes and transport of D-glucose and L-leucine. The levels of total cholesterol and phospholipids were similar in all groups. The data on fatty acid composition of membrane phospholipids showed that, at 2 en% of linoleic acid in the diet, trans fatty acids lowered arachidonic acid and increased linoleic acid contents indicating altered polyunsaturated fatty acid metabolism. Alkaline phosphatase activity was increased while the activities of sucrase, gamma-glutamyl transpeptidase and transport of D-glucose and L-leucine were not altered by dietary trans fatty acids. However at higher intake of linoleic acid in the diet, trans fatty acids have no effect on polyunsaturated fatty acid composition and alkaline phosphatase activity of intestinal brush border membrane. These data suggest that feeding dietary fat high in trans fatty acids is associated with alteration in intestinal brush border membrane polyunsaturated fatty acid composition and alkaline phosphatase activity only when the dietary linoleic acid is low. PMID:11182555

  6. Pros and cons of fatty acids in bone biology.

    PubMed

    Wauquier, Fabien; Léotoing, Laurent; Philippe, Claire; Spilmont, Mélanie; Coxam, Véronique; Wittrant, Yohann

    2015-04-01

    Despite the growing interest in deciphering the causes and consequences of obesity-related disorders, the mechanisms linking fat intake to bone behaviour remain unclear. Since bone fractures are widely associated with increased morbidity and mortality, most notably in elderly and obese people, bone health has become a major social and economic issue. Consistently, public health system guidelines have encouraged low-fat diets in order to reduce associated complications. However, from a bone point of view, mechanisms linking fat intake to bone alteration remain quite controversial. Thus, after more than a decade of dedicated studies, this timely review offers a comprehensive overview of the relationships between bone and fatty acids. Using clinical evidences as a starting-point to more complex molecular elucidation, this work highlights the complexity of the system and reveals that bone alteration that cannot be solved simply by taking ω-3 pills. Fatty acid effects on bone metabolism can be both direct and indirect and require integrated investigations. Furthermore, even at the level of a single cell, one fatty acid is able to trigger several different independent pathways (receptors, metabolites…) which may all have a say in the final cellular metabolic response. PMID:25835096

  7. Omega-3 Fatty Acid Supplementation for the Treatment of Children with Attention-Deficit/Hyperactivity Disorder Symptomatology: Systematic Review and Meta-Analysis

    ERIC Educational Resources Information Center

    Bloch, Michael H.; Qawasmi, Ahmad

    2011-01-01

    Objective: Several studies have demonstrated differences in omega-3 fatty acid composition in plasma and in erythrocyte membranes in patients with attention-deficit/hyperactivity disorder (ADHD) compared with unaffected controls. Omega-3 fatty acids have anti-inflammatory properties and can alter central nervous system cell membrane fluidity and…

  8. Endocrine causes of nonalcoholic fatty liver disease

    PubMed Central

    Marino, Laura; Jornayvaz, François R

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

  9. Polyunsaturated Fatty Acids in Children

    PubMed Central

    2013-01-01

    Polyunsaturated fatty acids (PUFAs) are the major components of brain and retina, and are the essential fatty acids with important physiologically active functions. Thus, PUFAs should be provided to children, and are very important in the brain growth and development for fetuses, newborn infants, and children. Omega-3 fatty acids decrease coronary artery disease and improve blood flow. PUFAs have been known to have anti-inflammatory action and improved the chronic inflammation such as auto-immune diseases or degenerative neurologic diseases. PUFAs are used for metabolic syndrome related with obesity or diabetes. However, there are several considerations related with intake of PUFAs. Obsession with the intake of unsaturated fatty acids could bring about the shortage of essential fatty acids that are crucial for our body, weaken the immune system, and increase the risk of heart disease, arrhythmia, and stroke. In this review, we discuss types, physiologic mechanism of action of PUFAs, intake of PUFAs for children, recommended intake of PUFAs, and considerations for the intake of PUFAs. PMID:24224148

  10. Copper toxicity towards Saccharomyces cerevisiae: dependence on plasma membrane fatty acid composition.

    PubMed Central

    Avery, S V; Howlett, N G; Radice, S

    1996-01-01

    in cellular and plasma membrane fatty acid compositions can dramatically alter microbial sensitivity to copper. PMID:8899983

  11. A high-performance direct transmethylation method for total fatty acids assessment in biological and foodstuff samples.

    PubMed

    Castro-Gómez, Pilar; Fontecha, Javier; Rodríguez-Alcalá, Luis M

    2014-10-01

    Isolation is the main bottleneck in the analysis of fatty acids in biological samples and foods. In the last few decades some methods described direct derivatization procedures bypassing these steps. They involve the utilization of methanolic HCL or BF3 as catalysts, but several evidences from previous works suggest these reagents are unstable, lead to the formation of artifacts and alter the distribution of specific compounds as hydroxy fatty acids or CLA. However, the main issue is that they are excellent esterification reagents but poor in transterification, being not suitable for the analysis of all lipid classes and leading to erroneous composition quantitations. The present research work is a comprehensive comparison of six general methylation protocols using base, acid or base/acid catalysts plus a proposed method in the analysis of total fatty acids in lipid standards mixtures, foodstuff and biological samples. The addition of aprotic solvents to the reaction mixture to avoid alterations was also tested. Results confirmed that procedures solely involving acid catalyst resulted in incomplete derivatizations and alteration of the fatty acid profile, partially corrected by addition of the aprotic solvent. The proposed method combining sodium methoxyde and sulfuric acid showed absence of alteration of the FAME profile and the best values for response factors (short chain fatty acids to PUFA), accuracy in the determination of total cholesterol and derivatization performance, thus showing a high reliability in the determination of the total fatty acid composition in biological samples and foods. PMID:25059195

  12. Fatty alcohols production by oleaginous yeast.

    PubMed

    Fillet, Sandy; Gibert, Jordi; Suárez, Beatriz; Lara, Armando; Ronchel, Carmen; Adrio, José L

    2015-11-01

    We have engineered Rhodosporidium toruloides to produce fatty alcohols by expressing a fatty acyl-CoA reductase from Marinobacter aquaeolei VT8. Production of fatty alcohols in flasks was achieved in different fermentation media at titers ranging from 0.2 to 2 g/L. In many of the conditions tested, more than 80 % of fatty alcohols were secreted into the cultivation broth. Through fed-batch fermentation in 7 L bioreactors, over 8 g/L of C(16)-C(18) fatty alcohols were produced using sucrose as the substrate. This is the highest titer ever reported on microbial production of fatty alcohols to date. PMID:26318028

  13. Neutrophil fatty acid composition: effect of a single session of exercise and glutamine supplementation.

    PubMed

    Lagranha, C J; Alba-Loureiro, T C; Martins, E F; Pithon-Curi, T C; Curi, R

    2008-06-01

    The fatty acid composition of immune cells appears to contribute to variations of cell function. The independent and combined effects of a single session of exercise (SSE) and glutamine supplementation (GS) on neutrophil fatty acid composition were investigated. Compared to control (no treatment given--i.e. neither SSE or GS), single session of exercise decreased myristic, palmitic and eicosapentaenoic (EPA) acids, and increased lauric, oleic, linoleic, arachidonic (AA) and docosahexaenoic (DHA) acids whereas glutamine supplementation combined with SSE (GS+SSE) increased oleic acid. Polyunsaturated/saturated fatty acid ratio and Unsaturation index were higher in neutrophils from the SSE and GS groups as compared with control. These findings support the proposition that SSE and GS may modulate neutrophil function through alterations in fatty acid composition. PMID:17721676

  14. [Association of fatty acid metabolism with systemic inflammatory response in chronic respiratory diseases].

    PubMed

    Denisenko, Y K; Novgorodtseva, T P; Zhukova, N V; Antonuk, M V; Lobanova, E G; Kalinina, E P

    2016-03-01

    We examined composition of plasma non-esterified fatty acids (NFAs), erythrocyte fatty acids, levels of eicosanoids in patients with asthma and chronic obstructive pulmonary disease (COPD) with different type of the inflammatory response. The results of our study show that asthma and COPD in remission are associated with changes in the composition NFAs of plasma, FA of erythrocytes, level eicosanoid despite the difference in the regulation of immunological mechanisms of systemic inflammation. These changes are characterized by excessive production of arachidonic acid (20:4n-6) and cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) and deficiency of their functional antagonist, eicosapentaenoic acid (20:5n-3). The recognized association between altered fatty acid composition and disorders of the immune mechanisms of regulation of systemic inflammation in COPD and asthma demonstrated the important role of fatty acids and their metabolites in persistence of inflammatory processes in diseases of the respiratory system in the condition of remission. PMID:27420629

  15. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis

    PubMed Central

    Wiese, Dawn M.; Horst, Sara N.; Brown, Caroline T.; Allaman, Margaret M.; Hodges, Mallary E.; Slaughter, James C.; Druce, Jennifer P.; Beaulieu, Dawn B.; Schwartz, David A.; Wilson, Keith T.; Coburn, Lori A.

    2016-01-01

    Background and Aims Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. Methods Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. Results UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. Conclusions In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC. PMID:27227540

  16. Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals.

    PubMed

    Runguphan, Weerawat; Keasling, Jay D

    2014-01-01

    As the serious effects of global climate change become apparent and access to fossil fuels becomes more limited, metabolic engineers and synthetic biologists are looking towards greener sources for transportation fuels. In recent years, microbial production of high-energy fuels by economically efficient bioprocesses has emerged as an attractive alternative to the traditional production of transportation fuels. Here, we engineered the budding yeast Saccharomyces cerevisiae to produce fatty acid-derived biofuels and chemicals from simple sugars. Specifically, we overexpressed all three fatty acid biosynthesis genes, namely acetyl-CoA carboxylase (ACC1), fatty acid synthase 1 (FAS1) and fatty acid synthase 2 (FAS2), in S. cerevisiae. When coupled to triacylglycerol (TAG) production, the engineered strain accumulated lipid to more than 17% of its dry cell weight, a four-fold improvement over the control strain. Understanding that TAG cannot be used directly as fuels, we also engineered S. cerevisiae to produce drop-in fuels and chemicals. Altering the terminal "converting enzyme" in the engineered strain led to the production of free fatty acids at a titer of approximately 400 mg/L, fatty alcohols at approximately 100mg/L and fatty acid ethyl esters (biodiesel) at approximately 5 mg/L directly from simple sugars. We envision that our approach will provide a scalable, controllable and economic route to this important class of chemicals. PMID:23899824

  17. Fatty acid metabolism in pulmonary arterial hypertension: role in right ventricular dysfunction and hypertrophy

    PubMed Central

    2015-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a complex, multifactorial disease in which an increase in pulmonary vascular resistance leads to increased afterload on the right ventricle (RV), causing right heart failure and death. Our understanding of the pathophysiology of RV dysfunction in PAH is limited but is constantly improving. Increasing evidence suggests that in PAH RV dysfunction is associated with various components of metabolic syndrome, such as insulin resistance, hyperglycemia, and dyslipidemia. The relationship between RV dysfunction and fatty acid/glucose metabolites is multifaceted, and in PAH it is characterized by a shift in utilization of energy sources toward increased glucose utilization and reduced fatty acid consumption. RV dysfunction may be caused by maladaptive fatty acid metabolism resulting from an increase in fatty acid uptake by fatty acid transporter molecule CD36 and an imbalance between glucose and fatty acid oxidation in mitochondria. This leads to lipid accumulation in the form of triglycerides, diacylglycerol, and ceramides in the cytoplasm, hallmarks of lipotoxicity. Current interventions in animal models focus on improving RV dysfunction through altering fatty acid oxidation rates and limiting lipid accumulation, but more specific and effective therapies may be available in the coming years based on current research. In conclusion, a deeper understanding of the complex mechanisms of the metabolic remodeling of the RV will aid in the development of targeted treatments for RV failure in PAH. PMID:26064451

  18. [Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].

    PubMed

    Pár, Alajos; Pár, Gabriella

    2016-06-19

    In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease. PMID:27287838

  19. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.

    PubMed

    Abruzzese, Giselle Adriana; Heber, Maria Florencia; Ferreira, Silvana Rocio; Velez, Leandro Martin; Reynoso, Roxana; Pignataro, Omar Pedro; Motta, Alicia Beatriz

    2016-07-01

    Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. PMID:27179108

  20. Fatty tumours of the uterus.

    PubMed Central

    Pounder, D J

    1982-01-01

    Uterine fatty tumours (UFT) are uncommon and have received little attention in the English literature. They have aroused interest as a consequence of occasional diagnostic confusion with sarcomas and the continuing unresolved dispute as to their histogenesis. Three cases of UFT are described and the pathological features of note discussed. The viewpoint that these tumours are hamartomas/choristomas is rejected. UFT most probably represent tumour metaplasia within a leiomyoma. There is no uniform accepted nomenclature for such tumours and it is suggested that they be designated "uterine fatty tumours" and subdivided into "lipoma" and "mixed lipoma/leiomyoma" (synonym lipoleiomyoma). Images PMID:7174848

  1. Diets containing traditional and novel green leafy vegetables improve liver fatty acid profiles of spontaneously hypertensive rats

    PubMed Central

    2013-01-01

    Background The consumption of green leafy vegetables (GLVs) has been demonstrated to reduce the risks associated with cardiovascular and other diseases. However, no literature exists that examines the influence of traditional and novel GLVs on the liver fatty acid profile of an animal model genetically predisposed to developing hypertension. The aim of the present study was to examine the effects of diets containing 4% collard greens, purslane or sweet potato greens on the liver fatty acid profiles of four-week old male spontaneously hypertensive rats (SHRs, N = 44). Following four weeks consumption of the diets, liver fatty acid profiles were determined by gas–liquid chromatography of transesterified fatty acid methyl esters. Results SHRs consuming the control diet had greater percentages of liver saturated fatty acid and less omega-3 fatty acid percentages. SHRs consuming the diets containing vegetables had significantly greater liver concentrations of γ- linolenic, docosahexaenoic and docosahexaenoic acids, as well as lower levels of lauric, palmitic and arachidonic acids. SHRs consuming the control diet had significantly greater percentages (p < 0.05) of oleic; significantly less γ-linolenic and docosahexaenoic acids. Conclusions This study demonstrates the ability of GLVs to modulate liver fatty acid composition, thus providing protection against elevations in atherogenic fatty acids, which may be involved in CVD pathogenesis. Consequently, dietary recommendations for the prevention of CVD should consider the possible cardioprotective benefits and the subsequent alterations in fatty acid profiles afforded by diets containing collard greens, purslane and sweet potato greens. PMID:24192144

  2. Tailored fatty acid synthesis via dynamic control of fatty acid elongation

    SciTech Connect

    Torella, JP; Ford, TJ; Kim, SN; Chen, AM; Way, JC; Silver, PA

    2013-07-09

    Medium-chain fatty acids (MCFAs, 4-12 carbons) are valuable as precursors to industrial chemicals and biofuels, but are not canonical products of microbial fatty acid synthesis. We engineered microbial production of the full range of even-and odd-chain-length MCFAs and found that MCFA production is limited by rapid, irreversible elongation of their acyl-ACP precursors. To address this limitation, we programmed an essential ketoacyl synthase to degrade in response to a chemical inducer, thereby slowing acyl-ACP elongation and redirecting flux from phospholipid synthesis to MCFA production. Our results show that induced protein degradation can be used to dynamically alter metabolic flux, and thereby increase the yield of a desired compound. The strategy reported herein should be widely useful in a range of metabolic engineering applications in which essential enzymes divert flux away from a desired product, as well as in the production of polyketides, bioplastics, and other recursively synthesized hydrocarbons for which chain-length control is desired.

  3. Adipose tissue fatty acid metabolism during pregnancy in swine.

    PubMed

    McNamara, J P; Dehoff, M H; Collier, R J; Bazer, F W

    1985-08-01

    In vitro adipose tissue fatty acid pool size (POOL), fatty acid release (FAR) and esterification (EST) were measured in peritoneal (PFP) and subcutaneous mammary (MFP) fat pads of swine at d 15, 30, 45, 60, 75, 90, 105 and 112 of pregnancy. Plasma free fatty acids (FFA) and triglycerides (TG) were not altered by stage of pregnancy. Basal EST in PFP was generally constant across pregnancy with a peak at d 75. Basal EST in MFP was elevated at d 30, 75 and 112. Esterification in response to norepinephrine stimulus (NE) was lower than basal rates in both fat depots. Basal FAR was constant throughout pregnancy in PFP, but elevated at d 75 and 90 in MFP. Fatty acid release in response to NE was biphasic with peaks at d 30 and in late pregnancy (in MFP, micromolar FAR in response to NE was 69.3% greater on d 75 to 112 than on d 45 to 60). Basal POOL was constant throughout pregnancy in both depots and lower than NE-stimulated POOL. All responses to NE were greater in MFP than in PFP, indicating that adipose tissue surrounding the developing mammary gland had higher metabolic activity and a greater response to NE than peritoneal adipose. Changes in fatty acid metabolism during pregnancy in swine are temporally related to published values for plasma steroids, fetal growth and mammary development. Metabolic adaptations in adipose and mannary epithelial tissue occur in synchrony with changing plasma estrogen concentrations, redirecting energy flow from maternal adipose tissue toward developing mammary and fetal tissue. PMID:4044440

  4. Expression of fatty acid synthase in nonalcoholic fatty liver disease

    PubMed Central

    Dorn, Christoph; Riener, Marc-Oliver; Kirovski, Georgi; Saugspier, Michael; Steib, Kathrin; Weiss, Thomas S; Gäbele, Erwin; Kristiansen, Glen; Hartmann, Arndt; Hellerbrand, Claus

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which starts with simple hepatic steatosis and may progress toward inflammation (nonalcoholic steatohepatitis [NASH]). Fatty acid synthase (FASN) catalyzes the last step in fatty acid biosynthesis, and thus, it is believed to be a major determinant of the maximal hepatic capacity to generate fatty acids by de novo lipogenesis. The aim of this study was to analyze the correlation between hepatic steatosis and inflammation with FASN expression. In vitro incubation of primary human hepatocytes with fatty acids dose-dependently induced cellular lipid-accumulation and FASN expression, while stimulation with TNF did not affect FASN levels. Further, hepatic FASN expression was significantly increased in vivo in a murine model of hepatic steatosis without significant inflammation but not in a murine NASH model as compared to control mice. Also, FASN expression was not increased in mice subjected to bile duct ligation, an experimental model characterized by severe hepatocellular damage and inflammation. Furthermore, FASN expression was analyzed in 102 human control or NAFLD livers applying tissue micro array technology and immunohistochemistry, and correlated significantly with the degree of hepatic steatosis, but not with inflammation or ballooning of hepatocytes. Quantification of FASN mRNA expression in human liver samples confirmed significantly higher FASN levels in hepatic steatosis but not in NASH, and expression of SREBP1, which is the main transcriptional regulator of FASN, paralleled FASN expression levels in human and experimental NAFLD. In conclusion, the transcriptional induction of FASN expression in hepatic steatosis is impaired in NASH, while hepatic inflammation in the absence of steatosis does not affect FASN expression, suggesting that FASN may serve as a new diagnostic marker or therapeutic target for the progression of NAFLD. PMID:20606731

  5. Expression of fatty acid synthase in nonalcoholic fatty liver disease.

    PubMed

    Dorn, Christoph; Riener, Marc-Oliver; Kirovski, Georgi; Saugspier, Michael; Steib, Kathrin; Weiss, Thomas S; Gäbele, Erwin; Kristiansen, Glen; Hartmann, Arndt; Hellerbrand, Claus

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which starts with simple hepatic steatosis and may progress toward inflammation (nonalcoholic steatohepatitis [NASH]). Fatty acid synthase (FASN) catalyzes the last step in fatty acid biosynthesis, and thus, it is believed to be a major determinant of the maximal hepatic capacity to generate fatty acids by de novo lipogenesis. The aim of this study was to analyze the correlation between hepatic steatosis and inflammation with FASN expression. In vitro incubation of primary human hepatocytes with fatty acids dose-dependently induced cellular lipid-accumulation and FASN expression, while stimulation with TNF did not affect FASN levels. Further, hepatic FASN expression was significantly increased in vivo in a murine model of hepatic steatosis without significant inflammation but not in a murine NASH model as compared to control mice. Also, FASN expression was not increased in mice subjected to bile duct ligation, an experimental model characterized by severe hepatocellular damage and inflammation. Furthermore, FASN expression was analyzed in 102 human control or NAFLD livers applying tissue micro array technology and immunohistochemistry, and correlated significantly with the degree of hepatic steatosis, but not with inflammation or ballooning of hepatocytes. Quantification of FASN mRNA expression in human liver samples confirmed significantly higher FASN levels in hepatic steatosis but not in NASH, and expression of SREBP1, which is the main transcriptional regulator of FASN, paralleled FASN expression levels in human and experimental NAFLD. In conclusion, the transcriptional induction of FASN expression in hepatic steatosis is impaired in NASH, while hepatic inflammation in the absence of steatosis does not affect FASN expression, suggesting that FASN may serve as a new diagnostic marker or therapeutic target for the progression of NAFLD. PMID:20606731

  6. Origins of metabolic complications in obesity: adipose tissue and free fatty acid trafficking

    PubMed Central

    Mittendorfer, Bettina

    2013-01-01

    Purpose of review Obesity is associated with a number of serious medical complications that are risk factors for cardiovascular disease (e.g., insulin resistance, dyslipidemia and liver fat accumulation). Alterations in fatty acid trafficking, both between tissues and within cells, represent a key feature in the pathophysiology of the metabolic complications in obese subjects. The ways by which fatty acid “re-routing” may affect metabolic function are summarized in this article. Recent findings Ectopic fat accumulation (i.e., fat accumulation in non-adipose tissues) appears to be a key feature distinguishing metabolically healthy from metabolically abnormal subjects. This observation has led to the believe that an imbalance in fatty acid trafficking away from adipose tissue towards non-adipose tissues is a primary cause for the development of metabolic alterations in obese subjects. More recently, however, it has become apparent that fatty acid trafficking with within non-adipose tissues cells (i.e., towards storage - in the form of triglycerides - and oxidation) may be equally important in determining risk for development of metabolic disease. Summary The pathophysiology of the metabolic alterations associated with obesity is probably multifactorial within a complex network of coordinated physiological responses. Only through the integration of multiple concepts will it be possible to further our understanding in this area and to help prevent the metabolic alterations associated with obesity. PMID:21849896

  7. Nonalcoholic fatty liver disease and hepatocellular carcinoma.

    PubMed

    Zoller, Heinz; Tilg, Herbert

    2016-08-01

    The fastest growing cause of cancer-related death is hepatocellular carcinoma (HCC), which is at least partly attributable to the rising prevalence of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to malignant transformation into hepatocellular cancer. The estimated annual HCC incidence in the progressive form of NAFLD - non-alcoholic steatohepatitis (NASH) - is about 0.3%. The risk of HCC development is higher in men and increases with age, more advanced fibrosis, progressive obesity, insulin resistance and diabetes mellitus. Studies on the molecular mechanism of HCC development in NAFLD have shown that hepatocarcinogenesis is associated with complex changes at the immunometabolic interface. In line with these clinical risk factors, administration of a choline-deficient high-fat diet to mice over a prolonged period results in spontaneous HCC development in a high percentage of animals. The role of altered insulin signaling in tumorigenesis is further supported by the observation that components of the insulin-signaling cascade are frequently mutated in hepatocellular cancer cells. These changes further enhance insulin-mediated growth and cell division of hepatocytes. Furthermore, studies investigating nuclear factor kappa B (NF-κB) signaling and HCC development allowed dissection of the complex links between inflammation and carcinogenesis. To conclude, NAFLD reflects an important risk factor for HCC, develops also in non-cirrhotic livers and is a prototypic cancer involving inflammatory and metabolic pathways. STRENGTHS/WEAKNESSES AND SUMMARY OF THE TRANSLATIONAL POTENTIAL OF THE MESSAGES IN THE PAPER: The systematic review summarizes findings from unbiased clinical and translational studies on hepatocellular cancer in non-alcoholic fatty liver disease. This provides a concise overview on the epidemiology, risk factors and molecular

  8. Non-Alcoholic Fatty Liver Disease (NAFLD)

    MedlinePlus

    Non-Alcoholic Fatty Liver Disease What is Non-alcoholic fatty liver disease (NAFLD)? FAT N AFLD is a name that is given to a ... and under “Liver Health Information view ‘Nonalcoholic fatty liver Disease (NAFLD/NASH)’ IMPORTANT REMINDER: This information from the ...

  9. Dietary fatty acids and minerals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulating evidence in animals and humans shows that dietary fatty acids influence the absorption and utilization of certain mineral elements. Fat intake exceeding 10% of energy intake reduces calcium uptake and use by the body, and this effect is more pronounced with saturated compared to unsatu...

  10. Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

    PubMed

    Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

    2011-09-01

    This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. PMID:22024496

  11. Susceptibility of mammary tumor cells to complement-mediated cytolysis after in vitro or in vivo fatty acid manipulation.

    PubMed

    Erickson, K L; Thomas, I K

    1985-08-01

    The susceptibility of line 168 murine mammary tumor cells to complement (C)-mediated lysis was tested after in vitro treatment with several saturated or unsaturated fatty acids dissolved in different solvents or presented in the form of micelles to the cells. The lytic susceptibility of these cultured cells was compared with similar tumor cells obtained either from mice maintained on diets containing different concentrations and saturations of fatty acids or from cultures supplemented with serum from tumor-free control mice fed pair-matched diets. Although changes in dietary fat concentration and saturation resulted in alterations of the tumor cell fatty acid composition, those alterations did not influence the susceptibility of tumor cells to C-mediated lysis. However, single, or combinations of, unsaturated fatty acids dissolved in ethanol, unlike saturated fatty acids, reduced the lytic susceptibility of tumor cells in vitro. Hexane added to culture medium significantly suppressed the lytic susceptibility; however, when used as a carrier no significant differences were observed among treatments with the individual fatty acids at several concentrations. This result may be due to the effect of hexane on the cell membrane because this treatment also affected the osmotic fragility of the cells. Fatty acids as micelles did not influence the susceptibility of tumor cells to lysis. We concluded that only in vitro manipulation of fatty acids in some vehicles influenced the susceptibility of target tumor cells to C-mediated lysis; this finding did not parallel the situation that occurred in vivo. Moreover, the use of different vehicles to present fatty acids to tumor cells may further alter the susceptibility to C-mediated lysis. PMID:3860685

  12. Role of CoA and acetyl-CoA in regulating cardiac fatty acid and glucose oxidation.

    PubMed

    Abo Alrob, Osama; Lopaschuk, Gary D

    2014-08-01

    CoA (coenzyme A) and its derivatives have a critical role in regulating cardiac energy metabolism. This includes a key role as a substrate and product in the energy metabolic pathways, as well as serving as an allosteric regulator of cardiac energy metabolism. In addition, the CoA ester malonyl-CoA has an important role in regulating fatty acid oxidation, secondary to inhibiting CPT (carnitine palmitoyltransferase) 1, a key enzyme involved in mitochondrial fatty acid uptake. Alterations in malonyl-CoA synthesis by ACC (acetyl-CoA carboxylase) and degradation by MCD (malonyl-CoA decarboxylase) are important contributors to the high cardiac fatty acid oxidation rates seen in ischaemic heart disease, heart failure, obesity and diabetes. Additional control of fatty acid oxidation may also occur at the level of acetyl-CoA involvement in acetylation of mitochondrial fatty acid β-oxidative enzymes. We find that acetylation of the fatty acid β-oxidative enzymes, LCAD (long-chain acyl-CoA dehydrogenase) and β-HAD (β-hydroxyacyl-CoA dehydrogenase) is associated with an increase in activity and fatty acid oxidation in heart from obese mice with heart failure. This is associated with decreased SIRT3 (sirtuin 3) activity, an important mitochondrial deacetylase. In support of this, cardiac SIRT3 deletion increases acetylation of LCAD and β-HAD, and increases cardiac fatty acid oxidation. Acetylation of MCD is also associated with increased activity, decreases malonyl-CoA levels and an increase in fatty acid oxidation. Combined, these data suggest that malonyl-CoA and acetyl-CoA have an important role in mediating the alterations in fatty acid oxidation seen in heart failure. PMID:25110000

  13. Influence of a subinhibitory dose of antifungal fatty acids from Sporothrix flocculosa on cellular lipid composition in fungi.

    PubMed

    Benyagoub, M; Willemot, C; Bélanger, R R

    1996-10-01

    Antifungal fatty acids produced by the biocontrol fungus Sporothrix flocculosa were studied on the basis of their effect on growth and cellular lipid composition of three fungi, Cladosporium cucumerinum, Fusarium oxysporum, and S. flocculosa, whose growth was decreased by 51, 33, and 5%, respectively, when exposed to 0.4 mg fatty acid per ml. The sensitivity to fatty acid antibiotics from S. flocculosa was related to a high degree of unsaturation of phospholipid fatty acids and a low proportion of sterols. The major responses of sensitive fungi to sublethal doses of antifungal fatty acids from liquid culture of S. flocculosa were: (i) a decrease in total lipid; (ii) an increase in the degree of fatty acid unsaturation (18:1 > 18:2 > 18:3); (iii) an increase in free fatty acids and phosphatidic acid and a decrease in total phospholipids; and (iv) an increase in sterol/phospholipid ratio. These modifications in lipid composition led to an increase in membrane fluidity in sensitive fungi as demonstrated by assessment of fluoresence anisotropy using liposomes and 1,6-diphenyl-1,3,5-hexatriene probe. This alteration in the physical state of lipids appears to be responsible for the previously demonstrated alteration of membrane structure and function in fungi confronted to S. flocculosa. PMID:8898307

  14. Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: An update

    PubMed Central

    Yan, Sheng; Yang, Xue-Feng; Liu, Hao-Lei; Fu, Nian; Ouyang, Yan; Qing, Kai

    2015-01-01

    Long-chain acyl-CoA synthetase (ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-CoAs, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or loss-of-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolism-associated effects of ACSLs in diseases. PMID:25834313

  15. Nitrated fatty acids: Synthesis and measurement

    PubMed Central

    Woodcock, Steven R.; Bonacci, Gustavo; Gelhaus, Stacy L.; Schopfer, Francisco J.

    2012-01-01

    Nitrated fatty acids are the product of nitrogen dioxide reaction with unsaturated fatty acids. The discovery of peroxynitrite and peroxidase-induced nitration of biomolecules led to the initial reports of endogenous nitrated fatty acids. These species increase during ischemia reperfusion, but concentrations are often at or near the limits of detection. Here, we describe multiple methods for nitrated fatty acid synthesis, sample extraction from complex biological matrices, and a rigorous method of qualitative and quantitative detection of nitrated fatty acids by LC-MS. In addition, optimized instrument conditions and caveats regarding data interpretation are discussed. PMID:23200809

  16. NF-E2-related factor 2 deletion facilitates hepatic fatty acids metabolism disorder induced by high-fat diet via regulating related genes in mice.

    PubMed

    Wang, Xinghe; Li, Chunyan; Xu, Shang; Ishfaq, Muhammad; Zhang, Xiuying

    2016-08-01

    There is increasing evidence that Nrf2 participates in hepatic fatty acid metabolism in non-alcoholic fatty liver disease; however, the mechanism remains unclear. We investigated the role of Nrf2 in hepatic fatty acid metabolism disorder induced by high-fat diet (HFD). Mice fed HFD developed hepatic steatosis and exhibited Nrf2 deficiency. Change of fatty acid composition mediated by Nrf2 deletion was observed predominantly in the liver and not the serum. HFD-induced variations in hepatic 18-carbon and 22-carbon fatty acids were enhanced by Nrf2 deficiency. In the HFD group, Nrf2 deficiency led to increases in the mRNA expression of PPARα, FXR, FAS, LXR and ACC-1, while levels of PGC-1α and Srebp-1c mRNA were decreased. Nrf2 mRNA expression was enhanced in the liver of HFD-induced wild type mice, whereas it was undetectable in Nrf2-null mice. These results suggest that Nrf2 deficiency induced by HFD promoted hepatic fatty acid metabolism disorder by altering 18-carbon and 22-carbon fatty acid composition. Changes in fatty acid content were also associated with alteration of the transcription of genes involved in hepatic fatty acid metabolism. PMID:27311796

  17. [Altered states of consciousness].

    PubMed

    Gora, E P

    2005-01-01

    The review of modern ideas concerning the altered states of consciousness is presented in this article. Various methods of entry into the altered states of consciousness are looked over. It is shown that the altered states of consciousness are insufficiently known, but important aspects of human being existence. The role of investigation of the altered states of consciousness for the creation of integrative scientific conception base is discussed. PMID:15810684

  18. Fatty acid metabolism in neonatal chickens (Gallus domesticus) treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,3',4,4',5-pentachlorobiphenyl (PCB-126) in ovo.

    PubMed

    Stanton, Beckye; DeWitt, Jamie; Henshel, Diane; Watkins, Steven; Lasley, Bill

    2003-09-01

    Treatment of chickens as pre-incubation embryos with TCDD or PCB-126 altered fatty acid concentrations in their plasma 21 days later, compared with their oil vehicles (sunflower and corn oils, respectively). TCDD increased the concentrations of total fatty acids, lipid classes (phospholipids and cholesterol ester), fatty acid families (saturated, n-7 and n-6), and many specific fatty acids. The only fatty acid concentrations decreased by TCDD treatment were those of cholesterol ester fatty acids 20:3n3 and 24:6n3 and overall plasma 24:6n3. In contrast, PCB-126 treatment decreased total phospholipid, saturated and plasmogen fatty acid concentrations with generally decreasing trends in specific fatty acid concentrations. However, both TCDD and PCB-126 treatments increased total 22:1n9 and decreased 24:6n3 concentrations compared with their respective vehicles. The potential relationship between those fatty acid concentrations altered by toxicant treatment and alterations in brain symmetry was then examined using correlation analysis. Several fatty acid concentrations were significantly correlated with differences in brain morphology between the right and left hemispheres and these potential associations were different between toxicant and vehicle. PMID:14522600

  19. New radiohalogenated alkenyl tellurium fatty acids

    SciTech Connect

    Srivastava, P.C.; Knapp, F.F. Jr.; Kabalka, G.W.

    1987-01-01

    Radiolabeled long-chain fatty acids have diagnostic value as radiopharmaceutical tools in myocardial imaging. Some applications of these fatty acids are limited due to their natural metabolic degradation in vivo with subsequent washout of the radioactivity from the myocardium. The identification of structural features that will increase the myocardial residence time without decreasing the heart uptake of long-chain fatty acids is of interest. Fatty acids containing the tellurium heteroatom were the first modified fatty acids developed that show unique prolonged myocardial retention and low blood levels. Our detailed studies with radioiodinated vinyliodide substituted tellurium fatty acids demonstrate that heart uptake is a function of the tellurium position. New techniques of tellurium and organoborane chemistry have been developed for the synthesis of a variety of radioiodinated iodoalkenyl tellurium fatty acids. 9 refs., 3 figs., 2 tabs.

  20. Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.

    PubMed

    Bourre, J M

    2004-01-01

    Among various organs, in the brain, the fatty acids most extensively studied are omega-3 fatty acids. Alpha-linolenic acid (18:3omega3) deficiency alters the structure and function of membranes and induces minor cerebral dysfunctions, as demonstrated in animal models and subsequently in human infants. Even though the brain is materially an organ like any other, that is to say elaborated from substances present in the diet (sometimes exclusively), for long it was not accepted that food can have an influence on brain structure, and thus on its function. Lipids, and especially omega-3 fatty acids, provided the first coherent experimental demonstration of the effect of diet (nutrients) on the structure and function of the brain. In fact the brain, after adipose tissue, is the organ richest in lipids, whose only role is to participate in membrane structure. First it was shown that the differentiation and functioning of cultured brain cells requires not only alpha-linolenic acid (the major component of the omega-3, omega3 family), but also the very long omega-3 and omega-6 carbon chains (1). It was then demonstrated that alpha-linolenic acid deficiency alters the course of brain development, perturbs the composition and physicochemical properties of brain cell membranes, neurones, oligodendrocytes, and astrocytes (2). This leads to physicochemical modifications, induces biochemical and physiological perturbations, and results in neurosensory and behavioural upset (3). Consequently, the nature of polyunsaturated fatty acids (in particular omega-3) present in formula milks for infants (premature and term) conditions the visual and cerebral abilities, including intellectual. Moreover, dietary omega-3 fatty acids are certainly involved in the prevention of some aspects of cardiovascular disease (including at the level of cerebral vascularization), and in some neuropsychiatric disorders, particularly depression, as well as in dementia, notably Alzheimer's disease. Recent

  1. Fatty acid uptake in normal human myocardium

    SciTech Connect

    Vyska, K.; Meyer, W.; Stremmel, W.; Notohamiprodjo, G.; Minami, K.; Machulla, H.J.; Gleichmann, U.; Meyer, H.; Koerfer, R. )

    1991-09-01

    Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an unstirred layer were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 {plus minus} 0.024 mumol/g and 0.37 {plus minus} 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells.

  2. An in vitro model for essential fatty acid deficiency: HepG2 cells permanently maintained in lipid-free medium.

    PubMed

    Furth, E E; Sprecher, H; Fisher, E A; Fleishman, H D; Laposata, M

    1992-11-01

    A stable essential fatty acid-deficient cell type, known as HepG2-EFD, was derived from the lipoprotein-producing human hepatoma cell line HepG2. These cells are particularly useful for quantitative studies involving essential fatty acids (n-6 and n-3 fatty acids) in secreted lipoproteins. Radiolabeled essential fatty acids can be delivered to these cells without altering the specific activity of the fatty acids, since the deficient cells contain no endogenous essential fatty acids. Using these cells, radioactivity data (dpm) from metabolic studies can be converted directly to mass, and masses as low as a few pmoles can be accurately measured. HepG2-EFD cell cultures were established by growing HepG2 cells in medium containing delipidated serum. After 10 days of growth in delipidated medium, HepG2 cells were completely depleted of all essential fatty acids. Compensatory increases in nonessential fatty acids (n-9 and n-7 fatty acids) including 20:3n-9 (the Mead acid), which is the hallmark fatty acid of essential fatty acid deficiency, were also observed in HepG2-EFD cells. Despite the lack of exogenous fatty acids in the medium and the lack of essential fatty acids in the cells, export of very low density lipoprotein (VLDL)-associated apolipoprotein B by HepG2-EFD was the same as observed for parent HepG2 cells. However, the activity of beta-oxidation of fatty acids in HepG2-EFD cells was much lower than in the parent cell line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1464755

  3. Angiotensin (1-7)/Mas receptor axis activation ameliorates the changes in fatty acid composition in diabetic rats with nephropathy

    PubMed Central

    Singh, Kulwinder; Singh, Tajinder; Sharma, PL

    2010-01-01

    Diabetes mellitus is often associated with altered fatty acids composition. This study was designed to investigate the role of angiotensin (Ang) (1-7)/Mas receptor in improving fatty acids composition in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats. Rats treated with STZ (50 mg/kg, i.p. once) developed DN after 8 weeks. Fatty acid composition was estimated in renal cortical tissue by gas chromatography. Treatment with Ang (1-7), A-779, and Ang (1-7) plus A-779 was given from week 4 to week 8. Diabetic rats exhibited a significant increase in levels of saturated fatty acids and a significant decrease in levels of polyunsaturated fatty acids (PUFAs). Treatment with Ang (1-7) significantly attenuated these diabetes-induced changes. In diabetic rats, prior administration of A-779 significantly attenuated the increase in PUFAs produced by Ang (1-7); however, for saturated fatty acids, A-779 significantly blocked the decrease in palmitic acid only. Our study, for the first time, documented that endogenous Ang (1-7) modulates fatty acid composition in rats. Further, treatment with Ang (1-7) significantly attenuated diabetes-induced changes in fatty acids composition. This may be an additional mechanism implying the renoprotective role of Ang (1-7) in diabetic rats.

  4. [Prevalence of no alcohol fatty liver disease (NAFLD) in a population of obese children in Valencia, Venezuela].

    PubMed

    Pontiles de Sánchez, Milagros; Morón de Salim, Alba; Rodríguez de Perdomo, Henny; Perdomo Oramas, Germán

    2014-06-01

    No Alcoholic Fatty Liver Disease (NAFLD) is characterized by an abnormal accumulation of fat in hepatocytes, without alcohol, where overweight and obesity are determinants. Ecosonografia evaluated the prevalence of fatty liver in obese pediatric patients and its relation to nutritional assessment. The sample consisted of 85 children (51 females, 34 males), age 3-17. The abdominal ecosonography, BMI, waist circumference were performed; Godard Test for physical activity, history of diabetes, dyslipidemia, obesity and cardiovascular disease were questioned. Lipid profile, glucose and insulin resistance were determined. Data analyzed from descriptive and comparative tables. We obtained: mean age 9.8 ± 2.7 females and males 9.6 ± 2.7 years. The ecosonography indicated 50% and 50% fatty liver-pancreas fatty liver in children aged 3-6 years; 7-11 years 39.7% fatty liver-pancreas; 12-17yrs 31.6% fatty liver-pancreas (p > 0.05); BMI > 26 kg/m2 42.9% fatty liver-pancreas; 21 to 25 kg/m2 44.7% fatty liver; 15 to 20 kg/m2 60%fatty liver-pancreas (p> 0.05). 97.6% with high CC; 68.2% with inadequate physical activity; high frequency of history of chronic non-communicable diseases. We concluded that this population had predominantly fatty liver fatty replacement of the pancreas (HG-RGP) in the groups with higher BMI, CC and high male unrelated insulin resistance, altered lipid profile and diagnosis HG. We inferred that the anthropometric assessment of waist circumference and abdominal ecosonography indicate the presence of visceral obesity, a condition that predisposes to hepatic steatosis, pancreas and/or liver-pancreas. PMID:25799683

  5. Sleep Apnea and Fatty Liver Are Coupled Via Energy Metabolism.

    PubMed

    Arısoy, Ahmet; Sertoğullarından, Bunyamin; Ekin, Selami; Özgökçe, Mesut; Bulut, Mehmet Deniz; Huyut, Mehmet Tahir; Ölmez, Şehmus; Turan, Mahfuz

    2016-01-01

    BACKGROUND Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by intermittent hypoxia. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease worldwide. We aimed to evaluate the relationship between OSA and fatty liver. MATERIAL AND METHODS We enrolled 176 subjects to this study who underwent polysomnography (PSG) for suspected OSA. The control group included 42 simple snoring subjects. PSG, biochemical tests, and ultrasonographic examination were performed all subjects. RESULTS The simple snoring and mild, moderate, and severe OSA groups included 18/42 (42.86%), 33/52 (63.5%), 27/34 (79.4%), and 28/48 (79.2%) subjects with hepatosteatosis, respectively. There were significant differences in hepatosteatosis and hepatosteatosis grade between the simple snoring and the moderate and severe OSA groups. Logistic regression analysis showed that BMI and average desaturation were independently and significantly related to hepatic steatosis. CONCLUSIONS Our study shows that BMI and the average desaturation contribute to non-alcoholic fatty liver in subjects with OSA. In this regard, sleep apnea may trigger metabolic mitochondrial energy associated processes thereby altering lipid metabolism and obesity as well. PMID:26993969

  6. Sleep Apnea and Fatty Liver Are Coupled Via Energy Metabolism

    PubMed Central

    Arısoy, Ahmet; Sertoğullarından, Bunyamin; Ekin, Selami; Özgökçe, Mesut; Bulut, Mehmet Deniz; Huyut, Mehmet Tahir; Ölmez, Şehmus; Turan, Mahfuz

    2016-01-01

    Background Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by intermittent hypoxia. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease worldwide. We aimed to evaluate the relationship between OSA and fatty liver. Material/Methods We enrolled 176 subjects to this study who underwent polysomnography (PSG) for suspected OSA. The control group included 42 simple snoring subjects. PSG, biochemical tests, and ultrasonographic examination were performed all subjects. Results The simple snoring and mild, moderate, and severe OSA groups included 18/42 (42.86%), 33/52 (63.5%), 27/34 (79.4%), and 28/48 (79.2%) subjects with hepatosteatosis, respectively. There were significant differences in hepatosteatosis and hepatosteatosis grade between the simple snoring and the moderate and severe OSA groups. Logistic regression analysis showed that BMI and average desaturation were independently and significantly related to hepatic steatosis. Conclusions Our study shows that BMI and the average desaturation contribute to non-alcoholic fatty liver in subjects with OSA. In this regard, sleep apnea may trigger metabolic mitochondrial energy associated processes thereby altering lipid metabolism and obesity as well. PMID:26993969

  7. Omega-3 fatty acids for breast cancer prevention and survivorship.

    PubMed

    Fabian, Carol J; Kimler, Bruce F; Hursting, Stephen D

    2015-01-01

    Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship. PMID:25936773

  8. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  9. Obesity, fatty liver disease and intestinal microbiota

    PubMed Central

    Arslan, Nur

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations. PMID:25469013

  10. Dehydration of multilamellar fatty acid membranes: Towards a computational model of the stratum corneum

    NASA Astrophysics Data System (ADS)

    MacDermaid, Christopher M.; DeVane, Russell H.; Klein, Michael L.; Fiorin, Giacomo

    2014-12-01

    The level of hydration controls the cohesion between apposed lamellae of saturated free fatty acids found in the lipid matrix of stratum corneum, the outermost layer of mammalian skin. This multilamellar lipid matrix is highly impermeable to water and ions, so that the local hydration shell of its fatty acids may not always be in equilibrium with the acidity and relative humidity, which significantly change over a course of days during skin growth. The homeostasis of the stratum corneum at each moment of its growth likely requires a balance between two factors, which affect in opposite ways the diffusion of hydrophilic species through the stratum corneum: (i) an increase in water order as the lipid lamellae come in closer contact, and (ii) a decrease in water order as the fraction of charged fatty acids is lowered by pH. Herein molecular dynamics simulations are employed to estimate the impact of both effects on water molecules confined between lamellae of fatty acids. Under conditions where membrane undulations are energetically favorable, the charged fatty acids are able to sequester cations around points of contact between lamellae that are fully dehydrated, while essentially maintaining a multilamellar structure for the entire system. This observation suggests that the undulations of the fatty acid lamellae control the diffusion of hydrophilic species through the water phase by altering the positional and rotational order of water molecules in the embedded/occluded "droplets."

  11. The development of iodine-123-methyl-branched fatty acids and their applications in nuclear cardiology

    SciTech Connect

    Knapp, F.F. Jr.; Ambrose, K.R.; Kropp, J.; Biersack, H.J.; Goodman, M.M.; Franken, P.; Reske, S.N.; Som, P.; Sloof, G.W.; Visser, F.C.

    1993-06-01

    Continued Interest in the use of iodine-1 23-labeled fatty acids for myocardial Imaging results from observations from a variety of studies that in many types of cardiac disease, regional fatty acid myocardial uptake patterns are often different than regional distribution of flow tracers. These differences may reflect alterations in important parameters of metabolism which can be useful for patient management or therapeutic strategy decision making. In addition, use of iodine-I 23-labeled fatty acid distribution may represent a unique metabolic probe to relate some aspects of the metabolism of these substrates with the regional viability of cardiac tissue. The use of such viability markers could provide important prognostic information on myocardial salvage, helping to identify patients for revascularization or angioplasty. Clinical studies are currently in progress with the iodine-123-labeled 1 5-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue at several institutions. The goals of this paper are to discuss development of the concept of metabolic trapping of fatty acids, to briefly review development and evaluation of various radioiodinated methyl-branched fatty acids and to discuss recent patient studies with iodine-123 (BMIPP) using single photon emission computerized tomography (SPECT).

  12. The development of iodine-123-methyl-branched fatty acids and their applications in nuclear cardiology

    SciTech Connect

    Knapp, F.F. Jr.; Ambrose, K.R. ); Kropp, J.; Biersack, H.J. . Inst. fuer Klinische und Experimentelle Nuklearmedizin); Goodman, M.M. . Dept. of Radiology); Franken, P. . Nuclear Medicine Dept.); Reske, S.N. (Ulm Univ. (Germany

    1993-01-01

    Continued Interest in the use of iodine-1 23-labeled fatty acids for myocardial Imaging results from observations from a variety of studies that in many types of cardiac disease, regional fatty acid myocardial uptake patterns are often different than regional distribution of flow tracers. These differences may reflect alterations in important parameters of metabolism which can be useful for patient management or therapeutic strategy decision making. In addition, use of iodine-I 23-labeled fatty acid distribution may represent a unique metabolic probe to relate some aspects of the metabolism of these substrates with the regional viability of cardiac tissue. The use of such viability markers could provide important prognostic information on myocardial salvage, helping to identify patients for revascularization or angioplasty. Clinical studies are currently in progress with the iodine-123-labeled 1 5-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue at several institutions. The goals of this paper are to discuss development of the concept of metabolic trapping of fatty acids, to briefly review development and evaluation of various radioiodinated methyl-branched fatty acids and to discuss recent patient studies with iodine-123 (BMIPP) using single photon emission computerized tomography (SPECT).

  13. Manipulating Fatty Acid Biosynthesis in Microalgae for Biofuel through Protein-Protein Interactions

    PubMed Central

    Blatti, Jillian L.; Beld, Joris; Behnke, Craig A.; Mendez, Michael; Mayfield, Stephen P.; Burkart, Michael D.

    2012-01-01

    Microalgae are a promising feedstock for renewable fuels, and algal metabolic engineering can lead to crop improvement, thus accelerating the development of commercially viable biodiesel production from algae biomass. We demonstrate that protein-protein interactions between the fatty acid acyl carrier protein (ACP) and thioesterase (TE) govern fatty acid hydrolysis within the algal chloroplast. Using green microalga Chlamydomonas reinhardtii (Cr) as a model, a structural simulation of docking CrACP to CrTE identifies a protein-protein recognition surface between the two domains. A virtual screen reveals plant TEs with similar in silico binding to CrACP. Employing an activity-based crosslinking probe designed to selectively trap transient protein-protein interactions between the TE and ACP, we demonstrate in vitro that CrTE must functionally interact with CrACP to release fatty acids, while TEs of vascular plants show no mechanistic crosslinking to CrACP. This is recapitulated in vivo, where overproduction of the endogenous CrTE increased levels of short-chain fatty acids and engineering plant TEs into the C. reinhardtii chloroplast did not alter the fatty acid profile. These findings highlight the critical role of protein-protein interactions in manipulating fatty acid biosynthesis for algae biofuel engineering as illuminated by activity-based probes. PMID:23028438

  14. Detergent-assisted self assembly of fatty acid layers on mica in solution

    NASA Astrophysics Data System (ADS)

    Hand, Sean; Yang, Jie

    1997-03-01

    Fatty acids are well known for their ability to form monolayers at air-water interfaces. The conventional method to coat a solid surface with mono or multi layers of fatty acids uses a Langmuir trough, via X- or Y- type coatings. The major advantage of the Langmuir trough is the ability to control the monolayer pressure. The limiting factors are, however, the restricted size of the substrate, the physical size of the Langmuir trough, and the coating procedure. To circumvent some of these drawbacks, we have developed a method to cover a solid mica substrate with fatty acids by detergent assisted self assembly in aqueous solutions. It has been found that a molecular layer of fatty acids, possibly complexed with some detergent, are self-assembled on the mica surface. Thickness measurements of these self-assembled layers suggest that the layer is composed of two monolayers of fatty acids in a bilayer arrangement. The presence of cations in the solution has some effect on the assembly of the molecular layer, and may alter the orientation of individual fatty acids in the layer. Structural characteristics of such self assembled molecular layers are studied with atomic force microscopy. Details of the method of the detergent assisted self assembly and some structural features of the assembled molecular layers will be presented.

  15. Abnormalities in the Metabolism of Fatty Acids and Triacylglycerols in the Liver of the Goto-Kakizaki Rat: A Model for Non-Obese Type 2 Diabetes.

    PubMed

    Karahashi, Minako; Hirata-Hanta, Yuko; Kawabata, Kohei; Tsutsumi, Daisuke; Kametani, Misaki; Takamatsu, Nanako; Sakamoto, Takeshi; Yamazaki, Tohru; Asano, Satoshi; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

    2016-08-01

    The Goto-Kakizaki (GK) rat is widely used as an animal model for spontaneous-onset type 2 diabetes without obesity; nevertheless, little information is available on the metabolism of fatty acids and triacylglycerols (TAG) in their livers. We investigated the mechanisms underlying the alterations in the metabolism of fatty acids and TAG in their livers, in comparison with Zucker (fa/fa) rats, which are obese and insulin resistant. Lipid profiles, the expression of genes for enzymes and proteins related to the metabolism of fatty acid and TAG, de novo synthesis of fatty acids and TAG in vivo, fatty acid synthase activity in vitro, fatty acid oxidation in liver slices, and very-low-density-lipoprotein (VLDL)-TAG secretion in vivo were estimated. Our results revealed that (1) the TAG accumulation was moderate, (2) the de novo fatty acid synthesis was increased by upregulation of fatty acid synthase in a post-transcriptional manner, (3) fatty acid oxidation was also augmented through the induction of carnitine palmitoyltransferase 1a, and (4) the secretion rate of VLDL-TAG remained unchanged in the livers of GK rats. These results suggest that, despite the fact that GK rats exhibit non-obese type 2 diabetes, the upregulation of de novo lipogenesis is largely compensated by the upregulation of fatty acid oxidation, resulting in only moderate increase in TAG accumulation in the liver. PMID:27372943

  16. Fatty acid utilization in pressure-overload hypertrophied rat hearts

    SciTech Connect

    Reibel, D.K.; O'Rourke, B.

    1986-03-05

    The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H/sub 2/O left atrial filling pressure with a ventricular afterload of 80 cm of H/sub 2/O with buffer containing 1.2 mM /sup 14/C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. /sup 14/CO/sub 2/ production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by /sup 14/CO/sub 2/ production during this time was 0.728 +/- 0.06 ..mu..moles/min/g dry in control hearts and 0.710 +/- 0.02 ..mu..moles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O/sub 2/ consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 ..mu..moles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine.

  17. Liquid chromatography – high resolution mass spectrometry analysis of fatty acid metabolism

    PubMed Central

    Kamphorst, Jurre J.; Fan, Jing; Lu, Wenyun; White, Eileen; Rabinowitz, Joshua D.

    2011-01-01

    We present a liquid chromatography – mass spectrometry (LC-MS) method for long-chain and very-long-chain fatty acid analysis, and its application to 13C-tracer studies of fatty acid metabolism. Fatty acids containing 14 to 36 carbon atoms are separated by C8 reversed-phase chromatography using a water-methanol gradient with tributylamine as ion pairing agent, ionized by electrospray, and analyzed by a stand-alone orbitrap mass spectrometer. The median limit of detection is 5 ng/ml with a linear dynamic range of 100-fold. Ratios of unlabeled to 13C-labeled species are quantitated precisely and accurately (average relative standard deviation 3.2% and deviation from expectation 2.3%). In samples consisting of fatty acids saponified from cultured mammalian cells, 45 species are quantified, with average intraday relative standard deviations for independent biological replicates of 11%. The method enables quantitation of molecular ion peaks for all labeled forms of each fatty acid. Different degrees of 13C-labeling from glucose and glutamine correspond to fatty acid uptake from media, de novo synthesis, and elongation. To exemplify the utility of the method, we examined isogenic cell lines with and without activated Ras oncogene expression. Ras increases the abundance and alters the labeling patterns of saturated and monounsaturated very-long-chain fatty acids, with the observed pattern consistent with Ras leading to enhanced activity of ELOVL4 or an enzyme with similar catalytic activity. This LC-MS method and associated isotope tracer techniques should be broadly applicable to investigating fatty acid metabolism. PMID:22004349

  18. Fatty acids of Pinus elliottii tissues.

    NASA Technical Reports Server (NTRS)

    Laseter, J. L.; Lawler, G. C.; Walkinshaw, C. H.; Weete, J. D.

    1973-01-01

    The total fatty constituents of slash pine (Pinus elliottii) tissue cultures, seeds, and seedlings were examined by GLC and MS. Qualitatively, the fatty acid composition of these tissues was found to be very similar to that reported for other pine species. The fatty acid contents of the tissue cultures resembled that of the seedling tissues. The branched-chain C(sub 17) acid reported for several other Pinus species was confirmed as the anteiso isomer.

  19. Plasma phospholipids and fatty acid composition differ between liver biopsy-proven nonalcoholic fatty liver disease and healthy subjects

    PubMed Central

    Ma, D W L; Arendt, B M; Hillyer, L M; Fung, S K; McGilvray, I; Guindi, M; Allard, J P

    2016-01-01

    Background: There is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with perturbations in liver lipid metabolism. Liver phospholipid and fatty acid composition have been shown to be altered in NAFLD. However, detailed profiles of circulating lipids in the pathogenesis of NAFLD are lacking. Objective: Therefore, the objective of the present study was to examine circulating lipids and potential mechanisms related to hepatic gene expression between liver biopsy-proven simple steatosis (SS), nonalcoholic steatohepatitis (NASH) and healthy subjects. Subjects: Plasma phospholipid and fatty acid composition were determined in 31 healthy living liver donors as healthy controls (HC), 26 patients with simple hepatic steatosis (SS) and 20 with progressive NASH. Hepatic gene expression was analyzed by Illumina microarray in a subset of 22 HC, 16 SS and 14 NASH. Results: Concentrations of phosphatidylethanolamine (PE) increased relative to disease progression, HCFatty acid composition of phospholipids was also remodeled. In particular, docosahexaenoic and arachidonic acid were higher (P<0.05) in SS and NASH relative to HC in PS. Differentially expressed hepatic genes included ETNK1 and PLSCR1 that are involved in PE synthesis and PS transport, respectively. Conclusions: The present study demonstrates that there is a disruption in phospholipid metabolism that is present in SS, but more pronounced in NASH. Intervention studies targeted at lipid metabolism could benefit SS and NASH. PMID:27428872

  20. 21 CFR 172.859 - Sucrose fatty acid esters.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sucrose fatty acid esters. 172.859 Section 172.859... CONSUMPTION Multipurpose Additives § 172.859 Sucrose fatty acid esters. Sucrose fatty acid esters identified...) Sucrose fatty acid esters are the mono-, di-, and tri-esters of sucrose with fatty acids and are...

  1. 21 CFR 862.1290 - Fatty acids test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fatty acids test system. 862.1290 Section 862.1290....1290 Fatty acids test system. (a) Identification. A fatty acids test system is a device intended to measure fatty acids in plasma and serum. Measurements of fatty acids are used in the diagnosis...

  2. Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots.

    PubMed

    Long, N M; Rule, D C; Zhu, M J; Nathanielsz, P W; Ford, S P

    2012-07-01

    Maternal nutrient restriction leads to alteration in fetal adipose tissue, and offspring from obese mothers have an increased risk of developing obesity. We hypothesized that maternal obesity increases fetal adipogenesis. Multiparous ewes (Columbia/Rambouillet cross 3 to 5 yr of age) carrying twins were assigned to a diet of 100% (Control; CON; n = 4) or 150% (Obese; OB, n = 7) of NRC maintenance requirements from 60 d before conception until necropsy on d 135 of gestation. Maternal and fetal plasma were collected and stored at -80°C for glucose and hormone analyses. Fetal measurements were made at necropsy, and perirenal, pericardial, and subcutaneous adipose tissues were collected from 7 male twin fetuses per group and snap frozen at -80°C. Protein and mRNA expression of fatty acid translocase [cluster of differentiation (CD) 36], fatty acid transport proteins (FATP) 1 and 4, insulin-sensitive glucose transporter (GLUT-4), fatty acid synthase (FASN), and acetyl-coA carboxylase (ACC) was evaluated. Fetal weight was similar, but fetal carcass weight (FCW) was reduced (P < 0.05) in OB versus CON fetuses. Pericardial and perirenal adipose tissue weights were increased (P < 0.05) as a percentage of FCW in OB versus CON fetuses, as was subcutaneous fat thickness (P < 0.001). Average adipocyte diameter was greater (P < 0.01) in the perirenal fat and the pericardial fat (P = 0.06) in OB fetuses compared with CON fetuses. Maternal plasma showed no difference (P > 0.05) in glucose or other hormones, fetal plasma glucose was similar (P = 0.42), and cortisol, IGF-1, and thyroxine were reduced (P ≤ 0.05) in OB fetuses compared with CON fetuses. Protein and mRNA expression of CD 36, FATP 1 and 4, and GLUT-4 were increased (P ≤ 0.05) in all fetal adipose depots in OB versus CON fetuses. The mRNA expression of FASN and ACC was increased (P < 0.05) in OB vs. CON fetuses in all 3 fetal adipose tissue depots. Fatty acid concentrations were increased (P = 0.01) in the

  3. Genome-wide association and prediction of direct genomic breeding values for composition of fatty acids in Angus beef cattlea

    PubMed Central

    2013-01-01

    Background As consumers continue to request food products that have health advantages, it will be important for the livestock industry to supply a product that meet these demands. One such nutrient is fatty acids, which have been implicated as playing a role in cardiovascular disease. Therefore, the objective of this study was to determine the extent to which molecular markers could account for variation in fatty acid composition of skeletal muscle and identify genomic regions that harbor genetic variation. Results Subsets of markers on the Illumina 54K bovine SNPchip were able to account for up to 57% of the variance observed in fatty acid composition. In addition, these markers could be used to calculate a direct genomic breeding values (DGV) for a given fatty acids with an accuracy (measured as simple correlations between DGV and phenotype) ranging from -0.06 to 0.57. Furthermore, 57 1-Mb regions were identified that were associated with at least one fatty acid with a posterior probability of inclusion greater than 0.90. 1-Mb regions on BTA19, BTA26 and BTA29, which harbored fatty acid synthase, Sterol-CoA desaturase and thyroid hormone responsive candidate genes, respectively, explained a high percentage of genetic variance in more than one fatty acid. It was also observed that the correlation between DGV for different fatty acids at a given 1-Mb window ranged from almost 1 to -1. Conclusions Further investigations are needed to identify the causal variants harbored within the identified 1-Mb windows. For the first time, Angus breeders have a tool whereby they could select for altered fatty acid composition. Furthermore, these reported results could improve our understanding of the biology of fatty acid metabolism and deposition. PMID:24156620

  4. Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

    PubMed Central

    Yang, Min; Gong, Sitang; Ye, Shui Qing; Lyman, Beth; Geng, Lanlan; Chen, Peiyu; Li, Ding-You

    2014-01-01

    With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD. PMID:25353664

  5. Non-alcoholic fatty liver disease in children: focus on nutritional interventions.

    PubMed

    Yang, Min; Gong, Sitang; Ye, Shui Qing; Lyman, Beth; Geng, Lanlan; Chen, Peiyu; Li, Ding-You

    2014-11-01

    With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD. PMID:25353664

  6. Amazing Altered Books

    ERIC Educational Resources Information Center

    Kieling, Linda W.

    2006-01-01

    Linda Kieling, an art teacher at Rosemont Ridge Middle school in West Linn, Oregon, describes an altered book art project she introduced to her students. Alteration of books is a form of recycling that started in the eleventh century when Italian monks recycled old manuscripts written on vellum by scraping off the ink and adding new text and…

  7. Transformation with Oncogenic Ras and the Simian Virus 40 T Antigens Induces Caspase-Dependent Sensitivity to Fatty Acid Biosynthetic Inhibition

    PubMed Central

    Xu, Shihao; Spencer, Cody M.

    2015-01-01

    drive the transformation of normal cells to the cancerous state. These oncogenic alterations induce metabolic changes and dependencies that can be targeted to kill cancerous cells. Here, we find that the cellular transformation resulting from combined expression of the SV40 early region with an oncogenic Ras allele is sufficient to induce cellular susceptibility to fatty acid biosynthetic inhibition. Inhibition of fatty acid biosynthesis in these cells resulted in programmed cell death, which could be rescued by supplementing the medium with nonsaturated fatty acids. Similar results were observed with the expression of oncogenic Ras in nontransformed breast epithelial cells. Combined, our results suggest that specific oncogenic alleles induce metabolic dependencies that can be exploited to selectively kill cancerous cells. PMID:25855740

  8. Nickel Inhibits Mitochondrial Fatty Acid Oxidation

    PubMed Central

    Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.

    2015-01-01

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

  9. Historical perspectives on fatty acid chemistry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acids are basic renewable chemical building blocks that can be used as intermediates for a multitude of products. Today the global value of fatty acids exceeds 18 billion dollars and is expected to increase to nearly 26 billion over the period from 2014-2019. From it auspicious beginnings, the...

  10. 21 CFR 172.860 - Fatty acids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Fatty acids. 172.860 Section 172.860 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.860 Fatty...

  11. Biodiesel With Optimized Fatty Ester Composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biodiesel is largely composed of the mono-alkyl esters, usually methyl esters, of vegetable oils or animal fats with its fatty acid profile corresponding to that of the parent oil or fat. The different fatty esters have varying properties of relevance to biodiesel. The feedstock-dependent variatio...

  12. Physiological activities of hydroxyl fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the search of value-added products from surplus soybean oil, we produced many new hydroxy fatty acids through microbial bioconversion. Hydroxy fatty acids are used in a wide range of industrial products, such as resins, waxes, nylons plastics, lubricants, cosmetics, and additives in coatings and...

  13. Fatty acid profile of kenaf seed oil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fatty acid profile of kenaf (Hibiscus cannabinus L.) seed oil has been the subject of several previous reports in the literature. These reports vary considerably regarding the presence and amounts of specific fatty acids, notably epoxyoleic acid but also cyclic (cyclopropene and cyclopropane) fa...

  14. Phylogenomic reconstruction of archaeal fatty acid metabolism

    PubMed Central

    Dibrova, Daria V.; Galperin, Michael Y.; Mulkidjanian, Armen Y.

    2014-01-01

    While certain archaea appear to synthesize and/or metabolize fatty acids, the respective pathways still remain obscure. By analyzing the genomic distribution of the key lipid-related enzymes, we were able to identify the likely components of the archaeal pathway of fatty acid metabolism, namely, a combination of the enzymes of bacterial-type β-oxidation of fatty acids (acyl-CoA-dehydrogenase, enoyl-CoA hydratase, and 3-hydroxyacyl-CoA dehydrogenase) with paralogs of the archaeal acetyl-CoA C-acetyltransferase, an enzyme of the mevalonate biosynthesis pathway. These three β-oxidation enzymes working in the reverse direction could potentially catalyze biosynthesis of fatty acids, with paralogs of acetyl-CoA C-acetyltransferase performing addition of C2 fragments. The presence in archaea of the genes for energy-transducing membrane enzyme complexes, such as cytochrome bc complex, cytochrome c oxidase, and diverse rhodopsins, was found to correlate with the presence of the proposed system of fatty acid biosynthesis. We speculate that because these membrane complexes functionally depend on fatty acid chains, their genes could have been acquired via lateral gene transfer from bacteria only by those archaea that already possessed a system of fatty acid biosynthesis. The proposed pathway of archaeal fatty acid metabolism operates in extreme conditions and therefore might be of interest in the context of biofuel production and other industrial applications. PMID:24818264

  15. Polyunsaturated fatty acids and insulin resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have reviewed results from published studies regarding the effects of polyunsaturated fatty acids (PUFA) intake on insulin resistance (IR) in human subjects. Evidence has been gathered from epidemiological, cross-sectional and interventions studies. Increased intake of trans fatty acids (TFA) inc...

  16. Fatty Aldehyde and Fatty Alcohol Metabolism: Review and Importance for Epidermal Structure and Function

    PubMed Central

    Rizzo, William B.

    2014-01-01

    Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal function. PMID:24036493

  17. Short chain fatty acids and colon cancer.

    PubMed

    Augenlicht, Leonard H; Mariadason, John M; Wilson, Andrew; Arango, Diego; Yang, WanCai; Heerdt, Barbara G; Velcich, Anna

    2002-12-01

    The development of intestinal cancer involves complex genetic and epigenetic alterations in the intestinal mucosa. The principal signaling pathway responsible for the initiation of tumor formation, the APC-beta-catenin-TCF4 pathway, regulates both cell proliferation and colonic cell differentiation, but many other intrinsic and extrinsic signals also modulate these cell maturation pathways. The challenge is to understand how signaling and cell maturation are also modulated by nutritional agents. Through gene expression profiling, we have gained insight into the mechanisms by which short chain fatty acids regulate these pathways and the differences in response of gene programs, and of the specific regulation of the c-myc gene, to physiological regulators of intestinal cell maturation, such as butyrate, compared with pharmacological regulators such as the nonsteroidal antiinflammatory drug sulindac. Moreover, we used a combination of gene expression profiling of the response of cells in culture to sulindac and the response of the human mucosa in subjects treated with sulindac for 1 month, coupled with a mouse genetic model approach, to identify the cyclin dependent kinase inhibitor p21(WAF1/Cip1) as an important suppressor of Apc-initiated intestinal tumor formation and a necessary component for tumor inhibition by sulindac. Finally, the mucous barrier, secreted by intestinal goblet cells, is the interface between the luminal contents and the intestinal mucosa. We generated a mouse genetic model with a targeted inactivation of the Muc2 gene that encodes the major intestinal mucin. These mice have no recognizable goblet cells due to the failure of cells to synthesize and store mucin. This leads to perturbations in intestinal crypt architecture, increased cellular proliferation and rates of cell migration, decreased apoptosis and development of adenomas and adenocarcinomas in the small and large intestine and the rectum. PMID:12468628

  18. Polyunsaturated fatty acids affect the localization and signaling of PIP3/AKT in prostate cancer cells.

    PubMed

    Gu, Zhennan; Wu, Jiansheng; Wang, Shihua; Suburu, Janel; Chen, Haiqin; Thomas, Michael J; Shi, Lihong; Edwards, Iris J; Berquin, Isabelle M; Chen, Yong Q

    2013-09-01

    AKT is a serine-threonine protein kinase that plays important roles in cell growth, proliferation and apoptosis. It is activated after binding to phosphatidylinositol phosphates (PIPs) with phosphate groups at positions 3,4 and 3,4,5 on the inositol ring. In spite of extensive research on AKT, one aspect has been largely overlooked, namely the role of the fatty acid chains on PIPs. PIPs are phospholipids composed of a glycerol backbone with fatty acids at the sn-1 and sn-2 position and inositol at the sn-3 position. Here, we show that polyunsaturated fatty acids (PUFAs) modify phospholipid content. Docosahexaenoic acid (DHA), an ω3 PUFA, can replace the fatty acid at the sn-2 position of the glycerol backbone, thereby changing the species of phospholipids. DHA also inhibits AKT(T308) but not AKT(S473) phosphorylation, alters PI(3,4,5)P3 (PIP3) and phospho-AKT(S473) protein localization, decreases pPDPK1(S241)-AKT and AKT-BAD interaction and suppresses prostate tumor growth. Our study highlights a potential novel mechanism of cancer inhibition by ω3 PUFA through alteration of PIP3 and AKT localization and affecting the AKT signaling pathway. PMID:23633519

  19. Bactericidal Activity of the Human Skin Fatty Acid cis-6-Hexadecanoic Acid on Staphylococcus aureus

    PubMed Central

    Cartron, Michaël L.; England, Simon R.; Chiriac, Alina Iulia; Josten, Michaele; Turner, Robert; Rauter, Yvonne; Hurd, Alexander; Sahl, Hans-Georg; Jones, Simon

    2014-01-01

    Human skin fatty acids are a potent aspect of our innate defenses, giving surface protection against potentially invasive organisms. They provide an important parameter in determining the ecology of the skin microflora, and alterations can lead to increased colonization by pathogens such as Staphylococcus aureus. Harnessing skin fatty acids may also give a new avenue of exploration in the generation of control measures against drug-resistant organisms. Despite their importance, the mechanism(s) whereby skin fatty acids kill bacteria has remained largely elusive. Here, we describe an analysis of the bactericidal effects of the major human skin fatty acid cis-6-hexadecenoic acid (C6H) on the human commensal and pathogen S. aureus. Several C6H concentration-dependent mechanisms were found. At high concentrations, C6H swiftly kills cells associated with a general loss of membrane integrity. However, C6H still kills at lower concentrations, acting through disruption of the proton motive force, an increase in membrane fluidity, and its effects on electron transfer. The design of analogues with altered bactericidal effects has begun to determine the structural constraints on activity and paves the way for the rational design of new antistaphylococcal agents. PMID:24709265

  20. Polyunsaturated Fatty Acid-Derived Lipid Mediators and T Cell Function

    PubMed Central

    Nicolaou, Anna; Mauro, Claudio; Urquhart, Paula; Marelli-Berg, Federica

    2014-01-01

    Fatty acids are involved in T cell biology both as nutrients important for energy production as well as signaling molecules. In particular, polyunsaturated fatty acids are known to exhibit a range of immunomodulatory properties that progress through T cell mediated events, although the molecular mechanisms of these actions have not yet been fully elucidated. Some of these immune activities are linked to polyunsaturated fatty acid-induced alteration of the composition of cellular membranes and the consequent changes in signaling pathways linked to membrane raft-associated proteins. However, significant aspects of the polyunsaturated fatty acid bioactivities are mediated through their transformation to specific lipid mediators, products of cyclooxygenase, lipoxygenase, or cytochrome P450 enzymatic reactions. Resulting bioactive metabolites including prostaglandins, leukotrienes, and endocannabinoids are produced by and/or act upon T leukocytes through cell surface receptors and have been shown to alter T cell activation and differentiation, proliferation, cytokine production, motility, and homing events. Detailed appreciation of the mode of action of these lipids presents opportunities for the design and development of therapeutic strategies aimed at regulating T cell function. PMID:24611066

  1. [Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease].

    PubMed

    Hagymási, Krisztina; Reismann, Péter; Rácz, Károly; Tulassay, Zsolt

    2009-11-29

    The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future. PMID:19923096

  2. ATGL is a major hepatic lipase that regulates TAG turnover and fatty acid signaling and partitioning

    PubMed Central

    Ong, Kuok Teong; Mashek, Mara T.; Bu, So Young; Greenberg, Andrew S.; Mashek, Douglas G.

    2010-01-01

    Despite advances into our understanding of how nutrient oversupply and triacylglycerol (TAG) anabolism contribute to hepatic steatosis, little is known about the lipases responsible for regulating hepatic TAG turnover. Recent studies have identified adipose triglyceride lipase (ATGL) as a major lipase in adipose tissue although its role in the liver is largely unknown. Thus, we tested the contribution of ATGL to hepatic lipid metabolism and signaling. Adenoviral-mediated knockdown of hepatic ATGL resulted in steatosis in mice and decreased hydrolysis of TAG in primary hepatocyte cultures and in vitro assays. In addition to altering TAG hydrolysis, ATGL is shown to play a significant role in partitioning hydrolyzed fatty acids between metabolic pathways. Whereas ATGL gain- and loss-of-function did not alter hepatic TAG secretion, fatty acid oxidation was increased by ATGL overexpression and decreased by ATGL knockdown. The effects on fatty acid oxidation coincided with decreased expression of PPAR-α and its target genes in mice with suppressed hepatic ATGL expression. However, PPAR-α agonism was unable to normalize the effects of ATGL knockdown on PPAR-α target gene expression suggesting that ATGL influences PPAR-α activity independent of ligand-induced activation. Taken together, these data show that ATGL is a major hepatic TAG lipase that plays an integral role in fatty acid partitioning and signaling to control energy metabolism. PMID:20967758

  3. Trans fatty acid intake and emotion regulation.

    PubMed

    Holt, Megan E; Lee, Jerry W; Morton, Kelly R; Tonstad, Serena

    2015-06-01

    We examined whether there is a relationship between trans fatty acid intakes and emotion regulation, mediated by positive or negative affect. Archival data on 1699 men and 3293 women were used to measure trans fatty acid intake at baseline, positive, and negative affects and emotion regulation at follow-up. Higher trans fatty acid intake related to subsequent difficulties with emotional awareness (p = 0.045), clarity (p = 0.012), and regulation strategies (p = 0.009). Affect mediated these relationships. Lower trans fatty acid intake associated with increased positive and decreased negative affects which, in turn, associated with improved emotion regulation. Trans fatty acid intakes may be associated with subsequent ability to regulate emotions. PMID:26032795

  4. Effects of Fatty Acids and Glycation on Drug Interactions with Human Serum Albumin.

    PubMed

    Anguizola, Jeanethe A; Basiaga, Sara B G; Hage, David S

    2013-09-01

    The presence of elevated glucose concentrations in diabetes is a metabolic change that leads to an increase in the amount of non-enzymatic glycation that occurs for serum proteins. One protein that is affected by this process is the main serum protein, human serum albumin (HSA), which is also an important carrier agent for many drugs and fatty acids in the circulatory system. Sulfonylureas drugs, used to treat type 2 diabetes, are known to have significant binding to HSA. This study employed ultrafiltration and high-performance affinity chromatography to examine the effects of HSA glycation on the interactions of several sulfonylurea drugs (i.e., acetohexamide, tolbutamide and gliclazide) with fatty acids, whose concentrations in serum are also affected by diabetes. Similar overall changes in binding were noted for these drugs with normal HSA or glycated HSA and in the presence of the fatty acids. For most of the tested drugs, the addition of physiological levels of the fatty acids to normal HSA and glycated HSA produced weaker binding. At low fatty acid concentrations, many of these systems followed a direct competition model while others involved a mixed-mode interaction. In some cases, there was a change in the interaction mechanism between normal HSA and glycated HSA, as seen with linoleic acid. Systems with only direct competition also gave notable changes in the affinities of fatty acids at their sites of drug competition when comparing normal HSA and glycated HSA. This research demonstrated the importance of considering how changes in the concentrations and types of metabolites (e.g., in this case, glucose and fatty acids) can alter the function of a protein such as HSA and its ability to interact with drugs or other agents. PMID:24349966

  5. Effects of Fatty Acids and Glycation on Drug Interactions with Human Serum Albumin

    PubMed Central

    Anguizola, Jeanethe A.; Basiaga, Sara B. G.; Hage, David S.

    2013-01-01

    The presence of elevated glucose concentrations in diabetes is a metabolic change that leads to an increase in the amount of non-enzymatic glycation that occurs for serum proteins. One protein that is affected by this process is the main serum protein, human serum albumin (HSA), which is also an important carrier agent for many drugs and fatty acids in the circulatory system. Sulfonylureas drugs, used to treat type 2 diabetes, are known to have significant binding to HSA. This study employed ultrafiltration and high-performance affinity chromatography to examine the effects of HSA glycation on the interactions of several sulfonylurea drugs (i.e., acetohexamide, tolbutamide and gliclazide) with fatty acids, whose concentrations in serum are also affected by diabetes. Similar overall changes in binding were noted for these drugs with normal HSA or glycated HSA and in the presence of the fatty acids. For most of the tested drugs, the addition of physiological levels of the fatty acids to normal HSA and glycated HSA produced weaker binding. At low fatty acid concentrations, many of these systems followed a direct competition model while others involved a mixed-mode interaction. In some cases, there was a change in the interaction mechanism between normal HSA and glycated HSA, as seen with linoleic acid. Systems with only direct competition also gave notable changes in the affinities of fatty acids at their sites of drug competition when comparing normal HSA and glycated HSA. This research demonstrated the importance of considering how changes in the concentrations and types of metabolites (e.g., in this case, glucose and fatty acids) can alter the function of a protein such as HSA and its ability to interact with drugs or other agents. PMID:24349966

  6. Circulating concentrations of non-esterified fatty acids (NEFA) as mediators of the innate immune response in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported that temperamental cattle have greater non-esterified fatty acid (NEFA) concentrations and an altered innate immune response compared to calm cattle. Therefore, this trial was designed to determine if increasing energy availability via a lipid infusion or bolus dextrose inject...

  7. Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings.

    PubMed

    Uranga, Carla C; Beld, Joris; Mrse, Anthony; Córdova-Guerrero, Iván; Burkart, Michael D; Hernández-Martínez, Rufina

    2016-04-01

    The Botryosphaeriaceae are a family of trunk disease fungi that cause dieback and death of various plant hosts. This work sought to characterize fatty acid derivatives in a highly virulent member of this family, Lasiodiplodia theobromae. Nuclear magnetic resonance and gas chromatography-mass spectrometry of an isolated compound revealed (Z, Z)-9,12-ethyl octadecadienoate, (trivial name ethyl linoleate), as one of the most abundant fatty acid esters produced by L. theobromae. A variety of naturally produced esters of fatty acids were identified in Botryosphaeriaceae. In comparison, the production of fatty acid esters in the soil-borne tomato pathogen Fusarium oxysporum, and the non-phytopathogenic fungus Trichoderma asperellum was found to be limited. Ethyl linoleate, ethyl hexadecanoate (trivial name ethyl palmitate), and ethyl octadecanoate, (trivial name ethyl stearate), significantly inhibited tobacco seed germination and altered seedling leaf growth patterns and morphology at the highest concentration (0.2 mg/mL) tested, while ethyl linoleate and ethyl stearate significantly enhanced growth at low concentrations, with both still inducing growth at 98 ng/mL. This work provides new insights into the role of naturally esterified fatty acids from L. theobromae as plant growth regulators with similar activity to the well-known plant growth regulator gibberellic acid. PMID:26926564

  8. Mitochondrial fatty acid synthesis is required for normal mitochondrial morphology and function in Trypanosoma brucei

    PubMed Central

    Guler, Jennifer L.; Kriegova, Eva; Smith, Terry K.; Lukeš, Julius; Englund, Paul T.

    2013-01-01

    Summary Trypanosoma brucei use microsomal elongases for de novo synthesis of most of its fatty acids. In addition, this parasite utilizes an essential mitochondrial type II synthase for production of octanoate (a lipoic acid precursor) as well as longer fatty acids such as palmitate. Evidence from other organisms suggests that mitochondrially synthesized fatty acids are required for efficient respiration but the exact relationship remains unclear. In procyclic form trypanosomes, we also found that RNAi depletion of the mitochondrial acyl carrier protein, an important component of the fatty acid synthesis machinery, significantly reduces cytochrome-mediated respiration. This reduction was explained by RNAi-mediated inhibition of respiratory complexes II, III and IV, but not complex I. Other effects of RNAi, such as changes in mitochondrial morphology and alterations in membrane potential, raised the possibility of a change in mitochondrial membrane composition. Using mass spectrometry, we observed a decrease in total and mitochondrial phosphatidylinositol and mitochondrial phosphatidylethanolamine. Thus, we conclude that the mitochondrial synthase produces fatty acids needed for maintaining local phospholipid levels that are required for activity of respiratory complexes and preservation of mitochondrial morphology and function. PMID:18221265

  9. Directed evolution increases desaturation of a cyanobacterial fatty acid desaturase in eukaryotic expression systems.

    PubMed

    Bai, Shuangyi; Wallis, James G; Denolf, Peter; Browse, John

    2016-07-01

    Directed evolution of a cyanobacterial Δ9 fatty acid desaturase (DSG) from Synechococcus elongatus, PCC6301 created new, more productive desaturases and revealed the importance of certain amino acid residues to increased desaturation. A codon-optimized DSG open reading frame with an endoplasmic-reticulum retention/retrieval signal appended was used as template for random mutagenesis. Increased desaturation was detected using a novel screen based on complementation of the unsaturated fatty acid auxotrophy of Saccharomyces cerevisiae mutant ole1Δ. Amino acid residues whose importance was discovered by the random processes were further examined by saturation mutation to determine the best amino acid at each identified location in the peptide chain and by combinatorial analysis. One frequently-detected single amino acid change, Q240R, yielded a nearly 25-fold increase in total desaturation in S. cerevisiae. Several other variants of the protein sequence with multiple amino acid changes increased total desaturation more than 60-fold. Many changes leading to increased desaturation were in the vicinity of the canonical histidine-rich regions known to be critical for electron transfer mediated by these di-iron proteins. Expression of these evolved proteins in the seed of Arabidopsis thaliana altered the fatty acid composition, increasing monounsaturated fatty acids and decreasing the level of saturated fatty acid, suggesting a potential application of these desaturases in oilseed crops. Biotechnol. Bioeng. 2016;113: 1522-1530. © 2016 Wiley Periodicals, Inc. PMID:26724425

  10. Changes in fatty acid composition in plant tissues expressing a mammalian delta9 desaturase.

    PubMed

    Moon, H; Hazebroek, J; Hildebrand, D F

    2000-05-01

    Plant tissues expressing a mammalian stearoyl-CoA delta9 desaturase were reported to accumulate delta9 hexadecenoic acid (16:1), normally very minor in most plant tissues. The transgenic plants were thoroughly analyzed for alterations of individual lipids in different subcellular sites. Western blot analysis indicated that the animal desaturase was targeted to the microsomes. The delta9 16:1 was incorporated into both the sn-1 and sn-2 positions of all the major membrane lipids tested, indicating that the endoplasmic reticulum acyltransferases do not exclude unsaturated C16 fatty acids from the sn-2 position. In addition to increases in monounsaturated and decreases in saturated fatty acids, accumulation of 16:1 was accompanied by a reduction in 18:3 in all the lipids tested except phosphatidylglycerol, and increases in 18:2 in phospholipids. Total C16 fatty acid content in the galactolipids of the transgenics was significantly higher than that in the control, but those in the phospholipids were unchanged. In transgenics, delta11 18:1 was detected in the sn-1 position of the lipids tested except phosphatidylinositol and phosphatidylserine. Introduction of the animal desaturase, controlled by a seed-specific phaseolin promoter, into soybean somatic embryo resulted in a significant reduction in saturated fatty acids. Such effects were greater in cotyledons than hypocotyl-radicles. This study demonstrated that the animal desaturase can be used to decrease the levels of saturated fatty acids in a crop plant. PMID:10907781

  11. Efficacy of sodium borate in the prevention of fatty liver in dairy cows.

    PubMed

    Basoglu, Abdullah; Sevinc, Mutlu; Birdane, Fatih M; Boydak, Murat

    2002-01-01

    The effects of sodium borate (100 mg/kg body weight, p.o., 15 days) from a month before expected calving until a month after calving were evaluated in dairy cows susceptible to fatty liver. Cows received either sodium borate (n = 13) or no treatment (n = 10). All cows had mild fatty livers and increased plasma triglycerides and very low density lipoprotein (VLDL) concentrations at the beginning of the experiment. The control group of cows developed significant fatty liver after calving, and 2 of them had severe fatty liver associated with clinical and biochemical abnormalities. There were no clinicopathological signs related to sodium borate administration. Serum triglycerides and VLDL concentrations before calving decreased significantly at calving and after calving in controls, and they were within the normal range only after calving. There were significant alterations during the experiment in some hematological and chemical variables between groups, within period, but they were within the normal range. Unlike treated cows, serum triglycerides and VLDL concentrations correlated with liver fat content after calving in untreated cows. Our results document that sodium borate decreases the degree of fatty liver in dairy cows during early lactation. PMID:12465773

  12. Cold Shock Response of Bacillus subtilis: Isoleucine-Dependent Switch in the Fatty Acid Branching Pattern for Membrane Adaptation to Low Temperatures†

    PubMed Central

    Klein, Wolfgang; Weber, Michael H. W.; Marahiel, Mohamed A.

    1999-01-01

    Bacillus subtilis has developed sophisticated mechanisms to withstand fluctuations in temperature. Membrane fatty acids are the major determinants for a sufficiently fluid membrane state to ensure the membrane’s function at all temperatures. The fatty acid profile of B. subtilis is characterized by a high content of branched fatty acids irrespective of the growth medium. Here, we report on the importance of isoleucine for B. subtilis to survive cold shock from 37 to 15°C. Cold shock experiments with strain JH642 revealed a cold-protective function for all intermediates of anteiso-branched fatty acid biosynthesis. Metabolites related to iso-branched or straight-chain fatty acid biosynthesis were not protective. Fatty acid profiles of different B. subtilis wild-type strains proved the altered branching pattern by an increase in the anteiso-branched fatty acid content and a concomitant decrease of iso-branched species during cold shock. There were no significant changes in the fatty acid saturation or acyl chain length. The cold-sensitive phenotype of isoleucine-deficient strains in the absence of isoleucine correlated with their inability to synthesize more anteiso-branched fatty acids, as shown by the fatty acid profile. The switch to a fatty acid profile dominated by anteiso-C15:0 and C17:0 at low temperatures and the cold-sensitive phenotype of isoleucine-deficient strains in the absence of isoleucine focused our attention on the critical role of anteiso-branched fatty acids in the growth of B. subtilis in the cold. PMID:10464205

  13. De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids.

    PubMed

    Tucci, Sara; Behringer, Sidney; Spiekerkoetter, Ute

    2015-11-01

    An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal β-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal β-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing. PMID:26284828

  14. Potency of pre–post treatment of coenzyme Q10 and melatonin supplement in ameliorating the impaired fatty acid profile in rodent model of autism

    PubMed Central

    El-Ansary, Afaf; Al-Ghamdi, Mashael; Bhat, Ramesa Shafi; Al-daihan, Sooad; Al-Ayadhi, Laila

    2016-01-01

    Background Abnormalities in fatty acid metabolism and membrane fatty acid composition play a part in a wide range of neurodevelopmental and psychiatric disorders. Altered fatty acid homeostasis as a result of insufficient dietary supplementation, genetic defects, the function of enzymes involved in their metabolism, or mitochondrial dysfunction contributes to the development of autism. Objective This study evaluates the association of altered brain lipid composition and neurotoxicity related to autism spectrum disorders in propionic acid (PA)–treated rats. Design Forty-eight young male western albino rats were used in this study. They were grouped into six equal groups with eight rats in each. The first group received only phosphate buffered saline (control group). The second group received a neurotoxic dose of buffered PA (250 mg/kg body weight/day for 3 consecutive days). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for 1 week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for 1 week prior to PA (protected groups). Methyl esters of fatty acid were extracted with hexane, and the fatty acid composition of the extract was analyzed on a gas chromatography. Results The obtained data proved that fatty acids are altered in brain tissue of PA-treated rats. All saturated fatty acids were increased while all unsaturated fatty acids were significantly decreased in the PA-treated group and relatively ameliorated in the pre–post melatonin and coenzyme Q groups. Conclusions Melatonin and coenzyme Q were effective in restoring normal level of most of the impaired fatty acids in PA-intoxicated rats which could help suggest both as supplements to ameliorate the autistic features induced in rat pups. PMID:26945230

  15. Molten fatty acid based microemulsions.

    PubMed

    Noirjean, Cecile; Testard, Fabienne; Dejugnat, Christophe; Jestin, Jacques; Carriere, David

    2016-06-21

    We show that ternary mixtures of water (polar phase), myristic acid (MA, apolar phase) and cetyltrimethylammonium bromide (CTAB, cationic surfactant) studied above the melting point of myristic acid allow the preparation of microemulsions without adding a salt or a co-surfactant. The combination of SANS, SAXS/WAXS, DSC, and phase diagram determination allows a complete characterization of the structures and interactions between components in the molten fatty acid based microemulsions. For the different structures characterized (microemulsion, lamellar or hexagonal phases), a similar thermal behaviour is observed for all ternary MA/CTAB/water monophasic samples and for binary MA/CTAB mixtures without water: crystalline myristic acid melts at 52 °C, and a thermal transition at 70 °C is assigned to the breaking of hydrogen bounds inside the mixed myristic acid/CTAB complex (being the surfactant film in the ternary system). Water determines the film curvature, hence the structures observed at high temperature, but does not influence the thermal behaviour of the ternary system. Myristic acid is partitioned in two "species" that behave independently: pure myristic acid and myristic acid associated with CTAB to form an equimolar complex that plays the role of the surfactant film. We therefore show that myristic acid plays the role of a solvent (oil) and a co-surfactant allowing the fine tuning of the structure of oil and water mixtures. This solvosurfactant behaviour of long chain fatty acid opens the way for new formulations with a complex structure without the addition of any extra compound. PMID:27241163

  16. PREECLAMPSIA IS ASSOCIATED WITH COMPROMISED MATERNAL SYNTHESIS OF LONG CHAIN POLYUNSATURATED FATTY ACIDS LEADING TO OFFSPRING DEFICIENCY

    PubMed Central

    Mackay, Vanessa A; Huda, Shahzya S; Stewart, Frances M; Tham, Kahmeng; McKenna, Louise A; Martin, Iain; Jordan, Fiona; Brown, E Ann; Hodson, Leanne; Greer, Ian A; Meyer, Barbara J; Freeman, Dilys J

    2013-01-01

    Obesity and excessive lipolysis are implicated in preeclampsia. Intrauterine growth restriction is associated with low maternal body mass index and decreased lipolysis. Our aim was to assess how maternal and offspring fatty acid metabolism is altered in mothers in the third trimester of pregnancy with preeclampsia (n=62) or intrauterine growth restriction (n=23) compared to healthy pregnancies (n=164). Markers of lipid metabolism and erythrocyte fatty acid concentrations were measured. Maternal adipose tissue fatty acid composition and mRNA expression of adipose tissue fatty acid metabolizing enzymes and placental fatty acid transporters were compared. Mothers with preeclampsia had higher plasma triglyceride (21%, p<0.001) and non-esterified fatty acid (50%, p<0.001) concentrations than Controls. Concentrations of major n-6 and n-3 long chain polyunsaturated fatty acids in erythrocytes were 23-60% lower (all p<0.005) in preeclampsia and intrauterine growth restriction mothers and offspring compared to Controls. Subcutaneous adipose tissue Δ-5 and Δ-6 desaturase and very long chain fatty acid elongase mRNA expression was lower in preeclampsia than Controls [Control 3.38(2.96) vs preeclampsia 1.83(1.91), p=0.030; 3.33(2.25) vs 1.03(0.96), p<0.001; 0.40 (0.81) vs 0.00 (0.00), p=0.038 (square root) expression relative to control gene respectively]. Low maternal and fetal long chain polyunsaturated fatty acid concentrations in preeclampsia may be the result of decreased maternal synthesis. PMID:22949531

  17. Effect of a diet enriched with omega-6 and omega-3 fatty acids on the pig liver transcriptome.

    PubMed

    Szostak, Agnieszka; Ogłuszka, Magdalena; Te Pas, Marinus F W; Poławska, Ewa; Urbański, Paweł; Juszczuk-Kubiak, Edyta; Blicharski, Tadeusz; Pareek, Chandra Shekhar; Dunkelberger, Jenelle R; Horbańczuk, Jarosław O; Pierzchała, Mariusz

    2016-01-01

    The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping the homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n = 12) were fed diet enriched with linoleic acid (LA, omega-6) and α-linolenic acid (ALA, omega-3) or standard diet as a control. The fatty acid profiling was assayed in order to verify how feeding influenced the fatty acid content in the liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified using DAVID and Cytoscape tools. Fatty acid profile analysis indicated a higher contribution of PUFAs in the liver for LA- and ALA-enriched diet group, particularly for the omega-3 fatty acid family, but not omega-6. Next-generation sequencing identified 3565 DEG, 1484 of which were induced and 2081 were suppressed by PUFA supplementation. A low ratio of omega-6/omega-3 fatty acids resulted in the modulation of fatty acid metabolism pathways and over-representation of genes involved in energy metabolism, signal transduction, and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and would influence animal health status. PMID:27482299

  18. Fatty acid mobilization and comparison to milk fatty acid content in northern elephant seals.

    PubMed

    Fowler, Melinda A; Debier, Cathy; Mignolet, Eric; Linard, Clementine; Crocker, Daniel E; Costa, Daniel P

    2014-01-01

    A fundamental feature of the life history of true seals, bears and baleen whales is lactation while fasting. This study examined the mobilization of fatty acids from blubber and their subsequent partitioning into maternal metabolism and milk production in northern elephant seals (Mirounga angustirostris). The fatty acid composition of blubber and milk was measured in both early and late lactation. Proportions of fatty acids in milk and blubber were found to display a high degree of similarity both early and late in lactation. Seals mobilized an enormous amount of lipid (~66 kg in 17 days), but thermoregulatory fatty acids, those that remain fluid at low temperatures, were relatively conserved in the outer blubber layer. Despite the stratification, the pattern of mobilization of specific fatty acids conforms to biochemical predictions. Long chain (>20C) monounsaturated fatty acids (MUFAs) were the least mobilized from blubber and the only class of fatty acids that showed a proportional increase in milk in late lactation. Polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs) were more mobilized from the blubber, but neither proportion increased in milk at late lactation. These data suggest that of the long chain MUFA mobilized, the majority is directed to milk synthesis. The mother may preferentially use PUFA and SFA for her own metabolism, decreasing the availability for deposition into milk. The potential impacts of milk fatty acid delivery on pup diving development and thermoregulation are exciting avenues for exploration. PMID:24126964

  19. Orthogonal Fatty Acid Biosynthetic Pathway Improves Fatty Acid Ethyl Ester Production in Saccharomyces cerevisiae.

    PubMed

    Eriksen, Dawn T; HamediRad, Mohammad; Yuan, Yongbo; Zhao, Huimin

    2015-07-17

    Fatty acid ethyl esters (FAEEs) are a form of biodiesel that can be microbially produced via a transesterification reaction of fatty acids with ethanol. The titer of microbially produced FAEEs can be greatly reduced by unbalanced metabolism and an insufficient supply of fatty acids, resulting in a commercially inviable process. Here, we report on a pathway engineering strategy in Saccharomyces cerevisiae for enhancing the titer of microbially produced FAEEs by providing the cells with an orthogonal route for fatty acid synthesis. The fatty acids generated from this heterologous pathway would supply the FAEE production, safeguarding endogenous fatty acids for cellular metabolism and growth. We investigated the heterologous expression of a Type-I fatty acid synthase (FAS) from Brevibacterium ammoniagenes coupled with WS/DGAT, the wax ester synthase/acyl-coenzyme that catalyzes the transesterification reaction with ethanol. Strains harboring the orthologous fatty acid synthesis yielded a 6.3-fold increase in FAEE titer compared to strains without the heterologous FAS. Variations in fatty acid chain length and degree of saturation can affect the quality of the biodiesel; therefore, we also investigated the diversity of the fatty acid production profile of FAS enzymes from other Actinomyces organisms. PMID:25594225

  20. Alterations in carbohydrate metabolism and its regulation in PPARalpha null mouse hearts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although a shift from fatty acids (FAs) to carbohydrates (CHOs) is considered beneficial for the diseased heart, it is unclear why subjects with FA beta-oxidation defects are prone to cardiac decompensation under stress conditions. The present study investigated potential alterations in the myocardi...

  1. Histopathological alterations in the liver of freshwater teleost Tilapia mossambica in response to cadmium toxicity

    SciTech Connect

    Usha Rani, A.; Ramamurthi, R.

    1989-04-01

    The effects of lethal (50 ppm) and sublethal (5 ppm) concentrations of CdCl/sub 2/ on the liver of the freshwater teleost Tilapia mossambica were studied by routine histological techniques. Engorged blood vessels, congestion, vacuolar degeneration of hepatocytes, necrosis of pancreatic cells, and fatty changes in the peripancreatic hepatocytes were the pathological alterations observed in liver.

  2. Agricultural practices altered soybean seed protein, oil, fattyacids,sugars, and minerals in the Midsouth USA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Management practices such as seeding rate (SR), planting date (PD), and row-type (RT: single- and twin-rows) may alter seed nutrition in soybean. The objective of this research was to investigate the effects of SR and PD on soybean seed composition (protein, oil, fatty acids, and sugars) and mineral...

  3. Fatty acid synthesis is inhibited by inefficient utilization of unusual fatty acids for glycerolipid assembly

    PubMed Central

    Bates, Philip D.; Johnson, Sean R.; Cao, Xia; Li, Jia; Nam, Jeong-Won; Jaworski, Jan G.; Ohlrogge, John B.; Browse, John

    2014-01-01

    Degradation of unusual fatty acids through β-oxidation within transgenic plants has long been hypothesized as a major factor limiting the production of industrially useful unusual fatty acids in seed oils. Arabidopsis seeds expressing the castor fatty acid hydroxylase accumulate hydroxylated fatty acids up to 17% of total fatty acids in seed triacylglycerols; however, total seed oil is also reduced up to 50%. Investigations into the cause of the reduced oil phenotype through in vivo [14C]acetate and [3H]2O metabolic labeling of developing seeds surprisingly revealed that the rate of de novo fatty acid synthesis within the transgenic seeds was approximately half that of control seeds. RNAseq analysis indicated no changes in expression of fatty acid synthesis genes in hydroxylase-expressing plants. However, differential [14C]acetate and [14C]malonate metabolic labeling of hydroxylase-expressing seeds indicated the in vivo acetyl–CoA carboxylase activity was reduced to approximately half that of control seeds. Therefore, the reduction of oil content in the transgenic seeds is consistent with reduced de novo fatty acid synthesis in the plastid rather than fatty acid degradation. Intriguingly, the coexpression of triacylglycerol synthesis isozymes from castor along with the fatty acid hydroxylase alleviated the reduced acetyl–CoA carboxylase activity, restored the rate of fatty acid synthesis, and the accumulation of seed oil was substantially recovered. Together these results suggest a previously unidentified mechanism that detects inefficient utilization of unusual fatty acids within the endoplasmic reticulum and activates an endogenous pathway for posttranslational reduction of fatty acid synthesis within the plastid. PMID:24398521

  4. Short-chain fatty acids regulate IGF-binding protein secretion by intestinal epithelial cells.

    PubMed

    Nishimura, A; Fujimoto, M; Oguchi, S; Fusunyan, R D; MacDermott, R P; Sanderson, I R

    1998-07-01

    Gastrointestinal epithelial cells secrete insulin-like growth factor (IGF)-binding proteins (IGFBPs), which modulate the actions of IGFs on cell proliferation and differentiation. Short-chain fatty acids are bacterial metabolites from unabsorbed carbohydrate (including fiber). We hypothesized that they may alter the pattern of IGFBPs secreted by epithelial cells as part of a wider phenomenon by which luminal molecules regulate gastrointestinal epithelial cell signaling. The intestinal epithelial cell line, Caco-2, predominantly secretes IGFBP-3; however, butyrate increased the secretion of IGFBP-2 in a dose-dependent and reversible manner. Butyrate decreased the secretion of IGFBP-3. Butyrate altered only the synthesis and not the cell sorting of IGFBPs because 1) the secretion of IGFBPs remained polarized despite changes in their rates of production, and 2) IGFBP secretion corresponded to mRNA accumulation. The ability of short-chain fatty acids or the fungicide trichostatin A to stimulate IGFBP-2 correlated with their actions on histone acetylation. In conclusion, intestinal epithelial cells respond to short-chain fatty acids by altering secretion of IGFBPs. PMID:9688874

  5. Hemostasis alterations in metabolic syndrome (review).

    PubMed

    Palomo, Iván; Alarcón, Marcelo; Moore-Carrasco, Rodrigo; Argilés, Josep M

    2006-11-01

    Metabolic syndrome (MS) is characterized by the presence of at least three of the following alterations: enlargement of the waist diameter, higher levels of arterial pressure, low density lipoprotein cholesterol and glycemia, and reduction of high density lipoprotein cholesterol. The prevalence of MS reaches 23% in young adults, a percentage that increases with age. People with MS have a greater risk of suffering from cardiovascular disease (CVD). The physiopathologic alterations now found to exist in MS are diverse; among them is endothelial dysfunction, which triggers atherogenic lesions and hypercoagulability characterized by alterations of the coagulation factors and the regulatory proteins of fibrinolysis such as the plasminogen activator inhibitor (PAI-1). The increase in oxidative stress and/or the reactive oxygen species in patients with MS is partially related to the oxidation state of the lipoproteins, especially of the low density lipoproteins. This fact favors atherogenesis. Moreover, the oxidative stress produces alterations in the production of adipokines, cytokines secreted by the adipose tissues. The abnormality in the transport of lipoprotein diminishes the catabolism of the very low density lipoprotein (VLDL) and increases the catabolism of the high density lipoprotein (HDL), which creates insulin resistance. This process is associated with a lower concentration of adiponectin that in turn regulates the catabolism of VLDL and HDL; consequently increasing the flow of fatty acids from the adipose tissue to the liver and muscles. The proinflammatory cytokines, among them tumor necrosis factor alpha (TNF-alpha), are of great importance in MS regulating different processes and molecules such as PAI-1. PAI-1 is controlled by the group of transcription factors peroxisome proliferator-activated receptor (PPAR), especially by PPAR gamma and alpha ligands. In summary, MS includes multiple alterations related to insulin resistance at several levels: hepatic

  6. Desaturation of fatty acids in Trypanosoma cruzi

    SciTech Connect

    de Lema, M.G.; Aeberhard, E.E.

    1986-11-01

    Uptake and metabolism of saturated (16:0, 18:0) and unsaturated (18:1(n-9), 18:2(n-6), 18:3(n-3)) fatty acids by cultured epimastigotes of Trypanosoma cruzi were studied. Between 17.5 and 33.5% of the total radioactivity of (1-/sup 14/C)labeled fatty acids initially added to the culture medium was incorporated into the lipids of T. cruzi and mostly choline and ethanolamine phospholipids. As demonstrated by argentation thin layer chromatography, gas liquid chromatography and ozonolysis of the fatty acids synthesized, exogenous palmitic acid was elongated to stearic acid, and the latter was desaturated to oleic acid and 18:2 fatty acid. The 18:2 fatty acid was tentatively identified as linoleic acid with the first bond in the delta 9 position and the second bond toward the terminal methyl end. Exogenous stearic acid was also desaturated to oleic and 18:2 fatty acid, while oleic acid was only converted into 18:2. All of the saturated and unsaturated fatty acids investigated were also converted to a small extent (2-4%) into polyunsaturated fatty acids. No radioactive aldehyde methyl ester fragments of less than nine carbon atoms were detected after ozonolysis of any of the fatty acids studied. These results demonstrate the existence of delta 9 and either delta 12 or delta 15 desaturases, or both, in T. cruzi and suggest that delta 6 desaturase or other desaturases of the animal type are likely absent in cultured forms of this organism.

  7. Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol.

    PubMed

    Devaraj, Gopi N; Parakh, S R; Devraj, Ravi; Apte, S S; Rao, B Ramesh; Rambhau, D

    2002-07-15

    MA concentration is kept constant at 50 mole% and the ratio of PGDS and PS-80 was altered, significant changes in entrapment efficiency and the release rate were observed. However, this ratio did not exhibit any relation with encapsulation efficiency or release rate. The release rate and entrapment exhibited an inverse correlation (r(2)=0.8774 at p<0.02 for the data of molar ratios of PGDS:MA:PS80; r(2)=0.975 at p<0.001 for the data of acyl chain length variation of polysorbates). It can be concluded that stable niosomes of polyglyceryl-3-di-isostearate could be prepared with fatty alcohols and polysorbates instead of cholesterol and that the release of solutes from these niosomes can be optimized by altering membrane constituents and their concentrations. PMID:16290741

  8. Hepatic Fatty Acid Trafficking: Multiple Forks in the Road123

    PubMed Central

    Mashek, Douglas G.

    2013-01-01

    The liver plays a unique, central role in regulating lipid metabolism. In addition to influencing hepatic function and disease, changes in specific pathways of fatty acid (FA) metabolism have wide-ranging effects on the metabolism of other nutrients, extra-hepatic physiology, and the development of metabolic diseases. The high prevalence of nonalcoholic fatty liver disease (NAFLD) has led to increased efforts to characterize the underlying biology of hepatic energy metabolism and FA trafficking that leads to disease development. Recent advances have uncovered novel roles of metabolic pathways and specific enzymes in generating lipids important for cellular processes such as signal transduction and transcriptional activation. These studies have also advanced our understanding of key branch points involving FA partitioning between metabolic pathways and have identified new roles for lipid droplets in these events. This review covers recent advances in our understanding of FA trafficking and its regulation. An emphasis will be placed on branch points in these pathways and how alterations in FA trafficking contribute to NAFLD and related comorbidities. PMID:24228201

  9. Modulation of human erythrocyte shape and fatty acids by diet.

    PubMed

    Parsons, H G; Hill, R; Pencharz, P; Kuksis, A

    1986-08-21

    A semi-synthetic diet (Vivonex) was administered via nasogastric tube to three cystic fibrosis patients with pancreatic exocrine deficiency for 14 days to gain weight. Dietary essential fatty acids were provided as safflower oil, which constituted 1.3% of total calories. Plasma and red blood cells were analyzed for the content and composition of lipids at the start of the diet and at days 7 and 14 of the dietary period, and the results were correlated with the morphology of the cells. Feeding Vivonex to the patients led to an essential fatty acid deficiency, which was manifested in a 50% decrease in the linoleic acid content of the phosphatidylcholine of plasma and red blood cells at days 7 and 14 and in a 20% decrease in the linoleic acid content of red cell phosphatidylethanolamine at day 14. There was no significant alteration in the levels or composition of the other phospholipid classes and in the free cholesterol/phospholipid ratio. The decrease in the linoleic acid content of the erythrocytes was accompanied by a dramatic increase in the proportion of cells as echinocytes. We conclude that restricted linoleic acid availability in cystic fibrosis patients causes a change in red blood cell shape either directly by decreasing the linoleoylphosphatidylcholine content of the membrane or indirectly by affecting enzyme activity. PMID:3741859

  10. Polyunsaturated fatty acid supplementation reverses cystic fibrosis-related fatty acid abnormalities in CFTR-/- mice by suppressing fatty acid desaturases.

    PubMed

    Njoroge, Sarah W; Laposata, Michael; Boyd, Kelli L; Seegmiller, Adam C

    2015-01-01

    Cystic fibrosis patients and model systems exhibit consistent abnormalities in metabolism of polyunsaturated fatty acids that appear to play a role in disease pathophysiology. Recent in vitro studies have suggested that these changes are due to overexpression of fatty acid desaturases that can be reversed by supplementation with the long-chain polyunsaturated fatty acids docosahexaenoate and eicosapentaenoate. However, these findings have not been tested in vivo. The current study aimed to test these results in an in vivo model system, the CFTR(-/-) knockout mouse. When compared with wild-type mice, the knockout mice exhibited fatty acid abnormalities similar to those seen in cystic fibrosis patients and other model systems. The abnormalities were confined to lung, ileum and pancreas, tissues that are affected by the disease. Similar to in vitro models, these fatty acid changes correlated with increased expression of Δ5- and Δ6-desaturases and elongase 5. Dietary supplementation with high-dose free docosahexaenoate or a combination of lower-dose docosahexaenoate and eicosapentaenoate in triglyceride form corrected the fatty acid abnormalities and reduced expression of the desaturase and elongase genes in the ileum and liver of knockout mice. Only the high-dose docosahexaenoate reduced histologic evidence of disease, reducing mucus accumulation in ileal sections. These results provide in vivo support for the hypothesis that fatty acid abnormalities in cystic fibrosis result from abnormal expression and activity of metabolic enzymes in affected cell types. They further demonstrate that these changes can be reversed by dietary n-3 fatty acid supplementation, highlighting the potential therapeutic benefit for cystic fibrosis patients. PMID:25448610

  11. Four Trypanosoma brucei fatty acyl-CoA synthetases: fatty acid specificity of the recombinant proteins.

    PubMed Central

    Jiang, D W; Englund, P T

    2001-01-01

    As part of our investigation of fatty acid metabolism in Trypanosoma brucei, we have expressed four acyl-CoA synthetase (TbACS) genes in Esherichia coli. The recombinant proteins, with His-tags on their C-termini, were purified to near homogeneity using nickel-chelate affinity chromatography. Although these enzymes are highly homologous, they have distinct specificities for fatty acid chain length. TbACS1 prefers saturated fatty acids in the range C(11:0) to C(14:0) and TbACS2 prefers shorter fatty acids, mainly C(10:0). TbACS3 and 4, which have 95% sequence identity, have similar specificities, favouring fatty acids between C(14:0) and C(17:0). In addition, TbACS1, 3 and 4 function well with a variety of unsaturated fatty acids. PMID:11535136

  12. Evaluation of fatty proportion in fatty liver using least squares method with constraints.

    PubMed

    Li, Xingsong; Deng, Yinhui; Yu, Jinhua; Wang, Yuanyuan; Shamdasani, Vijay

    2014-01-01

    Backscatter and attenuation parameters are not easily measured in clinical applications due to tissue inhomogeneity in the region of interest (ROI). A least squares method(LSM) that fits the echo signal power spectra from a ROI to a 3-parameter tissue model was used to get attenuation coefficient imaging in fatty liver. Since fat's attenuation value is higher than normal liver parenchyma, a reasonable threshold was chosen to evaluate the fatty proportion in fatty liver. Experimental results using clinical data of fatty liver illustrate that the least squares method can get accurate attenuation estimates. It is proved that the attenuation values have a positive correlation with the fatty proportion, which can be used to evaluate the syndrome of fatty liver. PMID:25226986

  13. 21 CFR 178.3480 - Fatty alcohols, synthetic.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Fatty alcohols, synthetic. 178.3480 Section 178... § 178.3480 Fatty alcohols, synthetic. Synthetic fatty alcohols may be safely used as components of... following prescribed conditions: (a) The food additive consists of fatty alcohols meeting the...

  14. The role of essential fatty acids in development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acids are aliphatic monocarboxylic acids. They are classified as saturated, monounsaturated, or polyunsaturated fatty acids depending upon the number of double bonds in the carbon chain. Saturated fatty acids have no double bonds, monounsaturated fatty acids have 1 double bond, and polyunsat...

  15. Oxidation of fatty aldehydes to fatty acids by Escherichia coli cells expressing the Vibrio harveyi fatty aldehyde dehydrogenase (FALDH).

    PubMed

    Buchhaupt, Markus; Guder, Jan; Sporleder, Fenja; Paetzold, Melanie; Schrader, Jens

    2013-03-01

    Fatty acids represent an important renewable feedstock for the chemical industry. To enable biotechnological one carbon truncations of fatty acids, the enzymes α-dioxygenase and fatty aldehyde dehydrogenase (FALDH) have to be combined in a two-step process. We expressed an FALDH from V. harveyi in E. coli and characterized its substrate spectrum with a focus on the number and position of double bonds in the fatty aldehyde molecules. Synthesis of the expected fatty acid products was proven by analysis of whole cell biotransformation products. Coexpression of a H(2)O-forming NADPH oxidase (NOX) from Lactobacillus sanfranciscensis led to the implementation of a cofactor regeneration cycle in in vitro oxidation experiments. The presence of NOX in whole cell biotransformations improved reaction velocity but did not result in higher product yields. We could further demonstrate that at least part of the endogenous NAD(P)(+) regeneration capacity in the resting cells results from the respiratory chain. The whole cell catalyst with the high broad range FALDH activity described here is an important biotechnological module for lipid biotransformation processes, especially the shortening of fatty acids. PMID:23180547

  16. Attention Alters Perceived Attractiveness.

    PubMed

    Störmer, Viola S; Alvarez, George A

    2016-04-01

    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another. PMID:26966228

  17. Omega-3 Fatty Acids during Pregnancy

    MedlinePlus

    ... omega-3s. They are mostly found in fatty fish like salmon, sardines, and trout. Some eggs are ... and yogurt. Should I Worry About Eating Certain Fish? Because of mercury contamination of our oceans, rivers, ...

  18. Oxygenases for aliphatic hydrocarbons and fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxygenases catalyzing the insertion of oxygen into either aliphatic hydrocarbons or fatty acids have great similarity. There are two classes of oxygenases: monooxygenases and dioxygenases. Dioxygenase inserts both atoms of molecular oxygen into a substrate, whereas monooxygenase incorporates one a...

  19. Omega-3 Fatty Acid supplementation during pregnancy.

    PubMed

    Greenberg, James A; Bell, Stacey J; Ausdal, Wendy Van

    2008-01-01

    Omega-3 fatty acids are essential and can only be obtained from the diet. The requirements during pregnancy have not been established, but likely exceed that of a nonpregnant state. Omega-3 fatty acids are critical for fetal neurodevelopment and may be important for the timing of gestation and birth weight as well. Most pregnant women likely do not get enough omega-3 fatty acids because the major dietary source, seafood, is restricted to 2 servings a week. For pregnant women to obtain adequate omega-3 fatty acids, a variety of sources should be consumed: vegetable oils, 2 low-mercury fish servings a week, and supplements (fish oil or algae-based docosahexaenoic acid). PMID:19173020

  20. Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women’s Health Initiative Memory Study

    PubMed Central

    Harris, William S.; Luo, Juhua; Pottala, James V.; Margolis, Karen L.; Espeland, Mark A.; Robinson, Jennifer G.

    2016-01-01

    Context The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio. Objective To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes. Design Prospective observational cohort study nested in the Women’s Health Initiative Memory Study. Setting General population. Subjects Postmenopausal women. Main Outcome Measures Self-reported incident type 2 diabetes. Results There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81–0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04–1.25; and HR 1.24, 95% CI 1.14–1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids. Conclusions Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes. PMID:26881936

  1. Fatty acyl-CoA reductase

    SciTech Connect

    Reiser, Steven E.; Somerville, Chris R.

    1998-12-01

    The present invention relates to bacterial enzymes, in particular to an acyl-CoA reductase and a gene encoding an acyl-CoA reductase, the amino acid and nucleic acid sequences corresponding to the reductase polypeptide and gene, respectively, and to methods of obtaining such enzymes, amino acid sequences and nucleic acid sequences. The invention also relates to the use of such sequences to provide transgenic host cells capable of producing fatty alcohols and fatty aldehydes.

  2. Fatty Acid Profile of Milk and Cheese from Dairy Cows Supplemented a Diet with Palm Kernel Cake.

    PubMed

    Oliveira, Ronaldo; Faria, Mario; Silva, Raimundo; Bezerra, Leilson; Carvalho, Gleidson; Pinheiro, Alyson; Simionato, Juliana; Leão, André

    2015-01-01

    Lipid supplements (oilseeds vegetables) are included in ruminant diet to increase its energy density and improve fatty acid composition of milk and consequently of fresh cheese. Milk and cheeses were evaluated from crossbred Holstein × Zebu, fed diets enriched with 0%, 25%, 50%, and 75% inclusion levels of palm kernel cake in concentrated supplement, which were supplied daily (3.0 kg). Milk and fresh cheese (p = 0.001) fatty acids C12:0 exhibited quadratic negative values. Milk fatty acids C13:0, C20:0, C18:2t10c12, and C20:2n-6 presented positive quadratic values. The milk C18:2n-6 decreased linearly and in fresh cheese exhibited an increasing linear effect (p = 0.016). However, the fatty acids grouped in milk fat were not affected. The medium-chain fatty acids varied negatively and quadratically (p = 0.045). There was no effect on milk and fresh cheese chemical composition (p > 0.05). The milk fat was increased (p = 0.0065) quadratically (minimum point of 24.7%). Thus, the addition of palm kernel cake to cow diets negatively altered the fatty acid profile, it raises the percentage of lauric (C12) and tridecanoic (C13) acids fat which is not beneficial to human health from a nutraceutical perspective, although it did not influence the atherogenicity index. PMID:26305244

  3. Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity.

    PubMed

    Kaliannan, K; Wang, B; Li, X-Y; Bhan, A K; Kang, J X

    2016-06-01

    Early-life antibiotic exposure can disrupt the founding intestinal microbial community and lead to obesity later in life. Recent studies show that omega-3 fatty acids can reduce body weight gain and chronic inflammation through modulation of the gut microbiota. We hypothesize that increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life. Here, we utilize the fat-1 transgenic mouse model, which can endogenously produce omega-3 fatty acids and thereby eliminates confounding factors of diet, to show that elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver and dyslipidemia resulting from early-life exposure to azithromycin. These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice. These results demonstrate the beneficial effects of omega-3 fatty acids on antibiotic-induced gut dysbiosis and obesity, and suggest the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics. PMID:26876435

  4. 21 CFR 172.863 - Salts of fatty acids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Salts of fatty acids. 172.863 Section 172.863 Food... of fatty acids. The food additive salts of fatty acids may be safely used in food and in the... salts of the fatty acids conforming with § 172.860 and/or oleic acid derived from tall oil fatty...

  5. Splanchnic free fatty acid kinetics.

    PubMed

    Jensen, Michael D; Cardin, Sylvain; Edgerton, Dale; Cherrington, Alan

    2003-06-01

    These studies were conducted to assess the relationship between visceral adipose tissue free fatty acid (FFA) release and splanchnic FFA release. Steady-state splanchnic bed palmitate ([9,10-(3)H]palmitate) kinetics were determined from 14 sampling intervals from eight dogs with chronic indwelling arterial, portal vein, and hepatic vein catheters. We tested a model designed to predict the proportion of FFAs delivered to the liver from visceral fat by use of hepatic vein data. The model predicted that 15 +/- 2% of hepatic palmitate delivery originated from visceral lipolysis, which was greater (P = 0.004) than the 11 +/- 2% actually observed. There was a good relationship (r(2) = 0.63) between the predicted and observed hepatic palmitate delivery values, but the model overestimated visceral FFA release more at lower than at higher palmitate concentrations. The discrepancy could be due to differential uptake of FFAs arriving from the arterial vs. the portal vein or to release of FFAs in the hepatic circulatory bed. Splanchnic FFA release measured using hepatic vein samples was strongly related to visceral adipose tissue FFA release into the portal vein. This finding suggests that splanchnic FFA release is a good indicator of visceral adipose tissue lipolysis. PMID:12736157

  6. Quantum dots increased fat storage in intestine of Caenorhabditis elegans by influencing molecular basis for fatty acid metabolism.

    PubMed

    Wu, Qiuli; Zhi, Lingtong; Qu, Yangyang; Wang, Dayong

    2016-07-01

    Caenorhabditis elegans is a useful model animal for fat storage study. In nematodes, CdTe quantum dots (QDs) induced an increase in fat storage in intestine that is partially due to prolonged defecation cycle length, and not attributed to altered feeding or cadmium ion released from CdTe QDs. Moreover, CdTe QDs altered the molecular basis of both synthesis and degradation of fatty acid; however, CdTe QDs did not influence that of degradation of phospholipids. CdTe QDs increased expression of fasn-1 and pod-2 genes encoding enzymes required for fatty acid synthesis, and decreased expression of acs-2 and ech-1 genes encoding enzymes required for fatty acid β-oxidation. The altered molecular basis of fatty acid synthesis or degradation by CdTe QDs acted in intestine to regulate fat storage. Our study highlights the potential of CdTe QDs in influencing lipid metabolism in certain organs or tissues in animals. PMID:26956412

  7. Fatty acid oxidation and ketogenesis in astrocytes

    SciTech Connect

    Auestad, N.

    1988-01-01

    Astrocytes were derived from cortex of two-day-old rat brain and grown in primary culture to confluence. The metabolism of the fatty acids, octanoate and palmitate, to CO{sub 2} in oxidative respiration and to the formation of ketone bodies was examined by radiolabeled tracer methodology. The net production of acetoacetate was also determined by measurement of its mass. The enzymes in the ketogenic pathway were examined by measuring enzymic activity and/or by immunoblot analyses. Labeled CO{sub 2} and labeled ketone bodies were produced from the oxidation of fatty acids labeled at carboxy- and {omega}-terminal carbons, indicating that fatty acids were oxidized by {beta}-oxidation. The results from the radiolabeled tracer studies also indicated that a substantial proportion of the {omega}-terminal 4-carbon unit of the fatty acids bypassed the {beta}-ketothiolase step of the {beta}-oxidation pathway. The ({sup 14}C)acetoacetate formed from the (1-{sup 14}C)labeled fatty acids, obligated to pass through the acetyl-CoA pool, contained 50% of the label at carbon 3 and 50% at carbon 1. In contrast, the ({sup 14}C)acetoacetate formed from the ({omega}-1)labeled fatty acids contained 90% of the label at carbon 3 and 10% at carbon 1.

  8. Nutritional properties of trans fatty acids.

    PubMed

    Sambaiah, K; Lokesh, B R

    1999-08-01

    The role of trans fatty acids (TFA) present in partially hydrogenated fats widely consumed in food and their link with coronary heart disease has been examined in this review. Most of the studies carried out have been on the effects of TFA on blood-lipid profile. The perceived effects of TFA intake depend on the fat or oil with which they are compared and appears to be in between that of dietary saturated fats and monounsaturated fatty acids. When compared to saturated fat, TFA intake shows lower levels of total and LDL-cholesterol in blood. But when both TFA and saturated fatty acids are compared with cis fatty acids or native unhydrogenated oil, increase in total and LDL-cholesterol are noted. The effects of TFA on HDL-cholesterol and Lp(a) are not clearly established. The undesirable effects of TFA can be overcome by inclusion of essential fatty acids at a minimum of 2 energy per cent level in the diet. The link between trans fatty acid intake and coronary heart disease (CHD) are not unequivocally established. PMID:10650721

  9. Serum fatty acids and breast cancer incidence.

    PubMed

    Rissanen, Harri; Knekt, Paul; Järvinen, Ritva; Salminen, Irma; Hakulinen, Timo

    2003-01-01

    Fatty acid composition of the diet may be essential to the development of breast cancer. We studied the ability of several fatty acids of serum total lipids to predict breast cancer incidence in a case-control study nested within a longitudinal population study. The proportions of fatty acids in serum total lipids were determined from stored serum samples collected at baseline for 127 incident breast cancer cases and 242 matched controls. Women with a higher proportion of total polyunsaturated fatty acids (PUFAs) in serum had a reduced risk of breast cancer. The odds ratio (OR) between the highest and lowest tertiles of serum PUFA was 0.31 (95% confidence interval, CI = 0.12-0.77). This association was mainly due to n-6 PUFAs and especially to linoleic acid. The ORs were 0.35 (CI = 0.14-0.84) and 0.29 (CI = 0.12-0.73), respectively. Of the monounsaturated fatty acids (MUFAs), higher trans-11-18:1 levels were related to an increased breast cancer risk (OR = 3.69, CI = 1.35-10.06). The association was stronger in postmenopausal than in premenopausal women. The present study suggests that higher serum proportions of the n-6 PUFA linoleic acid and lower proportions of the MUFA trans-11-18:1 fatty acid predict a reduced incidence of breast cancer. PMID:12881010

  10. Surface lysine residues modulate the collisional transfer of fatty acid from adipocyte fatty acid binding protein to membranes.

    PubMed

    Herr, F M; Matarese, V; Bernlohr, D A; Storch, J

    1995-09-19

    The transfer of unesterified fatty acids (FA) from adipocyte fatty acid binding protein (A-FABP) to phospholipid membranes is proposed to occur via a collisional mechanism involving transient ionic and hydrophobic interactions [Wootan & Storch (1994) J. Biol. Chem. 269, 10517-10523]. In particular, it was suggested that membrane acidic phospholipids might specifically interact with basic residues on the surface of A-FABP. Here we addressed whether lysine residues on the surface of the protein are involved in this collisional transfer mechanism. Recombinant A-FABP was acetylated to neutralize all positively charged surface lysine residues. Protein fluorescence, CD spectra, and chemical denaturant data indicate that acetylation did not substantially alter the conformational integrity of the protein, and nearly identical affinities were obtained for binding of the fluorescently labeled FA [12-(9-anthroyloxy)oleate] to native and acetylated protein. Transfer of 2-(9-anthroyloxy)palmitate (2AP) from acetylated A-FABP to small unilamellar vesicles (SUV) was 35-fold slower than from native protein. In addition, whereas the 2AP transfer rate from native A-FABP was directly dependent on SUV concentration, 2AP transfer from acetylated protein was independent on the concentration of acceptor membranes. Factors which alter aqueous-phase solubility of FA, such as ionic strength and acyl chain length and saturation, affected the AOFA transfer rate from acetylated but not native A-FABP. Finally, an increase in the negative charge density of the acceptor SUV resulted in a marked increase in the rate of transfer from native A-FABP but did not increase the rate from acetylated A-FABP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7547918

  11. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance.

    PubMed

    Calder, Philip C

    2015-04-01

    Inflammation is a condition which contributes to a range of human diseases. It involves a multitude of cell types, chemical mediators, and interactions. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids found in oily fish and fish oil supplements. These fatty acids are able to partly inhibit a number of aspects of inflammation including leukocyte chemotaxis, adhesion molecule expression and leukocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines, and T-helper 1 lymphocyte reactivity. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of marine n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor peroxisome proliferator activated receptor γ and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked, although the full extent of this is not yet elucidated. Animal experiments demonstrate benefit from marine n-3 fatty acids in models of rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in RA demonstrate benefit, but clinical trials of fish oil in IBD and asthma are inconsistent with no overall clear evidence of efficacy. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". PMID:25149823

  12. GPCR-Based Chemical Biosensors for Medium-Chain Fatty Acids.

    PubMed

    Mukherjee, Kuntal; Bhattacharyya, Souryadeep; Peralta-Yahya, Pamela

    2015-12-18

    A key limitation to engineering microbes for chemical production is a reliance on low-throughput chromatography-based screens for chemical detection. While colorimetric chemicals are amenable to high-throughput screens, many value-added chemicals are not colorimetric and require sensors for high-throughput screening. Here, we use G-protein coupled receptors (GPCRs) known to bind medium-chain fatty acids in mammalian cells to rapidly construct chemical sensors in yeast. Medium-chain fatty acids are immediate precursors to the advanced biofuel fatty acid methyl esters, which can serve as a "drop-in" replacement for D2 diesel. One of the sensors detects even-chain C8-C12 fatty acids with a 13- to 17-fold increase in signal after activation, with linear ranges up to 250 μM. Introduction of a synthetic response unit alters both dynamic and linear range, improving the sensor response to decanoic acid to a 30-fold increase in signal after activation, with a linear range up to 500 μM. To our knowledge, this is the first report of a whole-cell medium-chain fatty acid biosensor, which we envision could be applied to the evolutionary engineering of fatty acid-producing microbes. Given the affinity of GPCRs for a wide range of chemicals, it should be possible to rapidly assemble new biosensors by simply swapping the GPCR sensing unit. These sensors should be amenable to a variety of applications that require different dynamic and linear ranges, by introducing different response units. PMID:25992593

  13. How Misinformation Alters Memories.

    ERIC Educational Resources Information Center

    Wright, Daniel B.; Loftus, Elizabeth F.

    1998-01-01

    Notes that a multitude of studies have demonstrated that misleading postevent information affects people's memories. Contents that the fuzzy-trace theory is a positive step toward understanding the malleability of memory. Discusses fuzzy-trace theory in terms of three primary areas of study: altered response format, maximized misinformation…

  14. Immunization alters body odor.

    PubMed

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. PMID:24524972

  15. Evaluation of fatty acid content of some Iranian fast foods with emphasis on trans fatty acids.

    PubMed

    Asgary, Seddigheh; Nazari, Bahar; Sarrafzadegan, Nizal; Parkhideh, Sahar; Saberi, Salbali; Esmaillzadeh, Ahmad; Azadbakht, Leila

    2009-01-01

    Although the disadvantages of trans fatty acids (TFAs) are widely mentioned, limited data are available on the TFAs contents of Iranian foods, including fast foods. The aim of this study was to quantify the amounts of common fatty acids in several fast foods in Iran, with specific focus on TFAs. The most commonly consumed fast foods in Iran: sausage, calbas, hamburgers and pizzas, were randomly selected seven times from products available in supermarkets and restaurants. Each time a 10 g sample was drawn and prepared for fatty acid analysis. Total and individual fatty acids were quantified according to standard methods by gas chromatography with 60 meter capillary column and flame ionization detector. The most common saturated fatty acids in Iranian fast foods is stearic acid (C18:0) which ranged from 14.0% to 20.9%. Saturated fatty acid content in calbas was significantly higher than that found in other groups. Trans fatty acids constitute almost 23.6% to 30.6% of total fatty acids of these products. The most common TFA in these fast foods was elaidic acid (C18:1 9t). Total cis unsaturated fatty acid content of tested fast foods varied from 25.3%(in sausage) to 46.8(in calbas) with oleic acid (C18:1 9c) followed by linoleic acid (C18:2) being the most common fatty acids in these products. This study showed higher TFAs contents in commercially available fast foods compared to the amounts recommended by dietary guidelines in Iran. Further studies must assess the effects of these fatty acids on human health. PMID:19713177

  16. Suberin-Associated Fatty Alcohols in Arabidopsis: Distributions in Roots and Contributions to Seed Coat Barrier Properties1[W

    PubMed Central

    Vishwanath, Sollapura J.; Kosma, Dylan K.; Pulsifer, Ian P.; Scandola, Sabine; Pascal, Stéphanie; Joubès, Jérôme; Dittrich-Domergue, Franziska; Lessire, René; Rowland, Owen; Domergue, Frédéric

    2013-01-01

    Suberin is found in a variety of tissues, such as root endoderms and periderms, storage tuber periderms, tree cork layer, and seed coats. It acts as a hydrophobic barrier to control the movement of water, gases, and solutes as well as an antimicrobial barrier. Suberin consists of polymerized phenolics, glycerol, and a variety of fatty acid derivatives, including primary fatty alcohols. We have conducted an in-depth analysis of the distribution of the C18:0 to C22:0 fatty alcohols in Arabidopsis (Arabidopsis thaliana) roots and found that only 20% are part of the root suberin polymer, together representing about 5% of its aliphatic monomer composition, while the remaining 80% are found in the nonpolymeric (soluble) fraction. Down-regulation of Arabidopsis FATTY ACYL REDUCTASE1 (FAR1), FAR4, and FAR5, which collectively produce the fatty alcohols found in suberin, reduced their levels by 70% to 80% in (1) the polymeric and nonpolymeric fractions from roots of tissue culture-grown plants, (2) the suberin-associated root waxes from 7-week-old soil-grown plants, and (3) the seed coat suberin polymer. By contrast, the other main monomers of suberin were not altered, indicating that reduced levels of fatty alcohols did not influence the suberin polymerization process. Nevertheless, the 75% reduction in total fatty alcohol and diol loads in the seed coat resulted in increased permeability to tetrazolium salts and a higher sensitivity to abscisic acid. These results suggest that fatty alcohols and diols play an important role in determining the functional properties of the seed coat suberin barrier. PMID:24019425

  17. Long-term effects of perinatal essential fatty acid deficiency on anxiety-related behavior in mice.

    PubMed

    Palsdottir, Vilborg; Månsson, Jan-Eric; Blomqvist, Maria; Egecioglu, Emil; Olsson, Bob

    2012-04-01

    Dietary essential fatty acids have been shown to regulate behavioral and cognitive functions in rodents. However, the long-term effect on behavior, besides memory and learning, of essential fatty acid deficiency (EFAD), i.e., lack of n-3 and n-6 fatty acids, during the perinatal period has not been investigated. Therefore, pregnant C57Bl/6 mice were given either an EFAD or an isoenergetic control diet from gestational day 16 and throughout lactation. The female offspring were given standard chow from 3 weeks of age, and at 12 to 14 weeks of age, open-field, object recognition, light-dark transition, elevated plus maze, and social interaction tests were performed. The brain glycerophospholipid fatty acid composition was investigated in 3-week-old and adult offspring by gas chromatography. The differences observed in behavior were indicative of lower anxiety in the EFAD mice compared to controls illustrated by more time spent in the open arms of the elevated plus maze (+ 41%, p < .05) and in the light compartment in the light-dark transition test (+ 63%, p < .05). The proportion of total n-3 fatty acids, especially 22:6n-3 in the brain, was lower with a compensatory increase in the proportion of total n-6 fatty acids, foremost 22:5n-6, in the EFAD mice compared to controls at 3 weeks of age. In the adult brains the fatty acid composition was normalized. In conclusion, our data show that EFAD during the perinatal period results in short-term alterations of fatty acid composition in brain and decreased anxiety in adult life. PMID:22352789

  18. Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes.

    PubMed

    Stanley, Christopher P; Wheal, Amanda J; Randall, Michael D; O'Sullivan, Saoirse E

    2013-11-15

    Circulating levels of anandamide are increased in diabetes, and cannabidiol ameliorates a number of pathologies associated with diabetes. The aim of the present study was to examine how exposure to anandamide or cannabidiol might affect endothelial dysfunction associated with Zucker Diabetic Fatty rats. Age-matched Zucker Diabetic Fatty and Zucker lean rats were killed by cervical dislocation and their arteries mounted on a myograph at 37 °C. Arteries were incubated for 2h with anandamide, cannabidiol or vehicle, contracted, and cumulative concentration-response curves to acetylcholine were constructed. Anandamide (10 µM, 2h) significantly improved the vasorelaxant responses to acetylcholine in aortae and femoral arteries from Zucker Diabetic Fatty rats but not Zucker lean rats. By contrast, anandamide (1 µM, 2h) significantly blunted acetylcholine-induced vasorelaxation in third-order mesenteric arteries (G3) from Zucker Diabetic Fatty rats. Cannabidiol incubation (10 µM, 2h) improved acetylcholine responses in the arteries of Zucker Diabetic Fatty rats (aorta and femoral) and Zucker lean (aorta, femoral and G3 mesenteric), and this effect was greater in the Zucker Diabetic Fatty rat. These studies suggest that increased circulating endocannabinoids may alter vascular function both positively and negatively in type 2 diabetes, and that part of the beneficial effect of cannabidiol in diabetes may be due to improved endothelium-dependent vasorelaxation. PMID:24120371

  19. Plant fatty acyl reductases: enzymes generating fatty alcohols for protective layers with potential for industrial applications.

    PubMed

    Rowland, Owen; Domergue, Frédéric

    2012-09-01

    Primary fatty alcohols are found throughout the biological world, either in free form or in a combined state. They are common components of plant surface lipids (i.e. cutin, suberin, sporopollenin, and associated waxes) and their absence can significantly perturb these essential barriers. Fatty alcohols and/or derived compounds are also likely to have direct functions in plant biotic and abiotic interactions. An evolutionarily related set of alcohol-forming fatty acyl reductases (FARs) is present in all kingdoms of life. Plant microsomal and plastid-associated FAR enzymes have been characterized, acting on acyl-coenzymeA (acyl-CoA) or acyl-acyl carrier protein (acyl-ACP) substrates, respectively. FARs have distinct substrate specificities both with regard to chain length and chain saturation. Fatty alcohols and wax esters, which are a combination of fatty alcohol and fatty acid, have a variety of commercial applications. The expression of FARs with desired specificities in transgenic microbes or oilseed crops would provide a novel means of obtaining these valuable compounds. In the present review, we report on recent progress in characterizing plant FAR enzymes and in understanding the biological roles of primary fatty alcohols, as well as describe the biotechnological production and industrial uses of fatty alcohols. PMID:22794916

  20. Analysis of mixtures of fatty acids and fatty alcohols in fermentation broth.

    PubMed

    Liu, Yilan; Chen, Ting; Yang, Maohua; Wang, Caixia; Huo, Weiyan; Yan, Daojiang; Chen, Jinjin; Zhou, Jiemin; Xing, Jianmin

    2014-01-01

    Microbial production of fatty acids and fatty alcohols has attracted increasing concerns because of energy crisis and environmental impact of fossil fuels. Therefore, simple and efficient methods for the extraction and quantification of these compounds become necessary. In this study, a high-performance liquid chromatography-refractive index detection (HPLC-RID) method was developed for the simultaneous quantification of fatty acids and fatty alcohols in these samples. The optimum chromatographic conditions are C18 column eluted with methanol:water:acetic acid (90:9.9:0.1, v/v/v); column temperature, 26°C; flow rate, 1.0mL/min. Calibration curves of all selected analytes showed good linearity (r(2)≥0.9989). The intra-day and inter-day relative standard deviations (RSDs) of the 10 compounds were less than 4.46% and 5.38%, respectively, which indicated that the method had good repeatability and precision. Besides, a method for simultaneous extraction of fatty acids and fatty alcohols from fermentation broth was optimized by orthogonal design. The optimal extraction conditions were as follows: solvent, ethyl acetate; solvent to sample ratio, 0.5:1; rotation speed, 2min at 260rpm; extraction temperature, 10°C. This study provides simple and fast methods to simultaneously extract and quantify fatty acids and fatty alcohols for the first time. It will be useful for the study of microbial production of these products. PMID:24290170

  1. A New Insight to Bone Turnover: Role of ω-3 Polyunsaturated Fatty Acids

    PubMed Central

    López-Frías, Magdalena; López-Aliaga, Inmaculada; Ochoa, Julio J.

    2013-01-01

    Background. Evidence has shown that long-chain polyunsaturated fatty acids (LCPUFA), especially the ω-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health and turnover. Objectives. This review summarizes findings from both in vivo and in vitro studies and the effects of LC PUFA on bone metabolism, as well as the relationship with the oxidative stress, the inflammatory process, and obesity. Results. Some studies in humans indicate that LCPUFA can increase bone formation, affect peak bone mass in adolescents, and reduce bone loss. However, the cellular mechanisms of action of the LCPUFA are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signaling pathways, cytokines, and growth factors, although in certain aspects there is still some controversy. LCPUFA affect receptor activator of nuclear factor κβ (RANK), a receptor found on the osteoclast, causing bone resorption, which controls osteoclast formation. Conclusions. Since fatty acids are an endogenous source of reactive oxygen species, free radicals alter the process of bone turnover; however, although there are clinical evidences linking bone metabolism and dietary lipids, more clinical trials are necessary to prove whether ω-3 PUFA supplementation plays a major role in bone health. PMID:24302863

  2. Can ω-3 fatty acids and tocotrienol-rich vitamin E reduce symptoms of neurodevelopmental disorders?

    PubMed

    Gumpricht, Eric; Rockway, Susie

    2014-01-01

    The incidence of childhood neurodevelopmental disorders, which include autism, attention-deficit hyperactivity disorders, and apraxia, are increasing worldwide and have a profound effect on the behaviors, cognitive skills, mood, and self-esteem of these children. Although the etiologies of these disorders are unclear, they often accompany genetic and biochemical abnormalities resulting in cognitive and communication difficulties. Because cognitive and neural development require essential fatty acids (particularly long-chain ω-3 fatty acids often lacking in mother's and children's diets) during critical growth periods, the potential behavior-modifying effects of these fatty acids as "brain nutrients" has attracted considerable attention. Additionally, there is compelling evidence for increased oxidative stress, altered antioxidant defenses, and neuroinflammation in these children. The purpose of this review is to provide a scientific rationale based on cellular, experimental animal model, observational, and clinical intervention studies for incorporating the combination of ω-3 fatty acids and tocotrienol-rich vitamin E as complementary nutritional therapies in children with neurodevelopmental disorders. Should this nutritional combination correct key clinical or biochemical outcomes and/or improve behavioral patterns, it would provide a safe, complementary option for these children. PMID:24631384

  3. Differential Effects of a Saturated and a Monounsaturated Fatty Acid on MHC Class I Antigen Presentation

    PubMed Central

    Shaikh, S. R.; Mitchell, D.; Carroll, E.; Li, M.; Schneck, J.; Edidin, M.

    2009-01-01

    Lipid overload, associated with metabolic disorders, occurs when fatty acids accumulate in non-adipose tissues. Cells of these tissues use major histocompatibility complex (MHC) class I molecules to present antigen to T cells in order to eliminate pathogens. As obesity is associated with impaired immune responses, we tested the hypothesis that the early stages of lipid overload with saturated fatty acids (SFA) alters MHC class I antigen presentation. Antigen presenting cells (APC) were treated with either the saturated palmitic acid (PA), abundant in the high fat Western diet, or the monounsaturated oleic acid (OA), a component of the Mediterranean diet. PA-treatment lowered APC lysis by activated cytotoxic T lymphocytes and inhibited APC ability to stimulate naïve T cells. Inhibition of immune responses with PA was due to a significant reduction in MHC class I surface expression, inhibition in the rate of APC–T-cell conjugation, and lowering of plasma membrane F-actin levels. OA-treatment had no effect on antigen presentation and upon exposure with PA, prevented the phenotypic effects of PA. OA-treatment conferred protection against changes in antigen presentation by accumulating fatty acids into triglyceride-rich lipid droplets of APC. Our findings establish for the first time a link between the early stages of lipid overload and antigen presentation and suggest that dietary SFA could impair immunity by affecting MHC I-mediated antigen presentation; this could be prevented, paradoxically, by accumulation of triglycerides rich in monounsaturated fatty acids. PMID:18533931

  4. Free fatty acids as a major component of the chlorosulfolipid membrane of Ochromonas danica

    SciTech Connect

    Winicov, I.

    1985-01-01

    This work is an attempt to determine whether or not free fatty acids are components of the natural membrane of Ochromonas danica. If the FFAs were artifacts, they would most likely have been produced during solvent extraction or during the procedure for flagellar detachment. Attempts to denature putative solvent-activated lipase(s) through exposure to boiling isopropanol or by crosslinking the flagella with glutaraldehyde prior to extraction failed to eliminate the free fatty acid fraction, nor to significantly alter its composition. Exposure of flagella to albumin resulted in the net transfer of FFAs to the supernatant phase, showing their presence is not caused by solvent activated lipolysis. Finally levels of labelled free fatty acids failed to rise as a function of time after deflagellation in cells grown in the presence of (10-/sup 14/C)-oleic acid. Acid hydrolysis of the total labelled lipid at elevated temperature increased the percentage of counts occurring as unesterified fatty acids (from 2.6% to 64.8%). This, taken together with a corresponding loss of the more polar labelled material (66.8% to 8.2%) indicates that some esterified lipids were present, but probably not broken down during the isolation procedure.

  5. Differential effects of a saturated and a monounsaturated fatty acid on MHC class I antigen presentation.

    PubMed

    Shaikh, S R; Mitchell, D; Carroll, E; Li, M; Schneck, J; Edidin, M

    2008-07-01

    Lipid overload, associated with metabolic disorders, occurs when fatty acids accumulate in non-adipose tissues. Cells of these tissues use major histocompatibility complex (MHC) class I molecules to present antigen to T cells in order to eliminate pathogens. As obesity is associated with impaired immune responses, we tested the hypothesis that the early stages of lipid overload with saturated fatty acids (SFA) alters MHC class I antigen presentation. Antigen presenting cells (APC) were treated with either the saturated palmitic acid (PA), abundant in the high fat Western diet, or the monounsaturated oleic acid (OA), a component of the Mediterranean diet. PA-treatment lowered APC lysis by activated cytotoxic T lymphocytes and inhibited APC ability to stimulate naïve T cells. Inhibition of immune responses with PA was due to a significant reduction in MHC class I surface expression, inhibition in the rate of APC-T-cell conjugation, and lowering of plasma membrane F-actin levels. OA-treatment had no effect on antigen presentation and upon exposure with PA, prevented the phenotypic effects of PA. OA-treatment conferred protection against changes in antigen presentation by accumulating fatty acids into triglyceride-rich lipid droplets of APC. Our findings establish for the first time a link between the early stages of lipid overload and antigen presentation and suggest that dietary SFA could impair immunity by affecting MHC I-mediated antigen presentation; this could be prevented, paradoxically, by accumulation of triglycerides rich in monounsaturated fatty acids. PMID:18533931

  6. Essential fatty acid consumption and risk of breast cancer.

    PubMed

    Godley, P A

    1995-07-01

    Animal and ecological studies of essential fatty acids suggest that omega-3 fatty acids found in fish oils and omega-6 fatty acids found in vegetable oils may be playing a role in the etiology of breast cancer. Essential fatty acids may modulate breast cancer risk by interacting with prostaglandins, which have immunosuppressive and platelet aggregative capabilities. The fatty acid composition of adipose tissue reflects the dietary consumption of essential fatty acids over a period of years. Biochemical techniques have been used in epidemiological studies to accurately estimate fatty acid consumption. However, analytical epidemiology studies that have used biochemical measurements of adipose tissue fatty acid composition, have not supported a relationship between consumption of these essential fatty acids and breast cancer risk. PMID:7612909

  7. Omega-3 fatty acids in the gravid pig uterus as affected by maternal supplementation with omega-3 fatty acids.

    PubMed

    Brazle, A E; Johnson, B J; Webel, S K; Rathbun, T J; Davis, D L

    2009-03-01

    Two experiments evaluated the ability of maternal fatty acid supplementation to alter conceptus and endometrial fatty acid composition. In Exp. 1, treatments were 1) the control, a corn-soybean meal diet; 2) flax, the control diet plus ground flax (3.75% of diet); and 3) protected fatty acids (PFA), the control plus a protected fish oil source rich in n-3 PUFA (Gromega, JBS United Inc., Sheridan, IN; 1.5% of diet). Supplements replaced equal parts of corn and soybean meal. When gilts reached 170 d of age, PG600 (PMSG and hCG, Intervet USA, Millsboro, DE) was injected to induce puberty, and dietary treatments (n = 8/treatment) were initiated. When detected in estrus, gilts were artificially inseminated. On d 40 to 43 of gestation, 7 gilts in the control treatment, 8 gilts in the PFA treatment, and 5 gilts in the flax treatment were pregnant and were slaughtered. Compared with the control treatment, the flax treatment tended to increase eicosapentaenoic acid (EPA: C20:5n-3) in fetuses (0.14 vs. 0.25 +/- 0.03 mg/g of dry tissue; P = 0.055), whereas gilts receiving PFA had more (P < 0.05) docosahexaenoic acid (DHA: C22:6n-3) in their fetuses (5.23 vs. 4.04 +/- 0.078 mg/g) compared with gilts fed the control diet. Both the flax and PFA diets increased (P < 0.05) DHA (0.60, 0.82, and 0.85 +/- 0.078 mg/g for the control, flax, and PFA diet, respectively) in the chorioallantois. In the endometrium, EPA and docosapentaenoic acid (C22:5n-3) were increased by the flax diet (P < 0.001; P < 0.05), whereas gilts receiving PFA had increased DHA (P < 0.001). The flax diet selectively increased EPA, and the PFA diet selectively increased DHA in the fetus and endometrium. In Exp. 2, gilts were fed diets containing PFA (1.5%) or a control diet beginning at approximately 170 of age (n = 13/treatment). A blood sample was collected after 30 d of treatment, and gilts were artificially inseminated when they were approximately 205 d old. Conceptus and endometrial samples were collected on

  8. Age-Specific Lipid and Fatty Acid Profiles of Atlantic Salmon Juveniles in the Varzuga River.

    PubMed

    Murzina, Svetlana A; Nefedova, Zinaida A; Pekkoeva, Svetlana N; Veselov, Alexey E; Efremov, Denis A; Nemova, Nina N

    2016-01-01

    The age-specific lipid and fatty acid profiles of juvenile Atlantic salmon at different ages (0+, 1+, and 2+ years) after hatching from nests located in the mainstream of a large Arctic River, the Varzuga River, and resettling to the favorable Sobachji shoal in autumn before overwinter are herein presented. The contemporary methods of the lipid analysis were used: thin layer chromatography and gas chromatography. The results show that the stability of the regulation of important functions in developing organisms is maintained through structural alterations in lipids. These alterations can be considered as a sequence of the modifications and changes in the ratios of certain lipid classes and fatty acids constituents. In general, changes in the lipids and fatty acids (FAs) maintained the physiological limits and controls through the adaptive systems of the organism. The mechanisms of juvenile fish biochemical adaptation to the environmental conditions in the studied biotope include the modification of the energy metabolism and anabolism, and here belongs to the energy characteristics of metabolic processes. PMID:27376274

  9. Proteomics-Based Metabolic Modeling Reveals That Fatty Acid Oxidation (FAO) Controls Endothelial Cell (EC) Permeability*

    PubMed Central

    Patella, Francesca; Schug, Zachary T.; Persi, Erez; Neilson, Lisa J.; Erami, Zahra; Avanzato, Daniele; Maione, Federica; Hernandez-Fernaud, Juan R.; Mackay, Gillian; Zheng, Liang; Reid, Steven; Frezza, Christian; Giraudo, Enrico; Fiorio Pla, Alessandra; Anderson, Kurt; Ruppin, Eytan; Gottlieb, Eyal; Zanivan, Sara

    2015-01-01

    Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability. PMID:25573745

  10. Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability.

    PubMed

    Patella, Francesca; Schug, Zachary T; Persi, Erez; Neilson, Lisa J; Erami, Zahra; Avanzato, Daniele; Maione, Federica; Hernandez-Fernaud, Juan R; Mackay, Gillian; Zheng, Liang; Reid, Steven; Frezza, Christian; Giraudo, Enrico; Fiorio Pla, Alessandra; Anderson, Kurt; Ruppin, Eytan; Gottlieb, Eyal; Zanivan, Sara

    2015-03-01

    Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability. PMID:25573745

  11. Age-Specific Lipid and Fatty Acid Profiles of Atlantic Salmon Juveniles in the Varzuga River

    PubMed Central

    Murzina, Svetlana A.; Nefedova, Zinaida A.; Pekkoeva, Svetlana N.; Veselov, Alexey E.; Efremov, Denis A.; Nemova, Nina N.

    2016-01-01

    The age-specific lipid and fatty acid profiles of juvenile Atlantic salmon at different ages (0+, 1+, and 2+ years) after hatching from nests located in the mainstream of a large Arctic River, the Varzuga River, and resettling to the favorable Sobachji shoal in autumn before overwinter are herein presented. The contemporary methods of the lipid analysis were used: thin layer chromatography and gas chromatography. The results show that the stability of the regulation of important functions in developing organisms is maintained through structural alterations in lipids. These alterations can be considered as a sequence of the modifications and changes in the ratios of certain lipid classes and fatty acids constituents. In general, changes in the lipids and fatty acids (FAs) maintained the physiological limits and controls through the adaptive systems of the organism. The mechanisms of juvenile fish biochemical adaptation to the environmental conditions in the studied biotope include the modification of the energy metabolism and anabolism, and here belongs to the energy characteristics of metabolic processes. PMID:27376274

  12. Bugs, genes, fatty acids, and serotonin: Unraveling inflammatory bowel disease?

    PubMed Central

    Kaunitz, Jonathan; Nayyar, Piyush

    2015-01-01

    The annual incidence of the inflammatory bowel diseases (IBDs) ulcerative colitis and Crohn’s disease has increased at an alarming rate. Although the specific pathophysiology underlying IBD continues to be elusive, it is hypothesized that IBD results from an aberrant and persistent immune response directed against microbes or their products in the gut, facilitated by the genetic susceptibility of the host and intrinsic alterations in mucosal barrier function. In this review, we will describe advances in the understanding of how the interaction of host genetics and the intestinal microbiome contribute to the pathogenesis of IBD, with a focus on bacterial metabolites such as short chain fatty acids (SCFAs) as possible key signaling molecules.  In particular, we will describe alterations of the intestinal microbiota in IBD, focusing on how genetic loci affect the gut microbial phylogenetic distribution and the production of their major microbial metabolic product, SCFAs. We then describe how enteroendocrine cells and myenteric nerves express SCFA receptors that integrate networks such as the cholinergic and serotonergic neural systems and the glucagon-like peptide hormonal pathway, to modulate gut inflammation, permeability, and growth as part of an integrated model of IBD pathogenesis.  Through this integrative approach, we hope that novel hypotheses will emerge that will be tested in reductionist, hypothesis-driven studies in order to examine the interrelationship of these systems in the hope of better understanding IBD pathogenesis and to inform novel therapies.

  13. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Changtao; Xie, Cen; Li, Fei; Zhang, Limin; Nichols, Robert G.; Krausz, Kristopher W.; Cai, Jingwei; Qi, Yunpeng; Fang, Zhong-Ze; Takahashi, Shogo; Tanaka, Naoki; Desai, Dhimant; Amin, Shantu G.; Albert, Istvan; Patterson, Andrew D.; Gonzalez, Frank J.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major worldwide health problem. Recent studies suggest that the gut microbiota influences NAFLD pathogenesis. Here, a murine model of high-fat diet–induced (HFD-induced) NAFLD was used, and the effects of alterations in the gut microbiota on NAFLD were determined. Mice treated with antibiotics or tempol exhibited altered bile acid composition, with a notable increase in conjugated bile acid metabolites that inhibited intestinal farnesoid X receptor (FXR) signaling. Compared with control mice, animals with intestine-specific Fxr disruption had reduced hepatic triglyceride accumulation in response to a HFD. The decrease in hepatic triglyceride accumulation was mainly due to fewer circulating ceramides, which was in part the result of lower expression of ceramide synthesis genes. The reduction of ceramide levels in the ileum and serum in tempol- or antibiotic-treated mice fed a HFD resulted in downregulation of hepatic SREBP1C and decreased de novo lipogenesis. Administration of C16:0 ceramide to antibiotic-treated mice fed a HFD reversed hepatic steatosis. These studies demonstrate that inhibition of an intestinal FXR/ceramide axis mediates gut microbiota–associated NAFLD development, linking the microbiome, nuclear receptor signaling, and NAFLD. This work suggests that inhibition of intestinal FXR is a potential therapeutic target for NAFLD treatment. PMID:25500885

  14. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  15. Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

    PubMed

    Mather, K J; Hutchins, G D; Perry, K; Territo, W; Chisholm, R; Acton, A; Glick-Wilson, B; Considine, R V; Moberly, S; DeGrado, T R

    2016-03-15

    Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. PMID:26732686

  16. Identification of a family of fatty acid-speciated Sonic Hedgehog proteins, whose members display differential biological properties

    PubMed Central

    Houel, Stephane; Rodgriguez-Blanco, Jezabel; Singh, Samer; Schilling, Neal; J.Capobianco, Anthony; Ahn, Natalie G.; Robbins, David J.

    2015-01-01

    SUMMARY Hedgehog (HH) proteins are proteolytically processed into a biologically active form, which is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is over-expressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels, and showed that it was more potent than SHH isolated from over-expressing cells. Furthermore, the SHH in our preparations were modified with a diverse spectrum of fatty acids on their amino-termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH affected its trafficking to lipid rafts, as well as its potency. Our results suggest that HH proteins exist as a family of diverse lipid-speciated proteins, which might be altered in different physiological and pathological contexts to regulate distinct properties of HH proteins. PMID:25732819

  17. TORC1 inhibits GSK3-mediated Elo2 phosphorylation to regulate very long chain fatty acid synthesis and autophagy.

    PubMed

    Zimmermann, Christine; Santos, Aline; Gable, Kenneth; Epstein, Sharon; Gururaj, Charulatha; Chymkowitch, Pierre; Pultz, Dennis; Rødkær, Steven V; Clay, Lorena; Bjørås, Magnar; Barral, Yves; Chang, Amy; Færgeman, Nils J; Dunn, Teresa M; Riezman, Howard; Enserink, Jorrit M

    2013-11-27

    Very long chain fatty acids (VLCFAs) are essential fatty acids with multiple functions, including ceramide synthesis. Although the components of the VLCFA biosynthetic machinery have been elucidated, how their activity is regulated to meet the cell's metabolic demand remains unknown. The goal of this study was to identify mechanisms that regulate the rate of VLCFA synthesis, and we discovered that the fatty acid elongase Elo2 is regulated by phosphorylation. Elo2 phosphorylation is induced upon inhibition of TORC1 and requires GSK3. Expression of nonphosphorylatable Elo2 profoundly alters the ceramide spectrum, reflecting aberrant VLCFA synthesis. Furthermore, VLCFA depletion results in constitutive activation of autophagy, which requires sphingoid base phosphorylation. This constitutive activation of autophagy diminishes cell survival, indicating that VLCFAs serve to dampen the amplitude of autophagy. Together, our data reveal a function for TORC1 and GSK3 in the regulation of VLCFA synthesis that has important implications for autophagy and cell homeostasis. PMID:24239358

  18. Bioluminescent determination of free fatty acids.

    PubMed

    Kather, H; Wieland, E

    1984-08-01

    A simple, highly specific, and sensitive bioluminescent method for determination of free fatty acids in unextracted plasma or serum has been developed. The method is based on the activation of free fatty acids by acyl-CoA synthetase (EC 6.2.1.3). The pyrophosphate formed is used to phosphorylate fructose 6-phosphate in a reaction catalyzed by the enzyme pyrophosphate-fructose-6-phosphate phosphotransferase (EC 4.1.2.13). The triosephosphates produced from fructose 1,6-bisphosphate by aldolase are oxidized by NAD in the presence of arsenate to 3-phosphoglycerate. The NADH is detected via the bacterial NADH-linked luciferase system. Excellent agreement has been obtained by comparison with accepted methods. In addition, for the determination of serum free fatty acids, the method is particularly applicable for following lipolysis of isolated adipocytes. PMID:6486422

  19. Fatty acid production in genetically modified cyanobacteria

    PubMed Central

    Liu, Xinyao; Sheng, Jie; Curtiss III, Roy

    2011-01-01

    To avoid costly biomass recovery in photosynthetic microbial biofuel production, we genetically modified cyanobacteria to produce and secrete fatty acids. Starting with introducing an acyl–acyl carrier protein thioesterase gene, we made six successive generations of genetic modifications of cyanobacterium Synechocystis sp. PCC6803 wild type (SD100). The fatty acid secretion yield was increased to 197 ± 14 mg/L of culture in one improved strain at a cell density of 1.0 × 109 cells/mL by adding codon-optimized thioesterase genes and weakening polar cell wall layers. Although these strains exhibited damaged cell membranes at low cell densities, they grew more rapidly at high cell densities in late exponential and stationary phase and exhibited less cell damage than cells in wild-type cultures. Our results suggest that fatty acid secreting cyanobacteria are a promising technology for renewable biofuel production. PMID:21482809

  20. Fatty acid composition of Swedish bakery products, with emphasis on trans-fatty acids.

    PubMed

    Trattner, Sofia; Becker, Wulf; Wretling, Sören; Öhrvik, Veronica; Mattisson, Irene

    2015-05-15

    Trans-fatty acids (TFA) have been associated with increased risk of coronary heart disease, by affecting blood lipids and inflammation factors. Current nutrition recommendations emphasise a limitation of dietary TFA intake. The aim of this study was to investigate fatty acid composition in sweet bakery products, with emphasis on TFA, on the Swedish market and compare fatty acid composition over time. Products were sampled in 2001, 2006 and 2007 and analysed for fatty acid composition by using GC. Mean TFA levels were 0.7% in 2007 and 5.9% in 2001 of total fatty acids. In 1995-97, mean TFA level was 14.3%. In 2007, 3 of 41 products had TFA levels above 2% of total fatty acids. TFA content had decreased in this product category, while the proportion of saturated (SFA) and polyunsaturated (PUFA) fatty acids had increased, mostly through increased levels of 16:0 and 18:2 n-6, respectively. The total fat content remained largely unchanged. PMID:25577101

  1. Plasma fatty acid profile and alternative nutrition.

    PubMed

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Klvanová, J

    1997-01-01

    Plasma profile of fatty acids was examined in a group of children consisting of 7 vegans, 15 lactoovovegetarians and 10 semivegetarians. The children were 11-15 years old and the average period of alternative nutrition was 3.4 years. The results were compared with a group of 19 omnivores that constituted an average sample with respect to biochemical and hematological parameters from a larger study of health and nutritional status of children in Slovakia. Alternative nutrition groups had significantly lower values of saturated fatty acids. The content of oleic acid was identical to omnivores. A significant increase was observed for linoleic and alpha-linolenic (n-3) acids. The dihomo-gamma-linolenic (n-6) acid and arachidonic (n-6) acid values were comparable to omnivores for all alternative nutrition groups. Values of n-3 polyunsaturated fatty acids in lactoovovegetarians were identical to those of omnivores whereas they were significantly increased in semivegetarians consuming fish twice a week. Due to the total exclusion of animal fats from the diet, vegans had significantly reduced values of palmitoleic acid as well as eicosapentaenoic (n-3) acid and docosahexaenoic (n-3) acid resulting in an increased n-6/n-3 ratio. Values of plasma fatty acids found in alternative nutrition groups can be explained by the higher intake of common vegetable oils (high content of linoleic acid), oils rich in alpha-linolenic acid (cereal germs, soybean oil, walnuts), as well as in n-3 polyunsaturated fatty acids (fish). The results of fatty acids (except n-3 in vegans) and other lipid parameters confirm the beneficial effect of vegetarian nutrition in the prevention of cardiovascular diseases. PMID:9491192

  2. Fatty acid-induced NLRP3-PYCARD inflammasome activation interferes with insulin signaling

    PubMed Central

    Wen, Haitao; Gris, Denis; Lei, Yu; Jha, Sushmita; Zhang, Lu; Huang, Max Tze-Han; Brickey, Willie June; Ting, Jenny P.-Y.

    2014-01-01

    High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1β plays a role in insulin resistance; yet, how IL-1β is induced by fatty acid with HFD, and how this alters insulin signaling is unclear. We show that the saturated fatty acid, palmitate, but not unsaturated oleate, induces the activation of NLRP3-PYCARD inflammasome, causing caspase-1, IL-1β, and IL-18 production. This involves mitochondrial reactive oxygen species and the AMP-activated protein kinase and ULK1 autophagy signaling cascade. Inflammasome activation in hematopoietic cells impairs insulin signaling in several target tissues to reduce glucose tolerance and insulin sensitivity. Furthermore, IL-1β affects insulin sensitivity via TNF-independent and dependent pathways. These findings provide insights into the association of inflammation, diet and T2D. PMID:21478880

  3. An Intimate Relationship between ROS and Insulin Signalling: Implications for Antioxidant Treatment of Fatty Liver Disease

    PubMed Central

    Besse-Patin, Aurèle; Estall, Jennifer L.

    2014-01-01

    Oxidative stress damages multiple cellular components including DNA, lipids, and proteins and has been linked to pathological alterations in nonalcoholic fatty liver disease (NAFLD). Reactive oxygen species (ROS) emission, resulting from nutrient overload and mitochondrial dysfunction, is thought to be a principal mediator in NAFLD progression, particularly toward the development of hepatic insulin resistance. In the context of insulin signalling, ROS has a dual role, as both a facilitator and inhibitor of the insulin signalling cascade. ROS mediate these effects through redox modifications of cysteine residues affecting phosphatase enzyme activity, stress-sensitive kinases, and metabolic sensors. This review highlights the intricate relationship between redox-sensitive proteins and insulin signalling in the context of fatty liver disease, and to a larger extent, the importance of reactive oxygen species as primary signalling molecules in metabolically active cells. PMID:24672550

  4. Ameliorative potential of Tamarindus indica on high fat diet induced nonalcoholic fatty liver disease in rats.

    PubMed

    Sasidharan, Suja Rani; Joseph, Joshua Allan; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Madhavan, Chandrasekharan Nair Ariyattu; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

  5. Determination of fatty acid composition and quality characteristics of oils from palm fruits using solvent extraction

    NASA Astrophysics Data System (ADS)

    Kasmin, Hasimah; Lazim, Azwan Mat; Awang, Roila

    2015-09-01

    Palm oil contains about 45% of saturated palmitic acid and 39% of mono-unsaturated oleic acid. Investigations made in the past to trace the fatty acid composition in palm revealed that ripeness of fresh fruit bunch (FFB) affect oil composition. However, there is no evidence that processing operations affect oil composition, although different stage of processing does affect the quality of oil extracted. An improved method for sterilizing the oil palm fruits by dry heating, followed by oil extraction has been studied. This method eliminates the use of water, thus, increasing the extraction of lipid soluble. The objective of this study is to determine the possibility production of palm oil with different fatty acid composition (FAC) as well as the changes in quality from conventional milling. The unripe and ripe FFB were collected, sterilized and extracted using different method of solvent extraction. Preliminary data have shown that variation in FAC will also alter the physical and chemical properties of the oil extracted.

  6. Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats

    PubMed Central

    Sasidharan, Suja Rani; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Ariyattu Madhavan, Chandrasekharan Nair; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

  7. Genetically Altered Plant Species

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Researchers in Robert Ferl's lab at the University of Florida in Gainesville, genetically altered this Arabdopsis Thaliana (a brassica species) plant to learn how extreme environments, such as the low atmospheric pressure on Mars, affect plant genes. They inserted green fluorescent protein (GFP) near the on/off switches for anoxia and drought genes. When those genes were turned on after exposure to reduced atmospheric pressure, GFP was turned on as well, causing cells expressing those genes to glow green under a blue light. The natural fluorescence of chlorophyll accounts for the red glow.

  8. Gut Microbiota of Nonalcoholic Fatty Liver Disease.

    PubMed

    Abdou, Reham M; Zhu, Lixin; Baker, Robert D; Baker, Susan S

    2016-05-01

    The prevalence of nonalcoholic fatty liver disease has been rapidly increasing worldwide. It has become a leading cause of liver transplantation. Accumulating evidence suggests a significant role for gut microbiota in its development and progression. Here we review the effect of gut microbiota on developing hepatic fatty infiltration and its progression. Current literature supports a possible role for gut microbiota in the development of liver steatosis, inflammation and fibrosis. We also review the literature on possible interventions for NAFLD that target the gut microbiota. PMID:26898658

  9. Fatty liver incidence and predictive variables.

    PubMed

    Tsuneto, Akira; Hida, Ayumi; Sera, Nobuko; Imaizumi, Misa; Ichimaru, Shinichiro; Nakashima, Eiji; Seto, Shinji; Maemura, Koji; Akahoshi, Masazumi

    2010-06-01

    Although fatty liver predicts ischemic heart disease, the incidence and predictors of fatty liver need examination. The objective of this study was to determine fatty liver incidence and predictive variables. Using abdominal ultrasonography, we followed biennially through 2007 (mean follow-up, 11.6+/-4.6 years) 1635 Nagasaki atomic bomb survivors (606 men) without fatty liver at baseline (November 1990 through October 1992). We examined potential predictive variables with the Cox proportional hazard model and longitudinal trends with the Wilcoxon rank-sum test. In all, 323 (124 men) new fatty liver cases were diagnosed. The incidence was 19.9/1000 person-years (22.3 for men, 18.6 for women) and peaked in the sixth decade of life. After controlling for age, sex, and smoking and drinking habits, obesity (relative risk (RR), 2.93; 95% confidence interval (CI), 2.33-3.69, P<0.001), low high-density lipoprotein-cholesterol (RR, 1.87; 95% CI, 1.42-2.47; P<0.001), hypertriglyceridemia (RR, 2.49; 95% CI, 1.96-3.15; P<0.001), glucose intolerance (RR, 1.51; 95% CI, 1.09-2.10; P=0.013) and hypertension (RR, 1.63; 95% CI, 1.30-2.04; P<0.001) were predictive of fatty liver. In multivariate analysis including all variables, obesity (RR, 2.55; 95% CI, 1.93-3.38; P<0.001), hypertriglyceridemia (RR, 1.92; 95% CI, 1.41-2.62; P<0.001) and hypertension (RR, 1.31; 95% CI, 1.01-1.71; P=0.046) remained predictive. In fatty liver cases, body mass index and serum triglycerides, but not systolic or diastolic blood pressure, increased significantly and steadily up to the time of the diagnosis. Obesity, hypertriglyceridemia and, to a lesser extent, hypertension might serve as predictive variables for fatty liver. PMID:20379184

  10. Technological Aspects of Chemoenzymatic Epoxidation of Fatty Acids, Fatty Acid Esters and Vegetable Oils: A Review.

    PubMed

    Milchert, Eugeniusz; Malarczyk, Kornelia; Kłos, Marlena

    2015-01-01

    The general subject of the review is analysis of the effect of technological parameters on the chemoenzymatic epoxidation processes of vegetable oils, fatty acids and alkyl esters of fatty acids. The technological parameters considered include temperature, concentration, amount of hydrogen peroxide relative to the number of unsaturated bonds, the amounts of enzyme catalysts, presence of solvent and amount of free fatty acids. Also chemical reactions accompanying the technological processes are discussed together with different technological options and significance of the products obtained. PMID:26633342

  11. [Fatty acid content of the lipid fraction of the liver and fatty tissues of fattened geese].

    PubMed

    Kostadinov, K; Monov, G

    1986-01-01

    The content of fatty acids in the lipid fraction of the liver and in the body fats of fattened gray Landen geese. Determinations were carried out with a gas chromatography Chrom 41 supplied with Determinations were carried out with a gas chromatograph Chrom 41 supplied with a flame-ionization detector. It was found that the average content of fatty acids (saturated and unsaturated) as expressed by percent of their total amount was 45.90% and 54.10% (liver), 36.58% and 63.42% (subcutaneous fatty tissue), 42.79% and 57.31% (inner lard), and 39.01% and 60.99% (skin fats). PMID:3727379

  12. Metabolic Flux Between Unsaturated and Saturated Fatty Acids is Controlled by the FabA:FabB Ratio in the Fully Reconstituted Fatty Acid Biosynthetic Pathway of E. coli#

    PubMed Central

    Xiao, Xirui; Yu, Xingye; Khosla, Chaitan

    2013-01-01

    The entire fatty acid biosynthetic pathway from Escherichia coli, starting from the acetyl-CoA carboxylase, has been reconstituted in vitro from fourteen purified protein components. Radiotracer analysis verified stoichiometric conversion of acetyl-CoA and NAD(P)H into the free fatty acid product, allowing implementation of a facile spectrophotometric assay for kinetic analysis of this multi-enzyme system. At steady state, a maximum turnover rate of 0.5 s−1 was achieved. Under optimal turnover conditions, the predominant products were C16 and C18 saturated as well as monounsaturated fatty acids. The reconstituted system allowed us to quantitatively interrogate the factors that influence metabolic flux toward unsaturated versus saturated fatty acids. In particular, the concentrations of the dehydratase FabA and the β-ketoacyl synthase FabB were found to be crucial for controlling this property. By altering these variables, the percentage of unsaturated fatty acid produced could be adjusted between 10 and 50% without significantly affecting the maximum turnover rate of the pathway. Our reconstituted system provides a powerful tool to understand and engineer rate-limiting and regulatory steps in this complex and practically significant metabolic pathway. PMID:24147979

  13. Fatty Acid Biosynthesis Revisited: Structure Elucidation and Metabolic Engineering

    PubMed Central

    Beld, Joris; Lee, D. John

    2014-01-01

    Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fatty acids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fatty acid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fatty acid synthases’ many intricate structural and regulatory elements. In this review, we summarize each enzymatic domain and discuss efforts to engineer fatty acid synthases, providing some clues to important challenges and opportunities in the field. PMID:25360565

  14. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... html Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering ... fatty beef and cheese was linked with more aggressive prostate cancer, the researchers found. A diet high ...

  15. Fatty acid biosynthesis revisited: structure elucidation and metabolic engineering.

    PubMed

    Beld, Joris; Lee, D John; Burkart, Michael D

    2015-01-01

    Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fatty acids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fatty acid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fatty acid synthases' many intricate structural and regulatory elements. In this review, we summarize each enzymatic domain and discuss efforts to engineer fatty acid synthases, providing some clues to important challenges and opportunities in the field. PMID:25360565

  16. 21 CFR 172.848 - Lactylic esters of fatty acids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... are prepared from lactic acid and fatty acids meeting the requirements of § 172.860(b) and/or oleic acid derived from tall oil fatty acids meeting the requirements of § 172.862. (b) They are used...

  17. 21 CFR 172.848 - Lactylic esters of fatty acids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... accordance with the following prescribed conditions: (a) They are prepared from lactic acid and fatty acids meeting the requirements of § 172.860(b) and/or oleic acid derived from tall oil fatty acids meeting...

  18. 21 CFR 172.848 - Lactylic esters of fatty acids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... are prepared from lactic acid and fatty acids meeting the requirements of § 172.860(b) and/or oleic acid derived from tall oil fatty acids meeting the requirements of § 172.862. (b) They are used...

  19. 21 CFR 172.848 - Lactylic esters of fatty acids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... are prepared from lactic acid and fatty acids meeting the requirements of § 172.860(b) and/or oleic acid derived from tall oil fatty acids meeting the requirements of § 172.862. (b) They are used...

  20. Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase.

    PubMed

    Gao, Xuefei; Li, Kuai; Hui, Xiaoyan; Kong, Xiangping; Sweeney, Gary; Wang, Yu; Xu, Aimin; Teng, Maikun; Liu, Pentao; Wu, Donghai

    2011-05-01

    The adipocyte is the principal cell type for fat storage. CPT1 (carnitine palmitoyltransferase-1) is the rate-limiting enzyme for fatty acid β-oxidation, but the physiological role of CPT1 in adipocytes remains unclear. In the present study, we focused on the specific role of CPT1A in the normal functioning of adipocytes. Three 3T3-L1 adipocyte cell lines stably expressing hCPT1A (human CPT1A) cDNA, mouse CPT1A shRNA (short-hairpin RNA) or GFP (green fluorescent protein) were generated and the biological functions of these cell lines were characterized. Alteration in CPT1 activity, either by ectopic overexpression or pharmacological inhibition using etomoxir, did not affect adipocyte differentiation. However, overexpression of hCPT1A significantly reduced the content of intracellular NEFAs (non-esterified fatty acids) compared with the control cells when adipocytes were challenged with fatty acids. The changes were accompanied by an increase in fatty acid uptake and a decrease in fatty acid release. Interestingly, CPT1A protected against fatty acid-induced insulin resistance and expression of pro-inflammatory adipokines such as TNF-α (tumour necrosis factor-α) and IL-6 (interleukin-6) in adipocytes. Further studies demonstrated that JNK (c-Jun N terminal kinase) activity was substantially suppressed upon CPT1A overexpression, whereas knockdown or pharmacological inhibition of CPT1 caused a significant enhancement of JNK activity. The specific inhibitor of JNK SP600125 largely abolished the changes caused by the shRNA- and etomoxir-mediated decrease in CPT1 activity. Moreover, C2C12 myocytes co-cultured with adipocytes pre-treated with fatty acids displayed altered insulin sensitivity. Taken together, our findings have identified a favourable role for CPT1A in adipocytes to attenuate fatty acid-evoked insulin resistance and inflammation via suppression of JNK. PMID:21348853

  1. The Response Regulator YycF Inhibits Expression of the Fatty Acid Biosynthesis Repressor FabT in Streptococcus pneumoniae

    PubMed Central

    Mohedano, Maria L.; Amblar, Mónica; de la Fuente, Alicia; Wells, Jerry M.; López, Paloma

    2016-01-01

    The YycFG (also known as WalRK, VicRK, MicAB, or TCS02) two-component system (TCS) is highly conserved among Gram-positive bacteria with a low G+C content. In Streptococcus pneumoniae the YycF response regulator has been reported to be essential due to its control of pcsB gene expression. Previously we showed that overexpression of yycF in S. pneumoniae TIGR4 altered the transcription of genes involved in cell wall metabolism and fatty acid biosynthesis, giving rise to anomalous cell division and increased chain length of membrane fatty acids. Here, we have overexpressed the yycFG system in TIGR4 wild-type strain and yycF in a TIGR4 mutant depleted of YycG, and analyzed their effects on expression of proteins involved in fatty acid biosynthesis during activation of the TCS. We demonstrate that transcription of the fab genes and levels of their products were only altered in the YycF overexpressing strain, indicating that the unphosphorylated form of YycF is involved in the regulation of fatty acid biosynthesis. In addition, DNA-binding assays and in vitro transcription experiments with purified YycF and the promoter region of the FabTH-acp operon support a direct inhibition of transcription of the FabT repressor by YycF, thus confirming the role of the unphosphorylated form in transcriptional regulation. PMID:27610104

  2. The Response Regulator YycF Inhibits Expression of the Fatty Acid Biosynthesis Repressor FabT in Streptococcus pneumoniae.

    PubMed

    Mohedano, Maria L; Amblar, Mónica; de la Fuente, Alicia; Wells, Jerry M; López, Paloma

    2016-01-01

    The YycFG (also known as WalRK, VicRK, MicAB, or TCS02) two-component system (TCS) is highly conserved among Gram-positive bacteria with a low G+C content. In Streptococcus pneumoniae the YycF response regulator has been reported to be essential due to its control of pcsB gene expression. Previously we showed that overexpression of yycF in S. pneumoniae TIGR4 altered the transcription of genes involved in cell wall metabolism and fatty acid biosynthesis, giving rise to anomalous cell division and increased chain length of membrane fatty acids. Here, we have overexpressed the yycFG system in TIGR4 wild-type strain and yycF in a TIGR4 mutant depleted of YycG, and analyzed their effects on expression of proteins involved in fatty acid biosynthesis during activation of the TCS. We demonstrate that transcription of the fab genes and levels of their products were only altered in the YycF overexpressing strain, indicating that the unphosphorylated form of YycF is involved in the regulation of fatty acid biosynthesis. In addition, DNA-binding assays and in vitro transcription experiments with purified YycF and the promoter region of the FabTH-acp operon support a direct inhibition of transcription of the FabT repressor by YycF, thus confirming the role of the unphosphorylated form in transcriptional regulation. PMID:27610104

  3. Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro[S

    PubMed Central

    Canfrán-Duque, Alberto; Casado, María E.; Pastor, Óscar; Sánchez-Wandelmer, Jana; de la Peña, Gema; Lerma, Milagros; Mariscal, Paloma; Bracher, Franz; Lasunción, Miguel A.; Busto, Rebeca

    2013-01-01

    Haloperidol, a typical antipsychotic, has been shown to inhibit cholesterol biosynthesis by affecting Δ7-reductase, Δ8,7-isomerase, and Δ14-reductase activities, which results in the accumulation of different sterol intermediates. In the present work, we investigated the effects of atypical or second-generation antipsychotics (SGA), such as clozapine, risperidone, and ziprasidone, on intracellular lipid metabolism in different cell lines. All the SGAs tested inhibited cholesterol biosynthesis. Ziprasidone and risperidone had the same targets as haloperidol at inhibiting cholesterol biosynthesis, although with different relative activities (ziprasidone > haloperidol > risperidone). In contrast, clozapine mainly affected Δ24-reductase and Δ8,7-isomerase activities. These amphiphilic drugs also interfered with the LDL-derived cholesterol egress from the endosome/lysosome compartment, thus further reducing the cholesterol content in the endoplasmic reticulum. This triggered a homeostatic response with the stimulation of sterol regulatory element-binding protein (SREBP)-regulated gene expression. Treatment with SGAs also increased the synthesis of complex lipids (phospholipids and triacylglycerides). Once the antipsychotics were removed from the medium, a rebound in the cholesterol biosynthesis rate was detected, and the complex-lipid synthesis further increased. In this condition, apolipoprotein B secretion was also stimulated as demonstrated in HepG2 cells. These effects of SGAs on lipid homeostasis may be relevant in the metabolic side effects of antipsychotics, especially hypertriglyceridemia. PMID:23175778

  4. Dietary Fatty Acid Composition Alters Magnesium Metabolism, Distribution, and Marginal Deficiency Response in Rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Based on dietary intake recommendations, magnesium deficiency commonly occurs throughout the world. However, widespread pathological conditions induced by dietary magnesium deficiency have not been identified. This discrepancy may be caused by other dietary factors ameliorating or exacerbating the r...

  5. Peroxisome proliferators and fatty acids negatively regulate liver X receptor-mediated activity and sterol biosynthesis.

    PubMed

    Johnson, T E; Ledwith, B J

    2001-04-01

    Peroxisome proliferators (PPs) are potent tumor promoters in rodents. The mechanism of hepatocarcinogenesis requires the nuclear receptor peroxisome proliferator activated receptor-alpha (PPARalpha), but might also involve the PPARalpha independent alteration of signaling pathways that regulate cell growth. Here, we studied the effects of PPs on the mevalonate pathway, a critical pathway that controls cell proliferation. Liver X receptors (LXRs) are nuclear receptors that act as sterol sensors in the mevalonate pathway. In gene reporter assays in COS-7 cells, the basal activity of the LXR responsive reporter gene (LXRE-luc) was suppressed by 10 microM lovastatin and zaragozic acid A, suggesting that this activity was attributed to the activation of native LXRs, by endogenously produced mevalonate products. The potent PP and rodent tumor promoter, pirinixic acid (WY-14643) also inhibited LXR-mediated transcription in a dose related manner (approximate IC(50) of 100 microM). As did several other PPs including ciprofibric acid and mono-ethylhexylphthalate. Polyunsaturated and medium to long chain fatty acids at 100 microM were also potent inhibitors; the arachidonic acid analogue eicosatetraynoic acid being the most active (approximate IC(50) of 10 microM). Of the PPs and fatty acids tested, there was a strong correlation between the ability of these agents to suppress de novo sterol synthesis in a rat hepatoma cell line, H4IIEC3, and inhibit LXR-mediated transcription in COS-7 cells, but a discordance between these endpoints and PPARalpha activation and fatty acid acyl-Co