Science.gov

Sample records for differentiation lipid metabolism

  1. Microarray analysis of differentially expressed genes regulating lipid metabolism during melanoma progression.

    PubMed

    Sumantran, Venil N; Mishra, Pratik; Sudhakar, N

    2015-04-01

    A new hallmark of cancer involves acquisition of a lipogenic phenotype which promotes tumorigenesis. Little is known about lipid metabolism in melanomas. Therefore, we used BRB (Biometrics Research Branch) class comparison tool with multivariate analysis to identify differentially expressed genes in human cutaneous melanomas, compared with benign nevi and normal skin derived from the microarray dataset (GDS1375). The methods were validated by identifying known melanoma biomarkers (CITED1, FGFR2, PTPRF, LICAM, SPP1 and PHACTR1) in our results. Eighteen genes regulating metabolism of fatty acids, lipid second messengers and gangliosides were 2-9 fold upregulated in melanomas of GDS-1375. Out of the 18 genes, 13 were confirmed by KEGG pathway analysis and 10 were also significantly upregulated in human melanoma cell lines of NCI-60 Cell Miner database. Results showed that melanomas upregulated PPARGC1A transcription factor and its target genes regulating synthesis of fatty acids (SCD) and complex lipids (FABP3 and ACSL3). Melanoma also upregulated genes which prevented lipotoxicity (CPT2 and ACOT7) and regulated lipid second messengers, such as phosphatidic acid (AGPAT-4, PLD3) and inositol triphosphate (ITPKB, ITPR3). Genes for synthesis of pro-tumorigenic GM3 and GD3 gangliosides (UGCG, HEXA, ST3GAL5 and ST8SIA1) were also upregulated in melanoma. Overall, the microarray analysis of GDS-1375 dataset indicated that melanomas can become lipogenic by upregulating genes, leading to increase in fatty acid metabolism, metabolism of specific lipid second messengers, and ganglioside synthesis.

  2. Moringa oleifera Lam. improves lipid metabolism during adipogenic differentiation of human stem cells.

    PubMed

    Barbagallo, I; Vanella, L; Distefano, A; Nicolosi, D; Maravigna, A; Lazzarino, G; Di Rosa, M; Tibullo, D; Acquaviva, R; Li Volti, G

    2016-12-01

    Moringa oleifera Lam., a multipurpose tree, is used traditionally for its nutritional and medicinal properties. It has been used for the treatment of a variety of conditions, including inflammation, cancer and metabolic disorders. We investigated the effect of Moringa oleifera Lam. on adipogenic differentiation of human adipose-derived mesenchymal stem cells and its impact on lipid metabolism and cellular antioxidant systems. We showed that Moringa oleifera Lam. treatment during adipogenic differentiation reduces inflammation, lipid accumulation and induces thermogenesis by activation of uncoupling protein 1 (UCP1), sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor alpha (PPARα), and coactivator 1 alpha (PGC1α). In addition, Moringa oleifera Lam. induces heme oxygenase-1 (HO-1), a well established protective and antioxidant enzyme. Finally Moringa oleifera Lam. significantly decreases the expression of molecules involved in adipogenesis and upregulates the expression of mediators involved in thermogenesis and lipid metabolism. Our results suggest that Moringa oleifera Lam. may promote the brown remodeling of white adipose tissue inducing thermogenesis and improving metabolic homeostasis.

  3. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    SciTech Connect

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha; Beisiegel, Ulrike; Heeren, Joerg

    2008-02-15

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor {gamma} (PPAR{gamma}) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPAR{gamma} agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPAR{gamma}-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake.

  4. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells.

    PubMed

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha; Beisiegel, Ulrike; Heeren, Joerg

    2008-02-15

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor gamma (PPARgamma) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPARgamma agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARgamma-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake.

  5. It’s a lipid’s world: Bioactive lipid metabolism and signaling in neural stem cell differentiation

    PubMed Central

    Bieberich, Erhard

    2012-01-01

    Lipids are often considered membrane components whose function is to embed proteins into cell membranes. In the last two decades, studies on brain lipids have unequivocally demonstrated that many lipids have critical cell signaling functions; they are called “bioactive lipids”. Pioneering work in Dr. Robert Ledeen’s laboratory has shown that two bioactive brain sphingolipids, sphingomyelin and the ganglioside GM1 are major signaling lipids in the nuclear envelope. In addition to derivatives of the sphingolipid ceramide, the bioactive lipids discussed here belong to the classes of terpenoids and steroids, eicosanoids, and lysophospholipids. These lipids act mainly through two mechanisms: 1) direct interaction between the bioactive lipid and a specific protein binding partner such as a lipid receptor, protein kinase or phosphatase, ion exchanger, or other cell signaling protein; and 2) formation of lipid microdomains or rafts that regulate the activity of a group of raft-associated cell signaling proteins. In recent years, a third mechanism has emerged, which invokes lipid second messengers as a regulator for the energy and redox balance of differentiating neural stem cells (NSCs). Interestingly, developmental niches such as the stem cell niche for adult NSC differentiation may also be metabolic compartments that respond to a distinct combination of bioactive lipids. The biological function of these lipids as regulators of NSC differentiation will be reviewed and their application in stem cell therapy discussed. PMID:22246226

  6. Triacylglycerol accumulation and oxidative stress in Rhodococcus species: differential effects of pro-oxidants on lipid metabolism.

    PubMed

    Urbano, Susana Bequer; Di Capua, Cecilia; Cortez, Néstor; Farías, María E; Alvarez, Héctor M

    2014-03-01

    In general, members of Rhodococcus genus are highly resistant to desiccation. Desiccation is a complex process which includes the formation of reactive oxygen species that results in significant damage to cells. In this study, we demonstrate that extremophile actinobacterial strains isolated from diverse environments, mainly belonging to Rhodococcus genus, exhibited high tolerance to the pro-oxidants hydrogen peroxide (H2O2) and methyl viologen (MV). In addition, we investigated the possible interconnections between the responses of the oleaginous Rhodococcus opacus PD630 to oxidative stress and lipid metabolism, since both processes demand a metabolic reorganization of cells. Experiments with metabolic inhibitors showed differential effects of both pro-oxidants on lipid metabolism in PD630 cells. The inhibition of carotenoid biosynthesis by the addition of diphenylamine to the media negatively affected the tolerance of cells to H2O2, but not to MV. The inhibition of triacylglycerol (TAG) biosynthesis and accumulation in PD630 did not affect the tolerance of cells to H2O2 and MV; whereas, the blockage of lipolysis decreased the tolerance of cells to H2O2 (but not MV) under carbon-starvation conditions. Interestingly, the addition of MV to the media (but not H2O2) induced a reduction of TAG accumulation by cells. Resuming, results of this study revealed metabolic connections between lipid metabolism and oxidative stress responses in R. opacus PD630, and probably in other extremophile TAG-accumulating rhodococci.

  7. Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading[S

    PubMed Central

    Fernandez-Ruiz, Irene; Puchalska, Patrycja; Narasimhulu, Chandrakala Aluganti; Sengupta, Bhaswati; Parthasarathy, Sampath

    2016-01-01

    The influence of the hypercholesterolemia associated with atherosclerosis on monocytes is poorly understood. Monocytes are exposed to high concentrations of lipids, particularly cholesterol and lysophosphatidylcholine (lyso-PC). Indeed, in line with recent reports, we found that monocytes accumulate cholesteryl esters (CEs) in hypercholesterolemic mice, demonstrating the need for studies that analyze the effects of lipid accumulation on monocytes. Here we analyze the effects of cholesterol and lyso-PC loading in human monocytes and macrophages. We found that cholesterol acyltransferase and CE hydrolase activities are lower in monocytes. Monocytes also showed a different expression profile of cholesterol influx and efflux genes in response to lipid loading and a different pattern of lyso-PC metabolism. In monocytes, increased levels of CE slowed the conversion of lyso-PC into PC. Interestingly, although macrophages accumulated glycerophosphocholine, phosphocholine was the main water-soluble choline metabolite being generated in monocytes, suggesting a role for mono- and diacylglycerol in the chemoattractability of these cells. In summary, monocytes and macrophages show significant differences in lipid metabolism and gene expression profiles in response to lipid loading. These findings provide new insights into the mechanisms of atherosclerosis and suggest potentials for targeting monocyte chemotactic properties not only in atherosclerosis but also in other diseases. PMID:26839333

  8. Differential Amino Acid, Carbohydrate and Lipid Metabolism Perpetuations Involved in a Subtype of Rheumatoid Arthritis with Chinese Medicine Cold Pattern

    PubMed Central

    Guo, Hongtao; Niu, Xuyan; Gu, Yan; Lu, Cheng; Xiao, Cheng; Yue, Kevin; Zhang, Ge; Pan, Xiaohua; Jiang, Miao; Tan, Yong; Kong, Hongwei; Liu, Zhenli; Xu, Guowang; Lu, Aiping

    2016-01-01

    Pattern classification is a key approach in Traditional Chinese Medicine (TCM), and it is used to classify the patients for intervention selection accordingly. TCM cold and heat patterns, two main patterns of rheumatoid arthritis (RA) had been explored with systems biology approaches. Different regulations of apoptosis were found to be involved in cold and heat classification in our previous works. For this study, the metabolic profiling of plasma was explored in RA patients with typical TCM cold or heat patterns by integrating liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) platforms in conjunction with the Ingenuity Pathway Analysis (IPA) software. Three main processes of metabolism, including amino acid, carbohydrate and lipid were focused on for function analysis. The results showed that 29 and 19 differential metabolites were found in cold and heat patterns respectively, compared with healthy controls. The perturbation of amino acid metabolism (increased essential amino acids), carbohydrate metabolism (galactose metabolism) and lipid metabolism, were found to be involved in both cold and heat pattern RA. In particular, more metabolic perturbations in protein and collagen breakdown, decreased glycolytic activity and aerobic oxidation, and increased energy utilization associated with RA cold pattern patients. These findings may be useful for obtaining a better understanding of RA pathogenesis and for achieving a better efficacy in RA clinical practice. PMID:27775663

  9. Fructose promotes the differentiation of 3T3-L1 adipocytes and accelerates lipid metabolism.

    PubMed

    Legeza, Balázs; Balázs, Zoltán; Odermatt, Alex

    2014-01-31

    Excessive fructose consumption and elevated glucocorticoids contribute to metabolic syndrome. We show that fructose as the only carbohydrate source is sufficient for the differentiation of 3T3-L1 fibroblasts into adipocytes. Differentiation of cells in fructose containing medium resulted in increased 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) expression and activity. Experiments with transfected HEK-293 cells suggested more efficient NADPH generation by fructose compared with glucose in the endoplasmic reticulum (ER). Adipocytes differentiated in the presence of fructose showed increased FABP4 expression, C/EBPα to C/EBPβ ratio and lipolysis. Thus, excessive fructose may cause adverse metabolic effects by enhancing 11β-HSD1 activity and increasing lipolysis in adipocytes. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Metabolism. Part III: Lipids.

    ERIC Educational Resources Information Center

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  11. Metabolism. Part III: Lipids.

    ERIC Educational Resources Information Center

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  12. Effects of retinoids on differentiation, lipid metabolism, epidermal growth factor, and low-density lipoprotein binding in squamous carcinoma cells

    SciTech Connect

    Ponec, M.; Weerheim, A. ); Havekes, L. ); Boonstra, J. )

    1987-08-01

    The relationship among keratinocyte differentiation capacity, lipid synthesis, low-density lipoprotein (LDL) metabolism, plasma membrane composition, and epidermal growth factor (EGF) binding has been studied in SCC-12F2 cells. The differentiation capacity of the cells, i.e., ionophore-induced cornified envelope formation, was inhibited by various retinoids and stimulated by hydrocortisone. Retinoids that caused a significant reduction of cornified envelope formation, i.e., retinoic acid and 13-cis-retinoic acid, caused only minor changes in lipid synthesis and plasma membrane composition. Arotinoid ethylsulfone, having a minor effect on cornified envelope formation, caused a drastic inhibition of cholesterol synthesis resulting in changes in the plasma membrane composition. Hydrocortisone stimulated cornified envelope formation but had only minor effects on lipid synthesis and plasma membrane composition. Of all retinoids tested, only arotinoid ethylsulfone caused a drastic increase in EGF binding, while hydrocortisone had no effect. These results clearly demonstrate that the plasma membrane composition is not related to keratinocyte differentiation capacity, but most likely does determine EGF binding. Furthermore, EGF binding does not determine keratinocyte differentiation capacity.

  13. Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

    PubMed

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A

    2016-01-01

    Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

  14. Effects of telmisartan on lipid metabolisms and proinflammatory factors secretion of differentiated 3T3-L1 adipocytes.

    PubMed

    Kang, Chen; Yijun, Li; Jingtao, Dou; Changyu, Pan; Wenhua, Yan; Baoan, Wang; Fangling, Ma; Xianling, Wang; Guoqing, Yang; Yiming, Mu; Juming, Lu

    2015-12-01

    To investigate the effect of telmisartan on the lipometabolisms and the proinflammatory factors secreted from 3T3-L1 adipocytes and to explore the possible mechanisms. Telmisartan was applied to interfere with mature 3T3-L1 adipocytes. The culture's free fatty acids, interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) were evaluated. Oil Red O staining was used to determine the adipogenesis of 3T3-L1 adipocytes. (18)F-FDG uptake levels corrected for protein content were determined by cellular radioactivity. The total RNA was isolated for hybridization experimentation in the microarray. Telmisartan reduced lipid storage and increased (18)F-FDG uptake in a dose-dependent manner, reduced the levels of IL-6 and TNFα and increased those of free fatty acids. One hundred and fifty-seven differentially expressed genes were found by microarray. The mitogen-activated protein kinase (MAPK) signaling pathway involved in the secretion of proinflammatory factor and lipid metabolisms was affected by telmisartan. The expression of endothelial nitric oxide synthetase gene 3 (Nos3) and carnitine palmitoyl transferase 1α (CPT1α) was up-regulated by telmisartan. Telmisartan affected lipometabolisms and the proinflammatory factors secreted from adipocytes. Nos3, CPT1α and the MAPK pathway being affected by telmisartan may be the underlying cause of the improvement in lipid metabolisms and secretion of proinflammatory factors of differentiated 3T3-L1 adipocytes. © The Author(s) 2014.

  15. Targeting Lipid Metabolic Reprogramming as Anticancer Therapeutics

    PubMed Central

    Cha, Ji-Young; Lee, Ho-Jae

    2016-01-01

    Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells can affect numerous cellular processes, including cell growth, proliferation, differentiation, and survival. The potential dependence of cancer cells on the deregulated lipid metabolism suggests that enzymes and regulating factors involved in this process are promising targets for cancer treatment. In this review, we focus on the features associated with the lipid metabolic pathways in cancer, and highlight recent advances on the therapeutic targets of specific lipid metabolic enzymes or regulating factors and target-directed small molecules that can be potentially used as anticancer drugs. PMID:28053954

  16. Cocoa and Whey Protein Differentially Affect Markers of Lipid and Glucose Metabolism and Satiety.

    PubMed

    Campbell, Caroline L; Foegeding, E Allen; Harris, G Keith

    2016-03-01

    Food formulation with bioactive ingredients is a potential strategy to promote satiety and weight management. Whey proteins are high in leucine and are shown to decrease hunger ratings and increase satiety hormone levels; cocoa polyphenolics moderate glucose levels and slow digestion. This study examined the effects of cocoa and whey proteins on lipid and glucose metabolism and satiety in vitro and in a clinical trial. In vitro, 3T3-L1 preadipocytes were treated with 0.5-100 μg/mL cocoa polyphenolic extract (CPE) and/or 1-15 mM leucine (Leu) and assayed for lipid accumulation and leptin production. In vivo, a 6-week clinical trial consisted of nine panelists (age: 22.6 ± 1.7; BMI: 22.3 ± 2.1) consuming chocolate-protein beverages once per week, including placebo, whey protein isolate (WPI), low polyphenolic cocoa (LP), high polyphenolic cocoa (HP), LP-WPI, and HP-WPI. Measurements included blood glucose and adiponectin levels, and hunger ratings at baseline and 0.5-4.0 h following beverage consumption. At levels of 50 and 100 μg/mL, CPE significantly inhibited preadipocyte lipid accumulation by 35% and 50%, respectively, and by 22% and 36% when combined with 15 mM Leu. Leu treatment increased adipocyte leptin production by 26-37%. In the clinical trial, all beverages significantly moderated blood glucose levels 30 min postconsumption. WPI beverages elicited lowest peak glucose levels and HP levels were significantly lower than LP. The WPI and HP beverage treatments significantly increased adiponectin levels, but elicited no significant changes in hunger ratings. These trends suggest that combinations of WPI and cocoa polyphenols may improve markers of metabolic syndrome and satiety.

  17. Alcohol and lipid metabolism

    PubMed Central

    Sozio, Margaret; Crabb, David W.

    2008-01-01

    Many new mechanisms for alcoholic steatosis have been suggested by work reported in the last five years. These include alterations of transcriptional controls of lipid metabolism, better understanding of the effects of abnormal methionine metabolism on the endoplasmic reticulum stress response, unraveling of the basis for sensitization of the Kupffer cell to lipopolysaccharide, a better understanding of the role of cytokines and adipokines in alcoholic liver disease, and implication of the innate immune and complement systems in responses to alcohol. Much of this work has been facilitated by work with knockout mice. Undoubtedly, there are interrelationships among these various pathogenic mechanisms that ultimately will provide a more cohesive picture of how heavy alcohol use deranges hepatic lipid metabolism. PMID:18349117

  18. Acyl-Lipid Metabolism

    PubMed Central

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  19. Acyl-Lipid Metabolism

    PubMed Central

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2010-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:22303259

  20. Dietary L-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle.

    PubMed

    Tan, Bie; Yin, Yulong; Liu, Zhiqiang; Tang, Wenjie; Xu, Haijun; Kong, Xiangfeng; Li, Xinguo; Yao, Kang; Gu, Wanting; Smith, Stephen B; Wu, Guoyao

    2011-05-01

    Obesity is a major health crisis worldwide and new treatments are needed to fight this epidemic. Using the swine model, we recently reported that dietary L-arginine (Arg) supplementation promotes muscle gain and reduces body-fat accretion. The present study tested the hypothesis that Arg regulates expression of key genes involved in lipid metabolism in skeletal muscle and white adipose tissue. Sixteen 110-day-old barrows were fed for 60 days a corn- and soybean-meal-based diet supplemented with 1.0% Arg or 2.05% L-alanine (isonitrogenous control). Blood samples, longissimus dorsi muscle and overlying subcutaneous adipose tissue were obtained from 170-day-old pigs for biochemical studies. Serum concentrations of leptin, alanine and glutamine were lower, but those for Arg and proline were higher in Arg-supplemented pigs than in control pigs. The percentage of oleic acid was higher but that of stearic acid and linoleic acid was lower in muscle of Arg-supplemented pigs, compared with control pigs. Dietary Arg supplementation increased mRNA levels for fatty acid synthase in muscle, while decreasing those for lipoprotein lipase, glucose transporter-4, and acetyl-coenzyme A carboxylase-α in adipose tissue. Additionally, mRNA levels for hormone sensitive lipase were higher in adipose tissue of Arg-supplemented pigs compared with control pigs. These results indicate that Arg differentially regulates expression of fat-metabolic genes in skeletal muscle and white adipose tissue, therefore favoring lipogenesis in muscle but lipolysis in adipose tissue. Our novel findings provide a biochemical basis for explaining the beneficial effect of Arg in improving the metabolic profile in mammals (including obese humans). Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Three dissimilar high fat diets differentially regulate lipid and glucose metabolism in obesity-resistant Slc:Wistar/ST rats.

    PubMed

    Hashimoto, Yoko; Yamada, Kazuyo; Tsushima, Hiromi; Miyazawa, Daisuke; Mori, Mayumi; Nishio, Koji; Ohkubo, Takeshi; Hibino, Hidehiko; Ohara, Naoki; Okuyama, Harumi

    2013-08-01

    Epidemiologic and ecologic studies suggest that dietary fat plays an important role in the development of obesity. Certain Wistar rat strains do not become obese when fed high-fat diets unlike others. In a preliminary study, we confirmed that Slc:Wistar/ST rats did not become obese when fed high-fat diets. The mechanisms governing the response of hepatic lipid-metabolizing enzymes to large quantities of dietary lipids consumed by obesity-resistant animals are unknown. The aim of the present study is to examine how obesity-resistant animals metabolize various types of high-fat diets and why they do not become obese. For this purpose, male Slc:Wistar/ST rats were fed a control low-fat diet (LS) or a high-fat diet containing fish oil (HF), soybean oil (HS), or lard (HL) for 4 weeks. We observed their phenotypes and determined lipid profiles in plasma and liver as well as mRNA expression levels in liver of genes related to lipid and glucose metabolism using DNA microarray and quantitative reverse transcriptase polymerase chain analyses. The body weights of all dietary groups were similar due to isocaloric intakes, whereas the weight of white adipose tissues in the LS group was significantly lower. The HF diet lowered plasma lipid levels by accelerated lipolysis in the peroxisomes and suppressed levels of very-low-density lipoprotein (VLDL) secretion. The HS diet promoted hepatic lipid accumulation by suppressed lipolysis in the peroxisomes and normal levels of VLDL secretion. The lipid profiles of rats fed the LS or HL diet were similar. The HL diet accelerated lipid and glucose metabolism.

  2. Computational Modeling of Lipid Metabolism in Yeast

    PubMed Central

    Schützhold, Vera; Hahn, Jens; Tummler, Katja; Klipp, Edda

    2016-01-01

    Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes. Here, we present an object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner. The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism. PMID:27730126

  3. Computational Modeling of Lipid Metabolism in Yeast.

    PubMed

    Schützhold, Vera; Hahn, Jens; Tummler, Katja; Klipp, Edda

    2016-01-01

    Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes. Here, we present an object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner. The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

  4. Circadian regulation of lipid metabolism.

    PubMed

    Gooley, Joshua J

    2016-11-01

    The circadian system temporally coordinates daily rhythms in feeding behaviour and energy metabolism. The objective of the present paper is to review the mechanisms that underlie circadian regulation of lipid metabolic pathways. Circadian rhythms in behaviour and physiology are generated by master clock neurons in the suprachiasmatic nucleus (SCN). The SCN and its efferent targets in the hypothalamus integrate light and feeding signals to entrain behavioural rhythms as well as clock cells located in peripheral tissues, including the liver, adipose tissue and muscle. Circadian rhythms in gene expression are regulated at the cellular level by a molecular clock comprising a core set of clock genes/proteins. In peripheral tissues, hundreds of genes involved in lipid biosynthesis and fatty acid oxidation are rhythmically activated and repressed by clock proteins, hence providing a direct mechanism for circadian regulation of lipids. Disruption of clock gene function results in abnormal metabolic phenotypes and impaired lipid absorption, demonstrating that the circadian system is essential for normal energy metabolism. The composition and timing of meals influence diurnal regulation of metabolic pathways, with food intake during the usual rest phase associated with dysregulation of lipid metabolism. Recent studies using metabolomics and lipidomics platforms have shown that hundreds of lipid species are circadian-regulated in human plasma, including but not limited to fatty acids, TAG, glycerophospholipids, sterol lipids and sphingolipids. In future work, these lipid profiling approaches can be used to understand better the interaction between diet, mealtimes and circadian rhythms on lipid metabolism and risk for obesity and metabolic diseases.

  5. Lipid Droplets And Cellular Lipid Metabolism

    PubMed Central

    Walther, Tobias C.; Farese, Robert V.

    2013-01-01

    Among organelles, lipid droplets (LDs) uniquely constitute a hydrophobic phase in the aqueous environment of the cytosol. Their hydrophobic core of neutral lipids stores metabolic energy and membrane components, making LDs hubs for lipid metabolism. In addition, LDs are implicated in a number of other cellular functions, ranging from protein storage and degradation to viral replication. These processes are functionally linked to many physiological and pathological conditions, including obesity and related metabolic diseases. Despite their important functions and nearly ubiquitous presence in cells, many aspects of LD biology are unknown. In the past few years, the pace of LD investigation has increased, providing new insights. Here, we review the current knowledge of LD cell biology and its translation to physiology. PMID:22524315

  6. TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology

    PubMed Central

    Entwistle, Lewis J.; Khoury, Hania; Papoutsopoulou, Stamatia; Mahmood, Radma; Mansour, Nuha R.; Ching-Cheng Huang, Stanley; Pearce, Edward J.; Pedro S. de Carvalho, Luiz; Ley, Steven C.

    2016-01-01

    Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8–/–mice was observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8–/–M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis. PMID:27487182

  7. Differential gene expression and lipid metabolism in fatty liver induced by acute ethanol treatment in mice

    SciTech Connect

    Yin Huquan; Kim, Mingoo; Kim, Ju-Han; Kong, Gu; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-IL; Lee, Mi-Ock; Lee, Byung-Hoon

    2007-09-15

    Ethanol induces cumulative liver damage including steatosis, steatohepatitis and cirrhosis. The aim of this study is to investigate the global intrahepatic gene expression profile in the mouse liver treated with ethanol. A single oral dose of 0.5 or 5 g/kg ethanol was administered to male ICR mice, and liver samples were obtained after 6, 24 and 72 h. Histopathological evaluation showed typical fatty livers in the high-dose group at 24 h. Microarray analysis identified 28 genes as being ethanol responsive (two-way ANOVA; p < 0.05), after adjustment by the Benjamini-Hochberg multiple testing correction; these genes displayed {>=} 2-fold induction or repression. The expression of genes that are known to be involved in fatty acid synthesis was examined. The transcript for lipogenic transcription factor, sterol regulatory element (SRE)-binding factor 1 (Srebf1), was upregulated by acute ethanol exposure. Of the genes known to contain SRE or SRE-like sequences and to be regulated by SRE-binding protein 1 (SREBP1), those encoding malic enzyme (Mod1), ATP-citrate lyase (Acly), fatty acid synthase (Fasn) and stearyl-CoA desaturase (Scd1) were induced by ethanol. Quantitative real-time PCR confirmed the changes in the expression levels of the selected genes. The change in the Srebf1 mRNA level correlates well with that of the SREBP1 protein expression as well as its binding to the promoters of the target genes. The present study identifies differentially expressed genes that can be applied to the biomarkers for alcohol-binge-induced fatty liver. These results support the hypothesis by which ethanol-induced steatosis in mice is mediated by the fatty acid synthetic pathway regulated by SREBP1.

  8. Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment

    PubMed Central

    Gallego-Ortega, David; Ramirez de Molina, Ana; Ramos, Maria Angeles; Valdes-Mora, Fatima; Barderas, Maria Gonzalez; Sarmentero-Estrada, Jacinto; Lacal, Juan Carlos

    2009-01-01

    Background The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKα and ChoKβ isoforms, the first one with two different variants of splicing. Recently ChoKα has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKβ in carcinogenesis has been reported. Methodology/Principal Findings Here we compare the in vitro and in vivo properties of ChoKα1 and ChoKβ in lipid metabolism, and their potential role in carcinogenesis. Both ChoKα1 and ChoKβ showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKβ display an ethanolamine kinase role, ChoKα1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKα1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKβ overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKα1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKβ mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKα1 than ChoKβ. Conclusion/Significance This study represents the first evidence of the distinct metabolic role of ChoKα and ChoKβ isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the

  9. Lipids and lipid metabolism in eukaryotic algae.

    PubMed

    Guschina, Irina A; Harwood, John L

    2006-03-01

    Eukaryotic algae are a very diverse group of organisms which inhabit a huge range of ecosystems from the Antarctic to deserts. They account for over half the primary productivity at the base of the food chain. In recent years studies on the lipid biochemistry of algae has shifted from experiments with a few model organisms to encompass a much larger number of, often unusual, algae. This has led to the discovery of new compounds, including major membrane components, as well as the elucidation of lipid signalling pathways. A major drive in recent research have been attempts to discover genes that code for expression of the various proteins involved in the production of very long-chain polyunsaturated fatty acids such as arachidonic, eicosapentaenoic and docosahexaenoic acids. Such work is described here together with information about how environmental factors, such as light, temperature or minerals, can change algal lipid metabolism and how adaptation may take place.

  10. Lipid Chaperones and Metabolic Inflammation

    PubMed Central

    Furuhashi, Masato; Ishimura, Shutaro; Ota, Hideki; Miura, Tetsuji

    2011-01-01

    Over the past decade, a large body of evidence has emerged demonstrating an integration of metabolic and immune response pathways. It is now clear that obesity and associated disorders such as insulin resistance and type 2 diabetes are associated with a metabolically driven, low-grade, chronic inflammatory state, referred to as “metaflammation.” Several inflammatory cytokines as well as lipids and metabolic stress pathways can activate metaflammation, which targets metabolically critical organs and tissues including adipocytes and macrophages to adversely affect systemic homeostasis. On the other hand, inside the cell, fatty acid-binding proteins (FABPs), a family of lipid chaperones, as well as endoplasmic reticulum (ER) stress, and reactive oxygen species derived from mitochondria play significant roles in promotion of metabolically triggered inflammation. Here, we discuss the molecular and cellular basis of the roles of FABPs, especially FABP4 and FABP5, in metaflammation and related diseases including obesity, diabetes, and atherosclerosis. PMID:22121495

  11. Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse.

    PubMed

    Kelly, Daniel M; Akhtar, Samia; Sellers, Donna J; Muraleedharan, Vakkat; Channer, Kevin S; Jones, T Hugh

    2016-11-01

    Testosterone deficiency is commonly associated with obesity, metabolic syndrome, type 2 diabetes and their clinical consequences-hepatic steatosis and atherosclerosis. The testicular feminised mouse (non-functional androgen receptor and low testosterone) develops fatty liver and aortic lipid streaks on a high-fat diet, whereas androgen-replete XY littermate controls do not. Testosterone treatment ameliorates these effects, although the underlying mechanisms remain unknown. We compared the influence of testosterone on the expression of regulatory targets of glucose, cholesterol and lipid metabolism in muscle, liver, abdominal subcutaneous and visceral adipose tissue. Testicular feminised mice displayed significantly reduced GLUT4 in muscle and glycolytic enzymes in muscle, liver and abdominal subcutaneous but not visceral adipose tissue. Lipoprotein lipase required for fatty acid uptake was only reduced in subcutaneous adipose tissue; enzymes of fatty acid synthesis were increased in liver and subcutaneous tissue. Stearoyl-CoA desaturase-1 that catalyses oleic acid synthesis and is associated with insulin resistance was increased in visceral adipose tissue and cholesterol efflux components (ABCA1, apoE) were decreased in subcutaneous and liver tissue. Master regulator nuclear receptors involved in metabolism-Liver X receptor expression was suppressed in all tissues except visceral adipose tissue, whereas PPARγ was lower in abdominal subcutaneous and visceral adipose tissue and PPARα only in abdominal subcutaneous. Testosterone treatment improved the expression (androgen receptor independent) of some targets but not all. These exploratory data suggest that androgen deficiency may reduce the buffering capability for glucose uptake and utilisation in abdominal subcutaneous and muscle and fatty acids in abdominal subcutaneous. This would lead to an overspill and uptake of excess glucose and triglycerides into visceral adipose tissue, liver and arterial walls.

  12. Lipid Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system (enzymes) break the food parts down into sugars ...

  13. Endoplasmic Reticulum Stress and Ca2+ Depletion Differentially Modulate the Sterol Regulatory Protein PCSK9 to Control Lipid Metabolism.

    PubMed

    Lebeau, Paul; Al-Hashimi, Ali; Sood, Sudesh; Lhoták, Šárka; Yu, Pei; Gyulay, Gabriel; Paré, Guillaume; Chen, S R Wayne; Trigatti, Bernardo; Prat, Annik; Seidah, Nabil G; Austin, Richard C

    2017-01-27

    Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER-localized transcription factor that directly up-regulates sterol regulatory genes, including PCSK9 Given that PCSK9 contributes to atherosclerosis by targeting low density lipoprotein (LDL) receptor (LDLR) degradation, this study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression. Herein, we demonstrate the existence of two independent effects of ER stress on PCSK9 expression and secretion. In cultured HuH7 and HepG2 cells, agents or conditions that cause ER Ca(2+) depletion, including thapsigargin, induced SREBP2-dependent up-regulation of PCSK9 expression. In contrast, a significant reduction in the secreted form of PCSK9 protein was observed in the media from both thapsigargin- and tunicamycin (TM)-treated HuH7 cells, mouse primary hepatocytes, and in the plasma of TM-treated C57BL/6 mice. Furthermore, TM significantly increased hepatic LDLR expression and reduced plasma LDL concentrations in mice. Based on these findings, we propose a model in which ER Ca(2+) depletion promotes the activation of SREBP2 and subsequent transcription of PCSK9. However, conditions that cause ER stress regardless of their ability to dysregulate ER Ca(2+) inhibit PCSK9 secretion, thereby reducing PCSK9-mediated LDLR degradation and promoting LDLR-dependent hepatic cholesterol uptake. Taken together, our studies provide evidence that the retention of PCSK9 in the ER may serve as a potential strategy for lowering LDL cholesterol levels.

  14. Lipid metabolism during fasting.

    PubMed

    Jensen, M D; Ekberg, K; Landau, B R

    2001-10-01

    These studies were conducted to understand the relationship between measures of systemic free fatty acid (FFA) reesterification and regional FFA, glycerol, and triglyceride metabolism during fasting. Indirect calorimetry was used to measure fatty acid oxidation in six men after a 60-h fast. Systemic and regional (splanchnic, renal, and leg) FFA ([(3)H]palmitate) and glycerol ([(3)H]glycerol) kinetics, as well as splanchnic triglyceride release, were measured. The rate of systemic FFA reesterification was 366 +/- 93 micromol/min, which was greater (P < 0.05) than splanchnic triglyceride fatty acid output (64 +/- 6 micromol/min), a measure of VLDL triglyceride fatty acid export. The majority of glycerol uptake occurred in the splanchnic and renal beds, although some leg glycerol uptake was detected. Systemic FFA release was approximately double that usually present in overnight postabsorptive men, yet the regional FFA release rates were of the same proportions previously observed in overnight postabsorptive men. In conclusion, FFA reesterification at rest during fasting far exceeds splanchnic triglyceride fatty acid output. This indicates that nonhepatic sites of FFA reesterification are important, and that peripheral reesterification of FFA exceeds the rate of simultaneous intracellular triglyceride fatty acid oxidation.

  15. Lipid metabolism is differentially modulated by salicylic acid and heptanoyl salicylic acid during the induction of resistance in wheat against powdery mildew.

    PubMed

    Tayeh, Christine; Randoux, Béatrice; Bourdon, Natacha; Reignault, Philippe

    2013-12-15

    Heptanoyl salicylic acid (HSA) is a salicylic acid (SA) derivative obtained by esterification of 2-OH benzoic acid with heptanoic acid. In wheat, the protection levels obtained against Blumeria graminis f. sp. tritici (Bgt) increased from 50% with SA to 95% with HSA. Using molecular, biochemical and cytological approaches, we investigated here how wheat lipid metabolism is differentially activated by SA and HSA in both infectious and non-infectious conditions, and how Bgt infectious process is altered by both inducers. First, in the absence of Bgt, continuous lipoxygenase (LOX)-encoding gene expression and corresponding activity were specifically induced by HSA. Moreover, compared to SA, HSA treatment resulted in earlier up-regulations of the phospholipase C2-encoding gene expression and it specifically affected the expression of a lipid transfer protein-encoding gene. In infectious context, both HSA and SA sprayings impaired penetration events and therefore haustorium formation, leading to less frequent fungal colonies. While this alteration only slowed down the evolution of Bgt infectious process in SA-sprayed leaves, it completely impaired the establishment of successful infectious events in HSA-sprayed leaves. In addition, HSA induced continuous increases of a LOX-encoding gene expression and of the corresponding LOX activity when compared to SA-sprayed leaves. Lipid metabolism is therefore overall highly responsive to HSA spraying and could represent effective defence mechanism triggered during the induction of resistance in wheat toward Bgt. The concepts of priming and energy costs of the defences induced by SA and HSA are also discussed.

  16. Azithromycin Treatment Alters Gene Expression in Inflammatory, Lipid Metabolism, and Cell Cycle Pathways in Well-Differentiated Human Airway Epithelia

    PubMed Central

    Ribeiro, Carla Maria P.; Hurd, Harry; Wu, Yichao; Martino, Mary E. B.; Jones, Lisa; Brighton, Brian; Boucher, Richard C.; O'Neal, Wanda K.

    2009-01-01

    Prolonged macrolide antibiotic therapy at low doses improves clinical outcome in patients affected with diffuse panbronchiolitis and cystic fibrosis. Consensus is building that the therapeutic effects are due to anti-inflammatory, rather than anti-microbial activities, but the mode of action is likely complex. To gain insights into how the macrolide azithromycin (AZT) modulates inflammatory responses in airways, well-differentiated primary cultures of human airway epithelia were exposed to AZT alone, an inflammatory stimulus consisting of soluble factors from cystic fibrosis airways, or AZT followed by the inflammatory stimulus. RNA microarrays were conducted to identify global and specific gene expression changes. Analysis of gene expression changes revealed that the AZT treatment alone altered the gene profile of the cells, primarily by significantly increasing the expression of lipid/cholesterol genes and decreasing the expression of cell cycle/mitosis genes. The increase in cholesterol biosynthetic genes was confirmed by increased filipin staining, an index of free cholesterol, after AZT treatment. AZT also affected genes with inflammatory annotations, but the effect was variable (both up- and down-regulation) and gene specific. AZT pretreatment prevented the up-regulation of some genes, such as MUC5AC and MMP9, triggered by the inflammatory stimulus, but the up-regulation of other inflammatory genes, e.g., cytokines and chemokines, such as interleukin-8, was not affected. On the other hand, HLA genes were increased by AZT. Notably, secreted IL-8 protein levels did not reflect mRNA levels, and were, in fact, higher after AZT pretreatment in cultures exposed to the inflammatory stimulus, suggesting that AZT can affect inflammatory pathways other than by altering gene expression. These findings suggest that the specific effects of AZT on inflamed and non-inflamed airway epithelia are likely relevant to its clinical activity, and their apparent complexity may help

  17. Differential gene expression pattern in hypothalamus of chickens during fasting-induced metabolic reprogramming: functions of glucose and lipid metabolism in the feed intake of chickens.

    PubMed

    Fang, Xin-Ling; Zhu, Xiao-Tong; Chen, Sheng-Feng; Zhang, Zhi-Qi; Zeng, Qing-Jie; Deng, Lin; Peng, Jian-Long; Yu, Jian-Jian; Wang, Li-Na; Wang, Song-Bo; Gao, Ping; Jiang, Qing-Yan; Shu, Gang

    2014-11-01

    Fasting-induced hypothalamic metabolic reprogramming is involved in regulating energy homeostasis and appetite in mammals, but this phenomenon remains unclear in poultry. In this study, the expression patterns of a panel of genes related to neuropeptides, glucose, and lipid metabolism enzymes in the hypothalamus of chickens during fasting and refeeding were characterized by microarray analysis and quantitative PCR. Results showed that 48 h of fasting upregulated (P < 0.05) the mRNA expressions of orexigenic neuropeptide Y and agouti-related protein but downregulated (P < 0.05) that of anorexigenic neuropeptide pro-opiomelanocortin; growth hormone-releasing hormone; islet amyloid polypeptide; thyroid-stimulating hormone, β; and glycoprotein hormones, α polypeptide. After 48 h of fasting, the mRNA expression of fatty acid β-oxidation [peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1A, and forkhead box O1], energy sensor protein [sirtuin 1 (SIRT1) and forkhead box O1], and glycolysis inhibitor (pyruvate dehydrogenase kinase, isozyme 4) were enhanced, but that of fatty acid synthesis and transport associated genes (acetyl-CoA carboxylase α, fatty acid synthase, apolipoprotein A-I, endothelial lipase, and fatty acid binding protein 7) were suppressed. Liver and muscle also demonstrated similar expression patterns of genes related to glucose and lipid metabolism with hypothalamus, except for that of acetyl-CoA carboxylase α, acyl-CoA synthetase long-chain family member 4, and apolipoprotein A-I. The results of intracerebroventricular (ICV) injection experiments confirmed that α-lipoic acid (ALA, pyruvate dehydrogenase kinase, isozyme 4 inhibitor, 0.10 μmol) and NADH (SIRT1 inhibitor, 0.80 μmol) significantly suppressed the appetite of chickens, whereas 2-deoxy-d-glucose (glycolytic inhibitor, 0.12 to 1.20 μmol) and NAD(+) (SIRT1 activator, 0.08 to 0.80 μmol) increased feed intake in chickens. The orexigenic effect of NAD

  18. Yeast lipid metabolism at a glance.

    PubMed

    Klug, Lisa; Daum, Günther

    2014-05-01

    During the last decades, lipids have gained much attention due to their involvement in health and disease. Lipids are required for the formation of membranes and contribute to many different processes such as cell signaling, energy supply, and cell death. Various organelles such as the endoplasmic reticulum, mitochondria, peroxisomes, and lipid droplets are involved in lipid metabolism. The yeast Saccharomyces cerevisiae has become a reliable model organism to study biochemistry, molecular biology, and cell biology of lipids. The availability of mutants bearing defects in lipid metabolic pathways and the ease of manipulation by culture conditions facilitated these investigations. Here, we summarize the current knowledge about lipid metabolism in yeast. We grouped this large topic into three sections dealing with (1) fatty acids; (2) membrane lipids; and (3) storage lipids. Fatty acids serve as building blocks for the synthesis of membrane lipids (phospholipids, sphingolipids) and storage lipids (triacylglycerols, steryl esters). Phospholipids, sterols, and sphingolipids are essential components of cellular membranes. Recent investigations addressing lipid synthesis, degradation, and storage as well as regulatory aspects are presented. The role of enzymes governing important steps of the different lipid metabolic pathways is described. Finally, the link between lipid metabolic and dynamic processes is discussed. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  19. Influence of Nutritional Factors on Lipid Metabolism.

    DTIC Science & Technology

    1980-12-01

    on lipid metabolism in the liver, muscle , a freuenlydiffers and is species dependent. Fatty acid ul UCASIFTED SECURITY CLASSIFICATION OF THIS PA49MhM...The effect of diet on lipid metabolism in the liver, muscle , and adipose tissue frequently differs and is species dependent. Fatty acid uptake...will encom- pass the effect of diet on lipid metabolism in the liver, muscle , and adipose tissue, with emphasis on fatty acid uptake, synthesis

  20. Dietary folate and choline status differentially affect lipid metabolism and behavior-mediated neurotransmitters in young rats

    USDA-ARS?s Scientific Manuscript database

    The relationship between choline and folate metabolisms is an important issue due to the essential role of these nutrients in brain plasticity and cognitive functions. Present study was designed to investigate whether modification of the dietary folate-choline status in young rats would affect brain...

  1. Sirtuins in glucose and lipid metabolism

    PubMed Central

    Ye, Xin; Li, Meiting; Hou, Tianyun; Gao, Tian; Zhu, Wei-guo; Yang, Yang

    2017-01-01

    Sirtuins are evolutionarily conserved protein, serving as nicotinamide adenine dinucleotide-dependent deacetylases or adenosine diphosphate-ribosyltransferases. The mammalian sirtuins family, including SIRT1~7, is involved in many biological processes such as cell survival, proliferation, senescence, stress response, genome stability and metabolism. Evidence accumulated over the past two decades has indicated that sirtuins not only serve as important energy status sensors but also protect cells against metabolic stresses. In this review, we summarize the background of glucose and lipid metabolism concerning sirtuins and discuss the functions of sirtuins in glucose and lipid metabolism. We also seek to highlight the biological roles of certain sirtuins members in cancer metabolism. PMID:27659520

  2. Computational Functional Analysis of Lipid Metabolic Enzymes.

    PubMed

    Bagnato, Carolina; Have, Arjen Ten; Prados, María B; Beligni, María V

    2017-01-01

    The computational analysis of enzymes that participate in lipid metabolism has both common and unique challenges when compared to the whole protein universe. Some of the hurdles that interfere with the functional annotation of lipid metabolic enzymes that are common to other pathways include the definition of proper starting datasets, the construction of reliable multiple sequence alignments, the definition of appropriate evolutionary models, and the reconstruction of phylogenetic trees with high statistical support, particularly for large datasets. Most enzymes that take part in lipid metabolism belong to complex superfamilies with many members that are not involved in lipid metabolism. In addition, some enzymes that do not have sequence similarity catalyze similar or even identical reactions. Some of the challenges that, albeit not unique, are more specific to lipid metabolism refer to the high compartmentalization of the routes, the catalysis in hydrophobic environments and, related to this, the function near or in biological membranes.In this work, we provide guidelines intended to assist in the proper functional annotation of lipid metabolic enzymes, based on previous experiences related to the phospholipase D superfamily and the annotation of the triglyceride synthesis pathway in algae. We describe a pipeline that starts with the definition of an initial set of sequences to be used in similarity-based searches and ends in the reconstruction of phylogenies. We also mention the main issues that have to be taken into consideration when using tools to analyze subcellular localization, hydrophobicity patterns, or presence of transmembrane domains in lipid metabolic enzymes.

  3. Differential effects of habitual chow-based and semi-purified diets on lipid metabolism in lactating rats and their offspring.

    PubMed

    Del Bas, Josep Maria; Caimari, Antoni; Ceresi, Enzo; Arola-Arnal, Anna; Palou, Andreu; Arola, Lluís; Crescenti, Anna

    2015-03-14

    Diet during pregnancy and lactation is a critical factor in relation to the health of dams and their offspring. Currently, control diets used in metabolic imprinting studies differ in composition and type, i.e. semi-purified diets (SD) or chow-based diets (ND). The aim of the present study was to determine whether two widely used control diets, a SD and a ND, that mainly differ in fat content (5·08 and 3·26 %, respectively) and its sources (soyabean oil for the SD and cereals and fish for the ND), fibre (6 and 15 %, respectively), and cholesterol (26 and 69 mg/kg diet, respectively) can influence the lipid metabolism of dams and their offspring. Wistar rats were fed either the SD or the ND during pregnancy and lactation. At weaning, SD-fed dams presented severe hepatic steatosis and increased levels of circulating TAG, NEFA and insulin. Importantly, the offspring presented an altered plasma lipid profile. In contrast, the ND allowed for a normal gestation and lactation process, and did not affect the metabolism of offspring. In parallel, virgin rats fed the SD showed no metabolic alterations. A higher intake of SFA and MUFA and a lower consumption of PUFA observed in SD-fed dams during the lactation period could contribute to explaining the observed effects. In conclusion, two different control diets produced very different outcomes in the lipid metabolism of lactating rats and their offspring. The present results highlight the importance of the assessment of the metabolic state of dams when interpreting the results of metabolic programming studies.

  4. Ovarian Lipid Metabolism Modulates Circulating Lipids in Premenopausal Women.

    PubMed

    Jensen, Jeffrey T; Addis, Ilana B; Hennebold, Jon D; Bogan, Randy L

    2017-09-01

    The premenopausal circulating lipid profile may be linked to the hormonal profile and ovarian lipid metabolism. Assess how estradiol, progesterone, and ovarian lipid metabolism contributes to the premenopausal lipid profile; and evaluate the acute effects of a common hormonal oral contraceptive (OC) on circulating lipids. Experimental crossover with repeated measures. Academic hospitals. Eight healthy, regularly menstruating women. Participants underwent periodic serum sampling during a normal menstrual cycle; a standard 21-day, monophasic combined hormonal OC cycle (30 µg of ethinyl estradiol and 150 µg of levonorgestrel per day); menopause simulated by leuprolide acetate (22.5-mg depot); and an artificial menstrual cycle achieved via transdermal estradiol (50 to 300 µg/d) and vaginal micronized progesterone (100 to 300 mg/d). Primary outcomes included evaluation of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, and the total cholesterol to HDL cholesterol ratio. To estimate the effect of estradiol, progesterone, and ovarian lipid metabolism, all specimens except those from the OC cycle were analyzed. Subgroup analysis was conducted on the follicular and luteal phases. In a separate analysis, the effect of the OC was evaluated relative to the normal menstrual cycle. Estradiol was significantly associated with increased levels of HDL cholesterol throughout the menstrual cycle and in the follicular phase. Ovarian effects were associated with reduced lipid levels, especially during the luteal phase. The OC was associated with an increased total cholesterol to HDL cholesterol ratio and triglycerides. Previously unappreciated factors including ovarian lipid metabolism may contribute to the premenopausal lipid profile.

  5. JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes

    SciTech Connect

    Ming, Guang-feng; Xiao, Di; Gong, Wei-jing; Liu, Hui-xia; Liu, Jun; Zhou, Hong-hao; Liu, Zhao-qian

    2014-03-14

    Highlights: • JAZF1 was significantly upregulated during the differentiation of 3T3-L1 preadipocytes. • JAZF1 overexpression inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes. • JAZF1 overexpression inhibited the expression of SREBP1, ACC, and FAS. • JAZF1 overexpression upregulated the expression of HSL and ATGL. • SREBP1 and JAZF1 could regulate each other in adipocytes. - Abstract: JAZF1 is a newly identified gene with unknown functions. A recent genome-wide association study showed that JAZF1 is associated with type 2 diabetes and is highly expressed in liver and adipose tissue. Studies have demonstrated that JAZF1 is the co-repressor for nuclear orphan receptor TAK1, whereas most nuclear orphan receptor family members are involved in the regulation of lipid metabolism. Therefore, JAZF1 could be closely related to glycolipid metabolism. In this study, JAZF1 was significantly upregulated during the induced differentiation process of 3T3-L1 preadipocytes. The overexpression of JAZF1 inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes and significantly inhibited the expression of SREBPl, ACC, and FAS, which were important in lipid synthesis, while upregulating the expression of key enzyme hormone-sensitive lipase in lipoclasis. Moreover, SREBPl exhibited an inhibitory function on the expression of JAZF1. SREBP1 reversed the inhibitory action on lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each other in adipocytes. Therefore, JAZF1 could regulate the expression of particular genes related to lipid metabolism and inhibit lipid accumulation in adipocytes. This result suggests that JAZF1 may be a potential target for the treatment of diseases, such as obesity and lipid metabolism disorders.

  6. Dietary soy isoflavones differentially regulate expression of the lipid-metabolic genes in different white adipose tissues of the female Bama mini-pigs.

    PubMed

    Jiang, Guoli; Li, Lili; Fan, Juexin; Zhang, Bin; Oso, A O; Xiao, Chaowu; Yin, Yulong

    2015-05-22

    Soy isoflavones have been shown to affect lipid metabolism, however the underlying molecular mechanism(s) have not yet been fully understood. The present study, using female Bama mini-pig as a model, examined the effects of soy isoflavones on lipid metabolism and involved gene expression in different white adipose tissues. Female Bama Xiang mini-pigs of 35 days old were fed a basal diet (control, Con), or basal diet supplemented with increasing amounts of soy isoflavones (250, 500, or 1250 mg/kg diet) for 120 days. The results showed that soy isoflavones did not affect the body weight, but decreased the dorsal subcutaneous adipose tissue (DSA) mass and increased the mass of abdominal subcutaneous adipose tissue (ASA) and perirenal adipose tissue (PRA). Besides, soy isoflavones decreased the expression of lipogenic genes and increased the expression of lipolytic genes in DSA, while the opposite effects were observed in ASA and PRA. In addition, the expression of lipoprotein lipase was down regulated in DSA while up regulated in ASA and PRA by soy isoflavones. Moreover, the expression of estrogen receptors (ERs) was up regulated in DSA, and down regulated in ASA and PRA by soy isoflavones. Our results suggest that soy isoflavones affected the lipid metabolism in white adipose tissues of Bama mini-pigs in a site-specific manner, which might be mediated through PPARs and ERs regulated gene expression. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Exercise and Regulation of Lipid Metabolism.

    PubMed

    Noland, Robert C

    2015-01-01

    The increased prevalence of hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, and fatty liver disease has provided increasingly negative connotations toward lipids. However, it is important to remember that lipids are essential components supporting life. Lipids are a class of molecules defined by their inherent insolubility in water. In biological systems, lipids are either hydrophobic (containing only polar groups) or amphipathic (possess polar and nonpolar groups). These characteristics lend lipids to be highly diverse with a multitude of functions including hormone and membrane synthesis, involvement in numerous signaling cascades, as well as serving as a source of metabolic fuel supporting energy production. Exercise can induce changes in the lipid composition of membranes that effect fluidity and cellular function, as well as modify the cellular and circulating environment of lipids that regulate signaling cascades. The purpose of this chapter is to focus on lipid utilization as metabolic fuel in response to acute and chronic exercise training. Lipids utilized as an energy source during exercise include circulating fatty acids bound to albumin, triglycerides stored in very-low-density lipoprotein, and intramuscular triglyceride stores. Dynamic changes in these lipid pools during and after exercise are discussed, as well as key factors that may be responsible for regulating changes in fat oxidation in response to varying exercise conditions. © 2015 Elsevier Inc. All rights reserved.

  8. Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins.

    PubMed

    Morales, Pablo Esteban; Bucarey, Jose Luis; Espinosa, Alejandra

    2017-01-01

    Skeletal muscle is one of the main regulators of carbohydrate and lipid metabolism in our organism, and therefore, it is highly susceptible to changes in glucose and fatty acid (FA) availability. Skeletal muscle is an extremely complex tissue: its metabolic capacity depends on the type of fibers it is made up of and the level of stimulation it undergoes, such as acute or chronic contraction. Obesity is often associated with increased FA levels, which leads to the accumulation of toxic lipid intermediates, oxidative stress, and autophagy in skeletal fibers. This lipotoxicity is one of the most common causes of insulin resistance (IR). In this scenario, the "isolation" of certain lipids in specific cell compartments, through the action of the specific lipid droplet, perilipin (PLIN) family of proteins, is conceived as a lifeguard compensatory strategy. In this review, we summarize the cellular mechanism underlying lipid mobilization and metabolism inside skeletal muscle, focusing on the function of lipid droplets, the PLIN family of proteins, and how these entities are modified in exercise, obesity, and IR conditions.

  9. Trypanosoma cruzi Infection and Host Lipid Metabolism

    PubMed Central

    Miao, Qianqian

    2014-01-01

    Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8 million people are thought to be affected worldwide. Several players in host lipid metabolism have been implicated in T. cruzi-host interactions in recent research, including macrophages, adipocytes, low density lipoprotein (LDL), low density lipoprotein receptor (LDLR), and high density lipoprotein (HDL). All of these factors are required to maintain host lipid homeostasis and are intricately connected via several metabolic pathways. We reviewed the interaction of T. cruzi with each of the relevant host components, in order to further understand the roles of host lipid metabolism in T. cruzi infection. This review sheds light on the potential impact of T. cruzi infection on the status of host lipid homeostasis. PMID:25276058

  10. Subclinical hypothyroidism, lipid metabolism and cardiovascular disease.

    PubMed

    Delitala, Alessandro P; Fanciulli, Giuseppe; Maioli, Margherita; Delitala, Giuseppe

    2017-03-01

    Subclinical hypothyroidism is defined by elevated serum thyrotropin in presence of normal free thyroid hormones. Lipid metabolism is influenced by thyroid hormone and many reports showed that lipids status worsen along with TSH level. Subclinical hypothyroidism has been also linked to other cardiovascular risk factors such as alteration in blood pressure and increased atherosclerosis. Further evidences suggested that mild dysfunction of thyroid gland is associated with metabolic syndrome and heart failure. Thyrotropin level seems the best predictor of cardiovascular disease, in particular when its levels are above 10mU/L. However, despite these observations, there is no clear evidence that levothyroxine therapy in subjects with milder form of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. In this review, we address the effect of thyroid hormone and cardiovascular risk, with a focus on lipid metabolism.

  11. Lipid metabolic reprogramming in cancer cells

    PubMed Central

    Beloribi-Djefaflia, S; Vasseur, S; Guillaumond, F

    2016-01-01

    Many human diseases, including metabolic, immune and central nervous system disorders, as well as cancer, are the consequence of an alteration in lipid metabolic enzymes and their pathways. This illustrates the fundamental role played by lipids in maintaining membrane homeostasis and normal function in healthy cells. We reviewed the major lipid dysfunctions occurring during tumor development, as determined using systems biology approaches. In it, we provide detailed insight into the essential roles exerted by specific lipids in mediating intracellular oncogenic signaling, endoplasmic reticulum stress and bidirectional crosstalk between cells of the tumor microenvironment and cancer cells. Finally, we summarize the advances in ongoing research aimed at exploiting the dependency of cancer cells on lipids to abolish tumor progression. PMID:26807644

  12. Lipid metabolism in Trypanosoma brucei

    PubMed Central

    Smith, Terry K.; Bütikofer, Peter

    2013-01-01

    Trypanosoma brucei membranes consist of all major eukaryotic glycerophospholipid and sphingolipid classes. These are de novo synthesized from precursors obtained either from the host or from catabolised endocytosed lipids. In recent years, substantial progress has been made in the molecular and biochemical characterisation of several of these lipid biosynthetic pathways, using gene knockout or RNA interference strategies or by enzymatic characterization of individual reactions. Together with the completed genome, these studies have highlighted several possible differences between mammalian and trypanosome lipid biosynthesis that could be exploited for the development of drugs against the diseases caused by these parasites. PMID:20382188

  13. PCSK9 targets important for lipid metabolism.

    PubMed

    Schulz, Rainer; Schlüter, Klaus-Dieter

    2017-03-01

    Ischemic heart disease is the main cause of death worldwide and it is accelerated by increased low-density lipoprotein (LDL) cholesterol (LDL-C) and/or lipoprotein (a) (Lp(a)) concentrations. Proprotein convertase subtilisin/kexin type 9 (PCSK9) alters both LDL-C and in part Lp(a) concentrations through its ability to induce degradation of the LDL receptor (LDLR). PCSK9, however, has additional targets which are potentially involved in lipid metabolism regulation such as the very low density lipoprotein receptor (VLDL), CD36 (cluster of differentiation 36) and the epithelial cholesterol transporter (NPC1L1) and it affects expression of apolipoprotein B48. The PCSK9 activity is tightly regulated at several levels by factors influencing its transcription, secretion, or by extracellular inactivation and clearance. Many comorbidities (kidney insufficiency, hypothyreoidism, hyperinsulinemia, inflammation) modify PCSK9 expression and release. Two humanized antibodies directed against extracellular PCSK9 received approval by the European and US authorities and additional PCSK9 directed therapeutics (such as silencing RNA) are already in clinical trials. Their results demonstrate a significant reduction in both LDL-C and Lp(a) concentrations - independent of the concomitant medication - and one of them reduced plaque size in high risk cardiovascular patients; results of two ongoing large clinical endpoints studies are awaited. In this review, we summarize and discuss the recent biological data on PCSK9, the regulation of PCSK9, and finally briefly summarize the data of recent clinical studies in the context of lipid metabolism.

  14. Role of peripheral serotonin in glucose and lipid metabolism.

    PubMed

    Watanabe, Hitoshi; Rose, Michael T; Aso, Hisashi

    2011-06-01

    Two independent serotonin systems exist, one in the brain and the other in the periphery. Serotonin is a well known monoaminergic neurotransmitter in the central nervous system and it is known to regulate feeding behavior, meal size, and body weight. On the other hand, there is much less evidence for the role of serotonin as a gastrointestinal hormone, particularly with respect to its effects on glucose and lipid metabolism. This review summarizes our current understanding of the role of peripheral serotonin on glucose and lipid metabolism and the implications of this for further research. The enterochromaffin cells of the gastrointestinal tract produce peripheral serotonin postprandially. In mice, it induces a decrease in the concentration of circulating lipids as well as hyperglycemia and hyperinsulinemia through its action on several serotonin receptors. Further, serotonin metabolites act as endogenous agonists for peroxisome proliferator-activated receptor γ and serotonin accelerates adipocyte differentiation via serotonin receptor 2A and 2C. Studies of serotonin are likely to provide new insights into the field of lipid accumulation and metabolism. Recent studies show new physiological functions of peripheral serotonin, linked to glucose and lipid metabolism. Peripheral serotonin may serve as an attractive new therapeutic target for the treatment of metabolic disorders in the near future.

  15. Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes

    SciTech Connect

    Ferrante, Maria C.; Amero, Paola; Santoro, Anna; Monnolo, Anna; Simeoli, Raffaele; Di Guida, Francesca; Mattace Raso, Giuseppina; Meli, Rosaria

    2014-09-15

    Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are highly lipophilic environmental contaminants that accumulate in lipid-rich tissues, such as adipose tissue. Here, we reported the effects induced by PCBs 101, 153 and 180, three of the six NDL-PCBs defined as indicators, on mature 3T3-L1 adipocytes. We observed an increase in lipid content, in leptin gene expression and a reduction of leptin receptor expression and signaling, when cells were exposed to PCBs, alone or in combination. These modifications were consistent with the occurrence of “leptin-resistance” in adipose tissue, a typical metabolic alteration related to obesity. Therefore, we investigated how PCBs affect the expression of pivotal proteins involved in the signaling of leptin receptor. We evaluated the PCB effect on the intracellular pathway JAK/STAT, determining the phosphorylation of STAT3, a downstream activator of the transcription of leptin gene targets, and the expression of SOCS3 and PTP1B, two important regulators of leptin resistance. In particular, PCBs 153 and 180 or all PCB combinations induced a significant reduction in pSTAT3/STAT3 ratio and an increase in PTP1B and SOCS3, evidencing an additive effect. The impairment of leptin signaling was associated with the reduction of AMPK/ACC pathway activation, leading to the increase in lipid content. These pollutants were also able to increase the transcription of inflammatory cytokines (IL-6 and TNFα). It is worthy to note that the PCB concentrations used are comparable to levels detectable in human adipose tissue. Our data strongly support the hypothesis that NDL-PCBs may interfere with the lipid metabolism contributing to the development of obesity and related diseases. - Highlights: • NDL-PCBs alter lipid content and metabolism in 3T3-L1 adipocytes. • Impairment of leptin signaling was induced by NDL-PCBs. • NDL-PCBs reduce AMPK and ACC activation. • NDL-PCBs induce the synthesis of pro-inflammatory cytokine by

  16. Physiology and pathophysiology of liver lipid metabolism.

    PubMed

    Ponziani, Francesca Romana; Pecere, Silvia; Gasbarrini, Antonio; Ojetti, Veronica

    2015-01-01

    Liver lipid metabolism and its modulation are involved in many pathologic conditions, such as obesity, non-alcoholic fatty liver disease, diabetes mellitus, atherosclerosis and cardiovascular disease. Metabolic disorders seem to share a similar background of low-grade chronic inflammation, even if the pathophysiological mechanisms leading to tissue and organ damage have not been completely clarified yet. The accumulation of neutral lipids in the liver is now recognized as a beneficial and protective mechanism; on the other hand, lipoperoxidation is involved in the development and progression of non-alcoholic steatohepatitis. The role of the gut microbiota in liver lipid metabolism has been the object of recent scientific investigations. It is likely that the gut microbiota is involved in a complex metabolic modulation and the translocation of gut microflora may also contribute to maintaining the low-grade inflammatory status of metabolic syndrome. Therefore, lipid metabolism pathology has vague limits and complex mechanisms, and the knowledge of these is essential to guide diagnostic and therapeutic decisions.

  17. Yeast and cancer cells - common principles in lipid metabolism.

    PubMed

    Natter, Klaus; Kohlwein, Sepp D

    2013-02-01

    One of the paradigms in cancer pathogenesis is the requirement of a cell to undergo transformation from respiration to aerobic glycolysis - the Warburg effect - to become malignant. The demands of a rapidly proliferating cell for carbon metabolites for the synthesis of biomass, energy and redox equivalents, are fundamentally different from the requirements of a differentiated, quiescent cell, but it remains open whether this metabolic switch is a cause or a consequence of malignant transformation. One of the major requirements is the synthesis of lipids for membrane formation to allow for cell proliferation, cell cycle progression and cytokinesis. Enzymes involved in lipid metabolism were indeed found to play a major role in cancer cell proliferation, and most of these enzymes are conserved in the yeast, Saccharomyces cerevisiae. Most notably, cancer cell physiology and metabolic fluxes are very similar to those in the fermenting and rapidly proliferating yeast. Both types of cells display highly active pathways for the synthesis of fatty acids and their incorporation into complex lipids, and imbalances in synthesis or turnover of lipids affect growth and viability of both yeast and cancer cells. Thus, understanding lipid metabolism in S. cerevisiae during cell cycle progression and cell proliferation may complement recent efforts to understand the importance and fundamental regulatory mechanisms of these pathways in cancer.

  18. Orphan enzymes in ether lipid metabolism.

    PubMed

    Watschinger, Katrin; Werner, Ernst R

    2013-01-01

    Ether lipids are an emerging class of lipids which have so far not been investigated and understood in every detail. They have important roles as membrane components of e.g. lens, brain and testis, and as mediators such as platelet-activating factor. The metabolic enzymes for biosynthesis and degradation have been investigated to some extent. As most involved enzymes are integral membrane proteins they are tricky to handle in biochemical protocols. The sequence of some ether lipid metabolising enzymes has only recently been reported and other sequences still remain obscure. Defined enzymes without assigned sequence are known as orphan enzymes. One of these enzymes with uncharacterised sequence is plasmanylethanolamine desaturase, a key enzyme for the biosynthesis of one of the most abundant phospholipids in our body, the plasmalogens. This review aims to briefly summarise known functions of ether lipids, give an overview on their metabolism including the most prominent members, platelet-activating factor and the plasmalogens. A special focus is set on the description of orphan enzymes in ether lipid metabolism and on the successful strategies how four previous orphans have recently been assigned a sequence. Only one of these four was characterised by classical protein purification and sequencing, whereas the other three required alternative strategies such as bioinformatic candidate gene selection and recombinant expression or development of an inhibitor and multidimensional metabolic profiling. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  19. Expression profile of malignant and nonmalignant lesions of esophagus and stomach: differential activity of functional modules related to inflammation and lipid metabolism.

    PubMed

    Gomes, Luciana I; Esteves, Gustavo H; Carvalho, Alex F; Cristo, Elier B; Hirata, Roberto; Martins, Waleska K; Marques, Sarah M; Camargo, Luiz P; Brentani, Helena; Pelosof, Adriane; Zitron, Cláudia; Sallum, Rubens A; Montagnini, André; Soares, Fernando A; Neves, E Jordão; Reis, Luiz F L

    2005-08-15

    Adenocarcinomas of stomach and esophagus are frequently associated with preceding inflammatory alterations of the normal mucosa. Whereas intestinal metaplasia of the gastric mucosa is associated with higher risk of malignization, Barrett's disease is a risk factor for adenocarcinoma of the esophagus. Barrett's disease is characterized by the substitution of the squamous mucosa of the esophagus by a columnar tissue classified histopathologically as intestinal metaplasia. Using cDNA microarrays, we determined the expression profile of normal gastric and esophageal mucosa as well as intestinal metaplasia and adenocarcinomas from both organs. Data were explored to define functional alterations related to the transformation from squamous to columnar epithelium and the malignant transformation from intestinal metaplasia to adenocarcinomas. Based on their expression profile, adenocarcinomas of the esophagus showed stronger correlation with intestinal metaplasia of the stomach than with Barrett's mucosa. Second, we identified two functional modules, lipid metabolism and cytokine, as being altered with higher statistical significance. Whereas the lipid metabolism module is active in samples representing intestinal metaplasia and inactive in adenocarcinomas, the cytokine module is inactive in samples representing normal esophagus and esophagitis. Using the concept of relevance networks, we determined the changes in linear correlation of genes pertaining to these two functional modules. Exploitation of the data presented herein will help in the precise molecular characterization of adenocarcinoma from the distal esophagus, avoiding the topographical and descriptive classification that is currently adopted, and help with the proper management of patients with Barrett's disease.

  20. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    SciTech Connect

    Christopher Benning

    2011-02-04

    This is the second Gordon Research Conference on 'Plant Lipids: Structure, Metabolism & Function'. It covers current topics in lipid structure, metabolism and function in eukaryotic photosynthetic organisms including seed plants, algae, mosses and ferns. Work in photosynthetic bacteria is considered as well as it serves the understanding of specific aspects of lipid metabolism in plants. Breakthroughs are discussed in research on plant lipids as diverse as glycerolipids, sphingolipids, lipids of the cell surface, isoprenoids, fatty acids and their derivatives. The program covers nine concepts at the forefront of research under which afore mentioned plant lipid classes are discussed. The goal is to integrate areas such as lipid signaling, basic lipid metabolism, membrane function, lipid analysis, and lipid engineering to achieve a high level of stimulating interaction among diverse researchers with interests in plant lipids. One Emphasis is on the dynamics and regulation of lipid metabolism during plant cell development and in response to environmental factors.

  1. Differential effects of triacylglycerol positional isomers containing n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/6J mice.

    PubMed

    Yoshinaga, Kazuaki; Sasaki, Keiichi; Watanabe, Hiroyuki; Nagao, Koji; Inoue, Nao; Shirouchi, Bungo; Yanagita, Teruyoshi; Nagai, Toshiharu; Mizobe, Hoyo; Kojima, Koichi; Beppu, Fumiaki; Gotoh, Naohiro

    2015-01-01

    The present study investigated the effects of binding position of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to triacylglycerol (TAG) on lipid metabolism in C57BL/6J mice. Mice were treated with pure TAG positional isomers, including 1,2(2,3)-dipalmitoyl-3(1)-eicosapentaenoyl glycerol, 1,3-dipalmitoyl-2-eicosapentaenoyl glycerol, 1,2(2,3)-dipalmitoyl-3(1)-docosahexaenoyl glycerol, and 1,3-dipalmitoyl-2-docosahexaenoyl glycerol. Compared to DHA bound to the α-position of TAG, DHA bound to the β-position more effectively inhibited fatty acid synthetic enzymes and cholesterol-metabolism enzymes and thus reduced TAG and cholesterol concentrations in the serum and liver. EPA bound to the α-position of TAG, but not EPA bound to the β-position of TAG, significantly decreased hepatic cholesterol concentrations. Additionally, EPA bound to the α-position of TAG increased the ratio of PGI2 to TXA2 to a higher degree than EPA bound to the β-position. These results suggested that the binding position of EPA and DHA to TAG affected TAG and cholesterol metabolism as well as eicosanoid production in C57BL/6J mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Dengue virus induced autophagy regulates lipid metabolism

    PubMed Central

    Heaton, Nicholas S.; Randall, Glenn

    2010-01-01

    Summary Autophagy influences numerous cellular processes, including innate and adaptive immunity against intracellular pathogens. However, some viruses, including dengue virus (DENV), usurp autophagy to enhance their replication. The mechanism for a positive role of autophagy in DENV infection is unclear. We present data that DENV induction of autophagy regulates cellular lipid metabolism. DENV infection leads to an autophagy-dependent processing of lipid droplets and triglycerides to release free fatty acids. This results in an increase in cellular β-oxidation, which generates ATP. These processes are required for efficient DENV replication. Importantly, exogenous fatty acids can supplant the requirement of autophagy in DENV replication. These results define a role for autophagy in DENV infection and provide a mechanism by which viruses can alter cellular lipid metabolism to promote their replication. PMID:21075353

  3. [Exploration of regulating blood lipids metabolism by integrative medicine].

    PubMed

    Liu, Shan-shan; Wu, Wei; Qing, Li-jin

    2015-02-01

    Hyperlipidemia is an important risk factor of cardio-/cerebrovascular disease, and reducing lipids has become an important project for itsclinical preventing and treating. Western medicine, with its confirmative efficacy and clear mechanism, has played an irreplaceable role. Along with the development of modern medicine, integrative medicine has gradually become a growing trend in regulating blood lipids metabolism. It not only could make up the insufficient power for Chinese medicine in lowering lipids, but also could reduce adverse reactions and economic costs brought by long-term administration of Western medicine. As a modern practitioner of Chinese medicine, we should keep clear that integrative medicine regulating blood lipids metabolism does not mean a simple combination of traditional Chinese medicine and Western medicine. We should treat it guided by systematic theories. We combine disease identification and syndrome differentiation, guide lipids lowering by integrative medicine including selecting Western drugs for blood lipids lowering, Chinese medical prescriptions for syndrome typing, and effective Chinese herbs based on modern pharmacologies.

  4. A High-Fat Diet Differentially Affects the Gut Metabolism and Blood Lipids of Rats Depending on the Type of Dietary Fat and Carbohydrate

    PubMed Central

    Jurgoński, Adam; Juśkiewicz, Jerzy; Zduńczyk, Zenon

    2014-01-01

    The aim of this model study was to investigate how selected gut functions and serum lipid profile in rats on high-fat diets differed according to the type of fat (saturated vs. unsaturated) and carbohydrate (simple vs. complex). The experiment was conducted using 32 male Wistar rats distributed into 4 groups of 8 animals each. For 4 weeks, the animals were fed group-specific diets that were either rich in lard or soybean oil (16% of the diet) as the source of saturated or unsaturated fatty acids, respectively; further, each lard- and soybean oil-rich diet contained either fructose or corn starch (45.3% of the diet) as the source of simple or complex carbohydrates, respectively. Both dietary factors contributed to changes in the caecal short-chain fatty acid concentrations, especially to the butyrate concentration, which was higher in rats fed lard- and corn starch-rich diets compared to soybean oil- and fructose-rich diets, respectively. The lowest butyrate concentration was observed in rats fed the soybean oil- and fructose-rich diet. On the other hand, the lard- and fructose-rich diet vs. the other dietary combinations significantly increased serum total cholesterol concentration, to more than two times serum triglyceride concentration and to more than five times the atherogenic index. In conclusion, a high-fat diet rich in fructose can unfavorably affect gut metabolism when unsaturated fats are predominant in the diet or the blood lipids when a diet is rich in saturated fats. PMID:24496299

  5. A high-fat diet differentially affects the gut metabolism and blood lipids of rats depending on the type of dietary fat and carbohydrate.

    PubMed

    Jurgoński, Adam; Juśkiewicz, Jerzy; Zduńczyk, Zenon

    2014-02-03

    The aim of this model study was to investigate how selected gut functions and serum lipid profile in rats on high-fat diets differed according to the type of fat (saturated vs. unsaturated) and carbohydrate (simple vs. complex). The experiment was conducted using 32 male Wistar rats distributed into 4 groups of 8 animals each. For 4 weeks, the animals were fed group-specific diets that were either rich in lard or soybean oil (16% of the diet) as the source of saturated or unsaturated fatty acids, respectively; further, each lard- and soybean oil-rich diet contained either fructose or corn starch (45.3% of the diet) as the source of simple or complex carbohydrates, respectively. Both dietary factors contributed to changes in the caecal short-chain fatty acid concentrations, especially to the butyrate concentration, which was higher in rats fed lard- and corn starch-rich diets compared to soybean oil- and fructose-rich diets, respectively. The lowest butyrate concentration was observed in rats fed the soybean oil- and fructose-rich diet. On the other hand, the lard- and fructose-rich diet vs. the other dietary combinations significantly increased serum total cholesterol concentration, to more than two times serum triglyceride concentration and to more than five times the atherogenic index. In conclusion, a high-fat diet rich in fructose can unfavorably affect gut metabolism when unsaturated fats are predominant in the diet or the blood lipids when a diet is rich in saturated fats.

  6. Fatty Acids from Membrane Lipids Become Incorporated into Lipid Bodies during Myxococcus xanthus Differentiation

    PubMed Central

    Bhat, Swapna; Boynton, Tye O.; Pham, Dan; Shimkets, Lawrence J.

    2014-01-01

    Myxococcus xanthus responds to amino acid limitation by producing fruiting bodies containing dormant spores. During development, cells produce triacylglycerides in lipid bodies that become consumed during spore maturation. As the cells are starved to induce development, the production of triglycerides represents a counterintuitive metabolic switch. In this paper, lipid bodies were quantified in wild-type strain DK1622 and 33 developmental mutants at the cellular level by measuring the cross sectional area of the cell stained with the lipophilic dye Nile red. We provide five lines of evidence that triacylglycerides are derived from membrane phospholipids as cells shorten in length and then differentiate into myxospores. First, in wild type cells, lipid bodies appear early in development and their size increases concurrent with an 87% decline in membrane surface area. Second, developmental mutants blocked at different stages of shortening and differentiation accumulated lipid bodies proportionate with their cell length with a Pearson's correlation coefficient of 0.76. Third, peripheral rods, developing cells that do not produce lipid bodies, fail to shorten. Fourth, genes for fatty acid synthesis are down-regulated while genes for fatty acid degradation are up regulated. Finally, direct movement of fatty acids from membrane lipids in growing cells to lipid bodies in developing cells was observed by pulse labeling cells with palmitate. Recycling of lipids released by Programmed Cell Death appears not to be necessary for lipid body production as a fadL mutant was defective in fatty acid uptake but proficient in lipid body production. The lipid body regulon involves many developmental genes that are not specifically involved in fatty acid synthesis or degradation. MazF RNA interferase and its target, enhancer-binding protein Nla6, appear to negatively regulate cell shortening and TAG accumulation whereas most cell-cell signals activate these processes. PMID:24906161

  7. Melatonin regulates lipid metabolism in porcine oocytes.

    PubMed

    Jin, Jun-Xue; Lee, Sanghoon; Taweechaipaisankul, Anukul; Kim, Geon A; Lee, Byeong Chun

    2017-03-01

    It is being increasingly recognized that the processes of lipogenesis and lipolysis are important for providing an essential energy source during oocyte maturation and embryo development. Recent studies demonstrated that melatonin has a role in lipid metabolism regulation, including lipogenesis, lipolysis, and mitochondrial biogenesis. In this study, we attempted to investigate the effects of melatonin on lipid metabolism during porcine oocyte in vitro maturation. Melatonin treatment significantly enhanced the number of lipid droplets (LDs) and upregulated gene expression related to lipogenesis (ACACA, FASN, PPARγ, and SREBF1). Oocytes treated with melatonin formed smaller LDs and abundantly expressed several genes associated with lipolysis, including ATGL, CGI-58, HSL, and PLIN2. Moreover, melatonin significantly increased the content of fatty acids, mitochondria, and ATP, as indicated by fluorescent staining. Concomitantly, melatonin treatment upregulated gene expression related to fatty acid β-oxidation (CPT1a, CPT1b, CPT2, and ACADS) and mitochondrial biogenesis (PGC-1α, TFAM, and PRDX2). Overall, melatonin treatment not only altered both the morphology and amount of LDs, but also increased the content of fatty acids, mitochondria, and ATP. In addition, melatonin upregulated mRNA expression levels of lipogenesis, lipolysis, β-oxidation, and mitochondrial biogenesis-related genes in porcine oocytes. These results indicated that melatonin promoted lipid metabolism and thereby provided an essential energy source for oocyte maturation and subsequent embryonic development. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Recent advances in niacin and lipid metabolism.

    PubMed

    Kamanna, Vaijinath S; Ganji, Shobha H; Kashyap, Moti L

    2013-06-01

    This review focuses on the current understanding of the physiological mechanisms of action of niacin on lipid metabolism and atherosclerosis. Emerging findings indicate that niacin decreases hepatic triglyceride synthesis and subsequent VLDL/LDL secretion by directly and noncompetitively inhibiting hepatocyte diacylglycerol acyltransferase 2. Recent studies in mice lacking niacin receptor GPR109A and human clinical trials with GPR109A agonists disproved the long believed hypothesis of adipocyte triglyceride lipolysis as the mechanism for niacin's effect on serum lipids. Niacin, through inhibiting hepatocyte surface expression of β-chain ATP synthase, inhibits the removal of HDL-apolipoprotein (apo) AI resulting in increased apoAI-containing HDL particles. Additional recent findings suggest that niacin by increasing hepatic ATP-binding cassette transporter A1-mediated apoAI lipidation increases HDL biogenesis, thus stabilizing circulation of newly secreted apoAI. New concepts have also emerged on lipid-independent actions of niacin on vascular endothelial oxidative and inflammatory events, myeloperoxidase release from neutrophils and its impact on HDL function, and GPR109A-mediated macrophage inflammatory events involved in atherosclerosis. Recent advances have provided physiological mechanisms of action of niacin on lipid metabolism and atherosclerosis. Better understanding of niacin's actions on multiple tissues and targets may be helpful in designing combination therapy and new treatment strategies for atherosclerosis.

  9. Dietary lipids differentially modulate the initiation of experimental breast carcinogenesis through their influence on hepatic xenobiotic metabolism and DNA damage in the mammary gland.

    PubMed

    Manzanares, Miguel Ángel; de Miguel, Cristina; Ruiz de Villa, M Carme; Santella, Regina M; Escrich, Eduard; Solanas, Montserrat

    2017-02-10

    Breast cancer is the most common malignancy among women worldwide. In addition to reproductive factors, environmental factors such as nutrition and xenobiotic exposure have a role in the etiology of this malignancy. A stimulating and a potentially protective effect on experimental breast cancer has been previously described for high corn oil and high extra-virgin olive oil diets, respectively. This work investigates the effect of these lipids on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon that can initiate carcinogenesis and its consequences in an experimental rat breast cancer model. The PUFA n-6-enriched diet increased expression of Phase I enzymes prior to DMBA administration and raised the activity of CYP1s in the hours immediately after induction, while reducing the activity of Phase II enzymes, mainly NQO1. The levels of reactive metabolites measured in plasma by GC-MS and DMBA-DNA adducts in the mammary gland of the animals fed the high corn oil diet were also higher than in the other groups. On the other hand, the high extra-virgin olive oil diet and the control low-fat diet exhibited better coordinated Phase I and Phase II activity, with a lower production of reactive metabolites and less DNA damage in the mammary gland. The concordance between these effects and the different efficacy of the carcinogenesis process due to the dietary treatment suggest that lipids may differently modify mammary gland susceptibility or resistance to cancer initiation over the exposure to environmental carcinogens.

  10. Apolipoprotein gene involved in lipid metabolism

    DOEpatents

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  11. Differential tissue accumulation of 2,3,7,8-Tetrachlorinated dibenzo-p-dioxin in Arabidopsis thaliana affects plant chronology, lipid metabolism and seed yield.

    PubMed

    Hanano, Abdulsamie; Almousally, Ibrahem; Shaban, Mouhnad; Moursel, Nour; Shahadeh, AbdAlbaset; Alhajji, Eskander

    2015-08-11

    Dioxins are one of the most toxic groups of persistent organic pollutants. Their biotransmission through the food chain constitutes a potential risk for human health. Plants as principal actors in the food chain can play a determinant role in removing dioxins from the environment. Due to the lack of data on dioxin/plant research, this study sets out to determine few responsive reactions adopted by Arabidopsis plant towards 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins. Using a high resolution gas chromatography/mass spectrometry, we demonstrated that Arabidopsis plant uptakes TCDD by the roots and accumulates it in the vegetative parts in a tissue-specific manner. TCDD mainly accumulated in rosette leaves and mature seeds and less in stem, flowers and immature siliques. Moreover, we observed that plants exposed to high doses of TCDD exhibited a delay in flowering and yielded fewer seeds of a reduced oil content with a low vitality. A particular focus on the plant fatty acid metabolism showed that TCDD caused a significant reduction in C18-unsaturated fatty acid level in plant tissues. Simultaneously, TCDD induced the expression of 9-LOX and 13-LOX genes and the formation of their corresponding hydroperoxides, 9- and 13-HPOD as well as 9- or 13-HPOT, derived from linoleic and linolenic acids, respectively. The current work highlights a side of toxicological effects resulting in the administration of 2,3,7,8-TCDD on the Arabidopsis plant. Similarly to animals, it seems that plants may accumulate TCDD in their lipids by involving few of the FA-metabolizing enzymes for sculpting a specific oxylipins "signature" typified to plant TCDD-tolerance. Together, our results uncover novel responses of Arabidopsis to dioxin, possibly emerging to overcome its toxicity.

  12. Alterations of lipid metabolism in Wilson disease

    PubMed Central

    2011-01-01

    Introduction Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to date. Patients and Methods This cohort study involved 251 patients examined at the Heidelberg and Dresden (Germany) University Hospitals. Patients were analysed on routine follow-up examinations for serum lipid profile, including triglycerides, cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL). Data on these parameters at time of diagnosis were retrieved by chart review where available. For statistical testing, patients were subgrouped by sex, manifestation (hepatic, neurological, mixed and asymptomatic) and treatment (D-penicillamine, trientine, zinc or combination). Results A significant difference in total serum cholesterol was found in patients with hepatic symptoms, which diminished under therapy. No alterations were observed for HDL, LDL and triglycerides. Conclusion Contradictory to previous reports using WD animal models (Atp7b-/- and LEC rats), the most obvious alteration in our cohort was a lower serum cholesterol level in hepatic-affected patients, which might be related to liver injury. Our data suggested unimpaired cholesterol metabolism in Wilson disease under therapy, independent of the applied medical treatment. PMID:21595966

  13. Microtargeting cancer metabolism: opening new therapeutic windows based on lipid metabolism.

    PubMed

    Gómez de Cedrón, Marta; Ramírez de Molina, Ana

    2016-02-01

    Metabolic reprogramming has emerged as a hallmark of cancer. MicroRNAs are noncoding RNAs that posttranscriptionally repress the expression of target mRNAs implicated in multiple physiological processes, including apoptosis, differentiation, and cancer. MicroRNAs can affect entire biological pathways, making them good candidates for therapeutic intervention compared with classical single target approaches. Moreover, microRNAs may become more relevant in the fine-tuning adaptation to stress situations, such as oncogenic events, hypoxia, nutrient deprivation, and oxidative stress. Furthermore, artificial microRNAs can be designed to modulate the expression of multiple targets of a specific pathway. In this review, we describe the metabolic reprogramming associated to cancer, with a special interest in the altered lipid metabolism. Next, we describe specific features of microRNAs that make them relevant to target cancer cell metabolism. Finally, in an attempt to open new therapeutic windows, we emphasize two exciting scenarios for microRNA-mediated intervention that need to be further explored: 1) the cooperation between FA biosynthesis (lipogenesis) and FA oxidation as complementary partners for the survival of cancer cells; and 2) the regulation of the intracellular lipid content modulating both lipid storage into lipid droplets, and lipid mobilization through lipolysis and/or lipophagy. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  14. Microtargeting cancer metabolism: opening new therapeutic windows based on lipid metabolism

    PubMed Central

    Gómez de Cedrón, Marta; Ramírez de Molina, Ana

    2016-01-01

    Metabolic reprogramming has emerged as a hallmark of cancer. MicroRNAs are noncoding RNAs that posttranscriptionally repress the expression of target mRNAs implicated in multiple physiological processes, including apoptosis, differentiation, and cancer. MicroRNAs can affect entire biological pathways, making them good candidates for therapeutic intervention compared with classical single target approaches. Moreover, microRNAs may become more relevant in the fine-tuning adaptation to stress situations, such as oncogenic events, hypoxia, nutrient deprivation, and oxidative stress. Furthermore, artificial microRNAs can be designed to modulate the expression of multiple targets of a specific pathway. In this review, we describe the metabolic reprogramming associated to cancer, with a special interest in the altered lipid metabolism. Next, we describe specific features of microRNAs that make them relevant to target cancer cell metabolism. Finally, in an attempt to open new therapeutic windows, we emphasize two exciting scenarios for microRNA-mediated intervention that need to be further explored: 1) the cooperation between FA biosynthesis (lipogenesis) and FA oxidation as complementary partners for the survival of cancer cells; and 2) the regulation of the intracellular lipid content modulating both lipid storage into lipid droplets, and lipid mobilization through lipolysis and/or lipophagy. PMID:26630911

  15. Follistatin promotes adipocyte differentiation, browning, and energy metabolism[S

    PubMed Central

    Braga, Melissa; Reddy, Srinivasa T.; Vergnes, Laurent; Pervin, Shehla; Grijalva, Victor; Stout, David; David, John; Li, Xinmin; Tomasian, Venina; Reid, Christopher B.; Norris, Keith C.; Devaskar, Sherin U.; Reue, Karen; Singh, Rajan

    2014-01-01

    Follistatin (Fst) functions to bind and neutralize the activity of members of the transforming growth factor-β superfamily. Fst has a well-established role in skeletal muscle, but we detected significant Fst expression levels in interscapular brown and subcutaneous white adipose tissue, and further investigated its role in adipocyte biology. Fst expression was induced during adipogenic differentiation of mouse brown preadipocytes and mouse embryonic fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins including uncoupling protein 1, PR domain containing 16, and PPAR gamma coactivator-1α was attenuated, but could be rescued by treatment with recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO groups, suggesting that Fst produced by adipocytes may act in a paracrine manner. Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic differentiation identified several genes implicated in lipid and energy metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst treatment significantly increases cellular respiration in Fst-deficient cells. Our results implicate a novel role of Fst in the induction of brown adipocyte character and regulation of energy metabolism. PMID:24443561

  16. Red clover polyphenol oxidase and lipid metabolism.

    PubMed

    Van Ranst, G; Lee, M R F; Fievez, V

    2011-02-01

    Increasing the polyunsaturated fatty acid (PUFA) composition of milk is acknowledged to be of benefit to consumer health. Despite the high PUFA content of forages, milk fat contains only about 3% of PUFA and only about 0.5% of n-3 fatty acids. This is mainly due to intensive lipid metabolism in the rumen (lipolysis and biohydrogenation) and during conservation (lipolysis and oxidation) such as drying (hay) and ensiling (silage). In red clover, polyphenol oxidase (PPO) has been suggested to protect lipids against degradation, both in the silage as well as in the rumen, leading to a higher output of PUFA in ruminant products (meat and milk). PPO mediates the oxidation of phenols and diphenols to quinones, which will readily react with nucleophilic binding sites. Such binding sites can be found on proteins, resulting in the formation of protein-bound phenols. This review summarizes the different methods that have been used to assess PPO activity in red clover, and an overview on the current understanding of PPO activity and activation in red clover. Knowledge on these aspects is of major importance to fully harness PPO's lipid-protecting role. Furthermore, we review the studies that evidence PPO-mediated lipid protection and discuss its possible importance in lab-scale silages and further in an in vitro rumen system. It is demonstrated that high (induction of) PPO activity can lead to lower lipolysis in the silage and lower biohydrogenation in the rumen. There are three hypotheses on its working mechanism: (i) protein-bound phenols could directly bind to enzymes (e.g. lipases) as such inhibiting them; (ii) binding of quinones in and between proteins embedded in a lipid membrane (e.g. in the chloroplast) could lead to encapsulation of the lipids; (iii) direct binding of quinones to nucleophilic sites in polar lipids also could lead to protection. There is no exclusive evidence on which mechanism is most important, although there are strong indications that only lipid

  17. Carbohydrate and lipid metabolism in farm animals.

    PubMed

    Nafikov, Rafael A; Beitz, Donald C

    2007-03-01

    Much research on carbohydrate and lipid metabolism in farm animals conducted over the second half of the 20th century has focused primarily on increasing the production efficiency and improving the quality and acceptability of animal-derived foods. Research was also performed with the express interest in greater understanding of biochemistry and metabolism of livestock species with ultimate application in the food industry. Knowledge about basic nutritional concepts and differences in metabolism among farm animals, however, has been accumulated and has been used successfully to better understand different health problems in humans such as obesity, atherosclerosis, diabetes, and others that are associated with disturbances in metabolism and nutrition. Here we focus on researchers who made major contributions to our understanding of the synthesis and degradation including digestion of carbohydrates and lipids during the past half-century and to our understanding of the growth and development of meat-producing animals (e.g., pigs and cattle) and milk-producing dairy cattle. These findings will serve as the basis for current and future animal biologists to develop newer concepts and methods for use in improving the efficiency of conversion of animal feed to food and the healthfulness of that food for human consumers.

  18. MicroRNA Regulation of Lipid Metabolism

    PubMed Central

    Flowers, Elena; Froelicher, Erika Sivarajan; Aouizerat, Bradley E.

    2012-01-01

    MicroRNA are structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. Recently, there is significant interest in the application of microRNA as a blood-based biomarker of underlying physiologic conditions, and the therapeutic administration of microRNA inhibitors and mimics. The purpose of this review is to describe the current body of knowledge on microRNA regulation of genes involved in lipid metabolism, and to introduce the role of microRNA in development and progression of atherosclerosis. PMID:22607769

  19. A global perspective on FOXO1 in lipid metabolism and lipid-related diseases.

    PubMed

    Li, Yue; Ma, Zhiqiang; Jiang, Shuai; Hu, Wei; Li, Tian; Di, Shouyin; Wang, Dongjin; Yang, Yang

    2017-04-06

    Lipid metabolism is a complex physiological process that is involved in nutrient adjustment, hormone regulation, and homeostasis. An unhealthy lifestyle and chronic nutrient overload can cause lipid metabolism disorders, which may lead to serious lipid-related diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), and type 2 diabetes mellitus (T2DM). Therefore, tools for preventing dysfunctional lipid metabolism are urgently needed. The transcription factor forkhead box protein O1 (FOXO1) is involved in lipid metabolism and plays a critical role in the development of lipid-related diseases. In this review, we provide a global perspective on the role of FOXO1 in lipid metabolism and lipid-related diseases. The information included here may be useful for the design of future studies and advancing investigations of FOXO1 as a therapeutic target.

  20. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism.

    PubMed

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill; Ruckerbauer, David E; Hannibal-Bach, Hans Kristian; Zanghellini, Jürgen; Jensen, Ole N; Ejsing, Christer S

    2015-03-19

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level.

  1. Lipid metabolites as metabolic messengers in inter-organ communication

    PubMed Central

    Liu, Sihao; Alexander, Ryan K.; Lee, Chih-Hao

    2014-01-01

    Metabolic homeostasis is achieved through coordinated regulation across several tissues. Studies using mouse genetic models have shown that perturbation of specific pathways of lipid metabolism in metabolically active tissues impacts systemic metabolic homeostasis. The use of metabolomic technologies combined with genetic models has helped identify several potential lipid mediators that serve as metabolic messengers to communicate energy status and modulate substrate utilization among tissues. When provided exogenously, these lipid metabolites exhibit biological effects on glucose and lipid metabolism, implicating a therapeutic potential for treating metabolic diseases. In this review, we will summarize recent advances in inter-organ communication through novel mechanisms with a focus on lipid mediators synthesized de novo or derived from dietary sources and discuss challenges and future directions. PMID:24895003

  2. Regulation of lipid metabolism via a connection between the endoplasmic reticulum and lipid droplets.

    PubMed

    Suzuki, Michitaka

    2017-01-01

    Lipid droplets (LDs) are ubiquitous organelles that store and supply lipids to regulate cellular lipid homeostasis. Fatty acids are packaged as triglyceride and cholesterol ester into endoplasmic reticulum (ER) membranes to synthesize LDs. Cytosolic LDs move dynamically and interact with organelles, including other LDs. In this process, functional proteins for metabolism are also transferred to LDs. In this review, I focus on interactions between the ER and LDs related to lipid metabolism.

  3. Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism.

    PubMed

    Sinha, Rohit A; Singh, Brijesh K; Yen, Paul M

    2014-10-01

    Thyroid hormone (TH) has important roles in regulating hepatic lipid, cholesterol, and glucose metabolism. Recent findings suggest that clinical conditions such as non-alcoholic fatty liver disease and type 2 diabetes mellitus, which are associated with dysregulated hepatic metabolism, may involve altered intracellular TH action. In addition, TH has key roles in lipophagy in lipid metabolism, mitochondrial quality control, and the regulation of metabolic genes. In this review, we discuss recent findings regarding the functions of TH in hepatic metabolism, the relationship between TH and metabolic disorders, and the potential therapeutic use of thyromimetics to treat metabolic dysfunction in the liver. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Genetic Basis for Sex Differences in Obesity and Lipid Metabolism.

    PubMed

    Link, Jenny C; Reue, Karen

    2017-08-21

    Men and women exhibit significant differences in obesity, cardiovascular disease, and diabetes. To provide better diagnosis and treatment for both sexes, it is important to identify factors that underlie the observed sex differences. Traditionally, sex differences have been attributed to the differential effects of male and female gonadal secretions (commonly referred to as sex hormones), which substantially influence many aspects of metabolism and related diseases. Less appreciated as a contributor to sex differences are the fundamental genetic differences between males and females, which are ultimately determined by the presence of an XX or XY sex chromosome complement. Here, we review the mechanisms by which gonadal hormones and sex chromosome complement each contribute to lipid metabolism and associated diseases, and the current approaches that are used to study them. We focus particularly on genetic approaches including genome-wide association studies in humans and mice, -omics and systems genetics approaches, and unique experimental mouse models that allow distinction between gonadal and sex chromosome effects.

  5. Mathematical modelling of hepatic lipid metabolism.

    PubMed

    Pratt, Adrian C; Wattis, Jonathan A D; Salter, Andrew M

    2015-04-01

    The aim of this paper is to develop a mathematical model capable of simulating the metabolic response to a variety of mixed meals in fed and fasted conditions with particular emphasis placed on the hepatic triglyceride element of the model. Model validation is carried out using experimental data for the ingestion of three mixed composition meals over a 24-h period. Comparison with experimental data suggests the model predicts key plasma lipids accurately given a prescribed insulin profile. One counter-intuitive observation to arise from simulations is that liver triglyceride initially decreases when a high fat meal is ingested, a phenomenon potentially explained by the carbohydrate portion of the meal raising plasma insulin. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Phosphatidylserine decarboxylases, key enzymes of lipid metabolism.

    PubMed

    Schuiki, Irmgard; Daum, Günther

    2009-02-01

    Phosphatidylserine decarboxylases (PSDs) (E.C. 4.1.1.65) are enzymes which catalyze the formation of phosphatidylethanolamine (PtdEtn) by decarboxylation of phosphatidylserine (PtdSer). This enzymatic activity has been identified in both prokaryotic and eukaryotic organisms. PSDs occur as two types of proteins depending on their localization and the sequence of a conserved motif. Type I PSDs include enzymes of eukaryotic mitochondria and bacterial origin which contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are found in the endomembrane system of eukaryotes and contain a typical GGST motif. These characteristic motifs are considered as autocatalytic cleavage sites where proenzymes are split into alpha- and beta-subunits. The S-residue set free by this cleavage serves as an attachment site of a pyruvoyl group which is required for the activity of the enzymes. Moreover, PSDs harbor characteristic binding sites for the substrate PtdSer. Substrate supply to eukaryotic PSDs requires lipid transport because PtdSer synthesis and decarboxylation are spatially separated. Targeting of PSDs to their proper locations requires additional intramolecular domains. Mitochondrially localized type I PSDs are directed to the inner mitochondrial membrane by N-terminal targeting sequences. Type II PSDs also contain sequences in their N-terminal extensions which might be required for subcellular targeting. Lack of PSDs causes various defects in different cell types. The physiological relevance of these findings and the central role of PSDs in lipid metabolism will be discussed in this review.

  7. Lipid metabolism during encystment of Azotobacter vinelandii.

    PubMed Central

    Reusch, R N; Sadoff, H L

    1981-01-01

    The formation of cysts by Azotobacter vinelandii involves the synthesis of lipids as major metabolic products. Cells which encyst at low levels in aging glucose cultures undergo the same pattern of lipid synthesis as cells which undergo reasonably synchronous encystment in beta-hydroxybutyrate or n-butanol. The accumulation of poly-beta-hydroxybutyrate (PHB) precedes the synthesis of 5-n-heneicosylresorcinol and 5-n-tricosylresorcinol (AR1), which is then followed in about 6 h by the synthesis of the 5-n-alkylresorcinol galactosides (AR2). In the mature cyst, PHB, AR1, and AR2 account for 8, 5.6, and 4.5%, respectively, of the dry weight. Phospholipid formation levels off 4 h postinduction, which coincides with the final cell division, but fatty acids synthesis continues at a very low level throughout encystment, suggesting some turnover of fatty acid. Distribution studies show that AR1 and AR2 are found in roughly equal amounts in the exine and central body of the cysts, with only trace amounts recovered from the intine. Studies of cysts labeled during encystment with [14C]beta-hydroxybutyrate or during vegetative growth with [14C]glucose suggest that the exine structure is synthesized during encystment, but that the intine is composed largely of vegetative cell components. PMID:7462162

  8. Control of lipid metabolism by Tachykinin in Drosophila

    PubMed Central

    Song, Wei; Veenstra, Jan A.; Perrimon, Norbert

    2015-01-01

    Summary The intestine is a key organ for lipid uptake and distribution, and abnormal intestinal lipid metabolism is associated with obesity and hyperlipidemia. Although multiple regulatory gut hormones secreted from enteroendocrine cells (EEs) regulate systemic lipid homeostasis, such as appetite control and energy balance in adipose tissue, their respective roles regarding lipid metabolism in the intestine are not well understood. We demonstrate that Tachykinins (TKs), one of the most abundant secreted peptides expressed in midgut EEs, regulate intestinal lipid production and subsequently control systemic lipid homeostasis in Drosophila, and that TKs repress lipogenesis in enterocytes (ECs) associated with the TKR99D receptor and PKA signaling. Interestingly, nutrient deprivation enhances the production of TKs in the midgut. Finally, unlike the physiological roles of TKs produced from the brain, gut-derived TKs do not affect behavior, thus demonstrating that gut TK hormones specifically regulate intestinal lipid metabolism without affecting neuronal functions. PMID:25263556

  9. Maternal consumption of high-prebiotic fibre or -protein diets during pregnancy and lactation differentially influences satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring in rats.

    PubMed

    Maurer, Alannah D; Reimer, Raylene A

    2011-02-01

    Risk of developing the metabolic syndrome may be influenced by nutritional environment early in life. We examined the effects of high-fibre (HF) and high-protein (HP) diets consumed during pregnancy and lactation on satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring. Wistar dams were fed a control (C), HF or HP diets during pregnancy and lactation. At parturition, litters were culled to ten pups. At 21 d, all pups were weaned onto C diet. At 7, 14, 21, 28 and 35 d after birth, blood was analysed for satiety hormones and tissues for mRNA expression in offspring. No differences were observed in litter size or birth weight. At 21 d, offspring of HF dams had greater adjusted intestinal mass and lower liver weight than those of C but not of HP dams. Plasma glucose at 28 d and amylin at 7, 14 and 28 d were lower in HF v. C and HP offspring. Glucagon-like peptide-1 was higher in HP offspring than in HF offspring at 7 d but was higher in HF v. C offspring at 21 d. Offspring of HF dams had higher glucose transporter (GLUT2 and Na+-dependent glucose/galactose transporter) mRNA expression at 21 d v. C and HP offspring. In brown adipose tissue, HF and HP up-regulated uncoupling protein-1 and PPAR-γ coactivator. HP was associated with increased resistin and IL-6 mRNA expression. The present study demonstrates that maternal diet composition differentially regulates circulating satiety hormones and genes involved in glucose transport and energy metabolism in offspring. These early changes could have long-term consequences for obesity risk.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  11. Emerging roles of lipid metabolism in cancer metastasis.

    PubMed

    Luo, Xiangjian; Cheng, Can; Tan, Zheqiong; Li, Namei; Tang, Min; Yang, Lifang; Cao, Ya

    2017-04-11

    Cancer cells frequently display fundamentally altered cellular metabolism, which provides the biochemical foundation and directly contributes to tumorigenicity and malignancy. Rewiring of metabolic programmes, such as aerobic glycolysis and increased glutamine metabolism, are crucial for cancer cells to shed from a primary tumor, overcome the nutrient and energy deficit, and eventually survive and form metastases. However, the role of lipid metabolism that confers the aggressive properties of malignant cancers remains obscure. The present review is focused on key enzymes in lipid metabolism associated with metastatic disease pathogenesis. We also address the function of an important membrane structure-lipid raft in mediating tumor aggressive progression. We enumerate and integrate these recent findings into our current understanding of lipid metabolic reprogramming in cancer metastasis accompanied by new and exciting therapeutic implications.

  12. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation.

    PubMed

    Laugerette, Fabienne; Vors, Cécile; Peretti, Noël; Michalski, Marie-Caroline

    2011-01-01

    Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation.

  13. The pecan nut (Carya illinoinensis) and its oil and polyphenolic fractions differentially modulate lipid metabolism and the antioxidant enzyme activities in rats fed high-fat diets.

    PubMed

    Domínguez-Avila, Jesús A; Alvarez-Parrilla, Emilio; López-Díaz, José A; Maldonado-Mendoza, Ignacio E; Gómez-García, María Del Consuelo; de la Rosa, Laura A

    2015-02-01

    Tree nuts such as pecans (Carya illinoinensis) contain mostly oil but are also a source of polyphenols. Nut consumption has been linked to a reduction in serum lipid levels and oxidative stress. These effects have been attributed to the oil while overlooking the potential contribution of the polyphenols. Because the evidence regarding each fraction's bioactivity is scarce, we administered high-fat (HF) diets to male Wistar rats, supplementing them with pecan oil (HF+PO), pecan polyphenols (HF+PP) or whole pecans (HF+WP), and analysed the effects of each fraction. The HF diet increased the serum leptin and total cholesterol (TC) with respect to the control levels. The HF+WP diet prevented hyperleptinemia and decreased the TC compared with the control. The HF+WP diet upregulated the hepatic expression of apolipoprotein B and LDL receptor mRNAs with respect to the HF levels. The HF+PO diet reduced the level of triacylglycerols compared with the control. The HF+PP diet stimulated the hepatic expression of liver X receptor alpha mRNA. The HF+WP diet increased the activities of hepatic catalase, glutathione peroxidase and glutathione S transferase compared with the control, and decreased the degree of lipid peroxidation compared with the HF diet. The most bioactive diet was the WP diet.

  14. 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

  15. Lipid mediators in the neural cell nucleus: their metabolism, signaling, and association with neurological disorders.

    PubMed

    Farooqui, Akhlaq A

    2009-08-01

    Lipid mediators are important endogenous regulators of neural cell proliferation, differentiation, oxidative stress, inflammation, and apoptosis. They originate from enzymic degradation of glycerophospholipids, sphingolipids, and cholesterol by phospholipases, sphingomyelinases, and cytochrome P450 hydroxylases, respectively. Arachidonic acid-derived lipid mediators are called eicosanoids. Eicosanoids have emerged as key regulators of cell proliferation, differentiation, oxidative stress, and neuroinflammation. Another arachidonic acid-derived lipid mediator is lipoxin. Eicosanoids have proinflammatory effects, whereas lipoxins produce antiinflammatory effects. The crossponding lipid mediators of docosahexaenoic acid metabolism are named docosanoids. They include resolvins, protectins, and neuroprotectins. Docosanoids produce antioxidant, anti-inflammatory, and antiapoptotic effects in the brain tissue. Other glycerophospholipid-derived lipid mediators are platelet-activating factor, lysophosphatidic acid, and endocannabinoids. Degradation of sphingolipids also results in the generation of sphingolipid-derived lipid mediators. Sphingolipid-derived lipid mediators are ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. They mediate cellular differentiation, cell growth, and apoptosis. Similarly, cholesterol-derived lipid mediators hydroxycholesterol and oxycholesterol produce apoptosis. Most of these mediators originate from the plasma membrane. The nucleus has its own set of enzymes and lipid mediators that originate from the nuclear envelope and matrix. The purpose of this commentary is to describe basic and clinical information on lipid mediators in the nucleus.

  16. Metabolism of acyl-lipids in Chlamydomonas reinhardtii.

    PubMed

    Li-Beisson, Yonghua; Beisson, Fred; Riekhof, Wayne

    2015-05-01

    Microalgae are emerging platforms for production of a suite of compounds targeting several markets, including food, nutraceuticals, green chemicals, and biofuels. Many of these products, such as biodiesel or polyunsaturated fatty acids (PUFAs), derive from lipid metabolism. A general picture of lipid metabolism in microalgae has been deduced from well characterized pathways of fungi and land plants, but recent advances in molecular and genetic analyses of microalgae have uncovered unique features, pointing out the necessity to study lipid metabolism in microalgae themselves. In the past 10 years, in addition to its traditional role as a model for photosynthetic and flagellar motility processes, Chlamydomonas reinhardtii has emerged as a model organism to study lipid metabolism in green microalgae. Here, after summarizing data on total fatty acid composition, distribution of acyl-lipid classes, and major acyl-lipid molecular species found in C. reinhardtii, we review the current knowledge on the known or putative steps for fatty acid synthesis, glycerolipid desaturation and assembly, membrane lipid turnover, and oil remobilization. A list of characterized or putative enzymes for the major steps of acyl-lipid metabolism in C. reinhardtii is included, and subcellular localizations and phenotypes of associated mutants are discussed. Biogenesis and composition of Chlamydomonas lipid droplets and the potential importance of lipolytic processes in increasing cellular oil content are also highlighted.

  17. Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis

    PubMed Central

    Tsao, Chang-Hui; Shiau, Ming-Yuh; Chuang, Pei-Hua; Chang, Yih-Hsin; Hwang, Jaulang

    2014-01-01

    Long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous studies reveal significant associations between promoter single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 and T2DM, as well as between SNPs in genes encoding IL-4/IL-4 receptor and high density lipoproteins. Our animal study reveals that IL-4 regulates glucose/lipid metabolism by promoting glucose tolerance and inhibiting lipid deposits. The above results strongly suggest the involvement of IL-4 in energy homeostasis. In the present study, we focus on examining the regulatory mechanism of IL-4 to lipid metabolism. Our results show that IL-4 inhibits adipogenesis by downregulating the expression of peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein-α. Additionally, IL-4 promotes lipolysis by enhancing the activity and translocation of hormone sensitive lipase (HSL) in mature adipocytes, which suggests that IL-4 plays a pro-lipolytic role in lipid metabolism by boosting HSL activity. Our results demonstrate that IL-4 harbors pro-lipolysis capacity by inhibiting adipocyte differentiation and lipid accumulation as well as by promoting lipolysis in mature adipocytes to decrease lipid deposits. The above findings uncover the novel roles of IL-4 in lipid metabolism and provide new insights into the interactions among cytokine/immune responses, insulin sensitivity, and metabolism. PMID:24347527

  18. An annotated database of Arabidopsis mutants of acyl lipid metabolism

    DOE PAGES

    McGlew, Kathleen; Shaw, Vincent; Zhang, Meng; ...

    2014-12-10

    Mutants have played a fundamental role in gene discovery and in understanding the function of genes involved in plant acyl lipid metabolism. The first mutant in Arabidopsis lipid metabolism (fad4) was described in 1985. Since that time, characterization of mutants in more than 280 genes associated with acyl lipid metabolism has been reported. This review provides a brief background and history on identification of mutants in acyl lipid metabolism, an analysis of the distribution of mutants in different areas of acyl lipid metabolism and presents an annotated database (ARALIPmutantDB) of these mutants. The database provides information on the phenotypes ofmore » mutants, pathways and enzymes/proteins associated with the mutants, and allows rapid access via hyperlinks to summaries of information about each mutant and to literature that provides information on the lipid composition of the mutants. Mutants for at least 30 % of the genes in the database have multiple names, which have been compiled here to reduce ambiguities in searches for information. Furthermore, the database should also provide a tool for exploring the relationships between mutants in acyl lipid-related genes and their lipid phenotypes and point to opportunities for further research.« less

  19. An annotated database of Arabidopsis mutants of acyl lipid metabolism

    SciTech Connect

    McGlew, Kathleen; Shaw, Vincent; Zhang, Meng; Kim, Ryeo Jin; Yang, Weili; Shorrosh, Basil; Suh, Mi Chung; Ohlrogge, John

    2014-12-10

    Mutants have played a fundamental role in gene discovery and in understanding the function of genes involved in plant acyl lipid metabolism. The first mutant in Arabidopsis lipid metabolism (fad4) was described in 1985. Since that time, characterization of mutants in more than 280 genes associated with acyl lipid metabolism has been reported. This review provides a brief background and history on identification of mutants in acyl lipid metabolism, an analysis of the distribution of mutants in different areas of acyl lipid metabolism and presents an annotated database (ARALIPmutantDB) of these mutants. The database provides information on the phenotypes of mutants, pathways and enzymes/proteins associated with the mutants, and allows rapid access via hyperlinks to summaries of information about each mutant and to literature that provides information on the lipid composition of the mutants. Mutants for at least 30 % of the genes in the database have multiple names, which have been compiled here to reduce ambiguities in searches for information. Furthermore, the database should also provide a tool for exploring the relationships between mutants in acyl lipid-related genes and their lipid phenotypes and point to opportunities for further research.

  20. p53 as a Regulator of Lipid Metabolism in Cancer

    PubMed Central

    Parrales, Alejandro; Iwakuma, Tomoo

    2016-01-01

    Enhanced proliferation and survival are common features of cancer cells. Cancer cells are metabolically reprogrammed which aids in their survival in nutrient-poor environments. Indeed, changes in metabolism of glucose and glutamine are essential for tumor progression. Thus, metabolic reprogramming is now well accepted as a hallmark of cancer. Recent findings suggest that reprogramming of lipid metabolism also occurs in cancer cells, since lipids are used for biosynthesis of membranes, post-translational modifications, second messengers for signal transduction, and as a source of energy during nutrient deprivation. The tumor suppressor p53 is a transcription factor that controls the expression of proteins involved in cell cycle arrest, DNA repair, apoptosis, and senescence. p53 also regulates cellular metabolism, which appears to play a key role in its tumor suppressive activities. In this review article, we summarize non-canonical functions of wild-type and mutant p53 on lipid metabolism and discuss their association with cancer progression. PMID:27973397

  1. Perilipin-related protein regulates lipid metabolism in C. elegans

    PubMed Central

    Chughtai, Ahmed Ali; Kaššák, Filip; Kostrouchová, Markéta; Novotný, Jan Philipp; Krause, Michael W.; Kostrouch, Zdenek

    2015-01-01

    Perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue and likely orthologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets similarly as human perilipins 1 and 2. Downregulation or elimination of W01A8.1 affects the appearance of lipid droplets resulting in the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. Visualization of lipid containing structures by CARS microscopy in vivo showed that lipid-containing structures become gradually enlarged during oogenesis and relocate during the first zygotic division around the dividing nucleus. In mutant embryos, the lipid containing structures show defective intracellular distribution in subsequent embryonic divisions and become gradually smaller during further development. In contrast to embryos, lipid-containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals. Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism. PMID:26357594

  2. The Tumor Microenvironment Modulates Choline and Lipid Metabolism

    PubMed Central

    Mori, Noriko; Wildes, Flonné; Takagi, Tomoyo; Glunde, Kristine; Bhujwalla, Zaver M.

    2016-01-01

    An increase of cellular phosphocholine (PC) and total choline (tCho)-containing compounds as well as alterations in lipids have been consistently observed in cancer cells and tissue. These metabolic changes are closely related to malignant transformation, invasion, and metastasis. The study of cancer cells in culture plays an important role in understanding mechanisms leading to altered choline (Cho) and lipid metabolism in cancer, as it provides a carefully controlled environment. However, a solid tumor is a complex system with a unique tumor microenvironment frequently containing hypoxic and acidic regions and areas of nutrient deprivation and necrosis. Cancer cell–stromal cell interactions and the extracellular matrix may also alter Cho and lipid metabolism. Human tumor xenograft models in mice are useful to mimic the growth of human cancers and provide insights into the influence of in vivo conditions on metabolism. Here, we have compared metabolites, obtained with high resolution 1H MRS of extracts from human breast and prostate cancer cells in a 2-dimensional (2D) monolayer culture and from solid tumor xenografts derived from these cells, as well as the protein expression of enzymes that regulate Cho and lipid metabolism. Our data demonstrate significant differences in Cho and lipid metabolism and protein expression patterns between human breast and prostate cancer cells in culture and in tumors derived from these cells. These data highlight the influence of the tumor microenvironment on Cho and lipid metabolism. PMID:28066718

  3. Human cancer: is it linked to dysfunctional lipid metabolism?

    PubMed

    Hashmi, Sarwar; Wang, Yi; Suman, Devi S; Parhar, Ranjit S; Collison, Kate; Conca, Walter; Al-Mohanna, Futwan; Gaugler, Randy

    2015-02-01

    Lipid metabolism dysfunction leading to excess fat deposits (obesity) may cause tumor (cancer) development. Both obesity and cancer are the epicenter of important medical issues. Lipid metabolism and cell death/proliferation are controlled by biochemical and molecular pathways involving many proteins, and organelles; alteration in these pathways leads to fat accumulation or tumor growth. Mammalian Krüppel-like factors, KLFs play key roles in both lipid metabolism and tumor development. Substantial epidemiological and clinical studies have established strong association of obesity with a number of human cancers. However, we need more experimental verification to determine the exact role of this metabolic alteration in the context of tumor development. A clear understanding of molecules, pathways and the mechanisms involved in lipid metabolism and cell death/proliferation will have important implications in pathogenesis, and prevention of these diseases. The regulatory role of KLFs, in both cell death/proliferation and lipid metabolism suggests a common regulation of both processes. This provides an excellent model for delivering a precise understanding of the mechanisms linking altered expression of KLFs to obesity and tumor development. Currently, mouse and rats are the models of choice for investigating disease mechanisms and pharmacological therapies but a genetic model is needed for a thorough examination of KLF function in vivo during the development of an organism. The worm Caenorhabditis elegans is an ideal model to study the connectivity between lipid metabolism and cell death/proliferation. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Regulation of Carbohydrate Metabolism, Lipid Metabolism, and Protein Metabolism by AMPK.

    PubMed

    Angin, Yeliz; Beauloye, Christophe; Horman, Sandrine; Bertrand, Luc

    This chapter summarizes AMPK function in the regulation of substrate and energy metabolism with the main emphasis on carbohydrate and lipid metabolism, protein turnover, mitochondrial biogenesis, and whole-body energy homeostasis. AMPK acts as whole-body energy sensor and integrates different signaling pathway to meet both cellular and body energy requirements while inhibiting energy-consuming processes but also activating energy-producing ones. AMPK mainly promotes glucose and fatty acid catabolism, whereas it prevents protein, glycogen, and fatty acid synthesis.

  5. Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated metabolism are detected by analysis of lipid co-occurrence

    PubMed Central

    Narayanan, Sruthi; Prasad, P.V. Vara; Welti, Ruth

    2016-01-01

    Identifying lipids that experience coordinated metabolism during heat stress would provide information regarding lipid dynamics under stress conditions and assist in developing heat-tolerant wheat varieties. We hypothesized that co-occurring lipids, which are up-or-down-regulated together through time during heat stress, represent groups that can be explained by coordinated metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high day and/or night temperature stress, followed by a 4-day recovery period. Leaves were sampled at four time points, and 165 lipids were measured by electrospray ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160 leaf samples from each of two wheat genotypes revealed 13 groups of lipids. Lipids within each group co-occurred through the high day and night temperature stress treatments. The lipid groups can be broadly classified as groups containing: extraplastidic phospholipids, plastidic glycerolipids, oxidized glycerolipids, triacylglycerols, acylated sterol glycosides, and sterol glycosides. Current knowledge of lipid metabolism suggests that the lipids in each group co-occur because they are regulated by the same enzyme(s). The results suggest that increases in activities of desaturating, oxidizing, glycosylating, and acylating enzymes lead to simultaneous changes in levels of multiple lipid species during high day and night temperature stress in wheat. PMID:26436445

  6. Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated metabolism are detected by analysis of lipid co-occurrence.

    PubMed

    Narayanan, Sruthi; Prasad, P V Vara; Welti, Ruth

    2016-03-01

    Identifying lipids that experience coordinated metabolism during heat stress would provide information regarding lipid dynamics under stress conditions and assist in developing heat-tolerant wheat varieties. We hypothesized that co-occurring lipids, which are up-regulated or down-regulated together through time during heat stress, represent groups that can be explained by coordinated metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high day and/or night temperature stress, followed by a 4-day recovery period. Leaves were sampled at four time points, and 165 lipids were measured by electrospray ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160 leaf samples from each of two wheat genotypes revealed 13 groups of lipids. Lipids within each group co-occurred through the high day and night temperature stress treatments. The lipid groups can be broadly classified as groups containing extraplastidic phospholipids, plastidic glycerolipids, oxidized glycerolipids, triacylglycerols, acylated sterol glycosides and sterol glycosides. Current knowledge of lipid metabolism suggests that the lipids in each group co-occur because they are regulated by the same enzyme(s). The results suggest that increases in activities of desaturating, oxidizing, glycosylating and acylating enzymes lead to simultaneous changes in levels of multiple lipid species during high day and night temperature stress in wheat. © 2015 John Wiley & Sons Ltd.

  7. Lipid metabolism during bacterial growth, sporulation, and germination: differential synthesis of individual branched- and normal-chain fatty acids during spore germination and outgrowth of Bacillus thuringiensis.

    PubMed

    Nickerson, K W; Bulla, L A; Mounts, T L

    1975-12-01

    The biosynthesis of individual branched- and normal-chain fatty acids during Bacillus thuringiensis spore germination and outgrowth was studied by comparing pulsed and continuous labeling of these fatty acids with [U-14C]acetate. The relative specific activity of each fatty acid varies with time as the cell progresses through outgrowth. However, fatty acid synthesis does occur in two distinct phases. Upon germination, acetate is incorporated only into the iso-isomers i-C13, i-C14, and i-C16; no normal or anteiso synthesis occurs. Subsequent to T30, the full complement of branched- and normal-chain homologues is formed and there is a dramatic enhancement in the overall rate of fatty acid synthesis. Significantly, this rate increase coincides with a marked shift from the synthesis of short-chain to long-chain fatty acids. These findings illustrate a dichotomy in synthesis that may result from initial fatty acid formation by preexisting spore fatty acid biosynthetic enzymes in the absence of de novo protein synthesis. Elucidation of the timing and kinetics of individual fatty acid formation provides a biochemical profile of activities directly related to membrane differentiation and cellular development.

  8. Differential effects of cobalt and mercury on lipid metabolism in the white adipose tissue of high-fat diet-induced obesity mice

    SciTech Connect

    Kawakami, Takashige Hanao, Norihide; Nishiyama, Kaori; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2012-01-01

    Metals and metalloid species are involved in homeostasis in energy systems such as glucose metabolism. Enlarged adipocytes are one of the most important causes of obesity-associated diseases. In this study, we studied the possibility that various metals, namely, CoCl{sub 2}, HgCl{sub 2}, NaAsO{sub 2} and MnCl{sub 2} pose risk to or have beneficial effects on white adipose tissue (WAT). Exposure to the four metals resulted in decreases in WAT weight and the size of enlarged adipocytes in mice fed a high-fat diet (HFD) without changes in liver weight, suggesting that the size and function of adipocytes are sensitive to metals. Repeated administration of CoCl{sub 2} significantly increased serum leptin, adiponectin and high-density lipoprotein (HDL) cholesterol levels and normalized glucose level and adipose cell size in mice fed HFD. In contrast, HgCl{sub 2} treatment significantly decreased serum leptin level with the down-regulation of leptin mRNA expression in WAT and a reduction in adipocyte size. Next, we tried to investigate possible factors that affect adipocyte size. Repeated exposure to HgCl{sub 2} significantly decreased the expression levels of factors upon the regulation of energy such as the PPARα and PPARγ mRNA expression levels in adipocytes, whereas CoCl{sub 2} had little effect on those genes expressions compared with that in the case of the mice fed HFD with a vehicle. In addition, repeated administration of CoCl{sub 2} enhanced AMPK activation in a dose-dependent manner in the liver, skeletal muscle and WAT; HgCl{sub 2} treatment also enhanced AMPK activation in the liver. Thus, both Co and Hg reduced WAT weight and the size of enlarged adipocytes, possibly mediated by AMKP activation in the mice fed HFD. However, inorganic cobalt may have a preventive role in obesity-related diseases through increased leptin, adiponectin and HDL-cholesterol levels, whereas inorganic mercury may accelerate the development of such diseases. These results may lead

  9. Peroxisome proliferator-activated receptors as regulators of lipid metabolism; tissue differential expression in adipose tissues during cold acclimatization and hibernation of jerboa (Jaculus orientalis).

    PubMed

    Kabine, Mostafa; El Kebbaj, Zakaria; Oaxaca-Castillo, David; Clémencet, Marie-Claude; El Kebbaj, M'hammed Said; Latruffe, Norbert; Cherkaoui-Malki, Mustapha

    2004-11-01

    Brown (BAT) and white (WAT) adipose tissues play a key role in the body energy balance orchestrated by the central nervous system. Hibernators have developed a seasonal obesity to respond to inhospitable environment. Jerboa is one of the deep hibernator originated from sub-desert highlands. Thus, this animal represents an excellent model to study cold adaptation mechanism. We report that the adipogenic factor PPARgamma exhibits a differential expression between BAT and WAT at mRNA level. A specific induction was only seen in WAT of pre-hibernating jerboa. Interestingly, PPAR beta/delta is specifically induced in BAT and brain of pre-hibernating jerboa, highlighting for the first time the possible key role of this ubiquitous isoform in the cold adaptation of this true hibernator. Inductions of PPARgamma(2) in WAT and PPAR beta/delta in BAT are blunted by a hypolipemic drug, the ciprofibrate. These changes may be correlated with hibernation arrest and death of treated jerboa. Mitochondrial acyl-CoA dehydrogenase and peroxisomal acyl-CoA oxidase activities in brown and white adipose tissues are decreased up to 85% during cold acclimatization (without food privation). These enzyme activities are subject to a strong induction in BAT and in WAT (3.4-7.5 fold) during the hibernation period. The BAT thermogenesis marker is also largely induced (approximately 4 fold of UCP1 mRNA level) during pre-hibernation period. Unexpectedly, treatment with ciprofibrate deeply affects lipolysis in BAT by increasing acyl-CoA dehydrogenase activity (3.4 fold) and acyl-CoA oxidase at both activity and mRNA levels (2.8 and 3.8 fold, respectively) and enhances strongly UCP1 mRNA level (9.5 fold) during pre-hibernation.

  10. Neuronal models for studying lipid metabolism and transport.

    PubMed

    Karten, Barbara; Hayashi, Hideki; Campenot, Robert B; Vance, Dennis E; Vance, Jean E

    2005-06-01

    New methods have been developed for studying lipid metabolism and transport in primary cultures of neurons. Sympathetic neurons from rats and mice, as well as retinal ganglion neurons from rats, can be cultured in three-compartmented culture dishes in which the cell bodies reside in a compartment separate from that housing the distal axons. In addition, the three compartments contain completely independent fluid environments. Consequently, these neuronal cultures represent an excellent model for studying the intra-neuronal transport of lipids and proteins between cell bodies and distal axons. In addition, compartmented neuron cultures are particularly appropriate for investigating factors that regulate axonal growth and neuronal survival. The application of the compartmented culture model for use with murine neurons has opened up many new possibilities for studying lipid metabolism in neurons derived from genetically modified mice. Examples are given in which compartmented cultures of primary neurons have been used in studies on (i) lipid analysis of distal axons and cell bodies/proximal axons, (ii) immunoblotting of neuronal proteins involved in lipid metabolism, (iii) the compartmentalization of lipid metabolism, (iv) the role of lipids in axonal growth and survival, and (v) intracellular lipid transport.

  11. 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. © 2016 Society for Endocrinology.

  12. Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism

    PubMed Central

    Gnocchi, Davide; Pedrelli, Matteo; Hurt-Camejo, Eva; Parini, Paolo

    2015-01-01

    Disorders of lipid and lipoprotein metabolism and transport are responsible for the development of a large spectrum of pathologies, ranging from cardiovascular diseases, to metabolic syndrome, even to tumour development. Recently, a deeper knowledge of the molecular mechanisms that control our biological clock and circadian rhythms has been achieved. From these studies it has clearly emerged how the molecular clock tightly regulates every aspect of our lives, including our metabolism. This review analyses the organisation and functioning of the circadian clock and its relevance in the regulation of physiological processes. We also describe metabolism and transport of lipids and lipoproteins as an essential aspect for our health, and we will focus on how the circadian clock and lipid metabolism are greatly interconnected. Finally, we discuss how a deeper knowledge of this relationship might be useful to improve the recent spread of metabolic diseases. PMID:25665169

  13. Signalling mechanisms linking hepatic glucose and lipid metabolism.

    PubMed

    Weickert, M O; Pfeiffer, A F H

    2006-08-01

    Fatty liver and hepatic triglyceride accumulation are strongly associated with obesity, insulin resistance and type 2 diabetes, and are subject to nutritional influences. Hepatic regulation of glucose and lipid homeostasis is influenced by a complex system of hormones, hormonally regulated signalling pathways and transcription factors. Recently, considerable progress has been made in elucidating molecular pathways and potential factors that are affected in insulin-resistant states. In this review we discuss some of the key factors that are involved in both the regulation of glucose and lipid metabolism in the liver. Understanding the molecular network that links hepatic lipid accumulation and impaired glucose metabolism may provide targets for dietary or pharmacological interventions.

  14. Differential effects of conjugated linoleic acid isomers on macrophage glycerophospholipid metabolism[S

    PubMed Central

    Ecker, Josef; Liebisch, Gerhard; Scherer, Max; Schmitz, Gerd

    2010-01-01

    Conjugated linoleic acids (CLA) are dietary fatty acids. Whereas cis-9,trans-11-(c9,t11)-CLA can be found in meat and dairy products, trans-9,trans-11-(t9,t11)-CLA is a constituent of vegetable oils. Previous studies showed that these two isomers activate different nuclear receptors and, thus, expression of genes related to lipid metabolism. Here we show that these CLA isomers are differentially elongated and desaturated in primary monocyte-derived macrophages isolated from healthy volunteers by using gas chromatography-mass spectrometry (GC-MS). We further demonstrate that c9,t11-CLA incorporates in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species and activates de novo glycerophospholipid synthesis by quantitative electrospray ionization-tandem mass spectrometry (ESI-MS/MS). c9,t11-CLA leads to strong shifts of the species profiles to PC 18:2/18:2 and PE 18:2/18:2, which are due to de novo synthesis and fatty acid remodeling. In contrast, t9,t11-CLA is preferentially bound to neutral lipids, including triglycerides and cholesterol esters. Taken together our results show that c9,t11-CLA and t9,t11-CLA have differential effects on PC and PE metabolism. Moreover, these data demonstrate that the structure of fatty acids not only determines their incorporation into lipid classes but also modulates the kinetics of lipid metabolism, particularly PC synthesis. PMID:20522602

  15. Diurnal regulation of lipid metabolism and applications of circadian lipidomics.

    PubMed

    Gooley, Joshua J; Chua, Eric Chern-Pin

    2014-05-20

    The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporally coordinated with rest-activity and feeding cycles. At the cellular level, genes involved in lipid synthesis and fatty acid oxidation are rhythmically activated and repressed by core clock proteins in a tissue-specific manner. Consequently, loss of clock gene function or misalignment of circadian rhythms with feeding cycles (e.g., in shift work) results in impaired lipid homeostasis. Herein, we review recent progress in circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid metabolites, to characterize circadian-regulated lipid pathways in mammals. In mice, novel regulatory circuits involved in fatty acid metabolism have been identified in adipose tissue, liver, and muscle. Extensive diversity in circadian regulation of plasma lipids has also been revealed in humans using lipidomics and other metabolomics approaches. In future studies, lipidomics platforms will be increasingly used to better understand the effects of genetic variation, shift work, food intake, and drugs on circadian-regulated lipid pathways and metabolic health.

  16. The demands of lactation promote differential regulation of lipid stores in fasting elephant seals.

    PubMed

    Fowler, Melinda A; Debier, Cathy; Champagne, Cory D; Crocker, Daniel E; Costa, Daniel P

    2016-01-01

    Fasting animals must ration stored reserves appropriately for metabolic demands. Animals that experience fasting concomitant with other metabolically demanding activities are presented with conflicting demands of energy conservation and expenditure. Our objective was to understand how fasting northern elephant seals regulate the mobilization of lipid reserves and subsequently milk lipid content during lactation. We sampled 36 females early and 39 at the end of lactation. To determine the separate influences of lactation from fasting, we also sampled fasting but non-lactating females early and late (8 and 6 seals, respectively) in their molting fasting period. Mass and adiposity were measured, as well as circulating non-esterified fatty acid (NEFA), triacylglycerol (TAG), cortisol, insulin and growth hormone levels. Milk was collected from lactating females. Milk lipid content increased from 31% in early to 51% in late lactation. In lactating females plasma NEFA was positively related to cortisol and negatively related to insulin, but in molting seals, only variation in cortisol was related to NEFA. Milk lipid content varied with mass, adiposity, NEFA, TAG, cortisol and insulin. Surprisingly, growth hormone concentration was not related to lipid metabolites or milk lipid. Suppression of insulin release appears to be the differential regulator of lipolysis in lactating versus molting seals, facilitating mobilization of stored lipids and maintenance of high NEFA concentrations for milk synthesis. Milk lipid was strongly impacted by the supply of substrate to the mammary gland, indicating regulation at the level of mobilization of lipid reserves. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Lipid metabolism and body composition in Gclm(-/-) mice

    SciTech Connect

    Kendig, Eric L.; Chen, Ying; Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N.; Genter, Mary Beth; Nebert, Daniel W.; Shertzer, Howard G.

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

  18. Lipid droplet-based storage fat metabolism in Drosophila

    PubMed Central

    Kühnlein, Ronald P.

    2012-01-01

    The fruit fly Drosophila melanogaster is an emerging model system in lipid metabolism research. Lipid droplets are omnipresent and dynamically regulated organelles found in various cell types throughout the complex life cycle of this insect. The vital importance of lipid droplets as energy resources and storage compartments for lipoanabolic components has recently attracted research attention to the basic enzymatic machinery, which controls the delicate balance between triacylglycerol deposition and mobilization in flies. This review aims to present current insights in experimentally supported and inferred biological functions of lipogenic and lipolytic enzymes as well as regulatory proteins, which control the lipid droplet-based storage fat turnover in Drosophila. PMID:22566574

  19. Brain Natriuretic Peptide Stimulates Lipid Metabolism through Its Receptor NPR1 and the Glycerolipid Metabolism Pathway in Chicken Adipocytes.

    PubMed

    Huang, H Y; Zhao, G P; Liu, R R; Li, Q H; Zheng, M Q; Li, S F; Liang, Z; Zhao, Z H; Wen, J

    2015-11-03

    Brain natriuretic peptide (BNP) is related to lipid metabolism in mammals, but its effect and the molecular mechanisms underlying it in chickens are incompletely understood. We found that the level of natriuretic peptide precursor B (NPPB, which encodes BNP) mRNA expression in high-abdominal-fat chicken groups was significantly higher than that of low-abdominal-fat groups. Partial correlations indicated that changes in the weight of abdominal fat were positively correlated with NPPB mRNA expression level. In vitro, compared with the control group, preadipocytes with NPPB interference showed reduced levels of proliferation, differentiation, and glycerin in media. Treatments of cells with BNP led to enhanced proliferation and differentiation of cells and glycerin concentration, and mRNA expression of its receptor natriuretic peptide receptor 1 (NPR1) was upregulated significantly. In cells exposed to BNP, 482 differentially expressed genes were identified compared with controls without BNP. Four genes known to be related to lipid metabolism (diacylglycerol kinase; lipase, endothelial; 1-acylglycerol-3-phosphate O-acyltransferase 1; and 1-acylglycerol-3-phosphate O-acyltransferase 2) were enriched in the glycerolipid metabolism pathway and expressed differentially. In conclusion, BNP stimulates the proliferation, differentiation, and lipolysis of preadipocytes through upregulation of the levels of expression of its receptor NPR1 and key genes enriched in the glycerolipid metabolic pathway.

  20. Zebrafish yolk lipid processing: a tractable tool for the study of vertebrate lipid transport and metabolism

    PubMed Central

    Miyares, Rosa L.; de Rezende, Vitor B.; Farber, Steven A.

    2014-01-01

    Dyslipidemias are a major cause of morbidity and mortality in the world, particularly in developed nations. Investigating lipid and lipoprotein metabolism in experimentally tractable animal models is a crucial step towards understanding and treating human dyslipidemias. The zebrafish, a well-established embryological model, is emerging as a notable system for studies of lipid metabolism. Here, we describe the value of the lecithotrophic, or yolk-metabolizing, stages of the zebrafish as a model for studying lipid metabolism and lipoprotein transport. We demonstrate methods to assay yolk lipid metabolism in embryonic and larval zebrafish. Injection of labeled fatty acids into the zebrafish yolk promotes efficient uptake into the circulation and rapid metabolism. Using a genetic model for abetalipoproteinemia, we show that the uptake of labeled fatty acids into the circulation is dependent on lipoprotein production. Furthermore, we examine the metabolic fate of exogenously delivered fatty acids by assaying their incorporation into complex lipids. Moreover, we demonstrate that this technique is amenable to genetic and pharmacologic studies. PMID:24812437

  1. Lipid metabolism, adipocyte depot physiology and utilization of meat animals as experimental models for metabolic research

    PubMed Central

    Dodson, Michael V.; Hausman, Gary J.; Guan, LeLuo; Du, Min; Rasmussen, Theodore P.; Poulos, Sylvia P.; Mir, Priya; Bergen, Werner G.; Fernyhough, Melinda E.; McFarland, Douglas C.; Rhoads, Robert P.; Soret, Beatrice; Reecy, James M.; Velleman, Sandra G.; Jiang, Zhihua

    2010-01-01

    Meat animals are unique as experimental models for both lipid metabolism and adipocyte studies because of their direct economic value for animal production. This paper discusses the principles that regulate adipogenesis in major meat animals (beef cattle, dairy cattle, and pigs), the definition of adipose depot-specific regulation of lipid metabolism or adipogenesis, and introduces the potential value of these animals as models for metabolic research including mammary biology and the ontogeny of fatty livers. PMID:21103072

  2. Assessing compartmentalized flux in lipid metabolism with isotopes.

    PubMed

    Allen, Doug K

    2016-09-01

    Metabolism in plants takes place across multiple cell types and within distinct organelles. The distributions equate to spatial heterogeneity; though the limited means to experimentally assess metabolism frequently involve homogenizing tissues and mixing metabolites from different locations. Most current isotope investigations of metabolism therefore lack the ability to resolve spatially distinct events. Recognition of this limitation has resulted in inspired efforts to advance metabolic flux analysis and isotopic labeling techniques. Though a number of these efforts have been applied to studies in central metabolism; recent advances in instrumentation and techniques present an untapped opportunity to make similar progress in lipid metabolism where the use of stable isotopes has been more limited. These efforts will benefit from sophisticated radiolabeling reports that continue to enrich our knowledge on lipid biosynthetic pathways and provide some direction for stable isotope experimental design and extension of MFA. Evidence for this assertion is presented through the review of several elegant stable isotope studies and by taking stock of what has been learned from radioisotope investigations when spatial aspects of metabolism were considered. The studies emphasize that glycerolipid production occurs across several locations with assembly of lipids in the ER or plastid, fatty acid biosynthesis occurring in the plastid, and the generation of acetyl-CoA and glycerol-3-phosphate taking place at multiple sites. Considering metabolism in this context underscores the cellular and subcellular organization that is important to enhanced production of glycerolipids in plants. An attempt is made to unify salient features from a number of reports into a diagrammatic model of lipid metabolism and propose where stable isotope labeling experiments and further flux analysis may help address questions in the field. This article is part of a Special Issue entitled: Plant Lipid

  3. Lysosome/lipid droplet interplay in metabolic diseases.

    PubMed

    Dugail, Isabelle

    2014-01-01

    Lysosomes and lipid droplets are generally considered as intracellular compartments with divergent roles in cell metabolism, lipid droplets serving as lipid reservoirs in anabolic pathways, whereas lysosomes are specialized in the catabolism of intracellular components. During the last few years, new insights in the biology of lysosomes has challenged this view by providing evidence for the importance of lysosome recycling as a sparing mechanism to maintain cellular fitness. On the other hand the understanding of lipid droplets has evolved from an inert intracellular deposit toward the status of an intracellular organelle with dynamic roles in cellular homeostasis beyond storage. These unrelated aspects have also recently converged in the finding of unexpected lipid droplet/lysosome communication through autophagy, and the discovery of lysosome-mediated lipid droplet degradation called lipopagy. Furthermore, adipocytes which are professional cells for lipid droplet formation were also shown to be active in peptide antigen presentation a pathway requiring lysosomal activity. The potential importance of lipid droplet/lysosome interplay is discussed in the context of metabolic diseases and the setting of chronic inflammation.

  4. JAK-STAT in lipid metabolism of adipocytes.

    PubMed

    Xu, Dong; Yin, Chunyan; Wang, Sisi; Xiao, Yanfeng

    2013-10-01

    JAK-STAT signaling pathway plays an important role in the cells' development and homeostasis. Over the past decades, the studies have identified the role of the JAK-STAT pathway in cell proliferation and apoptosis. Here, we want to discuss that whether and how the JAK-STAT pathway affects the lipid metabolism of adipose tissue. A host of cytokines and hormones can regulate lipid metabolism through activating the JAK-STAT signaling pathway. Activated STATs can regulate lipid metabolism directly by influencing the expression of enzymes. We have summarized the relevant research and articles of JAK-STAT during the recent years. Within this review, we will introduce you the recent research and highlight the unresolved problems in understanding how JAK-STAT signaling pathway contribute to the lipid metabolism in mature adipocytes and preadipocytes. Dysregulation of the JAK-STAT pathway would lead to a multiple metabolism disorders and medicines for this signaling pathway maybe become a new idea for diseases such as metabolic syndrome, especially in children.

  5. Metabolic engineering of lipid catabolism increases microalgal lipid accumulation without compromising growth

    PubMed Central

    Trentacoste, Emily M.; Shrestha, Roshan P.; Smith, Sarah R.; Glé, Corine; Hartmann, Aaron C.; Hildebrand, Mark; Gerwick, William H.

    2013-01-01

    Biologically derived fuels are viable alternatives to traditional fossil fuels, and microalgae are a particularly promising source, but improvements are required throughout the production process to increase productivity and reduce cost. Metabolic engineering to increase yields of biofuel-relevant lipids in these organisms without compromising growth is an important aspect of advancing economic feasibility. We report that the targeted knockdown of a multifunctional lipase/phospholipase/acyltransferase increased lipid yields without affecting growth in the diatom Thalassiosira pseudonana. Antisense-expressing knockdown strains 1A6 and 1B1 exhibited wild-type–like growth and increased lipid content under both continuous light and alternating light/dark conditions. Strains 1A6 and 1B1, respectively, contained 2.4- and 3.3-fold higher lipid content than wild-type during exponential growth, and 4.1- and 3.2-fold higher lipid content than wild-type after 40 h of silicon starvation. Analyses of fatty acids, lipid classes, and membrane stability in the transgenic strains suggest a role for this enzyme in membrane lipid turnover and lipid homeostasis. These results demonstrate that targeted metabolic manipulations can be used to increase lipid accumulation in eukaryotic microalgae without compromising growth. PMID:24248374

  6. Metabolic engineering of lipid catabolism increases microalgal lipid accumulation without compromising growth.

    PubMed

    Trentacoste, Emily M; Shrestha, Roshan P; Smith, Sarah R; Glé, Corine; Hartmann, Aaron C; Hildebrand, Mark; Gerwick, William H

    2013-12-03

    Biologically derived fuels are viable alternatives to traditional fossil fuels, and microalgae are a particularly promising source, but improvements are required throughout the production process to increase productivity and reduce cost. Metabolic engineering to increase yields of biofuel-relevant lipids in these organisms without compromising growth is an important aspect of advancing economic feasibility. We report that the targeted knockdown of a multifunctional lipase/phospholipase/acyltransferase increased lipid yields without affecting growth in the diatom Thalassiosira pseudonana. Antisense-expressing knockdown strains 1A6 and 1B1 exhibited wild-type-like growth and increased lipid content under both continuous light and alternating light/dark conditions. Strains 1A6 and 1B1, respectively, contained 2.4- and 3.3-fold higher lipid content than wild-type during exponential growth, and 4.1- and 3.2-fold higher lipid content than wild-type after 40 h of silicon starvation. Analyses of fatty acids, lipid classes, and membrane stability in the transgenic strains suggest a role for this enzyme in membrane lipid turnover and lipid homeostasis. These results demonstrate that targeted metabolic manipulations can be used to increase lipid accumulation in eukaryotic microalgae without compromising growth.

  7. Expression profiling and comparative sequence derived insights into lipid metabolism

    SciTech Connect

    Callow, Matthew J.; Rubin, Edward M.

    2001-12-19

    Expression profiling and genomic DNA sequence comparisons are increasingly being applied to the identification and analysis of the genes involved in lipid metabolism. Not only has genome-wide expression profiling aided in the identification of novel genes involved in important processes in lipid metabolism such as sterol efflux, but the utilization of information from these studies has added to our understanding of the regulation of pathways participating in the process. Coupled with these gene expression studies, cross species comparison, searching for sequences conserved through evolution, has proven to be a powerful tool to identify important non-coding regulatory sequences as well as the discovery of novel genes relevant to lipid biology. An example of the value of this approach was the recent chance discovery of a new apolipoprotein gene (apo AV) that has dramatic effects upon triglyceride metabolism in mice and humans.

  8. Perfluorodecanoic Acid and Lipid Metabolism in the Rat

    DTIC Science & Technology

    1989-05-25

    2. To develop analogous methodologies for perfluorooctanoic acid (PFOA), a shorter-chain perfluorinated fatty acid similar to PFDA. 3. To validate...A5 TITLE (Includ Secuiq Oauahcatio0) Perfluorodecanoic Acid and Lipid Metabolism in the Rat 2 PERSONAL AUT)4O0(S) Ma’-c J. Van Rafelsehe. John P...fatty acid from those secondary to hypophagia. Carcass content of lipid phosphorus and free cholesterol decreased in dose-dependent fashion in both PFDA

  9. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    SciTech Connect

    Lasrich, Dorothee; Bartelt, Alexander; Grewal, Thomas; Heeren, Joerg

    2015-09-10

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  10. Control of Differentiation of a Mammary Cell Line by Lipids

    NASA Astrophysics Data System (ADS)

    Dulbecco, Renato; Bologna, Mauro; Unger, Michael

    1980-03-01

    A rat mammary cell line (LA7) undergoes spontaneous differentiation into domes due to production of specific inducers by the cells. Some of these inducers may be lipids, and we show that lipids regulate this differentiation as both inducers and inhibitors. One inhibitor is the tumor promoter tetradecanoyl-13 phorbol 12-acetate. The inducers are saturated fatty acids of two groups: butyric acid and acids with chain lengths from C13 to C16, especially myristic acid (C14). Other inducers are myristoyl and palmitoyl lysolecithins, myristic acid methyl ester, and two cationic detergents with a tetradecenyl chain. We propose that the lipids with a C14-C16 alkyl chain affect differentiation by recognizing specific receptors through their alkyl chains and that the effects obtained depend on the head groups. These lipids may be physiological regulators in the mammary gland.

  11. Peroxisomes: a Nexus for Lipid Metabolism and Cellular Signaling

    PubMed Central

    Lodhi, Irfan J.; Semenkovich, Clay F.

    2014-01-01

    Peroxisomes are often dismissed as the cellular hoi polloi, relegated to cleaning up reactive oxygen chemical debris discarded by other organelles. However, their functions extend far beyond hydrogen peroxide metabolism. Peroxisomes are intimately associated with lipid droplets and mitochondria, and their ability to carry out fatty acid oxidation and lipid synthesis, especially the production of ether lipids, may be critical for generating cellular signals required for normal physiology. Here we review the biology of peroxisomes and their potential relevance to human disorders including cancer, obesity-related diabetes, and degenerative neurologic disease. PMID:24508507

  12. Porphyromonas gingivalis Lipids Inhibit Osteoblastic Differentiation and Function▿

    PubMed Central

    Wang, Yu-Hsiung; Jiang, Jin; Zhu, Qiang; AlAnezi, Amer Z.; Clark, Robert B.; Jiang, Xi; Rowe, David W.; Nichols, Frank C.

    2010-01-01

    Porphyromonas gingivalis produces unusual sphingolipids that are known to promote inflammatory reactions in gingival fibroblasts and Toll-like receptor 2 (TLR2)-dependent secretion of interleukin-6 from dendritic cells. The aim of the present study was to examine whether P. gingivalis lipids inhibit osteoblastic function. Total lipids from P. gingivalis and two fractions, phosphoglycerol dihydroceramides and phosphoethanolamine dihydroceramides, were prepared free of lipid A. Primary calvarial osteoblast cultures derived from 5- to 7-day-old CD-1 mice were used to examine the effects of P. gingivalis lipids on mineralized nodule formation, cell viability, apoptosis, cell proliferation, and gene expression. P. gingivalis lipids inhibited osteoblast differentiation and fluorescence expression of pOBCol2.3GFP in a concentration-dependent manner. However, P. gingivalis lipids did not significantly alter osteoblast proliferation, viability, or apoptosis. When administered during specific intervals of osteoblast growth, P. gingivalis total lipids demonstrated inhibitory effects on osteoblast differentiation only after the proliferation stage of culture. Reverse transcription-PCR confirmed the downregulation of osteoblast marker genes, including Runx2, ALP, OC, BSP, OPG, and DMP-1, with concurrent upregulation of RANKL, tumor necrosis factor alpha, and MMP-3 genes. P. gingivalis total lipids and lipid fractions inhibited calvarial osteoblast gene expression and function in vivo, as determined by the loss of expression of another osteoblast differentiation reporter, pOBCol3.6GFPcyan, and reduced uptake of Alizarin complexone stain. Finally, lipid inhibition of mineral nodule formation in vitro was dependent on TLR2 expression. Our results indicate that inhibition of osteoblast function and gene expression by P. gingivalis lipids represents a novel mechanism for altering alveolar bone homeostasis at periodontal disease sites. PMID:20584977

  13. Comprehensive insights into microcystin-LR effects on hepatic lipid metabolism using cross-omics technologies.

    PubMed

    Zhang, Zongyao; Zhang, Xu-Xiang; Wu, Bing; Yin, Jinbao; Yu, Yunjiang; Yang, Liuyan

    2016-09-05

    Microcystin-LR (MC-LR) can induce hepatic tissue damages and molecular toxicities, but its effects on lipid metabolism remain unknown. This study investigated the effects of MC-LR exposure on mice lipid metabolism and uncovered the underlying mechanism through metabonomic, transcriptomic and metagenomic analyses after administration of mice with MC-LR by gavage for 28 d. Increased liver weight and abdominal fat weight, and evident hepatic lipid vacuoles accumulation were observed in the mice fed with 0.2mg/kg/d MC-LR. Serum nuclear magnetic resonance analysis showed that MC-LR treatment altered the levels of serum metabolites including triglyceride, unsaturated fatty acid (UFA) and very low density lipoprotein. Digital Gene Expression technology was used to reveal differential expression of hepatic transcriptomes, demonstrating that MC-LR treatment disturbed hepatic UFA biosynthesis and activated peroxisome proliferator-activated receptor (PPAR) signaling pathways via Pparγ, Fabp1 and Fabp2 over-expression. Metagenomic analyses of gut microbiota revealed that MC-LR exposure also increased abundant ratio of Firmicutes vs. Bacteroidetes in gut and altered biosynthetic pathways of various microbial metabolic and pro-inflammatory molecules. In conclusion, oral MC-LR exposure can induce hepatic lipid metabolism disorder mediated by UFA biosynthesis and PPAR activation, and gut microbial community shift may play an important role in the metabolic disturbance.

  14. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    USDA-ARS?s Scientific Manuscript database

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  15. Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

    PubMed Central

    Singh, Mahavir; Kapoor, Aniruddh; Bhatnagar, Aruni

    2015-01-01

    Extensive research has shown that increased production of reactive oxygen species (ROS) results in tissue injury under a variety of pathological conditions and chronic degenerative diseases. While ROS are highly reactive and can incite significant injury, polyunsaturated lipids in membranes and lipoproteins are their main targets. ROS-triggered lipid peroxidation reactions generate a range of reactive carbonyl species (RCS), and these RCS spread and amplify ROS-related injury. Several RCS generated in oxidizing lipids, such as 4-hydroxy trans-2-nonenal (HNE), 4-oxo-2-(E)-nonenal (ONE), acrolein, malondialdehyde (MDA) and phospholipid aldehydes have been shown to be produced under conditions of oxidative stress and contribute to tissue injury and dysfunction by depleting glutathione and other reductants leading to the modification of proteins, lipids, and DNA. To prevent tissue injury, these RCS are metabolized by several oxidoreductases, including members of the aldo-keto reductase (AKR) superfamily, aldehyde dehydrogenases (ALDHs), and alcohol dehydrogenases (ADHs). Metabolism via these enzymes results in RCS inactivation and detoxification, although under some conditions, it can also lead to the generation of signaling molecules that trigger adaptive responses. Metabolic transformation and detoxification of RCS by oxidoreductases prevent indiscriminate ROS toxicity, while at the same time, preserving ROS signaling. A better understanding of RCS metabolism by oxidoreductases could lead to the development of novel therapeutic interventions to decrease oxidative injury in several disease states and to enhance resistance to ROS-induced toxicity. PMID:25559856

  16. Arabidopsis ribosomal proteins control vacuole trafficking and developmental programs through the regulation of lipid metabolism

    DOE PAGES

    Li, Ruixi; Sun, Ruobai; Hicks, Glenn R.; ...

    2014-12-22

    The vacuole is the most prominent compartment in plant cells and is important for ion and protein storage. In our effort to search for key regulators in the plant vacuole sorting pathway, ribosomal large subunit 4 (rpl4d) was identified as a translational mutant defective in both vacuole trafficking and normal development. Polysome profiling of the rpl4d mutant showed reduction in polysome-bound mRNA compared with wild-type, but no significant change in the general mRNA distribution pattern. Ribsomal profiling data indicated that genes in the lipid metabolism pathways were translationally down-regulated in the rpl4d mutant. Live imaging studies by Nile red stainingmore » suggested that both polar and nonpolar lipid accumulation was reduced in meristem tissues of rpl4d mutants. Pharmacological evidence showed that sterol and sphingolipid biosynthetic inhibitors can phenocopy the defects of the rpl4d mutant, including an altered vacuole trafficking pattern. Genetic evidence from lipid biosynthetic mutants indicates that alteration in the metabolism of either sterol or sphingolipid biosynthesis resulted in vacuole trafficking defects, similar to the rpl4d mutant. Tissue-specific complementation with key enzymes from lipid biosynthesis pathways can partially rescue both vacuole trafficking and auxin-related developmental defects in the rpl4d mutant. These results indicate that lipid metabolism modulates auxin-mediated tissue differentiation and endomembrane trafficking pathways downstream of ribosomal protein function.« less

  17. Clofazimine modulates the expression of lipid metabolism proteins in Mycobacterium leprae-infected macrophages.

    PubMed

    Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi

    2012-01-01

    Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine.

  18. Differential scanning calorimetry of protein-lipid interactions.

    PubMed

    Cañadas, Olga; Casals, Cristina

    2013-01-01

    Differential scanning calorimetry (DSC) is a highly sensitive non-perturbing technique for measuring the thermodynamic properties of thermally induced transitions. This technique is particularly useful for the characterization of lipid/protein interactions. This chapter presents an introduction to DSC instrumentation, basic theory, and methods and describes DSC applications for characterizing protein effects on model lipid membranes. Examples of the use of DSC for the evaluation of protein effects on modulation of membrane domains and membrane stability are given.

  19. Alteration of lipid metabolism in cells infected with human cytomegalovirus.

    PubMed

    Sanchez, Veronica; Dong, Jennifer J

    2010-08-15

    The human cytomegalovirus (HCMV) envelope contains 12 virus-encoded glycoproteins and glycoprotein complexes but the lipid composition of the envelope has not been clearly defined. Given the specificity of the interactions between integral membrane proteins and lipids, it is likely that the lipid content of the virion envelope is regulated during infection. In an effort to determine the effects of HCMV infection on lipid metabolism, we have used PCR array technology to investigate how infection affects the expression of genes involved in lipoprotein signaling and cholesterol homeostasis pathways. Our results indicate that HCMV infection leads to down-regulation of the ABCA1 transporter. Decreased levels of ABCA1 appear to be the result of enhanced calpain-mediated cleavage in virus-infected cells. In addition, our data also show that HCMV infection inhibits the development of the foam cell phenotype in conditionally permissive THP-1 derived macrophages

  20. Fat taste and lipid metabolism in humans.

    PubMed

    Mattes, Richard D

    2005-12-15

    Dietary and body fat are essential for life. Fatty acids modulate fat detection, ingestion, digestion, absorption and elimination. Though direct effects occur throughout the body, much of this regulation stems from signals originating in the oral cavity. The predominant orosensory cue for dietary fat is textural, but accumulating electrophysiological, behavioral and clinical evidence supports olfactory and gustatory components. Orosensory stimulation with long-chain unsaturated, but possibly also saturated, fatty acids elicits an array of cephalic phase responses including release of gastric lipase, secretion of pancreatic digestive enzymes, mobilization of lipid stored in the intestine from the prior meal, pancreatic endocrine secretion and, probably indirectly, altered lipoprotein lipase activity. Combined, these processes influence postprandial lipemia. There is preliminary evidence of marked individual variability in fat "taste" with uncertain health implications. The possibility that fat taste sensitivity reflects systemic reactivity to fat warrants further evaluation.

  1. Dietary lipid-induced changes in enzymes of hepatic lipid metabolism.

    PubMed

    de Catalfo, Graciela E Hurtado; de Alaniz, María J T; Marra, Carlos A

    2013-02-01

    To investigate the effect of different dietary oils on the main hepatic enzymes involved in metabolism and their impact on oxidative stress status. Twenty-four male Wistar rats were fed for 60 d on the same basal diet plus different lipid sources from commercial oils: soybean (S), olive (O), coconut (C), and grape seed (G). After sacrifice, the liver lipid fatty acid composition, enzymatic and non-enzymatic components of the antioxidant defense system, and the activity of enzymes involved in lipid metabolism were determined. The concentration of Ca(2+) in plasma and liver homogenates was also measured. The diets produced significant changes in the total and polar lipid fatty acid compositions and alterations in key enzyme activities involved in lipid metabolism. The S and G groups showed significantly increased oxidative stress biomarkers. The enzymatic and non-enzymatic components of the antioxidant defense system were increased in the O and C groups. The highest levels of nitrite plus nitrate were observed in the S and G groups compared with the O and C groups in plasma and in liver homogenates. These were directly correlated with the Ca(2+) concentration. The most beneficial effects were obtained with olive oil. However, it is necessary to study in more detail appropriate mixtures of olive and soybean oils to provide an adequate balance between ω-3 and ω-6 fatty acids. Different dietary oils modify the lipid composition of the plasma and liver, local and systemic antioxidant statuses, and the activity of the key enzymes of lipid metabolism. The interrelation between Ca(2+) and nitrite plus nitrate could be the causal factor underlying the observed changes. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Microarray Analysis of the Gene Expression Profile and Lipid Metabolism in Fat-1 Transgenic Cattle.

    PubMed

    Liu, Xinfeng; Bai, Chunling; Ding, Xiangbin; Wei, Zhuying; Guo, Hong; Li, Guangpeng

    2015-01-01

    Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are beneficial for human health. However, humans and mammals are unable to synthesize n-3 PUFAs because they lack the n-3 desaturase gene fat-1 and must therefore obtain this type of fatty acid through their diet. Through the production of fat-1 transgenic animals, it is possible to obtain animal products that are rich in n-3 PUFAs, such as meat and milk. The aim of this study was to analyze the gene expression profile and the mechanism of lipid metabolism in fat-1 transgenic cattle and to accumulate important basic data that are required to obtain more efficient fat-1 transgenic cattle. Transcriptome profiling of fat-1 transgenic and wild-type cattle identified differentially expressed genes that are involved in 90 biological pathways, eight pathways of which were related to lipid metabolism processes 36 genes of which were related to lipid metabolism. This analysis also identified 11 significantly enriched genes that were involved in the peroxisome proliferator-activated receptor signaling pathway. These findings were verified by quantitative polymerase chain reaction. The information obtained in this study indicated that the introduction of an exogenous fat-1 gene into cattle affects the gene expression profile and the process of lipid metabolism in these animals. These results may provide important insights into how an exogenous fat-1 gene synthesizes n-3 PUFAs in transgenic cattle and other mammals.

  3. Microarray Analysis of the Gene Expression Profile and Lipid Metabolism in Fat-1 Transgenic Cattle

    PubMed Central

    Liu, Xinfeng; Bai, Chunling; Ding, Xiangbin; Wei, Zhuying; Guo, Hong; Li, Guangpeng

    2015-01-01

    Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are beneficial for human health. However, humans and mammals are unable to synthesize n-3 PUFAs because they lack the n-3 desaturase gene fat-1 and must therefore obtain this type of fatty acid through their diet. Through the production of fat-1 transgenic animals, it is possible to obtain animal products that are rich in n-3 PUFAs, such as meat and milk. The aim of this study was to analyze the gene expression profile and the mechanism of lipid metabolism in fat-1 transgenic cattle and to accumulate important basic data that are required to obtain more efficient fat-1 transgenic cattle. Transcriptome profiling of fat-1 transgenic and wild-type cattle identified differentially expressed genes that are involved in 90 biological pathways, eight pathways of which were related to lipid metabolism processes 36 genes of which were related to lipid metabolism. This analysis also identified 11 significantly enriched genes that were involved in the peroxisome proliferator-activated receptor signaling pathway. These findings were verified by quantitative polymerase chain reaction. The information obtained in this study indicated that the introduction of an exogenous fat-1 gene into cattle affects the gene expression profile and the process of lipid metabolism in these animals. These results may provide important insights into how an exogenous fat-1 gene synthesizes n-3 PUFAs in transgenic cattle and other mammals. PMID:26426396

  4. Retinal lipid and glucose metabolism dictates angiogenesis through lipid sensor Ffar1

    PubMed Central

    Joyal, Jean-Sébastien; Sun, Ye; Gantner, Marin L.; Shao, Zhuo; Evans, Lucy P.; Saba, Nicholas; Fredrick, Thomas; Burnim, Samuel; Kim, Jin Sung; Patel, Gauri; Juan, Aimee M.; Hurst, Christian G.; Hatton, Colman J.; Cui, Zhenghao; Pierce, Kerry A.; Bherer, Patrick; Aguilar, Edith; Powner, Michael B.; Vevis, Kristis; Boisvert, Michel; Fu, Zhongjie; Levy, Emile; Fruttiger, Marcus; Packard, Alan; Rezende, Flavio A.; Maranda, Bruno; Sapieha, Przemyslaw; Chen, Jing; Friedlander, Martin; Clish, Clary B.; Smith, Lois E.H.

    2016-01-01

    Tissues with high metabolic rates often use lipid as well as glucose for energy, conferring a survival advantage during feast and famine.1 Current dogma suggests that high-energy consuming photoreceptors depend on glucose.2,3 Here we show that retina also uses fatty acids (FA) β-oxidation for energy. Moreover, we identify a lipid sensor Ffar1 that curbs glucose uptake when FA are available. Very low-density lipoprotein receptor (VLDLR), expressed in tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived FA.4,5 Vldlr is present in photoreceptors.6 In Vldlr−/− retinas, Ffar1, sensing high circulating lipid levels despite decreased FA uptake5, suppresses glucose transporter Glut1. This impaired glucose entry into photoreceptors results in a dual lipid/glucose fuel shortage and reduction in the Krebs cycle intermediate α-ketoglutarate (KG). Low α-KG levels promote hypoxia-induced factor-1α (Hif1a) stabilization and vascular endothelial growth factor (Vegfa) secretion by starved Vldlr−/− photoreceptors, attracting neovessels to supply fuel. These aberrant vessels invading normally avascular photoreceptors in Vldlr−/− retinas are reminiscent of retinal angiomatous proliferation (RAP), a subset of neovascular age-related macular degeneration (AMD)7, associated with high vitreous VEGF levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in neovascular AMD and other retinal diseases. PMID:26974308

  5. A novel physiological role for cardiac myoglobin in lipid metabolism

    PubMed Central

    Hendgen-Cotta, Ulrike B.; Esfeld, Sonja; Coman, Cristina; Ahrends, Robert; Klein-Hitpass, Ludger; Flögel, Ulrich; Rassaf, Tienush; Totzeck, Matthias

    2017-01-01

    Continuous contractile activity of the heart is essential and the required energy is mostly provided by fatty acid (FA) oxidation. Myocardial lipid accumulation can lead to pathological responses, however the underlying mechanisms remain elusive. The role of myoglobin in dioxygen binding in cardiomyocytes and oxidative skeletal muscle has widely been appreciated. Our recent work established myoglobin as a protector of cardiac function in hypoxia and disease states. We here unravel a novel role of cardiac myoglobin in governing FA metabolism to ensure the physiological energy production through β-oxidation, preventing myocardial lipid accumulation and preserving cardiac functions. In vivo1H magnetic resonance spectroscopy unveils a 3-fold higher deposition of lipids in mouse hearts lacking myoglobin, which was associated with depressed cardiac function compared to wild-type hearts as assessed by echocardiography. Mass spectrometry reveals a marked increase in tissue triglycerides with preferential incorporation of palmitic and oleic acids. Phospholipid levels as well as the metabolome, transcriptome and proteome related to FA metabolism tend to be unaffected by myoglobin ablation. Our results reveal a physiological role of myoglobin in FA metabolism with the lipid accumulation-suppressing effects of myoglobin preventing cardiac lipotoxicity. PMID:28230173

  6. The Role of Microscopy in Understanding Atherosclerotic Lysosomal Lipid Metabolism

    NASA Astrophysics Data System (ADS)

    Gray Jerome, W.; Yancey, Patricia G.

    2003-02-01

    Microscopy has played a critical role in first identifying and then defining the role of lysosomes in formation of atherosclerotic foam cells. We review the evidence implicating lysosomal lipid accumulation as a factor in the pathogenesis of atherosclerosis with reference to the role of microscopy. In addition, we explore mechanisms by which lysosomal lipid engorgement occurs. Low density lipoproteins which have become modified are the major source of lipid for foam cell formation. These altered lipoproteins are taken into the cell via receptor-mediated endocytosis and delivered to lysosomes. Under normal conditions, lipids from these lipoproteins are metabolized and do not accumulate in lysosomes. In the atherosclerotic foam cell, this normal metabolism is inhibited so that cholesterol and cholesteryl esters accumulate in lysosomes. Studies of cultured cells incubated with modified lipoproteins suggests this abnormal metabolism occurs in two steps. Initially, hydrolysis of lipoprotein cholesteryl esters occurs normally, but the resultant free cholesterol cannot exit the lysosome. Further lysosomal cholesterol accumulation inhibits hydrolysis, producing a mixture of cholesterol and cholesteryl esters within swollen lysosomes. Various lipoprotein modifications can produce this lysosomal engorgement in vitro and it remains to be seen which modifications are most important in vivo.

  7. Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism.

    PubMed

    Michalski, M C; Genot, C; Gayet, C; Lopez, C; Fine, F; Joffre, F; Vendeuvre, J L; Bouvier, J; Chardigny, J M; Raynal-Ljutovac, K

    2013-10-01

    On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Absence of cumulus cells during in vitro maturation affects lipid metabolism in bovine oocytes.

    PubMed

    Auclair, Sylvain; Uzbekov, Rustem; Elis, Sébastien; Sanchez, Laura; Kireev, Igor; Lardic, Lionel; Dalbies-Tran, Rozenn; Uzbekova, Svetlana

    2013-03-15

    Cumulus cells (CC) surround the oocyte and are coupled metabolically through regulation of nutrient intake. CC removal before in vitro maturation (IVM) decreases bovine oocyte developmental competence without affecting nuclear meiotic maturation. The objective was to investigate the influence of CC on oocyte cytoplasmic maturation in relation to energy metabolism. IVM with either cumulus-enclosed (CEO) or -denuded (DO) oocytes was performed in serum-free metabolically optimized medium. Transmission electron microscopy revealed different distribution of membrane-bound vesicles and lipid droplets between metaphase II DO and CEO. By Nile Red staining, a significant reduction in total lipid level was evidenced in DO. Global transcriptomic analysis revealed differential expression of genes regulating energy metabolism, transcription, and translation between CEO and DO. By Western blot, fatty acid synthase (FAS) and hormone-sensitive phospholipase (HSL) proteins were detected in oocytes and in CC, indicating a local lipogenesis and lypolysis. FAS protein was significantly less abundant in DO that in CEO and more highly expressed in CC than in the oocytes. On the contrary, HSL protein was more abundant in oocytes than in CC. In addition, active Ser⁵⁶³-phosphorylated HSL was detected in the oocytes only after IVM, and its level was similar in CEO and DO. In conclusion, absence of CC during IVM affected lipid metabolism in the oocyte and led to suboptimal cytoplasmic maturation. Thus, CC may influence the oocyte by orienting the consumption of nutritive storage via regulation of local fatty acid synthesis and lipolysis to provide energy for maturation.

  9. Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

    PubMed

    Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

    2016-02-01

    In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

  10. Sirtuin 1 deacetylase: a key regulator of hepatic lipid metabolism.

    PubMed

    Kemper, Jongsook Kim; Choi, Sung-E; Kim, Dong Hyun

    2013-01-01

    Obesity is a serious medical problem worldwide and disruption of metabolic/energy homeostasis plays a pivotal role in this global epidemic. In obese people, fatty liver (steatosis) develops, which increases the risk for diabetes, cardiovascular disease, and even, liver cancer. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that functions as a key metabolic/energy sensor and mediates homeostatic responses to nutrient availability. Accumulating evidence indicates that SIRT1 is a master regulator of the transcriptional networks that control hepatic lipid metabolism. During energy-deprived conditions, SIRT1 deacetylates and alters the expression and activities of key transcriptional regulators involved in hepatic lipogenesis, fatty acid β-oxidation, and cholesterol/bile acid metabolism. This review will discuss the latest advances in this field, focusing on beneficial roles of SIRT1 in hepatic lipid metabolism including its potential as a therapeutic target for treatment of steatosis and other obesity-related metabolic diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Follistatin promotes adipocyte differentiation, browning, and energy metabolism.

    PubMed

    Braga, Melissa; Reddy, Srinivasa T; Vergnes, Laurent; Pervin, Shehla; Grijalva, Victor; Stout, David; David, John; Li, Xinmin; Tomasian, Venina; Reid, Christopher B; Norris, Keith C; Devaskar, Sherin U; Reue, Karen; Singh, Rajan

    2014-03-01

    Follistatin (Fst) functions to bind and neutralize the activity of members of the transforming growth factor-β superfamily. Fst has a well-established role in skeletal muscle, but we detected significant Fst expression levels in interscapular brown and subcutaneous white adipose tissue, and further investigated its role in adipocyte biology. Fst expression was induced during adipogenic differentiation of mouse brown preadipocytes and mouse embryonic fibroblasts (MEFs) as well as in cold-induced brown adipose tissue from mice. In differentiated MEFs from Fst KO mice, the induction of brown adipocyte proteins including uncoupling protein 1, PR domain containing 16, and PPAR gamma coactivator-1α was attenuated, but could be rescued by treatment with recombinant FST. Furthermore, Fst enhanced thermogenic gene expression in differentiated mouse brown adipocytes and MEF cultures from both WT and Fst KO groups, suggesting that Fst produced by adipocytes may act in a paracrine manner. Our microarray gene expression profiling of WT and Fst KO MEFs during adipogenic differentiation identified several genes implicated in lipid and energy metabolism that were significantly downregulated in Fst KO MEFs. Furthermore, Fst treatment significantly increases cellular respiration in Fst-deficient cells. Our results implicate a novel role of Fst in the induction of brown adipocyte character and regulation of energy metabolism.

  12. The tail wagging the dog--regulation of lipid metabolism by protein kinase C.

    PubMed

    Schmitz-Peiffer, Carsten

    2013-11-01

    Upon their discovery almost 40 years ago, isoforms of the lipid-activated protein kinase C (PKC) family were initially regarded only as downstream effectors of the second messengers calcium and diacylglycerol, undergoing activation upon phospholipid hydrolysis in response to acute stimuli. Subsequently, several isoforms were found to be associated with the inhibitory effects of lipid over-supply on glucose homeostasis, especially the negative cross-talk with insulin signal transduction, observed upon accumulation of diacylglycerol in insulin target tissues. The PKC family has therefore attracted much attention in diabetes and obesity research, because intracellular lipid accumulation is strongly correlated with defective insulin action and the development of type 2 diabetes. Causal roles for various isoforms in the generation of insulin resistance have more recently been confirmed using PKC-deficient mice. However, during characterization of these animals, it became increasingly evident that the enzymes play key roles in the modulation of lipid metabolism itself, and may control the supply of lipids between tissues such as adipose and liver. Molecular studies have also demonstrated roles for PKC isoforms in several aspects of lipid metabolism, such as adipocyte differentiation and hepatic lipogenesis. While the precise mechanisms involved, especially the identities of protein substrates, are still unclear, the emerging picture suggests that the currently held view of the contribution of PKC isoforms to metabolism is an over-simplification. Although PKCs may inhibit insulin signal transduction, these enzymes are not merely downstream effectors of lipid accumulation, but in fact control the fate of fatty acids, thus the tail wags the dog. © 2013 Commonwealth of Australia.

  13. Differential roles of breakfast only (one meal per day) and a bigger breakfast with a small dinner (two meals per day) in mice fed a high-fat diet with regard to induced obesity and lipid metabolism.

    PubMed

    Fuse, Yuta; Hirao, Akiko; Kuroda, Hiroaki; Otsuka, Makiko; Tahara, Yu; Shibata, Shigenobu

    2012-05-15

    Recent studies on humans and rodents have suggested that the timing of food intake plays an important role in circadian regulation and metabolic health. Consumption of high-fat foods during the inactive period or at the end of the awake period results in weight gain and metabolic syndrome in rodents. However, the distinct effects of breakfast size and the breakfast/dinner size ratio on metabolic health have not yet been fully examined in mice. We examined whether the parameters of metabolic syndrome were differentially affected in mice that consumed a large meal at the beginning of the awake period (breakfast; one meal group) and a relatively smaller meal at end of the awake period (dinner; two meals group). The mice of each group were provided equal food volume per day. Mice on one meal exhibited an increase in body weight gain, hyperinsulinemia, hyperleptinemia, and a decrease of gene expression associated with β-oxidation in adipose tissue and liver compared with those on two meals. The circadian expression pattern of the Clock gene in mice on one meal was disturbed compared with those on two meals. In conclusion, a bigger breakfast with a smaller dinner (two meals per day) but not breakfast only (one meal per day) helps control body weight and fat accumulation in mice on a high-fat meals schedule. The findings of this study suggest that dietary recommendations for weight reduction and/or maintenance should include information on the timing and quantity of dietary intake.

  14. The role of APP proteolytic processing in lipid metabolism.

    PubMed

    Grimm, Marcus O W; Rothhaar, Tatjana L; Hartmann, Tobias

    2012-04-01

    Amyloid plaques in brains are one of the major pathological hallmarks of Alzheimer's disease (AD). These plaques are mainly formed by aggregated Aβ, generated by proteolytic cleavage of the amyloid precursor protein (APP). Therefore, APP processing and Aβ production have been one of the central scopes in AD research in the past. Now, accumulating evidence suggests that besides its pathological impact, APP and its cleavage products also contribute to physiological functions. Proteolytic cleavage of APP is tightly regulated, and several lipids such as cholesterol and sphingolipids have been shown to influence APP processing and Aβ generation. In turn, Aβ as well as other APP cleavage products plays an essential role in regulating lipid homeostasis arguing for complex regulatory cycles in which lipids control APP processing and vice versa. This balanced regulation is disrupted under pathological conditions such as in AD. This article will review the physiological function of APP and its proteolytic products, especially Aβ and AICD, in regulating lipid homeostasis and which lipid species modulate APP processing. Furthermore, we summarize the alterations in lipid metabolism observed in AD patients and AD mouse models.

  15. [Gut microbiota may have influence on glucose and lipid metabolism].

    PubMed

    Hallundbæk Mikkelsen, Kristian; Nielsen, Morten Frost; Tvede, Michael; Hansen, Torben; Pedersen, Oluf Borbye; Holst, Jens Juul; Vilsbøll, Tina; Knop, Filip Krag

    2013-11-11

    New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism.

  16. 1H NMR-based metabolic profiling reveals the effects of fluoxetine on lipid and amino acid metabolism in astrocytes.

    PubMed

    Bai, Shunjie; Zhou, Chanjuan; Cheng, Pengfei; Fu, Yuying; Fang, Liang; Huang, Wen; Yu, Jia; Shao, Weihua; Wang, Xinfa; Liu, Meiling; Zhou, Jingjing; Xie, Peng

    2015-04-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is a prescribed and effective antidepressant and generally used for the treatment of depression. Previous studies have revealed that the antidepressant mechanism of fluoxetine was related to astrocytes. However, the therapeutic mechanism underlying its mode of action in astrocytes remains largely unclear. In this study, primary astrocytes were exposed to 10 µM fluoxetine; 24 h post-treatment, a high-resolution proton nuclear magnetic resonance (1H NMR)-based metabolomic approach coupled with multivariate statistical analysis was used to characterize the metabolic variations of intracellular metabolites. The orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots of the spectra demonstrated that the fluoxetine-treated astrocytes were significantly distinguished from the untreated controls. In total, 17 differential metabolites were identified to discriminate the two groups. These key metabolites were mainly involved in lipids, lipid metabolism-related molecules and amino acids. This is the first study to indicate that fluoxetine may exert antidepressant action by regulating the astrocyte's lipid and amino acid metabolism. These findings should aid our understanding of the biological mechanisms underlying fluoxetine therapy.

  17. Regulation of Lipid and Glucose Metabolism by Phosphatidylcholine Transfer Protein

    PubMed Central

    Kang, Hye Won; Wei, Jie; Cohen, David E.

    2010-01-01

    Phosphatidylcholine transfer protein (PC-TP, a.k.a. StARD2) binds phosphatidylcholines and catalyzes their intermembrane transfer and exchange in vitro. The structure of PC-TP comprises a hydrophobic pocket and a well-defined head-group binding site, and its gene expression is regulated by peroxisome proliferator activated receptor α. Recent studies have revealed key regulatory roles for PC-TP in lipid and glucose metabolism. Notably, Pctp−/− mice are sensitized to insulin action and exhibit more efficient brown fat-mediated thermogenesis. PC-TP appears to limit access of fatty acids to mitochondria by stimulating the activity of thioesterase superfamily member 2, a newly characterized long-chain fatty acyl-CoA thioesterase. Because PC-TP discriminates among phosphatidylcholines within lipid bilayers, it may function as a sensor that links metabolic regulation to membrane composition. PMID:20338778

  18. Functional crosstalk of CAR-LXR and ROR-LXR in drug metabolism and lipid metabolism.

    PubMed

    Xiao, Lei; Xie, Xinni; Zhai, Yonggong

    2010-10-30

    Nuclear receptor crosstalk represents an important mechanism to expand the functions of individual receptors. The liver X receptors (LXR, NR1H2/3), both the α and β isoforms, are nuclear receptors that can be activated by the endogenous oxysterols and other synthetic agonists. LXRs function as cholesterol sensors, which protect mammals from cholesterol overload. LXRs have been shown to regulate the expression of a battery of metabolic genes, especially those involved in lipid metabolism. LXRs have recently been suggested to play a novel role in the regulation of drug metabolism. The constitutive androstane receptor (CAR, NR1I3) is a xenobiotic receptor that regulates the expression of drug-metabolizing enzymes and transporters. Disruption of CAR alters sensitivity to toxins, increasing or decreasing it depending on the compounds. More recently, additional roles for CAR have been discovered. These include the involvement of CAR in lipid metabolism. Mechanistically, CAR forms an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the LXRs, in exerting its effect on lipid metabolism. Retinoid-related orphan receptors (RORs, NR1F1/2/3) have three isoforms, α, β and γ. Recent reports have shown that loss of RORα and/or RORγ can positively or negatively influence the expression of multiple drug-metabolizing enzymes and transporters in the liver. The effects of RORs on expression of drug-metabolizing enzymes were reasoned to be, at least in part, due to the crosstalk with LXR. This review focuses on the CAR-LXR and ROR-LXR crosstalk, and the implications of this crosstalk in drug metabolism and lipid metabolism.

  19. Digestible and indigestible carbohydrates: interactions with postprandial lipid metabolism.

    PubMed

    Lairon, Denis; Play, Barbara; Jourdheuil-Rahmani, Dominique

    2007-04-01

    The balance between fats and carbohydrates in the human diet is still a matter of very active debate. Indeed, the processing of ordinary mixed meals involves complex processes within the lumen of the upper digestive tract for digestion, in the small intestine mucosa for absorption and resecretion, and in peripheral tissues and in the circulation for final handling. The purpose of this review is to focus on available knowledge on the interactions of digestible or indigestible carbohydrates with lipid and lipoprotein metabolism in the postprandial state. The observations made in humans after test meals are reported and interpreted in the light of recent findings on the cellular and molecular levels regarding possible interplays between carbohydrates and lipid moieties in some metabolic pathways. Digestible carbohydrates, especially readily digestible starches or fructose, have been shown to exacerbate and/or delay postprandial lipemia, whereas some fiber sources can lower it. While interactions between dietary fibers and the process of lipid digestion and absorption have been studied mainly in the last decades, recent studies have shown that dietary carbohydrate moieties (e.g., glucose) can stimulate the intestinal uptake of cholesterol and lipid resecretion. In addition to the well-known glucose/fructose transporters, a number of transport proteins have recently been involved in intestinal lipid processing, whose implications in such interactions are discussed. The potential importance of postprandial insulinemia in these processes is also evaluated in the light of recent findings. The interactions of carbohydrates and lipid moieties in the postprandial state may result from both acute and chronic effects, both at transcriptional and posttranscriptional levels.

  20. FAT SIGNALS - Lipases and Lipolysis in Lipid Metabolism and Signaling

    PubMed Central

    Zechner, Rudolf; Zimmermann, Robert; Eichmann, Thomas O.; Kohlwein, Sepp D.; Haemmerle, Guenter; Lass, Achim; Madeo, Frank

    2012-01-01

    Lipolysis is defined as the catabolism of triacylglycerols stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed our perception of lipolysis and its impact on cellular metabolism. New findings that lipolytic products and intermediates participate in cellular signaling processes and that “lipolytic signaling” is particularly important in many nonadipose tissues unveil a previously underappreciated aspect of lipolysis, which may be relevant for human disease. PMID:22405066

  1. The central melanocortin system directly controls peripheral lipid metabolism

    PubMed Central

    Nogueiras, Ruben; Wiedmer, Petra; Perez-Tilve, Diego; Veyrat-Durebex, Christelle; Keogh, Julia M.; Sutton, Gregory M.; Pfluger, Paul T.; Castaneda, Tamara R.; Neschen, Susanne; Hofmann, Susanna M.; Howles, Philip N.; Morgan, Donald A.; Benoit, Stephen C.; Szanto, Ildiko; Schrott, Brigitte; Schürmann, Annette; Joost, Hans-Georg; Hammond, Craig; Hui, David Y.; Woods, Stephen C.; Rahmouni, Kamal; Butler, Andrew A.; Farooqi, I. Sadaf; O’Rahilly, Stephen; Rohner-Jeanrenaud, Françoise; Tschöp, Matthias H.

    2007-01-01

    Disruptions of the melanocortin signaling system have been linked to obesity. We investigated a possible role of the central nervous melanocortin system (CNS-Mcr) in the control of adiposity through effects on nutrient partitioning and cellular lipid metabolism independent of nutrient intake. We report that pharmacological inhibition of melanocortin receptors (Mcr) in rats and genetic disruption of Mc4r in mice directly and potently promoted lipid uptake, triglyceride synthesis, and fat accumulation in white adipose tissue (WAT), while increased CNS-Mcr signaling triggered lipid mobilization. These effects were independent of food intake and preceded changes in adiposity. In addition, decreased CNS-Mcr signaling promoted increased insulin sensitivity and glucose uptake in WAT while decreasing glucose utilization in muscle and brown adipose tissue. Such CNS control of peripheral nutrient partitioning depended on sympathetic nervous system function and was enhanced by synergistic effects on liver triglyceride synthesis. Our findings offer an explanation for enhanced adiposity resulting from decreased melanocortin signaling, even in the absence of hyperphagia, and are consistent with feeding-independent changes in substrate utilization as reflected by respiratory quotient, which is increased with chronic Mcr blockade in rodents and in humans with loss-of-function mutations in MC4R. We also reveal molecular underpinnings for direct control of the CNS-Mcr over lipid metabolism. These results suggest ways to design more efficient pharmacological methods for controlling adiposity. PMID:17885689

  2. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.

    PubMed

    Shimano, Hitoshi; Sato, Ryuichiro

    2017-08-29

    Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.

  3. Integration of Cytokine Biology and Lipid Metabolism in Stroke**

    PubMed Central

    Adibhatla, Rao Muralikrishna; Dempsey, R.; Hatcher, J. F.

    2007-01-01

    Cytokines regulate the innate and adaptive immune responses and are pleiotropic, redundant and multifunctional. Expression of most cytokines, including TNF-α and IL-1α/ß, is very low in normal brain. Metabolism of lipids is of particular interest due to their high concentration in the brain. Inflammatory response after stroke suggests that cytokines (TNF-α, IL-1 α/ß, IL-6), affect the phospholipid metabolism and subsequent production of eicosanoids, ceramide, and ROS that may potentiate brain injury. Phosphatidylcholine and sphingomyelin are source for lipid messengers. Sphingomyelin synthase serves as a bridge between metabolism of glycerolipids and sphingolipids. TNF-α and IL-1 α/ß can induce phospholipases (A2, C, and D) and sphingomyelinases, and concomitantly proteolyse phosphatidylcholine and sphingomyelin synthesizing enzymes. Together, these alterations contribute to loss of phosphatidylcholine and sphingomyelin after stroke that can be attenuated by inhibiting TNF-α or IL-1 α/ß signaling. Inflammatory responses are instrumental in the formation and destabilization of atherosclerotic plaques. Secretory PLA2 IIA is found in human atherosclerotic lesions and is implicated in initiation, progression and maturation of atherosclerosis, a risk factor for stroke. Lipoprotein-PLA2, part of apolipoprotein B-100 of LDL, plays a role in vascular inflammation and coronary endothelial dysfunction. Cytokine antagonism attenuated secretory PLA2 IIA actions, suggesting cytokine-lipid integration studies will lead to new concepts contributing to bench-to-bedside transition for stroke therapy. PMID:17981627

  4. Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.

    PubMed

    Park, Ju Yeon; Lee, Sang-Hak; Shin, Min-Jeong; Hwang, Geum-Sook

    2015-01-01

    Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.

  5. Metabolic map of osthole and its effect on lipids.

    PubMed

    Zhao, Qi; Li, Xin-Mei; Liu, Hong-Ning; Gonzalez, Frank J; Li, Fei

    2017-04-03

    1. Osthole, a coumarin compound from plants, is a promising agent for the treatment of metabolic diseases, including hyperglycemia, fatty liver, and cancers. Studies indicate that the peroxisome proliferator-activated receptors (PPAR) α and γ are involved in the pharmacological effects of osthole. The in vitro and in vivo metabolism of osthole and its biological activity are not completely understood. 2. In this study, ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics was used to determine the metabolic pathway of osthole and its influence on the levels of endogenous metabolites. Forty-one osthole metabolites, including 23 novel metabolites, were identified and structurally elucidated from its metabolism in vitro and in vivo. Recombinant cytochrome P450s (CYPs) screening showed that CYP3A4 and CYP3A5 were the primary enzymes contributing to osthole metabolism. 3. More importantly, osthole was able to decrease the levels of lysophosphatidylethanolamine (LPE) and lysophosphatidylcholine (LPC) in the plasma, which explains in part its modulatory effects on metabolic diseases. 4. This study gives the insights about the metabolic pathways of osthole in vivo, including hydroxylation, glucuronidation, and sulfation. Furthermore, the levels of the lipids regulated by osthole indicated its potential effects on adipogenesis. These data contribute to the understanding of the disposition and pharmacological activity of osthole in vivo.

  6. Monogenic hypocholesterolaemic lipid disorders and apolipoprotein B metabolism.

    PubMed

    Hooper, Amanda J; van Bockxmeer, Frank M; Burnett, John R

    2005-01-01

    The study of apolipoprotein (apo) B metabolism is central to our understanding of human lipoprotein metabolism. Moreover, the assembly and secretion of apoB-containing lipoproteins is a complex process. Increased plasma concentrations of apoB-containing lipoproteins are an important risk factor for the development of atherosclerotic coronary heart disease. In contrast, decreased levels of, but not the absence of, these apoB-containing lipoproteins is associated with resistance to atherosclerosis and potential long life. The study of inherited monogenic dyslipidaemias has been an effective means to elucidate key metabolic steps and biologically relevant mechanisms. Naturally occurring gene mutations in affected families have been useful in identifying important domains of apoB and microsomal triglyceride transfer protein (MTP) governing the metabolism of apoB-containing lipoproteins. Truncation-causing mutations in the APOB gene cause familial hypobetalipoproteinaemia, whereas mutations in MTP result in abetalipoproteinaemia; both rare conditions are characterised by marked hypocholesterolaemia. The purpose of this review is to examine the role of apoB in lipoprotein metabolism and to explore the key biochemical, clinical, metabolic and genetic features of the monogenic hypocholesterolaemic lipid disorders affecting apoB metabolism.

  7. Effects of intermittent fasting on glucose and lipid metabolism.

    PubMed

    Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

    2017-08-01

    Two intermittent fasting variants, intermittent energy restriction (IER) and time-restricted feeding (TRF), have received considerable interest as strategies for weight-management and/or improving metabolic health. With these strategies, the pattern of energy restriction and/or timing of food intake are altered so that individuals undergo frequently repeated periods of fasting. This review provides a commentary on the rodent and human literature, specifically focusing on the effects of IER and TRF on glucose and lipid metabolism. For IER, there is a growing evidence demonstrating its benefits on glucose and lipid homeostasis in the short-to-medium term; however, more long-term safety studies are required. Whilst the metabolic benefits of TRF appear quite profound in rodents, findings from the few human studies have been mixed. There is some suggestion that the metabolic changes elicited by these approaches can occur in the absence of energy restriction, and in the context of IER, may be distinct from those observed following similar weight-loss achieved via modest continuous energy restriction. Mechanistically, the frequently repeated prolonged fasting intervals may favour preferential reduction of ectopic fat, beneficially modulate aspects of adipose tissue physiology/morphology, and may also impinge on circadian clock regulation. However, mechanistic evidence is largely limited to findings from rodent studies, thus necessitating focused human studies, which also incorporate more dynamic assessments of glucose and lipid metabolism. Ultimately, much remains to be learned about intermittent fasting (in its various forms); however, the findings to date serve to highlight promising avenues for future research.

  8. Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges.

    PubMed

    Laforêt, Pascal; Vianey-Saban, Christine

    2010-11-01

    Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Systematic analysis of the regulatory functions of microRNAs in chicken hepatic lipid metabolism

    PubMed Central

    Li, Hong; Ma, Zheng; Jia, Lijuan; Li, Yanmin; Xu, Chunlin; Wang, Taian; Han, Ruili; Jiang, Ruirui; Li, Zhuanjian; Sun, Guirong; Kang, Xiangtao; Liu, Xiaojun

    2016-01-01

    Laying performance is an important economic trait in hens, and this physiological process is largely influenced by the liver function. The livers of hens at 20- and 30-week-old stages were investigated using the next generation sequencing to identify the differences of microRNA expression profiles. Compared with the 20-week-old hens, 67 down- and 13 up-regulated microRNAs were verified to be significant differentially expressed (false discovery rate, FDR ≤ 0.05) (SDE) in the 30-week-old. We also identified 13 down- and 6 up-regulated novel differentially expressed (DE) microRNAs. miR-22-3p and miR-146b-5p, which exhibit critical roles in mammalian lipid metabolism, showed the most abundant expression and the highest fold-change, respectively. A total of 648 potential target genes of the SDE microRNAs were identified through an integrated analysis of microRNAs and the DE genes obtained in previous RNA-sequencing, including FADS1, FADS2, ELOVL6 and ACSL5, which are critical lipid metabolism-related regulators. Bioinformatic analyses revealed that target genes were mainly enriched in lipid-related metabolism processes. This work provides the first study of the expression patterns of hepatic microRNAs between 20- and 30-week old hens. The findings may serve as a fundamental resource for understanding the detailed functions of microRNAs in the molecular regulatory systems of lipid metabolism. PMID:27535581

  10. Altered lipid metabolism in brain injury and disorders.

    PubMed

    Adibhatla, Rao Muralikrishna; Hatcher, J F

    2008-01-01

    Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice

  11. Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila

    PubMed Central

    Ishikawa, Zachary

    2017-01-01

    The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body. In a Drosophila genetic screen, we discovered that when haplo-insufficient, microsomal triglyceride transfer protein (mtp), required for the biosynthesis of apoB-lipoproteins, suppressed the development of diet-induced obesity. Tissue-specific inhibition of Mtp revealed that whereas knockdown of mtp only in the fat body decreases systemic triglyceride (TG) content on normal food diet (NFD) as expected, knockdown of mtp only in the cardiomyocytes also equally decreases systemic TG content on NFD, suggesting that the cardiomyocyte- and fat body-derived apoB-lipoproteins serve similarly important roles in regulating whole-body lipid metabolism. Unexpectedly, on high fat diet (HFD), knockdown of mtp in the cardiomyocytes, but not in fat body, protects against the gain in systemic TG levels. We further showed that inhibition of the Drosophila apoB homologue, apolipophorin or apoLpp, another gene essential for apoB-lipoprotein biosynthesis, affects systemic TG levels similarly to that of Mtp inhibition in the cardiomyocytes on NFD or HFD. Finally, we determined that HFD differentially alters Mtp and apoLpp expression in the cardiomyocytes versus the fat body, culminating in higher Mtp and apoLpp levels in the cardiomyocytes than in fat body and possibly underlying the predominant role of cardiomyocyte-derived apoB-lipoproteins in lipid metabolic regulation. Our findings reveal a novel and significant function of heart-mediated apoB-lipoproteins in controlling lipid homeostasis. PMID:28095410

  12. Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila.

    PubMed

    Lee, Sunji; Bao, Hong; Ishikawa, Zachary; Wang, Weidong; Lim, Hui-Ying

    2017-01-01

    The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body. In a Drosophila genetic screen, we discovered that when haplo-insufficient, microsomal triglyceride transfer protein (mtp), required for the biosynthesis of apoB-lipoproteins, suppressed the development of diet-induced obesity. Tissue-specific inhibition of Mtp revealed that whereas knockdown of mtp only in the fat body decreases systemic triglyceride (TG) content on normal food diet (NFD) as expected, knockdown of mtp only in the cardiomyocytes also equally decreases systemic TG content on NFD, suggesting that the cardiomyocyte- and fat body-derived apoB-lipoproteins serve similarly important roles in regulating whole-body lipid metabolism. Unexpectedly, on high fat diet (HFD), knockdown of mtp in the cardiomyocytes, but not in fat body, protects against the gain in systemic TG levels. We further showed that inhibition of the Drosophila apoB homologue, apolipophorin or apoLpp, another gene essential for apoB-lipoprotein biosynthesis, affects systemic TG levels similarly to that of Mtp inhibition in the cardiomyocytes on NFD or HFD. Finally, we determined that HFD differentially alters Mtp and apoLpp expression in the cardiomyocytes versus the fat body, culminating in higher Mtp and apoLpp levels in the cardiomyocytes than in fat body and possibly underlying the predominant role of cardiomyocyte-derived apoB-lipoproteins in lipid metabolic regulation. Our findings reveal a novel and significant function of heart-mediated apoB-lipoproteins in controlling lipid homeostasis.

  13. Differential roles of breakfast only (one meal per day) and a bigger breakfast with a small dinner (two meals per day) in mice fed a high-fat diet with regard to induced obesity and lipid metabolism

    PubMed Central

    2012-01-01

    Background Recent studies on humans and rodents have suggested that the timing of food intake plays an important role in circadian regulation and metabolic health. Consumption of high-fat foods during the inactive period or at the end of the awake period results in weight gain and metabolic syndrome in rodents. However, the distinct effects of breakfast size and the breakfast/dinner size ratio on metabolic health have not yet been fully examined in mice. Methods We examined whether the parameters of metabolic syndrome were differentially affected in mice that consumed a large meal at the beginning of the awake period (breakfast; one meal group) and a relatively smaller meal at end of the awake period (dinner; two meals group). The mice of each group were provided equal food volume per day. Results Mice on one meal exhibited an increase in body weight gain, hyperinsulinemia, hyperleptinemia, and a decrease of gene expression associated with β-oxidation in adipose tissue and liver compared with those on two meals. The circadian expression pattern of the Clock gene in mice on one meal was disturbed compared with those on two meals. Conclusions In conclusion, a bigger breakfast with a smaller dinner (two meals per day) but not breakfast only (one meal per day) helps control body weight and fat accumulation in mice on a high-fat meals schedule. The findings of this study suggest that dietary recommendations for weight reduction and/or maintenance should include information on the timing and quantity of dietary intake. PMID:22587351

  14. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    PubMed

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

  15. Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting

    PubMed Central

    Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/− mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting. PMID:25141153

  16. Consequences of lipid droplet coat protein downregulation in liver cells: abnormal lipid droplet metabolism and induction of insulin resistance.

    PubMed

    Bell, Ming; Wang, Hong; Chen, Hui; McLenithan, John C; Gong, Da-Wei; Yang, Rong-Zee; Yu, Daozhan; Fried, Susan K; Quon, Michael J; Londos, Constantine; Sztalryd, Carole

    2008-08-01

    Accumulation of intracellular lipid droplets (LDs) in non-adipose tissues is recognized as a strong prognostic factor for the development of insulin resistance in obesity. LDs are coated with perilipin, adipose differentiation-related protein, tail interacting protein of 47 kd (PAT) proteins that are thought to regulate LD turnover by modulating lipolysis. Our hypothesis is that PAT proteins modulate LD metabolism and therefore insulin resistance. We used a cell culture model (murine AML12 loaded with oleic acid) and small interfering RNA to directly assess the impact of PAT proteins on LD accumulation, lipid metabolism, and insulin action. PAT proteins associated with excess fat deposited in livers of diet-induced obese (DIO) mice were also measured. Cells lacking PAT proteins exhibited a dramatic increase in LD size and a decrease in LD number. Further, the lipolytic rate increased by approximately 2- to 2.5-fold in association with increased adipose triglyceride lipase (ATGL) at the LD surface. Downregulation of PAT proteins also produced insulin resistance, as indicated by decreased insulin stimulation of Akt phosphorylation (P < 0.001). Phosphoinositide-dependent kinase-1 and phosphoinositide 3-kinase decreased, and insulin receptor substrate-1 307 phosphorylation increased. Increased lipids in DIO mice livers were accompanied by changes in PAT composition but also increased ATGL, suggesting a relative PAT deficiency. These data establish an important role for PAT proteins as surfactant at the LD surface, packaging lipids in smaller units and restricting access of lipases and thus preventing insulin resistance. We suggest that a deficiency of PAT proteins relative to the quantity of ectopic fat could contribute to cellular dysfunction in obesity and type 2 diabetes.

  17. Dimethyl fumarate modulates antioxidant and lipid metabolism in oligodendrocytes.

    PubMed

    Huang, He; Taraboletti, Alexandra; Shriver, Leah P

    2015-08-01

    Oxidative stress contributes to pathology associated with inflammatory brain disorders and therapies that upregulate antioxidant pathways may be neuroprotective in diseases such as multiple sclerosis. Dimethyl fumarate, a small molecule therapeutic for multiple sclerosis, activates cellular antioxidant signaling pathways and may promote myelin preservation. However, it is still unclear what mechanisms may underlie this neuroprotection and whether dimethyl fumarate affects oligodendrocyte responses to oxidative stress. Here, we examine metabolic alterations in oligodendrocytes treated with dimethyl fumarate by using a global metabolomic platform that employs both hydrophilic interaction liquid chromatography-mass spectrometry and shotgun lipidomics. Prolonged treatment of oligodendrocytes with dimethyl fumarate induces changes in citric acid cycle intermediates, glutathione, and lipids, indicating that this compound can directly impact oligodendrocyte metabolism. These metabolic alterations are also associated with protection from oxidant challenge. This study provides insight into the mechanisms by which dimethyl fumarate could preserve myelin integrity in patients with multiple sclerosis.

  18. Effect of Eclipta prostrata on lipid metabolism in hyperlipidemic animals.

    PubMed

    Zhao, Yun; Peng, Lu; Lu, Wei; Wang, Yiqing; Huang, Xuefeng; Gong, Chen; He, Lin; Hong, Junhao; Wu, Songsong; Jin, Xin

    2015-02-01

    Eclipta prostrata (Linn.) Linn. is a traditional Chinese medicine and has previously been reported to have hypolipidemic effects. However, its mechanism of action is not well understood. This study was conducted to identify the active fraction of Eclipta, its toxicity, its effect on hyperlipidemia, and its mechanism of action. The ethanol extract (EP) of Eclipta and fractions EPF1-EPF4, obtained by eluting with different concentrations of ethanol from a HPD-450 macroporous resin column chromatography of the EP, were screened in hyperlipidemic mice for lipid-lowering activity, and EPF3 was the most active fraction. The LD50 of EPF3 was undetectable because no mice died with administration of EPF3 at 10.4 g/kg. Then, 48 male hamsters were used and randomly assigned to normal chow diet, high-fat diet, high-fat diet with Xuezhikang (positive control) or EPF3 (75, 150 and 250 mg/kg) groups. We evaluated the effects of EPF3 on body weight gain, liver weight gain, serum lipid concentration, antioxidant enzyme activity, and the expression of genes involved in lipid metabolism in hyperlipidemic hamsters. The results showed that EPF3 significantly decreased body-weight gain and liver-weight gain and reduced the serum lipid levels in hyperlipidemic hamsters. EPF3 also increased the activities of antioxidant enzymes; up-regulated the mRNA expression of peroxisome proliferator-activated receptor α (PPARα), low density lipoprotein receptor (LDLR), lecithin-cholesterol transferase (LCAT) and scavenger receptor class B type Ι receptor (SR-BI); and down-regulated the mRNA expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) in the liver. These results indicate that EPF3 ameliorates hyperlipidemia, in part, by reducing oxidative stress and modulating the transcription of genes involved in lipid metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Metabolism as a tool for understanding human brain evolution: lipid energy metabolism as an example.

    PubMed

    Wang, Shu Pei; Yang, Hao; Wu, Jiang Wei; Gauthier, Nicolas; Fukao, Toshiyuki; Mitchell, Grant A

    2014-12-01

    Genes and the environment both influence the metabolic processes that determine fitness. To illustrate the importance of metabolism for human brain evolution and health, we use the example of lipid energy metabolism, i.e. the use of fat (lipid) to produce energy and the advantages that this metabolic pathway provides for the brain during environmental energy shortage. We briefly describe some features of metabolism in ancestral organisms, which provided a molecular toolkit for later development. In modern humans, lipid energy metabolism is a regulated multi-organ pathway that links triglycerides in fat tissue to the mitochondria of many tissues including the brain. Three important control points are each suppressed by insulin. (1) Lipid reserves in adipose tissue are released by lipolysis during fasting and stress, producing fatty acids (FAs) which circulate in the blood and are taken up by cells. (2) FA oxidation. Mitochondrial entry is controlled by carnitine palmitoyl transferase 1 (CPT1). Inside the mitochondria, FAs undergo beta oxidation and energy production in the Krebs cycle and respiratory chain. (3) In liver mitochondria, the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) pathway produces ketone bodies for the brain and other organs. Unlike most tissues, the brain does not capture and metabolize circulating FAs for energy production. However, the brain can use ketone bodies for energy. We discuss two examples of genetic metabolic traits that may be advantageous under most conditions but deleterious in others. (1) A CPT1A variant prevalent in Inuit people may allow increased FA oxidation under nonfasting conditions but also predispose to hypoglycemic episodes. (2) The thrifty genotype theory, which holds that energy expenditure is efficient so as to maximize energy stores, predicts that these adaptations may enhance survival in periods of famine but predispose to obesity in modern dietary environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Lipid metabolism in Rhodnius prolixus: Lessons from the genome.

    PubMed

    Majerowicz, David; Calderón-Fernández, Gustavo M; Alves-Bezerra, Michele; De Paula, Iron F; Cardoso, Lívia S; Juárez, M Patricia; Atella, Georgia C; Gondim, Katia C

    2017-01-05

    The kissing bug Rhodnius prolixus is both an important vector of Chagas' disease and an interesting model for investigation into the field of physiology, including lipid metabolism. The publication of this insect genome will bring a huge amount of new molecular biology data to be used in future experiments. Although this work represents a promising scenario, a preliminary analysis of the sequence data is necessary to identify and annotate the genes involved in lipid metabolism. Here, we used bioinformatics tools and gene expression analysis to explore genes from different genes families and pathways, including genes for fat breakdown, as lipases and phospholipases, and enzymes from β-oxidation, fatty acid metabolism, and acyl-CoA and glycerolipid synthesis. The R. prolixus genome encodes 31 putative lipase genes, including 21 neutral lipases and 5 acid lipases. The expression profiles of some of these genes were analyzed. We were able to identify nine phospholipase A2 genes. A variety of gene families that participate in fatty acid synthesis and modification were studied, including fatty acid synthase, elongase, desaturase and reductase. Concerning the synthesis of glycerolipids, we found a second isoform of glycerol-3-phosphate acyltransferase that was ubiquitously expressed throughout the organs. Finally, all genes involved in fatty acid β-oxidation were identified, but not a long-chain acyl-CoA dehydrogenase. These results provide fundamental data to be used in future research on insect lipid metabolism and its possible relevance to Chagas' disease transmission. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The WWOX Gene Modulates HDL and Lipid Metabolism

    PubMed Central

    Iatan, Iulia; Choi, Hong Y.; Ruel, Isabelle; Linga Reddy, M.V. Prasad; Kil, Hyunsuk; Lee, Jaeho; Abu Odeh, Mohammad; Salah, Zaidoun; Abu-Remaileh, Muhannad; Weissglas-Volkov, Daphna; Nikkola, Elina; Civelek, Mete; Awan, Zuhier; Croce, Carlo M.; Aqeilan, Rami I.; Pajukanta, Päivi; Aldaz, C. Marcelo; Genest, Jacques

    2014-01-01

    Background Low high-density lipoprotein-cholesterol (HDL-C) constitutes a major risk factor for atherosclerosis. Recent studies from our group reported a genetic association between the WW domain-containing oxidoreductase (WWOX) gene and HDL-C levels. Here, through next-generation resequencing, in vivo functional studies and gene microarray analyses, we investigated the role of WWOX in HDL and lipid metabolism. Methods and Results Using next-generation resequencing of the WWOX region, we first identified 8 variants significantly associated and perfectly segregating with the low-HDL trait in two multi-generational French Canadian dyslipidemic families. To understand in vivo functions of WWOX, we used liver-specific Wwoxhep−/− and total Wwox−/− mice models, where we found decreased ApoA-I and ABCA1 levels in hepatic tissues. Analyses of lipoprotein profiles in Wwox−/−, but not Wwox hep−/− littermates, also showed marked reductions in serum HDL-C concentrations, concordant with the low-HDL findings observed in families. We next obtained evidence of a gender-specific effect in female Wwoxhep−/− mice, where an increase in plasma triglycerides and altered lipid metabolic pathways by microarray analyses were observed. We further identified a significant reduction in ApoA-I and LPL, and upregulation in Fas, Angptl4 and Lipg, suggesting that the effects of Wwox involve multiple pathways, including cholesterol homeostasis, ApoA-I/ABCA1 pathway, and fatty acid biosynthesis/triglyceride metabolism. Conclusions Our data indicate that WWOX disruption alters HDL and lipoprotein metabolism through several mechanisms and may account for the low-HDL phenotype observed in families expressing the WWOX variants. These findings thus describe a novel gene involved in cellular lipid homeostasis, which effects may impact atherosclerotic disease development. PMID:24871327

  2. siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle.

    PubMed

    Bouzakri, Karim; Zachrisson, Anna; Al-Khalili, Lubna; Zhang, Bei B; Koistinen, Heikki A; Krook, Anna; Zierath, Juleen R

    2006-07-01

    Type 2 diabetes is associated with defects in insulin signaling and the resulting abnormal glucose and lipid metabolism. The complexity of insulin signaling cascades is highlighted by the existence of multiple isoforms of target proteins implicated in metabolic and gene-regulatory events. We utilized siRNA to decipher the specific role of predominant insulin receptor substrates and Akt isoforms expressed in human skeletal muscle. Gene silencing revealed specialized roles of insulin signaling cascades to metabolic endpoints. IRS-1 and Akt2 were required for myoblast differentiation and glucose metabolism, whereas IRS-2 and Akt1 were dispensable. A key role of IRS-2 and Akt1 in lipid metabolism was revealed, highlighting reciprocal relationships between metabolic pathways. Unraveling the isoform-specific regulation of glucose and lipid metabolism by key elements along insulin signaling cascades through siRNA-mediated gene silencing in human tissues will facilitate the discovery of novel targets for the treatment of diabetes and related metabolic disorders.

  3. Plasma lipids, lipoprotein metabolism and HDL lipid transfers are equally altered in metabolic syndrome and in type 2 diabetes.

    PubMed

    Silva, Vanessa M; Vinagre, Carmen G C; Dallan, Luis A O; Chacra, Ana P M; Maranhão, Raul C

    2014-07-01

    Metabolic syndrome (MetS) refers to states of insulin resistance that predispose to development of cardiovascular disease and type 2 diabetes (T2DM). The aim was to investigate whether plasma lipids and lipid metabolism differ in MetS patients compared to those with T2DM with poor glycemic control (glycated hemoglobin > 7.0). Eighteen patients with T2DM, 18 with MetS and 14 controls, paired for age (40-70 years) and body mass index (BMI), were studied. Plasma lipids and the kinetics of a triacylglycerol-rich emulsion labeled with [(3)H]-triolein ([(3)H]-TAG) and [(14)C]-cholesteryl esters ([(14)C]-CE) injected intravenously followed by one-hour blood sampling were determined. Lipid transfers from an artificial nanoemulsion donor to high-density lipoprotien (HDL) were assayed in vitro. Low-density lipoprotein (LDL) and HDL cholesterol (mg/dl) were not different in T2DM (128 ± 7; 42 ± 7) and MetS (142 ± 6; 39 ± 3), but triacylglycerols were even higher in MetS (215 ± 13) than in T2DM (161 ±11, p < 0.05). Fractional clearance rate (FCR, in min(1)) of [(3)H]-TAG and [(14)C]-CE were equal in T2DM (0.008 ± 0.018; 0.005 ± 0.024) and MetS (0.010 ± 0.016; 0.006 ± 0.013), and both were reduced compared to controls. The transfer of non-esterified cholesterol, phospholipids and triacylglycerols to HDL was higher in MetS and T2DM than in controls (p < 0.01). Cholesteryl ester transfer and HDL size were equal in all groups. Results imply that MetS is equal to poorly controlled T2DM concerning the disturbances of plasma lipid metabolism examined here, and suggest that there are different thresholds for the insulin action on glucose and lipids. These findings highlight the magnitude of the lipid disturbances in MetS, and may have implications in the prevention of cardiovascular diseases.

  4. Metabolism in T cell activation and differentiation

    PubMed Central

    Pearce, Erika L

    2015-01-01

    When naïve or memory T cells encounter foreign antigen along with proper co-stimulation they undergo rapid and extensive clonal expansion. In mammals, this type of proliferation is fair1y unique to cells of the adaptive immune system and requires a considerable expenditure of energy and cellular resources. While research has often focused on the roles of cytokines, antigenic signals, and co-stimulation in guiding T cell responses, data indicate that, at a fundamental level, it is cellular metabolism that regulates T cell function and differentiation and therefore influences the final outcome of the adaptive immune response. This review will focus on some earlier fundamental observations regarding T cell bioenergetics and its role in regulating cellular function, as well as recent work that suggests that manipulating the immune response by targeting lymphocyte metabolism could prove useful in treatments against infection and cancer. PMID:20189791

  5. Lxr regulates lipid metabolic and visual perception pathways during zebrafish development.

    PubMed

    Pinto, Caroline Lucia; Kalasekar, Sharanya Maanasi; McCollum, Catherine W; Riu, Anne; Jonsson, Philip; Lopez, Justin; Swindell, Eric C; Bouhlatouf, Abdel; Balaguer, Patrick; Bondesson, Maria; Gustafsson, Jan-Åke

    2016-01-05

    The Liver X Receptors (LXRs) play important roles in multiple metabolic pathways, including fatty acid, cholesterol, carbohydrate and energy metabolism. To expand the knowledge of the functions of LXR signaling during embryonic development, we performed a whole-genome microarray analysis of Lxr target genes in zebrafish larvae treated with either one of the synthetic LXR ligands T0901317 or GW3965. Assessment of the biological processes enriched by differentially expressed genes revealed a prime role for Lxr in regulating lipid metabolic processes, similarly to the function of LXR in mammals. In addition, exposure to the Lxr ligands induced changes in expression of genes in the neural retina and lens of the zebrafish eye, including the photoreceptor guanylate cyclase activators and lens gamma crystallins, suggesting a potential novel role for Lxr in modulating the transcription of genes associated with visual function in zebrafish. The regulation of expression of metabolic genes was phenotypically reflected in an increased absorption of yolk in the zebrafish larvae, and changes in the expression of genes involved in visual perception were associated with morphological alterations in the retina and lens of the developing zebrafish eye. The regulation of expression of both lipid metabolic and eye specific genes was sustained in 1 month old fish. The transcriptional networks demonstrated several conserved effects of LXR activation between zebrafish and mammals, and also identified potential novel functions of Lxr, supporting zebrafish as a promising model for investigating the role of Lxr during development.

  6. Lxr regulates lipid metabolic and visual perception pathways during zebrafish development

    PubMed Central

    Pinto, Caroline Lucia; Kalasekar, Sharanya Maanasi; McCollum, Catherine W.; Riu, Anne; Jonsson, Philip; Lopez, Justin; Swindell, Eric; Bouhlatouf, Abdel; Balaguer, Patrick; Bondesson, Maria; Gustafsson, Jan-Åke

    2015-01-01

    The Liver X Receptors (LXRs) play important roles in multiple metabolic pathways, including fatty acid, cholesterol, carbohydrate and energy metabolism. To expand the knowledge of the functions of LXR signaling during embryonic development, we performed a whole-genome microarray analysis of Lxr target genes in zebrafish larvae treated with either one of the synthetic LXR ligands T0901317 or GW3965. Assessment of the biological processes enriched by differentially expressed genes revealed a prime role for Lxr in regulating lipid metabolic processes, similarly to the function of LXR in mammals. In addition, exposure to the Lxr ligands induced changes in expression of genes in the neural retina and lens of the zebrafish eye, including the photoreceptor guanylate cyclase activators and lens gamma crystallins, suggesting a potential novel role for Lxr in modulating the transcription of genes associated with visual function in zebrafish. The regulation of expression of metabolic genes was phenotypically reflected in an increased absorption of yolk in the zebrafish larvae, and changes in the expression of genes involved in visual perception were associated with morphological alterations in the retina and lens of the developing zebrafish eye. The regulation of expression of both lipid metabolic and eye specific genes was sustained in 1 month old fish. The transcriptional networks demonstrated several conserved effects of LXR activation between zebrafish and mammals, and also identified potential novel functions of Lxr, supporting zebrafish as a promising model for investigating the role of Lxr during development. PMID:26427652

  7. Strategies towards Improved Feed Efficiency in Pigs Comprise Molecular Shifts in Hepatic Lipid and Carbohydrate Metabolism

    PubMed Central

    Reyer, Henry; Oster, Michael; Magowan, Elizabeth; Dannenberger, Dirk; Ponsuksili, Siriluck

    2017-01-01

    Due to the central role of liver tissue in partitioning and metabolizing of nutrients, molecular liver-specific alterations are of considerable interest to characterize an efficient conversion and usage of feed in livestock. To deduce tissue-specific and systemic effects on nutrient metabolism and feed efficiency (FE) twenty-four animals with extreme phenotypes regarding residual feed intake (RFI) were analyzed. Transcriptome and fatty acid profiles of liver tissue were complemented with measurements on blood parameters and thyroid hormone levels. Based on 803 differentially-abundant probe sets between low- and high-FE animals, canonical pathways like integrin signaling and lipid and carbohydrate metabolism, were shown to be affected. Molecular alterations of lipid metabolism show a pattern of a reduced hepatic usage of fatty acids in high-FE animals. Complementary analyses at the systemic level exclusively pointed to increased circulating triglycerides which were, however, accompanied by considerably lower concentrations of saturated and polyunsaturated fatty acids in the liver of high-FE pigs. These results are in accordance with altered muscle-to-fat ratios usually ascribed to FE animals. It is concluded that strategies to improve FE might favor a metabolic shift from energy storage towards energy utilization and mobilization. PMID:28763040

  8. MRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas.

    PubMed

    Castelli, Martina Galatea; Rusten, Marte; Goksøyr, Anders; Routti, Heli

    2014-01-01

    There is a growing concern about the ability of persistent organic pollutants (POPs) to influence lipid metabolism. Although POPs are found at high concentrations in some populations of marine mammals, for example in the ringed seal (Pusa hispida) from the Baltic Sea, little is known about the effects of POPs on their lipid metabolism. An optimal regulation of lipid metabolism is crucial for ringed seals during the fasting/molting season. This is a physiologically stressful period, during which they rely on the energy stored in their fat reserves. The mRNA expression levels for seven genes involved in lipid metabolism were analyzed in liver and/or blubber tissue from molting ringed seals from the polluted Baltic Sea and a less polluted reference location, Svalbard (Norway). mRNA expression of genes encoding peroxisome proliferator-activated receptors (PPAR) α and γ and their target genes acyl-coenzyme A oxidase 1 (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA expression level of genes encoding PPARβ, PPARγ and their target genes encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were measured in inner and middle blubber layers. In addition, we evaluated the influence of molting status on hepatic mRNA expression of genes encoding PPARs and their target genes in ringed seals from Svalbard. Our results show higher mRNA expression of genes encoding hepatic PPARγ and adipose PPARβ, FABP4, and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive relationship between mRNA expressions of genes encoding hepatic PPARγ, adipose FABP4, adipose ADIPOQ and ΣPOP concentrations was observed. These findings suggest that lipid metabolism may be affected by contaminant exposure in the Baltic population. mRNA expression of genes encoding PPARβ, PPARγ, FABP4 and ADIPOQ were similar between the mid and inner adipose layer. Hepatic mRNA expression of genes encoding PPARα and PPARγ was higher in the pre

  9. Alterations in Lipid Metabolism and Antioxidant Status in Lichen Planus

    PubMed Central

    Panchal, Falguni H; Ray, Somshukla; Munshi, Renuka P; Bhalerao, Supriya S; Nayak, Chitra S

    2015-01-01

    Background: Lichen planus (LP), a T-cell-mediated inflammatory disorder, wherein inflammation produces lipid metabolism disturbances, is linked to increase in cardiovascular (CV) risk with dyslipidemia. Increased reactive oxygen species and lipid peroxides have also been implicated in its pathogenesis. Aim and Objective: The aim of the study was to evaluate the status on lipid disturbances, oxidative stress, and inflammation in LP patients. Materials and Methods: The study was initiated after obtaining Institutional Ethics Committee permission and written informed consent from participants. The study included 125 patients (74 LP patients and 51 age and sex-matched controls) visiting the outpatient clinic in the dermatology department of our hospital. Variables analyzed included lipid profile, C-reactive protein (CRP), malondialdehyde (MDA), and catalase (CAT) activity. Results: Analysis of lipid parameters revealed significantly higher levels of total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C) along with decreased levels of high-density lipoprotein cholesterol (HDL-C) in LP patients as compared to their respective controls. LP patients also presented with a significantly higher atherogenic index that is, (TC/HDL-C) and LDL-C/HDL-C ratios than the controls. A significant increase in CRP levels was observed among the LP patients. There was a statistically significant increase in the serum levels of the lipid peroxidation product, MDA and a statistically significant decrease in CAT activity in LP patients as compared to their respective controls. A statistically significant positive correlation (r = 0.96) was observed between serum MDA levels and duration of LP whereas a significantly negative correlation (r = −0.76) was seen between CAT activity and LP duration. Conclusion: Chronic inflammation in patients with LP may explain the association with dyslipidemia and CV risk. Our findings also suggest that an increase in oxidative

  10. Viperin Regulates Cellular Lipid Metabolism during Human Cytomegalovirus Infection

    PubMed Central

    Seo, Jun-Young; Cresswell, Peter

    2013-01-01

    Human cytomegalovirus (HCMV) has been shown to induce increased lipogenesis in infected cells, and this is believed to be required for proper virion envelopment. We show here that this increase is a consequence of the virus-induced redistribution of the host protein viperin to mitochondria and its capacity to interact with and block the function of the mitochondrial trifunctional protein (TFP), the enzyme that mediates fatty acid-β-oxidation. The resulting decrease in cellular ATP levels activates the enzyme AMP-activated protein kinase (AMPK), which induces expression of the glucose transporter GLUT4, resulting in increased glucose import and translocation to the nucleus of the glucose-regulated transcription factor ChREBP. This induces increased transcription of genes encoding lipogenic enzymes, increased lipid synthesis and lipid droplet accumulation, and generation of the viral envelope. Viperin-dependent lipogenesis is required for optimal production of infectious virus. We show that all of these metabolic outcomes can be replicated by direct targeting of viperin to mitochondria in the absence of HCMV infection, and that the motif responsible for Fe-S cluster binding by viperin is essential. The data indicate that viperin is the major effector underlying the ability of HCMV to regulate cellular lipid metabolism. PMID:23935494

  11. Associations between lipid metabolism and fertility in the dairy cow.

    PubMed

    Wathes, D Claire; Clempson, Andrew M; Pollott, Geoff E

    2012-01-01

    Dairy cows mobilise body tissues to support milk production and, because glucose supplies are limited, lipids are used preferentially for energy production. Lipogenic activity is switched off and lipolytic mechanisms in adipose tissue increase through changes in the expression of several key enzymes. This results in a loss of body condition, together with high circulating concentrations of non-esterified fatty acids. Changes in the synthesis, secretion and signalling pathways of somatotrophic hormones (insulin, growth hormone, insulin-like growth factor 1) and adipokines (e.g. leptin) are central to the regulation of these processes. A high reliance on fatty acids as an energy source in the peripartum period causes oxidative damage to mitochondria in metabolically active tissues, including the liver and reproductive tract. The expression of genes involved in insulin resistance (PDK4, AHSG) is increased, together with expression of TIEG1, a transcription factor that can induce apoptosis via the mitochondrial pathway. Polymorphisms in TFAM and UCP2, two autosomal mitochondrial genes, have been associated with longevity in dairy cows. Polymorphisms in many other genes that affect lipid metabolism also show some associations with fertility traits. These include DGAT1, SCD1, DECR1, CRH, CBFA2T1, GH, LEP and NPY. Excess lipid accumulation in oocytes and the regenerating endometrium reduces fertility via reductions in embryo survival and increased inflammatory changes, respectively.

  12. Role of TG-interacting factor (Tgif) in lipid metabolism.

    PubMed

    Pramfalk, Camilla; Eriksson, Mats; Parini, Paolo

    2015-01-01

    TG interacting factors (Tgifs) 1 and 2 are members of the TALE (three-amino-acid loop extension) superfamily of homeodomain proteins. These two proteins bind to the same DNA sequence and share a conserved C-terminal repression domain. Mutations in TGIF1 have been linked to holoprosencephaly, which is a human genetic disease that affects craniofacial development. As these proteins can interact with the ligand binding domain of retinoid X receptor α, a common heterodimeric partner of several nuclear receptors [e.g., liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs)], Tgif1 and Tgif2 might repress other transcriptional pathways activated by lipids. In line with this, Tgif1 interacts with LXRα and Tgif1 null mice have increased expression of the two Lxrα target genes apolipoproteins (Apo) c2 and a4. Also, we have recently identified Tgif1 to function as a transcriptional repressor of the cholesterol esterifying enzyme acyl-coenzyme A:cholesterol acyltransferase 2 (gene name SOAT2). As no studies yet have shown involvement of Tgif2 in the lipid metabolism, this review will focus on the role of Tgif1 in lipid and cholesterol metabolism. This article is part of a Special Issue entitled: Linking transcription to physiology in lipodomics. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Aspergillus awamori Feeding Modifies Lipid Metabolism in Rats

    PubMed Central

    Saleh, Ahmed A.; Ohtsuka, Akira; Yamamoto, Masahiro; Hayashi, Kunioki

    2013-01-01

    In the present study, an experiment was conducted to show that A. awamori modifies lipid metabolism in mammals. A total number of 24 rats at 6 weeks of age were divided into 2 groups (10% and 30% fat dietary groups), and each group was further divided into control and experimental groups (6 rats per group). Rats in the experimental groups were given diets containing 0.05% A. awamori. The diets were administered for 3 weeks to evaluate the effects of A. awamori on growth, plasma lipid profile, and the expressions of genes related to lipid metabolism in the liver. After the rats were fed A. awamori, body weight gain was increased, while food intake was decreased; therefore, food efficiency was increased in both A. awamori groups. Plasma triglycerides, LDL cholesterol, and glucose levels were decreased, but plasma HDL cholesterol levels were increased. Furthermore, saturated fatty acids were decreased while; unsaturated fatty acids were increased in the liver. The liver mRNA levels of FAS, ACC, delta-6-desaturase, and HMG-CoA reductase were increased, while the mRNA level of LDL receptor was decreased. From these data, it is proposed that A. awamori could be used as an effective probiotic to prevent lifestyle-related diseases in humans. PMID:23841078

  14. Lipid metabolism, adipocyte depot physiology and utilization of meat animals as experimental models for metabolic research

    USDA-ARS?s Scientific Manuscript database

    Meat animals are unique as experimental models for both lipid metabolism and adipocyte studies because of their direct economic value for animal production. This paper discusses the principles that regulate adipogenesis in major meat animals (beef cattle, dairy cattle, and pigs), the definition of a...

  15. Simulated microgravity enhances oligodendrocyte mitochondrial function and lipid metabolism.

    PubMed

    Espinosa-Jeffrey, Araceli; Nguyen, Kevin; Kumar, Shalini; Toshimasa, Ochiai; Hirose, Ryuji; Reue, Karen; Vergnes, Laurent; Kinchen, Jason; Vellis, Jean de

    2016-12-01

    The primary energy sources of mammalian cells are proteins, fats, and sugars that are processed by well-known biochemical mechanisms that have been discovered and studied in 1G (terrestrial gravity). Here we sought to determine how simulated microgravity (sim-µG) impacts both energy and lipid metabolism in oligodendrocytes (OLs), the myelin-forming cells in the central nervous system. We report increased mitochondrial respiration and increased glycolysis 24 hr after exposure to sim-µG. Moreover, examination of the secretome after 3 days' exposure of OLs to sim-µG increased the Krebs cycle (Krebs and Weitzman, ) flux in sim-µG. The secretome study also revealed a significant increase in the synthesis of fatty acids and complex lipids such as 1,2-dipalmitoyl-GPC (5.67); lysolipids like 1-oleoyl-GPE (4.48) were also increased by microgravity. Although longer-chain lipids were not observed in this study, it is possible that at longer time points OLs would have continued moving forward toward the synthesis of lipids that constitute myelin. For centuries, basic developmental biology research has been the pillar of an array of discoveries that have led to clinical applications; we believe that studies using microgravity will open new avenues to our understanding of the brain in health and disease-in particular, to the discovery of new molecules and mechanisms impossible to unveil while in 1G. © 2016 Wiley Periodicals, Inc.

  16. Separation and Classification of Lipids Using Differential Ion Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Shvartsburg, Alexandre A.; Isaac, Giorgis; Leveque, Nathalie; Smith, Richard D.; Metz, Thomas O.

    2011-07-01

    Correlations between the dimensions of a 2-D separation create trend lines that depend on structural or chemical characteristics of the compound class and thus facilitate classification of unknowns. This broadly applies to conventional ion mobility spectrometry (IMS)/mass spectrometry (MS), where the major biomolecular classes (e.g., lipids, peptides, nucleotides) occupy different trend line domains. However, strong correlation between the IMS and MS separations for ions of same charge has impeded finer distinctions. Differential IMS (or FAIMS) is generally less correlated to MS and thus could separate those domains better. We report the first observation of chemical class separation by trend lines using FAIMS, here for lipids. For lipids, FAIMS is indeed more independent of MS than conventional IMS, and subclasses (such as phospho-, glycero-, or sphingolipids) form distinct, often non-overlapping domains. Even finer categories with different functional groups or degrees of unsaturation are often separated. As expected, resolution improves in He-rich gases: at 70% He, glycerolipid isomers with different fatty acid positions can be resolved. These results open the door for application of FAIMS to lipids, particularly in shotgun lipidomics and targeted analyses of bioactive lipids.

  17. Differential Effect of Plant Lipids on Membrane Organization

    PubMed Central

    Grosjean, Kevin; Mongrand, Sébastien; Beney, Laurent; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

    2015-01-01

    The high diversity of the plant lipid mixture raises the question of their respective involvement in the definition of membrane organization. This is particularly the case for plant plasma membrane, which is enriched in specific lipids, such as free and conjugated forms of phytosterols and typical phytosphingolipids, such as glycosylinositolphosphoceramides. This question was here addressed extensively by characterizing the order level of membrane from vesicles prepared using various plant lipid mixtures and labeled with an environment-sensitive probe. Fluorescence spectroscopy experiments showed that among major phytosterols, campesterol exhibits a stronger ability than β-sitosterol and stigmasterol to order model membranes. Multispectral confocal microscopy, allowing spatial analysis of membrane organization, demonstrated accordingly the strong ability of campesterol to promote ordered domain formation and to organize their spatial distribution at the membrane surface. Conjugated sterol forms, alone and in synergy with free sterols, exhibit a striking ability to order membrane. Plant sphingolipids, particularly glycosylinositolphosphoceramides, enhanced the sterol-induced ordering effect, emphasizing the formation and increasing the size of sterol-dependent ordered domains. Altogether, our results support a differential involvement of free and conjugated phytosterols in the formation of ordered domains and suggest that the diversity of plant lipids, allowing various local combinations of lipid species, could be a major contributor to membrane organization in particular through the formation of sphingolipid-sterol interacting domains. PMID:25575593

  18. Rebamipide ameliorates atherosclerosis by controlling lipid metabolism and inflammation

    PubMed Central

    Jeong, Jeong-Hee; Na, Hyun Sik; Kim, Eun-Kyung; Lee, Seung Hoon; Jung, KyungAh; Min, Jun-Ki; Cho, Mi-La

    2017-01-01

    Atherosclerosis is a chronic inflammatory disease caused by the accumulation of excess lipid in the aorta and the severity is regulated by T lymphocytes subsets. Rebamipide has therapeutic activity in collagen induced arthritis (CIA) by controlling the balance between T helper (Th) 17 and regulatory T (Treg) cells. In this study, we aimed to determine whether rebamipide reduces the development of atherosclerosis. To investigate the therapeutic effect of rebamipide, ApoE-KO mice fed a western diet were administered rebamipide orally for 8 weeks. Mice were sacrificed followed by the evaluation of plaque formation in the aorta or immunohistochemistry for IL-17 and Foxp3. Serum was also prepared to determine the pro-inflammatory cytokine levels. The ability of rebamipide to regulate lipid metabolism or inflammation was confirmed ex vivo. Results The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases. PMID:28241014

  19. [Lipid metabolism of caddisfly larvae at low pH].

    PubMed

    Regerand, T I; Nefedova, Z A; Toĭvonen, L T; Dubrovina, L V; Vuory, K-M; Markova, L V; Ruokolaĭnen, T R

    2002-01-01

    The influence of low pH (5.0 and 4.0) on lipid metabolism of caddisworms Hydropsyche contubernalis L. (Trichoptera) was studied in 48 h toxicity experiments. The results were correlated with lipid composition of caddisworms directly isolated from natural water. Phospholipids, cholesterol, mono-, di-, triacylglycerols, and fatty acids were detected by thin-layer and liquid chromatography. Minimal environmental changes were shown to initiate the biochemical adaptation mechanisms strengthening the cellular membranes through their condensation due to additional phospholipid and cholesterol synthesis. In the natural medium the adaptation processes are more active than in the artificial medium. More serious changes, such as pH decrease to 4.0, suppress the adaptation processes in the first medium and terminated them in the second one.

  20. Roles of phosphatidate phosphatase enzymes in lipid metabolism

    PubMed Central

    Carman, George M.; Han, Gil-Soo

    2006-01-01

    Phosphatidate phosphatase (PAP) enzymes catalyze the dephosphorylation of phosphatidate, yielding diacylglycerol and inorganic phosphate. In eukaryotic cells, PAP activity has a central role in the synthesis of phospholipids and triacylglycerol through its product diacylglycerol, and it also generates and/or degrades lipid-signaling molecules that are related to phosphatidate. There are two types of PAP enzyme, Mg2+ dependent (PAP1) and Mg2+ independent (PAP2), but only genes encoding PAP2 enzymes had been identified until recently, when a gene (PAH1) encoding a PAP1 enzyme was found in Saccharomyces cerevisiae. This discovery has revealed a molecular function of the mammalian protein lipin, a deficiency of which causes lipodystrophy in mice. With molecular information now available for both types of PAP, the specific roles of these enzymes in lipid metabolism are being clarified. PMID:17079146

  1. Maternal chromium restriction modulates miRNA profiles related to lipid metabolism disorder in mice offspring.

    PubMed

    Zhang, Qian; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-08-01

    Increasing evidence shows that maternal nutrition status has a vital effect on offspring susceptibility to obesity. MicroRNAs are related to lipid metabolism processes. This study aimed to evaluate whether maternal chromium restriction could affect miRNA expression involved in lipid metabolism in offspring. Weaning C57BL/6J mice born from mothers fed with normal control diet or chromium-restricted diet were fed for 13 weeks. The adipose miRNA expression profile was analyzed by miRNA array analysis. At 16 weeks old, pups from dams fed with chromium-restricted diet exhibit higher body weight, fat weight, and serum TC, TG levels. Six miRNAs were identified as upregulated in the RC group compared with the CC group, whereas eight miRNAs were lower than the threshold level set in the RC group. In the validated target genes of these differentially expressed miRNA, the MAPK signaling pathway serves an important role in the influence of early life chromium-restricted diet on lipid metabolism through miRNA. Long-term programming on various specific miRNA and MAPK signaling pathway may be involved in maternal chromium restriction in the adipose of female offspring. Impact statement For the first time, our study demonstrates important miRNA differences in the effect of maternal chromium restriction in offspring. These miRNAs may serve as "bridges" between the mother and the offspring by affecting the MAPK pathway.

  2. Effects of aqueous extract of Arctium lappa L. roots on serum lipid metabolism.

    PubMed

    Hou, Bo; Wang, Wencheng; Gao, Hui; Cai, Shanglang; Wang, Chunbo

    2017-01-01

    Objective To identify potential genes that may be involved in lipid metabolism in rats after treatment with aqueous extract of Arctium lappa L (burdock). Methods Rats were randomly divided into six groups: (i) control (standard diet); (ii) model group (high-fat diet only); (iii) high-fat diet and low-dose aqueous burdock root extract (2 g/kg); (iv) high-fat diet and moderate-dose aqueous burdock root extract (4 g/kg); (v) high-fat diet and high-dose aqueous burdock root extract (8 g/kg); and (vi) a positive control group exposed to a high-fat diet and simvastatin (10 mg/kg). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to find the potential candidate genes involved in the modulation of blood lipids by treatment with aqueous burdock root extract. Results Burdock root extract reduced body weight and cholesterol levels in rats. KEGG analysis revealed 113 genes that were involved in metabolic pathways. Of these, 27 potential genes associated with blood lipid metabolism were identified. Conclusions Aqueous extract of burdock root reduced body weight and cholesterol in rats, possibly by modulating the differential expression of genes.

  3. Korean pine nut oil replacement decreases intestinal lipid uptake while improves hepatic lipid metabolism in mice

    PubMed Central

    Zhu, Shuang; Park, Soyoung; Lim, Yeseo; Shin, Sunhye

    2016-01-01

    BACKGROUND/OBJECTIVES Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS In intestine, significantly lower Cd36 mRNA expression (P < 0.05) and a tendency of lower ApoA4 mRNA levels (P = 0.07) was observed in PNO-fed mice, indicating that PNO consumption may decrease intestinal FA uptake and chylomicron assembly. PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P = 0.08) and Cpt1a (P = 0.05). Significantly higher hepatic mRNA levels of Acadl and ApoB100 were detected in mice fed PNO diet (P < 0.05). These results suggest that PNO could increase hepatic TAG metabolism; mitochondrial fatty acid oxidation and VLDL assembly. CONCLUSIONS PNO replacement in the diet might function in prevention of excessive lipid uptake by intestine and improve hepatic lipid metabolism in both control diet and HFD fed mice. PMID:27698954

  4. Analysis of miRNAs and their target genes associated with lipid metabolism in duck liver

    PubMed Central

    He, Jun; Wang, Weiqun; Lu, Lizhi; Tian, Yong; Niu, Dong; Ren, Jindong; Dong, Liyan; Sun, Siwei; Zhao, Yan; Chen, Li; Shen, Jianliang; Li, Xiuhong

    2016-01-01

    Fat character is an important index in duck culture that linked to local flavor, feed cost and fat intake for costumers. Since the regulation networks in duck lipid metabolism had not been reported very clearly, we aimed to explore the potential miRNA-mRNA pairs and their regulatory roles in duck lipid metabolism. Here, Cherry-Valley ducks were selected and treated with/without 5% oil added in feed for 2 weeks, and then fat content determination was performed on. The data showed that the fat contents and the fatty acid ratios of C17:1 and C18:2 were up-regulated in livers of oil-added ducks, while the C12:0 ratio was down-regulated. Then 21 differential miRNAs, including 10 novel miRNAs, were obtain from the livers by sequencing, and 73 target genes involved in lipid metabolic processes of these miRNAs were found, which constituted 316 miRNA-mRNA pairs. Two miRNA-mRNA pairs including one novel miRNA and one known miRNA, N-miR-16020-FASN and gga-miR-144-ELOVL6, were selected to validate the miRNA-mRNA negative relation. And the results showed that N-mir-16020 and gga-miR-144 could respectively bind the 3′-UTRs of FASN and ELOVL6 to control their expressions. This study provides new sights and useful information for future research on regulation network in duck lipid metabolism. PMID:27272010

  5. Analysis of miRNAs and their target genes associated with lipid metabolism in duck liver.

    PubMed

    He, Jun; Wang, Weiqun; Lu, Lizhi; Tian, Yong; Niu, Dong; Ren, Jindong; Dong, Liyan; Sun, Siwei; Zhao, Yan; Chen, Li; Shen, Jianliang; Li, Xiuhong

    2016-06-08

    Fat character is an important index in duck culture that linked to local flavor, feed cost and fat intake for costumers. Since the regulation networks in duck lipid metabolism had not been reported very clearly, we aimed to explore the potential miRNA-mRNA pairs and their regulatory roles in duck lipid metabolism. Here, Cherry-Valley ducks were selected and treated with/without 5% oil added in feed for 2 weeks, and then fat content determination was performed on. The data showed that the fat contents and the fatty acid ratios of C17:1 and C18:2 were up-regulated in livers of oil-added ducks, while the C12:0 ratio was down-regulated. Then 21 differential miRNAs, including 10 novel miRNAs, were obtain from the livers by sequencing, and 73 target genes involved in lipid metabolic processes of these miRNAs were found, which constituted 316 miRNA-mRNA pairs. Two miRNA-mRNA pairs including one novel miRNA and one known miRNA, N-miR-16020-FASN and gga-miR-144-ELOVL6, were selected to validate the miRNA-mRNA negative relation. And the results showed that N-mir-16020 and gga-miR-144 could respectively bind the 3'-UTRs of FASN and ELOVL6 to control their expressions. This study provides new sights and useful information for future research on regulation network in duck lipid metabolism.

  6. The Action of D-Dopachrome Tautomerase as an Adipokine in Adipocyte Lipid Metabolism

    PubMed Central

    Iwata, Takeo; Taniguchi, Hisaaki; Kuwajima, Masamichi; Taniguchi, Takako; Okuda, Yuko; Sukeno, Akiko; Ishimoto, Kyoko; Mizusawa, Noriko; Yoshimoto, Katsuhiko

    2012-01-01

    Adipose tissue is a critical exchange center for complex energy transactions involving triacylglycerol storage and release. It also has an active endocrine role, releasing various adipose-derived cytokines (adipokines) that participate in complex pathways to maintain metabolic and vascular health. Here, we found D-dopachrome tautomerase (DDT) as an adipokine secreted from human adipocytes by a proteomic approach. DDT mRNA levels in human adipocytes were negatively correlated with obesity-related clinical parameters such as BMI, and visceral and subcutaneous fat areas. Experiments using SGBS cells, a human preadipocyte cell line, revealed that DDT mRNA levels were increased in an adipocyte differentiation-dependent manner and DDT was secreted from adipocytes. In DDT knockdown adipocytes differentiated from SGBS cells that were infected with the adenovirus expressing shRNA against the DDT gene, mRNA levels of genes involved in both lipolysis and lipogenesis were slightly but significantly increased. Furthermore, we investigated AMP-activated protein kinase (AMPK) signaling, which phosphorylates and inactivates enzymes involved in lipid metabolism, including hormone-sensitive lipase (HSL) and acetyl-CoA carboxylase (ACC), in DDT knockdown adipocytes. The AMPK phosphorylation of HSL Ser-565 and ACC Ser-79 was inhibited in DDT knockdown cells and recovered in the cells treated with recombinant DDT (rDDT), suggesting that down-regulated DDT in adipocytes brings about a state of active lipid metabolism. Furthermore, administration of rDDT in db/db mice improved glucose intolerance and decreased serum free fatty acids levels. In the adipose tissue from rDDT-treated db/db mice, not only increased levels of HSL phosphorylated by AMPK, but also decreased levels of HSL phosphorylated by protein kinase A (PKA), which phosphorylates HSL to promote its activity, were observed. These results suggested that DDT acts on adipocytes to regulate lipid metabolism through AMPK and/or PKA

  7. Metabolic positron emission tomography imaging of cancer: Pairing lipid metabolism with glycolysis

    PubMed Central

    Kwee, Sandi A; Lim, John

    2016-01-01

    The limitations of fluorine-18 fluorodeoxy-D-glucose (FDG) in detecting some cancers has prompted a longstanding search for other positron emission tomography (PET) tracers to complement the imaging of glycolysis in oncology, with much attention paid to lipogenesis based on observations that the production of various lipid and lipid-containing compounds is increased in most cancers. Radiolabeled analogs of choline and acetate have now been used as oncologic PET probes for over a decade, showing convincingly improved detection sensitivity over FDG for certain cancers. However, neither choline nor acetate have been thoroughly validated as lipogenic biomarkers, and while acetyl-CoA produced from acetate is used in de-novo lipogenesis to synthesize fatty acids, acetate is also consumed by various other synthetic and metabolic pathways, with recent experimental observations challenging the assumption that lipogenesis is its predominant role in all cancers. Since tumors detected by acetate PET are also frequently detected by choline PET, imaging of choline metabolism might serve as an alternative albeit indirect marker of lipogenesis, particularly if the fatty acids produced in cancer cells are mainly destined for membrane synthesis through incorporation into phosphatidylcholines. Aerobic glycolysis may or may not coincide with changes in lipid metabolism, resulting in combinatorial metabolic phenotypes that may have different prognostic or therapeutic implications. Consequently, PET imaging using dual metabolic tracers, in addition to being diagnostically superior to imaging with individual tracers, could eventually play a greater role in supporting precision medicine, as efforts to develop small-molecule metabolic pathway inhibitors are coming to fruition. To prepare for this advent, clinical and translational studies of metabolic PET tracers must go beyond simply estimating tracer diagnostic utility, and aim to uncover potential therapeutic avenues associated with

  8. Elevated host lipid metabolism revealed by iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid of tuberculous meningitis patients

    SciTech Connect

    Mu, Jun; Yang, Yongtao; Chen, Jin; Cheng, Ke; Li, Qi; Wei, Yongdong; Zhu, Dan; Shao, Weihua; Zheng, Peng; Xie, Peng

    2015-10-30

    Purpose: Tuberculous meningitis (TBM) remains to be one of the most deadly infectious diseases. The pathogen interacts with the host immune system, the process of which is largely unknown. Various cellular processes of Mycobacterium tuberculosis (MTB) centers around lipid metabolism. To determine the lipid metabolism related proteins, a quantitative proteomic study was performed here to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n = 12) and healthy controls (n = 12). Methods: CSF samples were desalted, concentrated, labelled with isobaric tags for relative and absolute quantitation (iTRAQ™), and analyzed by multi-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene ontology and proteomic phenotyping analysis of the differential proteins were conducted using Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. ApoE and ApoB were selected for validation by ELISA. Results: Proteomic phenotyping of the 4 differential proteins was invloved in the lipid metabolism. ELISA showed significantly increased ApoB levels in TBM subjects compared to healthy controls. Area under the receiver operating characteristic curve analysis demonstrated ApoB levels could distinguish TBM subjects from healthy controls and viral meningitis subjects with 89.3% sensitivity and 92% specificity. Conclusions: CSF lipid metabolism disregulation, especially elevated expression of ApoB, gives insights into the pathogenesis of TBM. Further evaluation of these findings in larger studies including anti-tuberculosis medicated and unmedicated patient cohorts with other center nervous system infectious diseases is required for successful clinical translation. - Highlights: • The first proteomic study on the cerebrospinal fluid of tuberculous meningitis patients using iTRAQ. • Identify 4 differential proteins invloved in the lipid metabolism. • Elevated expression of ApoB gives

  9. Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism

    PubMed Central

    Cao, Haiming; Gerhold, Kristin; Mayers, Jared R.; Wiest, Michelle M.; Watkins, Steve M.; Hotamisligil, Gökhan S.

    2008-01-01

    Dysregulation of lipid metabolism in individual tissues can lead to systemic disruption of insulin action and glucose metabolism. Utilizing a comprehensive lipidomic platform and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious systemic effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a novel, lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis. PMID:18805087

  10. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism.

    PubMed

    Cao, Haiming; Gerhold, Kristin; Mayers, Jared R; Wiest, Michelle M; Watkins, Steven M; Hotamisligil, Gökhan S

    2008-09-19

    Dysregulation of lipid metabolism in individual tissues leads to systemic disruption of insulin action and glucose metabolism. Utilizing quantitative lipidomic analyses and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis.

  11. Zinc Regulates Lipid Metabolism and MMPs Expression in Lipid Disturbance Rabbits.

    PubMed

    Xu, Chenggui; Huang, Zhibin; Liu, Lijuan; Luo, Chufan; Lu, Guihua; Li, Qinglang; Gao, Xiuren

    2015-12-01

    Lipid disturbance induced by high-fat diet is a worldwide problem, and it can induce inflammation and oxidative stress in vivo. Zinc is considered as an antioxidant, anti-inflammatory agent. Since matrix metalloprotease 2 (MMP2) and matrix metalloprotease 9 (MMP9)'s expressions are changed under many pathological conditions, we would like to know how zinc affects lipid metabolism and MMP2, MMP9's expressions in the lipid disturbance rabbits. Twenty-four male New Zealand white rabbits were randomly divided into four groups. Each group had six rabbits, and they were fed with regular diet, high-fat diet, high-fat diet+zinc, and regular diet+zinc separately for 12 weeks. High-fat diet induced lipid disturbance significantly which raised the level of aspartate aminotransferase (p<0.01) and alanine transaminase (p<0.05) in the high-fat diet group, but zinc supplement reversed this phenomenon (p<0.05). Zinc did not reduce total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p>0.05), but it lowered triglyceride (TG) and raised high-density lipoprotein cholesterol (HDL-C) (p<0.01). Zinc also reduced high-sensitivity C-reactive protein (hs-CRP) (p<0.01) and interleukin-6 (IL-6)'s expressions (p<0.05). Zinc reduced the epicardial adipose tissue and alleviated the hepatic steatosis. Zinc suppressed MMP2 and MMP9's expressions in vivo, but it did not alleviate the aorta fatty streak's severity in the lipid disturbance rabbits. Zinc protected the liver, reduced TG, hs-CRP, and IL-6 and raised HDL-C in the lipid disturbance rabbits. Zinc suppressed MMP2 and MMP9's expressions in vivo, but it did not alleviate the severity of aorta fatty streak induced by the high-fat diet.

  12. Tumor lipids and liver lipid metabolism in the model human lung carcinoma/nude mice.

    PubMed

    de Antueno, R J; Niedfeld, G; De Tomás, M E; Mercuri, O F; Quintans, C

    1987-06-01

    Tumor lipids were studied in the experimental model Human Lung Carcinoma/nude mice as well as the effect of this human neoplasm on the host liver lipid metabolism. Fatty acid profiles from tumoral lipids revealed the loss of specificity for fatty acid composition in triglycerides. Host liver fatty acid composition and cholesterol metabolism were affected by the implanted human lung tissue. A noticeable increase ratio between saturated/unsaturated fatty acids was observed in host liver fatty acid phospholipids (1.17 +/- 0.17) in comparison to control liver (0.84 +/- 0.04). Cholesterol synthesis was assessed "in vivo" by means of [14C]acetate incorporation. The specific radioactivity of [14C] cholesterol was increased by a factor of about 6 in host liver as compared with control liver. This observation along with the marked decrease in the cholesterol content of host liver and the hypocholesterolemia detected in the host mice led us to suggest an increase in the liver cholesterol catabolism promoted by the presence of the tumor.

  13. Resistin: regulation of food intake, glucose homeostasis and lipid metabolism.

    PubMed

    Nogueiras, Ruben; Novelle, Marta G; Vazquez, María Jesús; Lopez, Miguel; Dieguez, Carlos

    2010-01-01

    Resistin has been identified as a hormone secreted by adipocytes that is under hormonal and nutritional control. This hormone has been suggested to be the link between obesity and type 2 diabetes. In rodents, resistin is mainly located and secreted from adipocytes, even though its expression was also found in several other tissues. However, in humans resistin is expressed primarily by macrophages and seems to be involved in the recruitment of other immune cells and the secretion of pro-inflammatory factors, although its role in insulin resistance cannot be ruled out. In addition to its role in glucose metabolism, resistin has been also involved in the control of hypothalamic and peripheral lipid metabolism and in the regulation of food intake. In this short review, we will summarize the most relevant findings of this hormone in rodents. Copyright 2010 S. Karger AG, Basel.

  14. Milk Polar Lipids Affect In Vitro Digestive Lipolysis and Postprandial Lipid Metabolism in Mice.

    PubMed

    Lecomte, Manon; Bourlieu, Claire; Meugnier, Emmanuelle; Penhoat, Armelle; Cheillan, David; Pineau, Gaëlle; Loizon, Emmanuelle; Trauchessec, Michèle; Claude, Mathilde; Ménard, Olivia; Géloën, Alain; Laugerette, Fabienne; Michalski, Marie-Caroline

    2015-08-01

    Polar lipid (PL) emulsifiers such as milk PLs (MPLs) may affect digestion and subsequent lipid metabolism, but focused studies on postprandial lipemia are lacking. We evaluated the impact of MPLs on postprandial lipemia in mice and on lipid digestion in vitro. Female Swiss mice were gavaged with 150 μL of an oil-in-water emulsion stabilized with 5.7 mg of either MPLs or soybean PLs (SPLs) and killed after 1, 2, or 4 h. Plasma lipids were quantified and in the small intestine, gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction. Emulsions were lipolyzed in vitro using a static human digestion model; triglyceride (TG) disappearance was followed by thin-layer chromatography. In mice, after 1 h, plasma TGs tended to be higher in the MPL group than in the SPL group (141 μg/mL vs. 90 μg/mL; P = 0.07) and nonesterified fatty acids (NEFAs) were significantly higher (64 μg/mL vs. 44 μg/mL; P < 0.05). The opposite was observed after 4 h with lower TGs (21 μg/mL vs. 35 μg/mL; P < 0.01) and NEFAs (20 μg/mL vs. 32 μg/mL; P < 0.01) in the MPL group compared with the SPL group. This was associated at 4 h with a lower gene expression of apolipoprotein B (Apob) and Secretion Associated, Ras related GTPase 1 gene homolog B (Sar1b), in the duodenum of MPL mice compared with SPL mice (P < 0.05). In vitro, during the intestinal phase, TGs were hydrolyzed more in the MPL emulsion than in the SPL emulsion (decremental AUCs were 1750%/min vs. 180%/min; P < 0.01). MPLs enhance lipid intestinal hydrolysis and promote more rapid intestinal lipid absorption and sharper kinetics of lipemia. Postprandial lipemia in mice can be modulated by emulsifying with MPLs compared with SPLs, partly through differences in chylomicron assembly, and TG hydrolysis rate as observed in vitro. MPLs may thereby contribute to the long-term regulation of lipid metabolism. © 2015 American Society for Nutrition.

  15. The effects of glucocorticoids on adipose tissue lipid metabolism.

    PubMed

    Peckett, Ashley J; Wright, David C; Riddell, Michael C

    2011-11-01

    Glucocorticoids (GCs) have long been accepted as being catabolic in nature, liberating energy substrates during times of stress to supply the increased metabolic demand of the body. The effects of GCs on adipose tissue metabolism are conflicting, however, because patients with elevated GCs present with central adiposity. We performed an extensive literature review of the effects of GCs on adipose tissue metabolism. The contradictory effects of GCs on lipid metabolism occur through a number of different mechanisms, some of which are well defined and others remain to be elucidated. Firstly, through increases in caloric and dietary fat intake, along with increased hydrolysis of circulating triglycerides (chylomicrons, very low-density lipoproteins) by lipoprotein lipase activity, GCs increase the amount of fatty acids in circulation, which are then available for ectopic fat distribution (liver, muscle, and central adipocytes). Glucocorticoids also increase de novo lipid production in hepatocytes through increased expression of fatty acid synthase. There is some controversy as to whether these same mechanisms occur in adipocytes, thereby contributing to adipose hypertrophy. Glucocorticoids promote preadipocyte conversion to mature adipocytes, causing hyperplasia of the adipose tissue. Glucocorticoids also have acute antilipolytic effect on adipocytes, whereas their genomic actions facilitate increased lipolysis after about 48 hours of exposure. The acute and long-term effects of GCs on adipose tissue lipolysis remain unclear. Although considerable evidence supports the notion that GCs increase lipolysis through glucocorticoid-induced increases of lipase expression, they clearly have antilipolytic effects within these same tissues and cell line models. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER.

    PubMed

    Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco; Hannibal-Bach, Hans K; Ejsing, Christer S; Rapoport, Tom A

    2014-01-16

    Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Separation and Classification of Lipids Using Differential Ion Mobility Spectrometry

    SciTech Connect

    Shvartsburg, Alexandre A.; Isaac, Georgis; Leveque, Nathalie; Smith, Richard D.; Metz, Thomas O.

    2011-04-12

    Correlations between the dimensions of a 2-D separation create trend lines that normally depend on structural or functional characteristics of the compound class and thus facilitate classification of unknowns. This broadly applies to conventional ion mobility spectrometry (IMS)/mass spectrometry (MS), where the major biomolecular classes (e.g., lipids, peptides, nucleotides) occupy different trend line domains. However, strong correlation between the IMS and MS separations for ions of same charge has impeded finer distinctions. Differential IMS (or FAIMS) is generally much less correlated to MS and thus should better separate the trend lines and associated domains. We report the first observation of chemical class separation by trend lines using FAIMS, here for lipids. For all lipids, FAIMS is indeed more independent of MS than conventional IMS, and subclasses (such as phospho-, glycero-, or sphingolipids) form distinct, often non-overlapping domains. Even finer categories with different functional groups or degrees of unsaturation are often separated. As expected, resolution improves in He-rich gases: at ~70% He, glycerolipid isomers with different positions of fatty acid attachment can be resolved. These results open the door for lipidomics application of FAIMS, particularly shotgun lipidomics and targeted analyses of bioactive lipids.

  18. Advancing oleaginous microorganisms to produce lipid via metabolic engineering technology.

    PubMed

    Liang, Ming-Hua; Jiang, Jian-Guo

    2013-10-01

    With the depletion of global petroleum and its increasing price, biodiesel has been becoming one of the most promising biofuels for global fuels market. Researchers exploit oleaginous microorganisms for biodiesel production due to their short life cycle, less labor required, less affection by venue, and easier to scale up. Many oleaginous microorganisms can accumulate lipids, especially triacylglycerols (TAGs), which are the main materials for biodiesel production. This review is covering the related researches on different oleaginous microorganisms, such as yeast, mold, bacteria and microalgae, which might become the potential oil feedstocks for biodiesel production in the future, showing that biodiesel from oleaginous microorganisms has a great prospect in the development of biomass energy. Microbial oils biosynthesis process includes fatty acid synthesis approach and TAG synthesis approach. In addition, the strategies to increase lipids accumulation via metabolic engineering technology, involving the enhancement of fatty acid synthesis approach, the enhancement of TAG synthesis approach, the regulation of related TAG biosynthesis bypass approaches, the blocking of competing pathways and the multi-gene approach, are discussed in detail. It is suggested that DGAT and ME are the most promising targets for gene transformation, and reducing PEPC activity is observed to be beneficial for lipid production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Association of Lipid Accumulation Product with Cardio-Metabolic Risk Factors in Postmenopausal Women.

    PubMed

    Namazi Shabestari, Alireza; Asadi, Mojgan; Jouyandeh, Zahra; Qorbani, Mostafa; Kelishadi, Roya

    2016-06-01

    The lipid accumulation product is a novel, safe and inexpensive index of central lipid over accumulation based on waist circumference and fasting concentration of circulating triglycerides. This study was designed to investigate the ability of lipid accumulation product to predict Cardio-metabolic risk factors in postmenopausal women. In this Cross-sectional study, 264 postmenopausal women by using convenience sampling method were selected from menopause clinic in Tehran. Cardio-metabolic risk factors were measured, and lipid accumulation product (waist-58×triglycerides [nmol/L]) was calculated. Optimal cut-off point of lipid accumulation product for predicting metabolic syndrome was estimated by ROC (Receiver-operating characteristic) curve analysis. Metabolic syndrome was diagnosed in 41.2% of subjects. Optimal cut-off point of lipid accumulation product for predicting metabolic syndrome was 47.63 (sensitivity:75%; specificity:77.9%). High lipid accumulation product increases risk of all Cardio-metabolic risk factors except overweight, high Total Cholesterol, high Low Density Lipoprotein Cholesterol and high Fasting Blood Sugar in postmenopausal women. Our findings show that lipid accumulation product is associated with metabolic syndrome and some Cardio-metabolic risk factors Also lipid accumulation product may have been a useful tool for predicting cardiovascular disease and metabolic syndrome risk in postmenopausal women.

  20. [The effect of microwaves on lipid peroxidation and on lipid and mineral metabolism in warm-blooded animals (experimental research)].

    PubMed

    Guliaev, V Iu; Tereshin, S Iu; Oranskiĭ, I E

    1990-01-01

    The experiments on 50 white mature male rats have provided evidence on the effect produced by microwave therapy on lipid peroxidation, lipid and mineral metabolism and weight of the animals. The effect varied with frequency, wavelength and the site of the exposure (abdominal or cervical zones).

  1. Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters.

    PubMed

    Dimastrogiovanni, Giorgio; Córdoba, Marlon; Navarro, Isabel; Jáuregui, Olga; Porte, Cinta

    2015-08-01

    This work investigates the suitability of the rainbow trout liver cell line (RTL-W1) as an in-vitro model to study the ability of model endocrine disrupters, namely TBT, TPT, 4-NP, BPA and DEHP, to act as metabolic disrupters by altering cellular lipids and markers of lipid metabolism. Among the tested compounds, BPA and DEHP significantly increased the intracellular accumulation of triacylglycerols (TAGs), while all the compounds -apart from TPT-, altered membrane lipids - phosphatidylcholines (PCs) and plasmalogen PCs - indicating a strong interaction of the toxicants with cell membranes and cell signaling. RTL-W1 expressed a number of genes involved in lipid metabolism that were modulated by exposure to BPA, TBT and TPT (up-regulation of FATP1 and FAS) and 4-NP and DEHP (down-regulation of FAS and LPL). Multiple and complex modes of action of these chemicals were observed in RTL-W1 cells, both in terms of expression of genes related to lipid metabolism and alteration of cellular lipids. Although further characterization is needed, this might be a useful model for the detection of chemicals leading to steatosis or other diseases associated with lipid metabolism in fish.

  2. Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism.

    PubMed

    Falcinelli, Silvia; Picchietti, Simona; Rodiles, Ana; Cossignani, Lina; Merrifield, Daniel L; Taddei, Anna Rita; Maradonna, Francesca; Olivotto, Ike; Gioacchini, Giorgia; Carnevali, Oliana

    2015-03-30

    The microbiome plays an important role in lipid metabolism but how the introduction of probiotic communities affects host lipid metabolism is poorly understood. Using a multidisciplinary approach we addressed this knowledge gap using the zebrafish model by coupling high-throughput sequencing with biochemical, molecular and morphological analysis to evaluate the changes in the intestine. Analysis of bacterial 16S libraries revealed that Lactobacillus rhamnosus was able to modulate the gut microbiome of zebrafish larvae, elevating the abundance of Firmicutes sequences and reducing the abundance of Actinobacteria. The gut microbiome changes modulated host lipid processing by inducing transcriptional down-regulation of genes involved in cholesterol and triglycerides metabolism (fit2, agpat4, dgat2, mgll, hnf4α, scap, and cck) concomitantly decreasing total body cholesterol and triglyceride content and increasing fatty acid levels. L. rhamnosus treatment also increased microvilli and enterocyte lengths and decreased lipid droplet size in the intestinal epithelium. These changes resulted in elevated zebrafish larval growth. This integrated system investigation demonstrates probiotic modulation of the gut microbiome, highlights a novel gene network involved in lipid metabolism, provides an insight into how the microbiome regulates molecules involved in lipid metabolism, and reveals a new potential role for L. rhamnosus in the treatment of lipid disorders.

  3. Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism

    PubMed Central

    Falcinelli, Silvia; Picchietti, Simona; Rodiles, Ana; Cossignani, Lina; Merrifield, Daniel L.; Taddei, Anna Rita; Maradonna, Francesca; Olivotto, Ike; Gioacchini, Giorgia; Carnevali, Oliana

    2015-01-01

    The microbiome plays an important role in lipid metabolism but how the introduction of probiotic communities affects host lipid metabolism is poorly understood. Using a multidisciplinary approach we addressed this knowledge gap using the zebrafish model by coupling high-throughput sequencing with biochemical, molecular and morphological analysis to evaluate the changes in the intestine. Analysis of bacterial 16S libraries revealed that Lactobacillus rhamnosus was able to modulate the gut microbiome of zebrafish larvae, elevating the abundance of Firmicutes sequences and reducing the abundance of Actinobacteria. The gut microbiome changes modulated host lipid processing by inducing transcriptional down-regulation of genes involved in cholesterol and triglycerides metabolism (fit2, agpat4, dgat2, mgll, hnf4α, scap, and cck) concomitantly decreasing total body cholesterol and triglyceride content and increasing fatty acid levels. L. rhamnosus treatment also increased microvilli and enterocyte lengths and decreased lipid droplet size in the intestinal epithelium. These changes resulted in elevated zebrafish larval growth. This integrated system investigation demonstrates probiotic modulation of the gut microbiome, highlights a novel gene network involved in lipid metabolism, provides an insight into how the microbiome regulates molecules involved in lipid metabolism, and reveals a new potential role for L. rhamnosus in the treatment of lipid disorders. PMID:25822072

  4. Glucose regulates lipid metabolism in fasting king penguins.

    PubMed

    Bernard, Servane F; Orvoine, Jord; Groscolas, René

    2003-08-01

    This study aims to determine whether glucose intervenes in the regulation of lipid metabolism in long-term fasting birds, using the king penguin as an animal model. Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo before, during, and after a 2-h glucose infusion under field conditions. All the birds were in the phase II fasting status (large fat stores, protein sparing) but differed by their metabolic and hormonal statuses, being either nonstressed (NSB; n = 5) or stressed (SB; n = 5). In both groups, glucose infusion at 5 mg.kg-1.min-1 induced a twofold increase in glycemia. In NSB, glucose had no effect on lipolysis (maintenance of plasma concentrations and rates of appearance of glycerol and nonesterified fatty acids) and no effect on the plasma concentrations of triacylglycerols (TAG), glucagon, insulin, or corticosterone. However, it limited fatty acid (FA) oxidation, as indicated by a 25% decrease in the plasma level of beta-hydroxybutyrate (beta-OHB). In SB, glucose infusion induced an approximately 2.5-fold decrease in lipolytic fluxes and a large decrease in FA oxidation, as reflected by a 64% decrease in the plasma concentration of beta-OHB. There were also a 35% decrease in plasma TAG, a 6.5- and 2.8-fold decrease in plasma glucagon and corticosterone, respectively, and a threefold increase in insulinemia. These data show that in fasting king penguins, glucose regulates lipid metabolism (inhibition of lipolysis and/or of FA oxidation) and affects hormonal status differently in stressed vs. nonstressed individuals. The results also suggest that in birds, as in humans, the availability of glucose, not of FA, is an important determinant of the substrate mix (glucose vs. FA) that is oxidized for energy production.

  5. Moringa Leaves Prevent Hepatic Lipid Accumulation and Inflammation in Guinea Pigs by Reducing the Expression of Genes Involved in Lipid Metabolism

    PubMed Central

    Almatrafi, Manal Mused; Vergara-Jimenez, Marcela; Murillo, Ana Gabriela; Norris, Gregory H.; Blesso, Christopher N.; Fernandez, Maria Luz

    2017-01-01

    To investigate the mechanisms by which Moringa oleifera leaves (ML) modulate hepatic lipids, guinea pigs were allocated to either control (0% ML), 10% Low Moringa (LM) or 15% High Moringa (HM) diets with 0.25% dietary cholesterol to induce hepatic steatosis. After 6 weeks, guinea pigs were sacrificed and liver and plasma were collected to determine plasma lipids, hepatic lipids, cytokines and the expression of genes involved in hepatic cholesterol (CH) and triglyceride (TG) metabolism. There were no differences in plasma lipids among groups. A dose-response effect of ML was observed in hepatic lipids (CH and TG) with the lowest concentrations in the HM group (p < 0.001), consistent with histological evaluation of lipid droplets. Hepatic gene expression of diglyceride acyltransferase-2 and peroxisome proliferator activated receptor-γ, as well as protein concentrations interleukin (IL)-1β and interferon-γ, were lowest in the HM group (p < 0.005). Hepatic gene expression of cluster of differentiation-68 and sterol regulatory element binding protein-1c were 60% lower in both the LM and HM groups compared to controls (p < 0.01). This study demonstrates that ML may prevent hepatic steatosis by affecting gene expression related to hepatic lipids synthesis resulting in lower concentrations of cholesterol and triglycerides and reduced inflammation in the liver. PMID:28640194

  6. Moringa Leaves Prevent Hepatic Lipid Accumulation and Inflammation in Guinea Pigs by Reducing the Expression of Genes Involved in Lipid Metabolism.

    PubMed

    Almatrafi, Manal Mused; Vergara-Jimenez, Marcela; Murillo, Ana Gabriela; Norris, Gregory H; Blesso, Christopher N; Fernandez, Maria Luz

    2017-06-22

    To investigate the mechanisms by which Moringa oleifera leaves (ML) modulate hepatic lipids, guinea pigs were allocated to either control (0% ML), 10% Low Moringa (LM) or 15% High Moringa (HM) diets with 0.25% dietary cholesterol to induce hepatic steatosis. After 6 weeks, guinea pigs were sacrificed and liver and plasma were collected to determine plasma lipids, hepatic lipids, cytokines and the expression of genes involved in hepatic cholesterol (CH) and triglyceride (TG) metabolism. There were no differences in plasma lipids among groups. A dose-response effect of ML was observed in hepatic lipids (CH and TG) with the lowest concentrations in the HM group (p < 0.001), consistent with histological evaluation of lipid droplets. Hepatic gene expression of diglyceride acyltransferase-2 and peroxisome proliferator activated receptor-γ, as well as protein concentrations interleukin (IL)-1β and interferon-γ, were lowest in the HM group (p < 0.005). Hepatic gene expression of cluster of differentiation-68 and sterol regulatory element binding protein-1c were 60% lower in both the LM and HM groups compared to controls (p < 0.01). This study demonstrates that ML may prevent hepatic steatosis by affecting gene expression related to hepatic lipids synthesis resulting in lower concentrations of cholesterol and triglycerides and reduced inflammation in the liver.

  7. PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation☆

    PubMed Central

    Varga, Tamas; Czimmerer, Zsolt; Nagy, Laszlo

    2011-01-01

    Cells are constantly exposed to a large variety of lipids. Traditionally, these molecules were thought to serve as simple energy storing molecules. More recently it has been realized that they can also initiate and regulate signaling events that will decisively influence development, cellular differentiation, metabolism and related functions through the regulation of gene expression. Multicellular organisms dedicate a large family of nuclear receptors to these tasks. These proteins combine the defining features of both transcription factors and receptor molecules, and therefore have the unique ability of being able to bind lipid signaling molecules and transduce the appropriate signals derived from lipid environment to the level of gene expression. Intriguingly, the members of a subfamily of the nuclear receptors, the peroxisome proliferator-activated receptors (PPARs) are able to sense and interpret fatty acid signals derived from dietary lipids, pathogenic lipoproteins or essential fatty acid metabolites. Not surprisingly, Peroxisome proliferator-activated receptors were found to be key regulators of lipid and carbohydrate metabolism. Unexpectedly, later studies revealed that Peroxisome proliferator-activated receptors are also able to modulate inflammatory responses. Here we summarize our understanding on how these transcription factors/receptors connect lipid metabolism to inflammation and some of the novel regulatory mechanisms by which they contribute to homeostasis and certain pathological conditions. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease. PMID:21382489

  8. Physiology and lipid metabolism of Littorina saxatilis infected with trematodes.

    PubMed

    Arakelova, Katherine S; Chebotareva, Marina A; Zabelinskii, Stanislav A

    2004-09-08

    Physiological and biochemical alterations in Littorina saxatilis infected with larval trematodes were investigated and compared with the metabolism of non-parasitized snails. Oxygen consumption rates of infected snails differed from those of non-infected controls in medium sized individuals (30 to 130 mg) but not in very large infected individuals (> 200 mg). Small snails (0.5 to 8.5 mg) were seldom infected by parasites, and this size-class consisted only of non-infected specimens. The specific oxygen consumption rate of infected snails was not dependent on their mass and remained constant over the size ranges investigated. Alterations in the snail metabolism appeared to be connected to injuries to digestive gland tissues caused by the parasites. The glycogen concentration and fatty acids of neutral lipids and phospholipids in the digestive gland were determined. Infected snails differed from uninfected snails in the complete absence of glycogen in digestive gland and had proportionally higher quantities of eicosenoic (20:1) acid in the total phospholipids. It remains unclear whether infection by trematodes activates enzymes in the snail's digestive gland to synthesize eicosenoic (20:1) acid, or whether the sporocysts themselves possess these enzymes. The role of phospholipid fatty acids in the regulation and maintenance of the parasite's metabolism is briefly considered. Biochemical alterations observed in the fatty acid composition may have an adaptive significance, by helping to stabilize the host-parasite system.

  9. The autonomic nervous system regulates postprandial hepatic lipid metabolism.

    PubMed

    Bruinstroop, Eveline; la Fleur, Susanne E; Ackermans, Mariette T; Foppen, Ewout; Wortel, Joke; Kooijman, Sander; Berbée, Jimmy F P; Rensen, Patrick C N; Fliers, Eric; Kalsbeek, Andries

    2013-05-15

    The liver is a key organ in controlling glucose and lipid metabolism during feeding and fasting. In addition to hormones and nutrients, inputs from the autonomic nervous system are also involved in fine-tuning hepatic metabolic regulation. Previously, we have shown in rats that during fasting an intact sympathetic innervation of the liver is essential to maintain the secretion of triglycerides by the liver. In the current study, we hypothesized that in the postprandial condition the parasympathetic input to the liver inhibits hepatic VLDL-TG secretion. To test our hypothesis, we determined the effect of selective surgical hepatic denervations on triglyceride metabolism after a meal in male Wistar rats. We report that postprandial plasma triglyceride concentrations were significantly elevated in parasympathetically denervated rats compared with control rats (P = 0.008), and VLDL-TG production tended to be increased (P = 0.066). Sympathetically denervated rats also showed a small rise in postprandial triglyceride concentrations (P = 0.045). On the other hand, in rats fed on a six-meals-a-day schedule for several weeks, a parasympathetic denervation resulted in >70% higher plasma triglycerides during the day (P = 0.001), whereas a sympathetic denervation had no effect. Our results show that abolishing the parasympathetic input to the liver results in increased plasma triglyceride levels during postprandial conditions.

  10. The effect of maternal chromium status on lipid metabolism in female elderly mice offspring and involved molecular mechanism

    PubMed Central

    Zhang, Qian; Sun, Xiaofang; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-01-01

    Maternal malnutrition leads to the incidence of metabolic diseases in offspring. The purpose of this project was to examine whether maternal low chromium could disturb normal lipid metabolism in offspring, altering adipose cell differentiation and leading to the incidence of lipid metabolism diseases, including metabolic syndrome and obesity. Female C57BL mice were given a control diet (CD) or a low chromium diet (LCD) during the gestational and lactation periods. After weaning, offspring was fed with CD or LCD. The female offspring were assessed at 32 weeks of age. Fresh adipose samples from CD–CD group and LCD–CD group were collected. Genome mRNA were analysed using Affymetrix GeneChip Mouse Gene 2.0 ST Whole Transcript-based array. Differentially expressed genes (DEGs) were analysed based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis database. Maternal low chromium irreversibly increased offspring body weight, fat-pad weight, serum triglyceride (TG) and TNF-α. Eighty five genes increased and 109 genes reduced in the offspring adipose of the maternal low chromium group. According to KEGG pathway and String analyses, the PPAR signalling pathway may be the key controlled pathway related to the effect of maternal low chromium on female offspring. Maternal chromium status have long-term effects of lipid metabolism in female mice offspring. Normalizing offspring diet can not reverse these effects. The potential underlying mechanisms are the disturbance of the PPAR signalling pathway in adipose tissue. PMID:28320771

  11. Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome.

    PubMed

    Basu, Arpita; Sanchez, Karah; Leyva, Misti J; Wu, Mingyuan; Betts, Nancy M; Aston, Christopher E; Lyons, Timothy J

    2010-02-01

    To compare the effects of supplementation of green tea beverage or green tea extracts with controls on body weight, glucose and lipid profile, biomarkers of oxidative stress, and safety parameters in obese subjects with metabolic syndrome. Randomized, controlled prospective trial. General Clinical Research Center (GCRC) at University of Oklahoma Health Sciences Center (OUHSC). Thirty-five subjects with obesity and metabolic syndrome were recruited in age- and gender-matched trios and were randomly assigned to the control (4 cups water/d), green tea (4 cups/d), or green tea extract (2 capsules and 4 cups water/d) group for 8 weeks. The tea and extract groups had similar dosing of epiogallocatechin-3-gallate (EGCG), the active compound in green tea. Anthropometrics, blood pressure, fasting glucose and lipids, nuclear magnetic resonance (NMR)-based lipid particle size, safety parameters, biomarkers of oxidative stress (oxidized low-density lipoprotein [LDL], myeloperoxidase [MPO], malondialdehyde and hydroxynonenals [MDA and HNE]), and free catechins were analyzed at screen and at 4 and 8 weeks of the study. Pairwise comparisons showed green tea beverage and green tea extracts caused a significant decrease in body weight and body mass index (BMI) versus controls at 8 weeks (-2.5 +/- 0.7 kg, p < 0.01, and -1.9 +/- 0.6, p < 0.05, respectively). Green tea beverage showed a decreasing trend in LDL-cholesterol and LDL/high-density lipoprotein (HDL) versus controls (p < 0.1). Green tea beverage also significantly decreased MDA and HNE (-0.39 +/- 0.06 microM, p < 0.0001) versus controls. Plasma free catechins were detectable in both beverage and extract groups versus controls at screen and at 8 weeks, indicating compliance and bioavailability of green tea catechins. Green tea beverage consumption (4 cups/d) or extract supplementation (2 capsules/d) for 8 weeks significantly decreased body weight and BMI. Green tea beverage further lowered lipid peroxidation versus age- and

  12. Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity

    PubMed Central

    Chu, Yajing; Rosso, Leonardo Gómez; Huang, Ping; Wang, Zhichao; Xu, Yichi; Yao, Xiao; Bao, Menghan; Yan, Jun; Song, Haiyun; Wang, Gang

    2014-01-01

    Mediator complex is a molecular hub integrating signaling, transcription factors, and RNA polymerase II (RNAPII) machinery. Mediator MED23 is involved in adipogenesis and smooth muscle cell differentiation, suggesting its role in energy homeostasis. Here, through the generation and analysis of a liver-specific Med23-knockout mouse, we found that liver Med23 deletion improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved the lipid profile and glucose tolerance. Mechanistically, MED23 participates in gluconeogenesis and cholesterol synthesis through modulating the transcriptional activity of FOXO1, a key metabolic transcription factor. Indeed, hepatic Med23 deletion impaired the Mediator and RNAPII recruitment and attenuated the expression of FOXO1 target genes. Moreover, this functional interaction between FOXO1 and MED23 is evolutionarily conserved, as the in vivo activities of dFOXO in larval fat body and in adult wing can be partially blocked by Med23 knockdown in Drosophila. Collectively, our data revealed Mediator MED23 as a novel regulator for energy homeostasis, suggesting potential therapeutic strategies against metabolic diseases. PMID:25223702

  13. Altered lipid metabolism in the aging kidney identified by three layered omic analysis.

    PubMed

    Braun, Fabian; Rinschen, Markus M; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H J; Schumacher, Björn; Dollé, Martijn E T; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E

    2016-03-01

    Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease.

  14. Altered lipid metabolism in the aging kidney identified by three layered omic analysis

    PubMed Central

    Braun, Fabian; Rinschen, Markus M.; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H.J.; Schumacher, Björn; Dollé, Martijn E.T.; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E.

    2016-01-01

    Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. PMID:26886165

  15. Proinflammatory and lipid biomarkers mediate metabolically healthy obesity: A proteomics study

    PubMed Central

    Zhou, Jie; Zhou, Ming; Prieto, DaRue; Rotimi, Charles N.; Adeyemo, Adebowale

    2016-01-01

    Objective The metabolically healthy obesity (MHO) phenotype is an important obesity subtype in which obesity is not accompanied by any metabolic comorbidity. However, the underlying molecular mechanisms remain elusive. In this study, a shotgun proteomics approach to identify circulating biomolecules and pathways associated with MHO was used. Methods The subjects were 20 African‐American women: 10 MHO cases and 10 metabolically abnormal individuals with obesity (MAO) controls. Serum proteins were detected and quantified using label‐free proteomics. Differential expression of proteins between the two groups was analyzed, and the list of differentially expressed proteins was analyzed to determine enriched biological pathways. Results Twenty proteins were differentially expressed between MHO and controls. These proteins included: hemoglobin subunits (HBA1, P = 6.00 × 10−18), haptoglobin‐related protein (HPR, P = 1.2 × 10−15), apolipoproteins (APOB‐100, P = 1.50 × 10−40; APOA4, P = 1.1 × 10−14), retinol‐binding protein 4 (RBP4, P = 7.1 × 10−08), and CRP (P = 2.0 × 10−04). MHO was associated with lower levels of proinflammatory and higher levels of anti‐inflammatory biomarkers when compared with MAO. Pathway analysis showed enrichment of lipids and inflammatory pathways, including LXR/RXR and FXR/RXR activation, and acute phase response signaling. Conclusions These findings suggested that protection from dysregulated inflammatory and lipid processes were primary molecular hallmarks of MHO. The candidate biomarkers (AHSG, RBP4, and APOA4) identified in this study are potential prognostic markers for MHO. PMID:27106679

  16. Lipids from heterotrophic microbes: advances in metabolism research.

    PubMed

    Kosa, Matyas; Ragauskas, Arthur J

    2011-02-01

    Heterotrophic oleaginous microorganisms are capable of producing over 20% of their weight in single cell oils (SCOs) composed of triacylglycerols (TAGs). These TAGs contain fatty acids, such as palmitic, stearic and oleic acids, that are well-suited for biodiesel applications. Although some of these microbes are able to accumulate SCOs while growing on inexpensive agro-industrial biomass, the competition with plant oil resources means that a significant increase in productivity is desired. The present review aims to summarize recent details in lipid metabolism research and engineering (e.g. direct fatty acid ethyl ester production), as well as culture condition optimization and innovations, such as solid-state or semi-solid-state fermentation, that can all contribute to higher productivity and further advancement of the field.

  17. Antiplatelet effect of differentially charged PEGylated lipid-polymer nanoparticles.

    PubMed

    Fuentes, Eduardo; Yameen, Basit; Bong, Soung-Jae; Salvador-Morales, Carolina; Palomo, Ivan; Vilos, Cristian

    2017-04-01

    PEGylated nanoparticles have been extensively investigated in different platforms for drug delivery. However, the physiological effects related to platelet activation, and the potential procoagulant activity which could lead to thrombosis and further cardiovascular diseases have not been widely examined. In this work, we studied the effect of differentially charged PEGylated lipid-polymer nanoparticles in the human platelet aggregation and activation by light transmission aggregometry and flow cytometry. PEGylated nanoparticles inhibited the platelet aggregation with a dose dependency (350, 700, and 1400μg/mL) in both ADP- and collagen-induced platelet aggregation, and P-selectin expression. Charged nanoparticles (anionic and cationic) presented higher inhibitions of the platelet aggregation compared to neutral nanoparticles, and particularly the cationic particles generated a slightly higher effect. The obtained results demonstrated the safety of the differentially charged PEGylated lipid-polymer nanoparticles, and their ability to inhibit the aggregation and activation of human platelets stimulated by two classic platelet activators. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Myocardial Function and Lipid Metabolism in the Chronic Alcoholic Animal

    PubMed Central

    Regan, Timothy J.; Khan, Mohammad I.; Ettinger, Philip O.; Haider, Bunyad; Lyons, Michael M.; Oldewurtel, Henry A.; Weber, Marilyn

    1974-01-01

    In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium. To evaluate myocardial lipid metabolism, [1-14C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced 14CO2 production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [14C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic. Images PMID:4368946

  19. [Oral contraceptives and cardiovascular disease--aspects of lipid metabolism].

    PubMed

    Crona, N; Silfverstolpe, G

    1984-02-08

    A review of the research data concerning cardiovascular disease induced by oral contraceptives (OC) relies on the findings of 3 US and British prospective studies involving 80,000 women. Pill users under 35 who were nonsmokers had 1/4 of the risk of dying as a result of this use than of pregnancy complications (in smokers, the risk is the same). Acute pathogenetical effects include blood coagulation homeostasis leading to thromboembolism and long-term disorders of lipid and carbohydrate metabolism. The estrogen component of OCs, ethinyl estradiol (EE), tends to increase Very Low Density Lipoprotein (VLDL) and High Density Lipoprotein (HDL) levels while decreasing Low Density Lipoprotein (LDL) levels. The gestagen component, a nortestosterone derivative, acts in the opposite way. The estrogen component also increases the level of triglycerides in the VLDL fraction and in serum. There seems to be an inverse ratio between VLDL and HDL levels (gestagen-dominant OCs lower the HDL cholesterol level). The thromboembolitic side effects of estrogen led to the introduction of low-dose pills in the 1970s (acute pancreatitis, a severe side effect, has been all but eliminated). The cardiovascular complications and cerebral insult induced by the gestagen component, a 19-nortestosterone derivative, have also resulted in decreased doses of gestagens in OCs. Non-alkylated estrogens ("natural" estrogens) have been favored recently because they do not increase VLDL levels, while still increasing HDL. A 17-alpha-hydroxprogesterone derivative as the gestagen component of pills has been used in recent years, since it is inert in lipid metabolism, unlike 19-nortestosterone. The effect of exogenous sexual steriods on prostaglandin synethis and on the balance of thromboxanes and prostacyclines will require futher study.

  20. Lipid Metabolic Versatility in Malassezia spp. Yeasts Studied through Metabolic Modeling

    PubMed Central

    Triana, Sergio; de Cock, Hans; Ohm, Robin A.; Danies, Giovanna; Wösten, Han A. B.; Restrepo, Silvia; González Barrios, Andrés F.; Celis, Adriana

    2017-01-01

    Malassezia species are lipophilic and lipid-dependent yeasts belonging to the human and animal microbiota. Typically, they are isolated from regions rich in sebaceous glands. They have been associated with dermatological diseases such as seborrheic dermatitis, pityriasis versicolor, atopic dermatitis, and folliculitis. The genomes of Malassezia globosa, Malassezia sympodialis, and Malassezia pachydermatis lack the genes related to fatty acid synthesis. Here, the lipid-synthesis pathways of these species, as well as of Malassezia furfur, and of an atypical M. furfur variant were reconstructed using genome data and Constraints Based Reconstruction and Analysis. To this end, the genomes of M. furfur CBS 1878 and the atypical M. furfur 4DS were sequenced and annotated. The resulting Enzyme Commission numbers and predicted reactions were similar to the other Malassezia strains despite the differences in their genome size. Proteomic profiling was utilized to validate flux distributions. Flux differences were observed in the production of steroids in M. furfur and in the metabolism of butanoate in M. pachydermatis. The predictions obtained via these metabolic reconstructions also suggested defects in the assimilation of palmitic acid in M. globosa, M. sympodialis, M. pachydermatis, and the atypical variant of M. furfur, but not in M. furfur. These predictions were validated via physiological characterization, showing the predictive power of metabolic network reconstructions to provide new clues about the metabolic versatility of Malassezia. PMID:28959251

  1. Lipid Metabolic Versatility in Malassezia spp. Yeasts Studied through Metabolic Modeling.

    PubMed

    Triana, Sergio; de Cock, Hans; Ohm, Robin A; Danies, Giovanna; Wösten, Han A B; Restrepo, Silvia; González Barrios, Andrés F; Celis, Adriana

    2017-01-01

    Malassezia species are lipophilic and lipid-dependent yeasts belonging to the human and animal microbiota. Typically, they are isolated from regions rich in sebaceous glands. They have been associated with dermatological diseases such as seborrheic dermatitis, pityriasis versicolor, atopic dermatitis, and folliculitis. The genomes of Malassezia globosa, Malassezia sympodialis, and Malassezia pachydermatis lack the genes related to fatty acid synthesis. Here, the lipid-synthesis pathways of these species, as well as of Malassezia furfur, and of an atypical M. furfur variant were reconstructed using genome data and Constraints Based Reconstruction and Analysis. To this end, the genomes of M. furfur CBS 1878 and the atypical M. furfur 4DS were sequenced and annotated. The resulting Enzyme Commission numbers and predicted reactions were similar to the other Malassezia strains despite the differences in their genome size. Proteomic profiling was utilized to validate flux distributions. Flux differences were observed in the production of steroids in M. furfur and in the metabolism of butanoate in M. pachydermatis. The predictions obtained via these metabolic reconstructions also suggested defects in the assimilation of palmitic acid in M. globosa, M. sympodialis, M. pachydermatis, and the atypical variant of M. furfur, but not in M. furfur. These predictions were validated via physiological characterization, showing the predictive power of metabolic network reconstructions to provide new clues about the metabolic versatility of Malassezia.

  2. Nanocellulose size regulates microalgal flocculation and lipid metabolism

    PubMed Central

    Yu, Sun Il; Min, Seul Ki; Shin, Hwa Sung

    2016-01-01

    Harvesting of microalgae is a cost-consuming step for biodiesel production. Cellulose has recently been studied as a biocompatible and inexpensive flocculant for harvesting microalgae via surface modifications such as cation-modifications. In this study, we demonstrated that cellulose nanofibrils (CNF) played a role as a microalgal flocculant via its network geometry without cation modification. Sulfur acid-treated tunicate CNF flocculated microalgae, but cellulose nanocrystals (CNC) did not. In addition, desulfurization did not significantly influence the flocculation efficiency of CNF. This mechanism is likely related to encapsulation of microalgae by nanofibrous structure formation, which is derived from nanofibrils entanglement and intra-hydrogen bonding. Moreover, flocculated microalgae were subject to mechanical stress resulting in changes in metabolism induced by calcium ion influx, leading to upregulated lipid synthesis. CNF do not require surface modifications such as cation modified CNC and flocculation is derived from network geometry related to nanocellulose size; accordingly, CNF is one of the least expensive cellulose-based flocculants ever identified. If this flocculant is applied to the biodiesel process, it could decrease the cost of harvest, which is one of the most expensive steps, while increasing lipid production. PMID:27796311

  3. Lipid metabolism is associated with developmental epigenetic programming.

    PubMed

    Marchlewicz, Elizabeth H; Dolinoy, Dana C; Tang, Lu; Milewski, Samantha; Jones, Tamara R; Goodrich, Jaclyn M; Soni, Tanu; Domino, Steven E; Song, Peter X K; F Burant, Charles; Padmanabhan, Vasantha

    2016-10-07

    Maternal diet and metabolism impact fetal development. Epigenetic reprogramming facilitates fetal adaptation to these in utero cues. To determine if maternal metabolite levels impact infant DNA methylation globally and at growth and development genes, we followed a clinical birth cohort of 40 mother-infant dyads. Targeted metabolomics and quantitative DNA methylation were analyzed in 1st trimester maternal plasma (M1) and delivery maternal plasma (M2) as well as infant umbilical cord blood plasma (CB). We found very long chain fatty acids, medium chain acylcarnitines, and histidine were: (1) stable in maternal plasma from pregnancy to delivery, (2) significantly correlated between M1, M2, and CB, and (3) in the top 10% of maternal metabolites correlating with infant DNA methylation, suggesting maternal metabolites associated with infant DNA methylation are tightly controlled. Global DNA methylation was highly correlated across M1, M2, and CB. Thus, circulating maternal lipids are associated with developmental epigenetic programming, which in turn may impact lifelong health and disease risk. Further studies are required to determine the causal link between maternal plasma lipids and infant DNA methylation patterns.

  4. Lipid metabolism is associated with developmental epigenetic programming

    PubMed Central

    Marchlewicz, Elizabeth H.; Dolinoy, Dana C.; Tang, Lu; Milewski, Samantha; Jones, Tamara R.; Goodrich, Jaclyn M.; Soni, Tanu; Domino, Steven E.; Song, Peter X. K.; F. Burant, Charles; Padmanabhan, Vasantha

    2016-01-01

    Maternal diet and metabolism impact fetal development. Epigenetic reprogramming facilitates fetal adaptation to these in utero cues. To determine if maternal metabolite levels impact infant DNA methylation globally and at growth and development genes, we followed a clinical birth cohort of 40 mother-infant dyads. Targeted metabolomics and quantitative DNA methylation were analyzed in 1st trimester maternal plasma (M1) and delivery maternal plasma (M2) as well as infant umbilical cord blood plasma (CB). We found very long chain fatty acids, medium chain acylcarnitines, and histidine were: (1) stable in maternal plasma from pregnancy to delivery, (2) significantly correlated between M1, M2, and CB, and (3) in the top 10% of maternal metabolites correlating with infant DNA methylation, suggesting maternal metabolites associated with infant DNA methylation are tightly controlled. Global DNA methylation was highly correlated across M1, M2, and CB. Thus, circulating maternal lipids are associated with developmental epigenetic programming, which in turn may impact lifelong health and disease risk. Further studies are required to determine the causal link between maternal plasma lipids and infant DNA methylation patterns. PMID:27713555

  5. 2009 Plant Lipids: Structure, Metabolism & Function Gordon Research Conference - February 1- 6 ,2009

    SciTech Connect

    Kent D. Chapman

    2009-02-06

    The Gordon Research Conference on 'Plant Lipids: Structure, Metabolism and Function' has been instituted to accelerate research productivity in the field of plant lipids. This conference will facilitate wide dissemination of research breakthroughs, support recruitment of young scientists to the field of plant lipid metabolism and encourage broad participation of the plant lipid community in guiding future directions for research in plant lipids. This conference will build upon the strengths of the successful, previous biannual meetings of the National Plant Lipid Cooperative (www.plantlipids.org) that began in 1993, but will reflect a broader scope of topics to include the biochemistry, cell biology, metabolic regulation, and signaling functions of plant acyl lipids. Most importantly, this conference also will serve as a physical focal point for the interaction of the plant lipid research community. Applications to attend this conference will be open to all researchers interested in plant lipids and will provide a venue for the presentation of the latest research results, networking opportunities for young scientists, and a forum for the development and exchange of useful lipid resources and new ideas. By bringing together senior- and junior-level scientists involved in plant lipid metabolism, a broad range of insights will be shared and the community of plant lipid researchers will function more as a network of vested partners. This is important for the vitality of the research community and for the perceived value that will encourage conference attendance into the future.

  6. Sec14 Like PITPs Couple Lipid Metabolism with Phosphoinositide Synthesis to Regulate Golgi Functionality

    PubMed Central

    Davison, James M.; Bankaitis, Vytas A.

    2017-01-01

    An interface coordinating lipid metabolism with proteins that regulate membrane trafficking is necessary to regulate Golgi morphology and dynamics. Such an interface facilitates the membrane deformations required for vesicularization, forms platforms for protein recruitment and assembly on appropriate sites on a membrane surface and provides lipid co-factors for optimal protein activity in the proper spatio-temporally regulated manner. Importantly, Sec14 and Sec14-like proteins are a unique superfamily of proteins that sense specific aspects of lipid metabolism, employing this information to potentiate phosphoinositide production. Therefore, Sec14 and Sec14 like proteins form central conduits to integrate multiple aspects of lipid metabolism with productive phosphoinositide signaling. PMID:22374094

  7. Dynamic changes in energy metabolism upon embryonic stem cell differentiation support developmental toxicant identification.

    PubMed

    van Dartel, Dorien A M; Schulpen, Sjors H; Theunissen, Peter T; Bunschoten, Annelies; Piersma, Aldert H; Keijer, Jaap

    2014-10-03

    Embryonic stem cells (ESC) are widely used to study embryonic development and to identify developmental toxicants. Particularly, the embryonic stem cell test (EST) is well known as in vitro model to identify developmental toxicants. Although it is clear that energy metabolism plays a crucial role in embryonic development, the modulation of energy metabolism in in vitro models, such as the EST, is not yet described. The present study is among the first studies that analyses whole genome expression data to specifically characterize metabolic changes upon ESC early differentiation. Our transcriptomic analyses showed activation of glycolysis, truncated activation of the tricarboxylic acid (TCA) cycle, activation of lipid synthesis, as well as activation of glutaminolysis during the early phase of ESC differentiation. Taken together, this energy metabolism profile points towards energy metabolism reprogramming in the provision of metabolites for biosynthesis of cellular constituents. Next, we defined a gene set that describes this energy metabolism profile. We showed that this gene set could be successfully applied in the EST to identify developmental toxicants known to modulate cellular biosynthesis (5-fluorouracil and methoxyacetic acid), while other developmental toxicants or the negative control did not modulate the expression of this gene set. Our description of dynamic changes in energy metabolism during early ESC differentiation, as well as specific identification of developmental toxicants modulating energy metabolism, is an important step forward in the definition of the applicability domain of the EST. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Biphasic Regulation of Lipid Metabolism: A Meta-Analysis of Icodextrin in Peritoneal Dialysis.

    PubMed

    Huang, Yan-Feng; Zhu, Da-Jian; Chen, Xiao-Wu; Ouyang, Man-Zhao; Zhang, Wei-Jie

    2015-01-01

    The objective of this systematic meta-analysis was to study the impact of icodextrin (ICO) on lipid profiles. MEDLINE, PubMed, Embase, Chinese Biomedical Literature, and the Cochrane Library and Reference lists were searched (last search September 2014) in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Searches identified 13 eligible trials with a total of 850 patients. The differentials of total cholesterol (TC) and free fatty acid (FFA) in the ICO group were greater than those in the GLU group. Metaregression analysis showed that TC levels positively correlated with its baseline levels. In the subgroup of patients with dialysis duration more than 6 months, TC and TG in the ICO group were less. In pooled data from cross-sectional studies, differential of TG in the ICO group was less. In the subgroup of patients with diabetes (Martikainen et al., 2005, Sniderman et al., 2014, and Takatori et al., 2011), differential of high-density lipoprotein cholesterol (HDL-C) in the ICO group was less. There was no significant effect on low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), or lipoprotein(a). ICO may be beneficial to lipid metabolism, especially for its biphasic regulation of plasma TC levels.

  9. Biphasic Regulation of Lipid Metabolism: A Meta-Analysis of Icodextrin in Peritoneal Dialysis

    PubMed Central

    Huang, Yan-Feng; Zhu, Da-Jian; Chen, Xiao-Wu; Ouyang, Man-Zhao; Zhang, Wei-Jie

    2015-01-01

    Objectives. The objective of this systematic meta-analysis was to study the impact of icodextrin (ICO) on lipid profiles. Methods. MEDLINE, PubMed, Embase, Chinese Biomedical Literature, and the Cochrane Library and Reference lists were searched (last search September 2014) in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Results. Searches identified 13 eligible trials with a total of 850 patients. The differentials of total cholesterol (TC) and free fatty acid (FFA) in the ICO group were greater than those in the GLU group. Metaregression analysis showed that TC levels positively correlated with its baseline levels. In the subgroup of patients with dialysis duration more than 6 months, TC and TG in the ICO group were less. In pooled data from cross-sectional studies, differential of TG in the ICO group was less. In the subgroup of patients with diabetes (Martikainen et al., 2005, Sniderman et al., 2014, and Takatori et al., 2011), differential of high-density lipoprotein cholesterol (HDL-C) in the ICO group was less. There was no significant effect on low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), or lipoprotein(a). Conclusions. ICO may be beneficial to lipid metabolism, especially for its biphasic regulation of plasma TC levels. PMID:26788499

  10. Interactions between dietary boron and thiamine affect lipid metabolism

    SciTech Connect

    Herbel, J.L.; Hunt, C.D. )

    1991-03-15

    An experiment was designed to test the hypothesis that dietary boron impacts upon the function of various coenzymes involved in energy metabolism. In a 2 {times} 7 factorially-arranged experiment, weanling, vitamin D{sub 3}-deprived rats were fed a ground corn-casein-corn oil based diet supplemented with 0 or 2 mg boron/kg and 50% of the requirement for thiamine (TM), riboflavin (RF), pantothenic acid (PA) or pyridoxine (PX); 0% for folic acid (FA) or nicotinic acid (NA). All vitamins were supplemented in adequate amounts in the control diet. At 8 weeks of age, the TM dietary treatment was the one most affected by supplemental dietary boron (SDB). In rats that were fed 50% TM, SDB increased plasma concentrations of triglyceride (TG) and activity of alanine transaminase (ALT), and the liver to body weight (L/B) ratio. However, in the SDB animals, adequate amounts of TM decreased the means of those variables to near that observed in non-SDB rats fed 50% TM. The findings suggest that an interaction between dietary boron and TM affects lipid metabolism.

  11. Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis

    PubMed Central

    Lee, Sang Hoon; Park, Moo Suk; Park, Byung Hoon; Jung, Won Jai; Lee, In Seon; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Chung, Kyung Soo

    2015-01-01

    Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n = 19] and septic shock [n = 98]) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p = 0.043, p = 0.020, p = 0.005, and p = 0.015, resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p = 0.018 and p = 0.008, resp.). Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients. PMID:26351639

  12. Arabidopsis ribosomal proteins control vacuole trafficking and developmental programs through the regulation of lipid metabolism

    SciTech Connect

    Li, Ruixi; Sun, Ruobai; Hicks, Glenn R.; Raikhel, Natasha V.

    2014-12-22

    The vacuole is the most prominent compartment in plant cells and is important for ion and protein storage. In our effort to search for key regulators in the plant vacuole sorting pathway, ribosomal large subunit 4 (rpl4d) was identified as a translational mutant defective in both vacuole trafficking and normal development. Polysome profiling of the rpl4d mutant showed reduction in polysome-bound mRNA compared with wild-type, but no significant change in the general mRNA distribution pattern. Ribsomal profiling data indicated that genes in the lipid metabolism pathways were translationally down-regulated in the rpl4d mutant. Live imaging studies by Nile red staining suggested that both polar and nonpolar lipid accumulation was reduced in meristem tissues of rpl4d mutants. Pharmacological evidence showed that sterol and sphingolipid biosynthetic inhibitors can phenocopy the defects of the rpl4d mutant, including an altered vacuole trafficking pattern. Genetic evidence from lipid biosynthetic mutants indicates that alteration in the metabolism of either sterol or sphingolipid biosynthesis resulted in vacuole trafficking defects, similar to the rpl4d mutant. Tissue-specific complementation with key enzymes from lipid biosynthesis pathways can partially rescue both vacuole trafficking and auxin-related developmental defects in the rpl4d mutant. These results indicate that lipid metabolism modulates auxin-mediated tissue differentiation and endomembrane trafficking pathways downstream of ribosomal protein function.

  13. Transcription factor Ctip2 controls epidermal lipid metabolism and regulates expression of genes involved in sphingolipid biosynthesis during skin development

    PubMed Central

    Wang, Zhixing; Kirkwood, Jay S.; Taylor, Alan W.; Stevens, Jan F.; Leid, Mark; Ganguli-Indra, Gitali; Indra, Arup K.

    2012-01-01

    The stratum corneum is composed of protein-enriched corneocytes embedded in an intercellular matrix of nonpolar lipids organized as lamellar layers and give rise to epidermal permeability barrier (EPB). EPB defects play an important role in the pathophysiology of skin diseases such as eczema. The transcriptional control of skin lipid metabolism is poorly understood. We have discovered that mouse lacking a transcription factor COUP-TF interacting protein 2 (Ctip2) exhibit EPB defects including altered keratinocyte terminal differentiation, delayed skin barrier development and interrupted neutral lipid distribution in the epidermis. We adapted herein a targeted lipidomic approach using mass spectrometry, and have determined that Ctip2−/− mice (germline deletion of Ctip2 gene) display altered composition of major epidermal lipids such as ceramides and sphingomyelins compared to wildtype at different stages of skin development. Interestingly, expressions of several genes involved in skin sphingolipid biosynthesis and metabolism were altered in mutant skin. Ctip2 was found to be recruited to the promoter region of a subset of those genes, suggesting their possible direct regulation by Ctip2. Our results confirm an important role of Ctip2 in regulating skin lipid metabolism and indicate that profiling of epidermal sphingolipid could be useful for designing effective strategies to improve barrier dysfunctions. PMID:23096701

  14. Nuclear receptors regulate lipid metabolism and oxidative stress markers in chondrocytes.

    PubMed

    Ratneswaran, Anusha; Sun, Margaret Man-Ger; Dupuis, Holly; Sawyez, Cynthia; Borradaile, Nica; Beier, Frank

    2017-04-01

    Joint homeostasis failure can result in osteoarthritis (OA). Currently, there are no treatments to alter disease progression in OA, but targeting early changes in cellular behavior has great potential. Recent data show that nuclear receptors contribute to the pathogenesis of OA and could be viable therapeutic targets, but their molecular mechanisms in cartilage are incompletely understood. This study examines global changes in gene expression after treatment with agonists for four nuclear receptor implicated in OA (LXR, PPARδ, PPARγ, and RXR). Murine articular chondrocytes were treated with agonists for LXR, PPARδ, PPARγ, or RXR and underwent microarray, qPCR, and cellular lipid analyses to evaluate changes in gene expression and lipid profile. Immunohistochemistry was conducted to compare two differentially expressed targets (Txnip, Gsta4) in control and cartilage-specific PPARδ knockout mice subjected to surgical destabilization of the medial meniscus (DMM). Nuclear receptor agonists induced different gene expression profiles with many responses affecting lipid metabolism. LXR activation downregulated gene expression of proteases involved in OA, whereas RXR agonism decreased expression of ECM components and increased expression of Mmp13. Functional assays indicate increases in cell triglyceride accumulation after PPARγ, LXR, and RXR agonism but a decrease after PPARδ agonism. PPARδ and RXR downregulate the antioxidant Gsta4, and PPARδ upregulates Txnip. Wild-type, but not PPARδ-deficient mice, display increased staining for Txnip after DMM. Collectively, these data demonstrate that nuclear receptor activation in chondrocytes primarily affects lipid metabolism. In the case of PPARδ, this change might lead to increased oxidative stress, possibly contributing to OA-associated changes.

  15. Mapping Condition-Dependent Regulation of Lipid Metabolism in Saccharomyces cerevisiae

    PubMed Central

    Jewett, Michael C.; Workman, Christopher T.; Nookaew, Intawat; Pizarro, Francisco A.; Agosin, Eduardo; Hellgren, Lars I.; Nielsen, Jens

    2013-01-01

    Lipids play a central role in cellular function as constituents of membranes, as signaling molecules, and as storage materials. Although much is known about the role of lipids in regulating specific steps of metabolism, comprehensive studies integrating genome-wide expression data, metabolite levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 13C-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis across eight environmental conditions revealed 2279 gene expression level-metabolite/lipid relationships that characterize the extent of transcriptional regulation in lipid metabolism relative to major metabolic hubs within the cell. To query this network, we developed integrative methods for correlation of multi-omics datasets that elucidate global regulatory signatures. Our data highlight many characterized regulators of lipid metabolism and reveal that sterols are regulated more at the transcriptional level than are amino acids. Beyond providing insights into the systems-level organization of lipid metabolism, we anticipate that our dataset and approach can join an emerging number of studies to be widely used for interrogating cellular systems through the combination of mathematical modeling and experimental biology. PMID:24062529

  16. Mapping condition-dependent regulation of lipid metabolism in Saccharomyces cerevisiae.

    PubMed

    Jewett, Michael C; Workman, Christopher T; Nookaew, Intawat; Pizarro, Francisco A; Agosin, Eduardo; Hellgren, Lars I; Nielsen, Jens

    2013-11-06

    Lipids play a central role in cellular function as constituents of membranes, as signaling molecules, and as storage materials. Although much is known about the role of lipids in regulating specific steps of metabolism, comprehensive studies integrating genome-wide expression data, metabolite levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 (13)C-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis across eight environmental conditions revealed 2279 gene expression level-metabolite/lipid relationships that characterize the extent of transcriptional regulation in lipid metabolism relative to major metabolic hubs within the cell. To query this network, we developed integrative methods for correlation of multi-omics datasets that elucidate global regulatory signatures. Our data highlight many characterized regulators of lipid metabolism and reveal that sterols are regulated more at the transcriptional level than are amino acids. Beyond providing insights into the systems-level organization of lipid metabolism, we anticipate that our dataset and approach can join an emerging number of studies to be widely used for interrogating cellular systems through the combination of mathematical modeling and experimental biology.

  17. SC-10DIVERGENT LIPID METABOLISM DRIVES SELF-RENEWAL IN GLIOBLASTOMA

    PubMed Central

    Hale, James; Gromovsky, Tony; Alex Brown, H.; Mark Brown, J.; Lathia, Justin

    2014-01-01

    The tumor microenvironment is essential to cancer stem cell (CSC) maintenance, providing discreet cues influencing cellular behavior. However, the mechanisms by which CSCs sense and respond to microenvironmental stresses, such as lipid availability, which regulates cellular metabolism and membrane turnover, are poorly understood. Scavenger receptors, a broad class of membrane receptors, are instrumental in the recognition and uptake of modified lipids, presenting a unique link between CSCs and the tumor microenvironment. Recent work published by our group utilizing patient-derived CSCs demonstrated elevated levels of the scavenger receptor CD36 in Glioblastoma (GBM) CSCs, with functional consequences on self-renewal and tumorigenesis. These results highlighted enhanced oxidized low-density lipoprotein uptake and utilization by CSCs and suggest that lipid metabolism is intimately linked to CSC maintenance. We therefore hypothesize that CSCs possess increased ability to take up and metabolize lipid species. We have observed increased lipid uptake and incorporation in CSCs as assessed by 14C acetate and 3H oleate. Despite increased uptake, CSCs show decreased lipid droplet accumulation as evidenced by Oil Red O staining. These results were confirmed by flow cytometry with the alternative lipid stain Nile Red. A metabolic shRNA screen is currently underway to identify potential targets in the regulation of lipid metabolism in CSCs. These data provide a paradigm by which CSCs utilize lipid species, providing survival and metabolic advantages and thereby allowing for tumor progression.

  18. Maternal obesity programs mitochondrial and lipid metabolism gene expression in infant umbilical vein endothelial cells

    PubMed Central

    Ramos Costa, Suzana Maria; Isganaitis, Elvira; Matthews, Tucker; Hughes, Katelyn; Daher, Grace; Dreyfuss, Jonathan M.; Pontes da Silva, Giselia Alves; Patti, Mary-Elizabeth

    2016-01-01

    Background/Objectives Maternal obesity increases risk for childhood obesity, but molecular mechanisms are not well understood. We hypothesized that primary umbilical vein endothelial cells (HUVEC) from infants of overweight and obese mothers would harbor transcriptional patterns reflecting offspring obesity risk. Subjects/Methods In this observational cohort study, we recruited 13 lean (pre-pregnancy BMI <25.0 kg/m2) and 24 overweight-obese (‘ov-ob’, BMI ≥25.0 kg/m2) women. We isolated primary HUVEC, and analyzed both gene expression (Primeview, Affymetrix) and cord blood levels of hormones and adipokines. Results 142 transcripts were differentially expressed in HUVEC from infants of overweight-obese mothers (false discovery rate, FDR <0.05). Pathway analysis revealed that genes involved in mitochondrial and lipid metabolism were negatively correlated with maternal BMI (FDR <0.05). To test whether these transcriptomic patterns were associated with distinct nutrient exposures in the setting of maternal obesity, we analyzed the cord blood lipidome and noted significant increases in levels of total free fatty acids (lean: 95.5 ± 37.1 ug/ml, ov-ob: 124.1 ± 46.0 ug/ml, P=0.049), palmitate (lean: 34.5 ± 12.7 ug/ml, ov-ob: 46.3 ± 18.4 ug/ml, P=0.03) and stearate (lean: 20.8 ± 8.2 ug/ml, ov-ob: 29.7 ± 17.2 ug/ml, P=0.04), in infants of overweight-obese mothers. Conclusion Prenatal exposure to maternal obesity alters HUVEC expression of genes involved in mitochondrial and lipid metabolism, potentially reflecting developmentally-programmed differences in oxidative and lipid metabolism. PMID:27531045

  19. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

    PubMed Central

    Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H. G.

    2011-01-01

    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders. PMID:21062955

  20. Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

    NASA Astrophysics Data System (ADS)

    Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-08-01

    Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.

  1. Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

    PubMed Central

    Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-01-01

    Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns. PMID:27502578

  2. Life style-related diseases of the digestive system: endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome.

    PubMed

    Wada, Koichiro; Sakamoto, Hirotada; Nishikawa, Kenji; Sakuma, Satoru; Nakajima, Atsushi; Fujimoto, Yohko; Kamisaki, Yoshinori

    2007-10-01

    Many reports indicated that endocrine disruptors (EDs) affect several hormonal functions in various living things. Here, we show the effect of EDs on lipid accumulation in target cells involved in the onset of metabolic syndrome. Treatment with nonylphenol and bisphenol A, typical EDs, stimulated the accumulation of triacylglycerol in differentiated adipocytes from 3T3-L1, preadipocytes, in time- and concentration-dependent manners. Up-regulation of gene expressions involved in lipid metabolism and metabolic syndrome were observed in adipocytes treated with EDs. Similarly, stimulatory effects of EDs were also observed on the human hepatoma cell line HuH-7. These observations indicate that exposure to EDs stimulates the lipid accumulation in target cells involved in the metabolic syndrome and may cause the dysfunction of those cells, resulting in induction of metabolic syndrome.

  3. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT.

    PubMed

    Bays, Harold E; Jones, Peter H; Jacobson, Terry A; Cohen, David E; Orringer, Carl E; Kothari, Shanu; Azagury, Dan E; Morton, John; Nguyen, Ninh T; Westman, Eric C; Horn, Deborah B; Scinta, Wendy; Primack, Craig

    2016-01-01

    Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents the contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on published data through June 2015. Part 1 of this 2 part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the full report of part 1.

  4. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: EXECUTIVE SUMMARY.

    PubMed

    Bays, Harold E; Jones, Peter H; Jacobson, Terry A; Cohen, David E; Orringer, Carl E; Kothari, Shanu; Azagury, Dan E; Morton, John; Nguyen, Ninh T; Westman, Eric C; Horn, Deborah B; Scinta, Wendy; Primack, Craig

    2016-01-01

    Bariatric procedures often improve lipid levels in patients with obesity. This 2-part scientific statement examines the potential lipid benefits of bariatric procedures and represents contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on data published through June 2015. Part 1 of this 2-part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on cardiovascular disease; and finally (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the executive summary of part 1.

  5. Multiphoton fluorescence lifetime imaging of metabolic status in mesenchymal stem cell during adipogenic differentiation

    NASA Astrophysics Data System (ADS)

    Meleshina, A. V.; Dudenkova, V. V.; Shirmanova, M. V.; Bystrova, A. S.; Zagaynova, E. V.

    2016-03-01

    Non-invasive imaging of cell metabolism is a valuable approach to assess the efficacy of stem cell therapy and understand the tissue development. In this study we analyzed metabolic trajectory of the mesenchymal stem cells (MCSs) during differentiation into adipocytes by measuring fluorescence lifetimes of free and bound forms of the reduced nicotinamide adenine dinucleotide (NAD(P)H) and flavine adenine dinucleotide (FAD). Undifferentiated MSCs and MSCs on the 5, 12, 19, 26 days of differentiation were imaged on a Zeiss 710 microscope with fluorescence lifetime imaging (FLIM) system B&H (Germany). Fluorescence of NAD(P)H and FAD was excited at 750 nm and 900 nm, respectively, by a femtosecond Ti:sapphire laser and detected in a range 455-500 nm and 500-550 nm, correspondingly. We observed the changes in the NAD(P)H and FAD fluorescence lifetimes and their relative contributions in the differentiated adipocytes compare to undifferentiated MSCs. Increase of fluorescence lifetimes of the free and bound forms of NAD(P)H and the contribution of protein-bound NAD(P)H was registered, that can be associated with a metabolic switch from glycolysis to oxidative phosphorylation and/or synthesis of lipids in adipogenically differentiated MSCs. We also found that the contribution of protein-bound FAD decreased during differentiation. After carrying out appropriate biochemical measurements, the observed changes in cellular metabolism can potentially serve to monitor stem cell differentiation by FLIM.

  6. Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection.

    PubMed

    Lovewell, Rustin R; Sassetti, Christopher M; VanderVen, Brian C

    2016-02-01

    The interplay between Mycobacterium tuberculosis lipid metabolism, the immune response and lipid homeostasis in the host creates a complex and dynamic pathogen-host interaction. Advances in imaging and metabolic analysis techniques indicate that M. tuberculosis preferentially associates with foamy cells and employs multiple physiological systems to utilize exogenously derived fatty-acids and cholesterol. Moreover, novel insights into specific host pathways that control lipid accumulation during infection, such as the PPARγ and LXR transcriptional regulators, have begun to reveal mechanisms by which host immunity alters the bacterial micro-environment. As bacterial lipid metabolism and host lipid regulatory pathways are both important, yet inherently complex, components of active tuberculosis, delineating the heterogeneity in lipid trafficking within disease states remains a major challenge for therapeutic design.

  7. The effect of maternal chromium status on lipid metabolism in female elderly mice offspring and involved molecular mechanism.

    PubMed

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-03-20

    Maternal malnutrition lead to the incidence of metabolic diseases in offspring. The purpose of this project was to exam whether maternal low chromium could disturb normal lipid metabolism in offspring, altering adipose cell differentiation and leading the incidence of lipid metabolism diseases, including metabolic syndrome and obesity. Female C57BL mice were given a control diet (CD) or a low chromium diet (LCD) during the gestational and lactation periods. After weaning, offspring was fed with CD or LCD. The female offspring were assessed at 32 weeks of age. Fresh adipose samples from CD-CD group and LCD-CD group were collected. Genome mRNA were analyzed using Affymetrix GeneChip Mouse Gene 2.0 ST Whole Transcript-based Array. Differently expressed genes were analyzed based on Gene Ontology and KEGG pathway analysis database. Maternal low chromium irreversibly increased offspring body weight, fat pad weight, serum TG and TNF-α. Eighty-five genes increased and 109 genes reduced in the offspring adipose of the maternal low chromium group. According to KEGG pathway and String analyses, the PPAR signaling pathway may be a key controlled pathway related to the effect of maternal low chromium on female offspring. Maternal chromium status have long-term effects of lipid metabolism in female mice offspring. Normalizing offspring diet can't reverse these effects. The potential underlying mechanisms are the disturbance of the PPAR signaling pathway in adipose tissue.

  8. (13)C-metabolic flux analysis of lipid accumulation in the oleaginous fungus Mucor circinelloides.

    PubMed

    Zhao, Lina; Zhang, Huaiyuan; Wang, Liping; Chen, Haiqin; Chen, Yong Q; Chen, Wei; Song, Yuanda

    2015-12-01

    The oleaginous fungus Mucor circinelloides is of industrial interest because it can produce high levels of polyunsaturated fatty acid γ-linolenic acid. M. circinelloides CBS 277.49 is able to accumulate less than 15% of cell dry weight as lipids, while M. circinelloides WJ11 can accumulate lipid up to 36%. In order to better understand the mechanisms behind the differential lipid accumulation in these two strains, tracer experiments with (13)C-glucose were performed with the growth of M. circinelloides and subsequent gas chromatography-mass spectrometric detection of (13)C-patterns in proteinogenic amino acids was carried out to identify the metabolic network topology and estimate intracellular fluxes. Our results showed that the high oleaginous strain WJ11 had higher flux of pentose phosphate pathway and malic enzyme, lower flux in tricarboxylic acid cycle, higher flux in glyoxylate cycle and ATP: citrate lyase, together, it might provide more NADPH and substrate acetyl-CoA for fatty acid synthesis.

  9. Adipose-Derived Mesenchymal Stem Cells Ameliorate Lipid Metabolic Disturbance in Mice.

    PubMed

    Liu, Guang-Yang; Liu, Jin; Wang, You-Liang; Liu, Yang; Shao, Yong; Han, Yan; Qin, Ya-Ru; Xiao, Feng-Jun; Li, Peng-Fei; Zhao, Lan-Jun; Gu, En-Yan; Chen, Si-Yu; Gao, Li-Hua; Wu, Chu-Tse; Hu, Xian-Wen; Duan, Hai-Feng

    2016-09-01

    : Adipose-derived mesenchymal stem cells (AD-MSCs) have been shown to ameliorate hyperglycemia in diabetic animals and individuals. However, little is known about whether AD-MSCs affect lipid metabolism. Here we have demonstrated for the first time that AD-MSC infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in db/db obese mice and diet-induced obesity mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia and associated cardiovascular diseases. Mesenchymal stem cells (MSCs) are considered one of the most promising types of stem cells for translational application because of their rich tissue sources, multilineage differentiation capacity, and easy amplification in vitro and unique immunobiological properties. This study demonstrated that adipose-derived MSCs (AD-MSCs) infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in obese mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue were demonstrated to contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia. ©AlphaMed Press.

  10. Effect of dietary cadmium on lipid metabolism and storage of aquatic bird Cairina moschata.

    PubMed

    Lucia, Magali; André, Jean-Marc; Gonzalez, Patrice; Baudrimont, Magalie; Bernadet, Marie-Dominique; Gontier, Karine; Maury-Brachet, Régine; Guy, Gérard; Davail, Stéphane

    2010-01-01

    In environment, birds often fast in connection with breeding, migration or drastic climatic conditions and need to mobilize lipid reserves during these periods. The impairment of lipid metabolism by cadmium (Cd; 1 mg kg(-1) added in diet) was investigated on palmiped Cairina moschata. Expression levels of genes involved in lipid metabolism, mitochondrial metabolism and detoxification were investigated in liver and muscle of ducks. Lipid content in muscle and liver were analysed and plasma triglycerides were quantified. After 20 days, ducks exposed to Cd displayed a lower body weight and lower lipid content in liver than controls. In muscle, the increase of lipid content was only significant for control ducks but not for exposed ducks. Exposed ducks appeared unable to sufficiently transport and store lipids into peripheral tissues. Cd impairs lipid metabolism by several ways. First, Cd triggered the down-regulation of fatty acids synthesis in liver even if the NADPH production and the mitochondrial metabolism are enhanced, suggesting a stronger energy needs. Secondly, the associated decrease of plasma triglycerides and lipoprotein lipase activity with Cd are consistent with impairment of lipids storage in peripheral tissues.

  11. FoxO integration of insulin signaling with glucose and lipid metabolism.

    PubMed

    Lee, Sojin; Dong, H Henry

    2017-05-01

    The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA-binding domain, known as 'forkhead box' domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senescence, autophagy and aging. Genetic mutations in FoxO genes or abnormal expression of FoxO proteins are associated with metabolic disease, cancer or altered lifespan in humans and animals. Of the FoxO family, FoxO6 is the least characterized member and is shown to play pivotal roles in the liver, skeletal muscle and brain. Altered FoxO6 expression is associated with the pathogenesis of insulin resistance, dietary obesity and type 2 diabetes and risk of neurodegeneration disease. FoxO6 is evolutionally divergent from other FoxO isoforms. FoxO6 mediates insulin action on target genes in a mechanism that is fundamentally different from other FoxO members. Here, we focus our review on the role of FoxO6, in contrast with other FoxO isoforms, in health and disease. We review the distinctive mechanism by which FoxO6 integrates insulin signaling to hepatic glucose and lipid metabolism. We highlight the importance of FoxO6 dysregulation in the dual pathogenesis of fasting hyperglycemia and hyperlipidemia in diabetes. We review the role of FoxO6 in memory consolidation and its contribution to neurodegeneration disease and aging. We discuss the potential therapeutic option of pharmacological FoxO6 inhibition for improving glucose and lipid metabolism in diabetes. © 2017 Society for Endocrinology.

  12. Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes.

    PubMed

    Luquet, Serge; Gaudel, Celine; Holst, Dorte; Lopez-Soriano, Joaquin; Jehl-Pietri, Chantal; Fredenrich, Alexandre; Grimaldi, Paul A

    2005-05-30

    Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARalpha, activated by polyunsaturated fatty acids and fibrates, is implicated in regulation of lipid metabolism, lipoprotein synthesis and metabolism and inflammatory response in liver and other tissues. PPARgamma plays important roles in regulation of proliferation and differentiation of several cell types, including adipose cells. Its activation by thiazolidinediones results in insulin sensibilization and antidiabetic action. Until recently, the physiological functions of PPARdelta remain elusive. The utilization of specific agonists and of appropriate cellular and animal models revealed that PPARdelta has an important role in metabolic adaptation of several tissues to environmental changes. Treatment of obese animals by specific PPARdelta agonists results in normalization of metabolic parameters and reduction of adiposity. The nuclear receptor appeared to be implicated in the regulation of fatty acid burning capacities of skeletal muscle and adipose tissue by controlling the expression of genes involved in fatty acid uptake, beta-oxidation and energy uncoupling. PPARdelta is also implicated in the adaptive metabolic response of skeletal muscle to endurance exercise by controlling the number of oxidative myofibers. Given the results obtained with animal models, PPARdelta agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue.

  13. Dietary fenofibrate reduces hepatic lipid deposition by regulating lipid metabolism in yellow catfish Pelteobagrus fulvidraco exposed to waterborne Zn.

    PubMed

    Zheng, Jia-Lang; Luo, Zhi; Hu, Wei; Pan, Ya-Xiong; Zhuo, Mei-Qing

    2015-04-01

    Fenofibrate is known to possess lipid-lowering effects by regulation of gene transcription involved in lipid metabolism. Waterborne Zn exposure induces lipid deposition in yellow catfish Pelteobagrus fulvidraco. Thus, the present working hypothesis is that dietary fenofibrate addition will reduce hepatic lipids in yellow catfish exposed to waterborne Zn. To this end, juvenile yellow catfish were exposed to 0.04 (control), 0.35 mg/L waterborne Zn, 0.15% dietary fenofibrate, and 0.35 mg Zn/l + 0.15% dietary fenofibrate for 8 weeks. Growth performance, lipid deposition and metabolism in the liver were determined. Dietary fenofibrate promoted growth performance and reduced hepatic lipid content of yellow catfish exposed to waterborne Zn. However, these effects did not appear in fish in normal water. The lipid-lowering effect of fenofibrate on fish exposed to waterborne Zn was associated with increased lipolysis, as indicated by increased CPT I activities and expression of lipolytic genes PPARα, CPT IA, ATGL and HSL, and with reduced lipogenesis as indicated by reduced activities of G6PD, 6PGD, ME and ICDH. Dietary fenofibrate significantly increased mRNA levels of FAS, LPL and ACCα, but reduced mRNA levels of ACCβ and PPARγ in fish exposed to waterborne Zn. Pearson correlations between transcriptional factors expression, and activities and expression of several enzymes were observed, indicating that changes at the molecular and enzymatic levels may underlie the patterns of lipid metabolism and accordingly affect hepatic fat storage. Taken together, our results suggest that the lipid-lowering effect of fenofibrate was attributed, in part, to the down-regulation of lipogenesis and up-regulation of fatty acid oxidation.

  14. Regulation of exercise-induced lipid metabolism in skeletal muscle.

    PubMed

    Jordy, Andreas Børsting; Kiens, Bente

    2014-12-01

    Exercise increases the utilization of lipids in muscle. The sources of lipids are long-chain fatty acids taken up from the plasma and fatty acids released from stores of intramuscular triacylglycerol by the action of intramuscular lipases. In the present review, we focus on the role of fatty acid binding proteins, particularly fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in the exercise- and contraction-induced increase in uptake of long-chain fatty acids in muscle. The FAT/CD36 translocates from intracellular depots to the surface membrane upon initiation of exercise/muscle contractions. This occurs independently of AMP-activated protein kinase, and data suggest that Ca(2+)-related signalling is responsible. The FAT/CD36 has an important role; long-chain fatty acid uptake is markedly decreased in FAT/CD36 knockout mice during contractions/exercise compared with wild-type control mice. In skeletal muscle, 98% of the lipase activity is accounted for by adipose triglyceride lipase and hormone-sensitive lipase. Give that inhibition or knockout of hormone-sensitive lipase does not impair lipolysis in muscle during contraction, the data point to an important role of adipose triglyceride lipase in regulation of muscle lipolysis. Although the molecular regulation of the lipases in muscle is not understood, it is speculated that intramuscular lipolysis may be regulated in part by the availability of the plasma concentration of long-chain fatty acids. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  15. Metabolic switches during the first steps of adipogenic stem cells differentiation.

    PubMed

    Drehmer, Daiana Leila; de Aguiar, Alessandra Melo; Brandt, Anna Paula; Petiz, Lyvia; Cadena, Sílvia Maria Suter Correia; Rebelatto, Carmen K; Brofman, Paulo R S; Filipak Neto, Francisco; Dallagiovanna, Bruno; Abud, Ana Paula Ressetti

    2016-09-01

    The understanding of metabolism during cell proliferation and commitment provides a greater insight into the basic biology of cells, allowing future applications. Here we evaluated the energy and oxidative changes during the early adipogenic differentiation of human adipose tissue-derived stromal cells (hASCs). hASCs were maintained under differentiation conditions during 3 and 7days. Oxygen consumption, mitochondrial mass and membrane potential, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) and catalase activities, non-protein thiols (NPT) concentration and lipid peroxidation were analyzed. We observed that 7days of adipogenic induction are required to stimulate cells to consume more oxygen and increase mitochondrial activity, indicating organelle maturation and a transition from glycolytic to oxidative energy metabolism. ROS production was only increased after 3days and may be involved in the differentiation commitment. ROS source was not only the mitochondria and we suggest that NOX proteins are related to ROS generation and therefore adipogenic commitment. ROS production did not change after 7days, but an increased activity of catalase and NPT concentration as well as a decreased lipid peroxidation were observed. Thus, a short period of differentiation induction is able to change the energetic and oxidative metabolic profile of hASCs and stimulate cytoprotection processes. Copyright © 2016. Published by Elsevier B.V.

  16. Maternal omega-3 fatty acids and micronutrients modulate fetal lipid metabolism: A review.

    PubMed

    Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-07-01

    It is well established that alterations in the mother's diet or metabolism during pregnancy has long-term adverse effects on the lipid metabolism in the offspring. There is growing interest in the role of specific nutrients especially omega-3 fatty acids in the pathophysiology of lipid disorders. A series of studies carried out in humans and rodents in our department have consistently suggested a link between omega-3 fatty acids especially docosahexaenoic acid and micronutrients (vitamin B12 and folic acid) in the one carbon metabolic cycle and its effect on the fatty acid metabolism, hepatic transcription factors and DNA methylation patterns. However the association of maternal intake or metabolism of these nutrients with fetal lipid metabolism is relatively less explored. In this review, we provide insights into the role of maternal omega-3 fatty acids and vitamin B12 and their influence on fetal lipid metabolism through various mechanisms which influence phosphatidylethanolamine-N-methyltransferase activity, peroxisome proliferator activated receptor, adiponectin signaling pathway and epigenetic process like chromatin methylation. This will help understand the possible mechanisms involved in fetal lipid metabolism and may provide important clues for the prevention of lipid disorders in the offspring.

  17. Storage lipids of yeasts: a survey of nonpolar lipid metabolism in Saccharomyces cerevisiae, Pichia pastoris, and Yarrowia lipolytica.

    PubMed

    Koch, Barbara; Schmidt, Claudia; Daum, Günther

    2014-09-01

    Biosynthesis and storage of nonpolar lipids, such as triacylglycerols (TG) and steryl esters (SE), have gained much interest during the last decades because defects in these processes are related to severe human diseases. The baker's yeast Saccharomyces cerevisiae has become a valuable tool to study eukaryotic lipid metabolism because this single-cell microorganism harbors many enzymes and pathways with counterparts in mammalian cells. In this article, we will review aspects of TG and SE metabolism and turnover in the yeast that have been known for a long time and combine them with new perceptions of nonpolar lipid research. We will provide a detailed insight into the mechanisms of nonpolar lipid synthesis, storage, mobilization, and degradation in the yeast S. cerevisiae. The central role of lipid droplets (LD) in these processes will be addressed with emphasis on the prevailing view that this compartment is more than only a depot for TG and SE. Dynamic and interactive aspects of LD with other organelles will be discussed. Results obtained with S. cerevisiae will be complemented by recent investigations of nonpolar lipid research with Yarrowia lipolytica and Pichia pastoris. Altogether, this review article provides a comprehensive view of nonpolar lipid research in yeast.

  18. Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.

    PubMed

    Li, Xin-Hua; Gong, Qi-Ming; Ling, Yun; Huang, Chong; Yu, De-Min; Gu, Lei-Lei; Liao, Xiang-Wei; Zhang, Dong-Hua; Hu, Xi-Qi; Han, Yue; Kong, Xiao-Fei; Zhang, Xin-Xin

    2014-12-05

    We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.

  19. Associations among Metabolic Syndrome, Ischemia, Inflammatory, Oxidatives, and Lipids Biomarkers

    PubMed Central

    Valle Gottlieb, Maria Gabriela; da Cruz, Ivana Beatrice Mânica; Duarte, Marta M. F.; Moresco, Rafael Noal; Wiehe, Mário; Schwanke, Carla Helena Augustin; Bodanese, Luiz Carlos

    2010-01-01

    Context: Metabolic syndrome (MS) is described as a cluster of cardiometabolic risk factors. Studies suggest that ischemia-modified albumin (IMA) is a biomarker of cardiovascular diseases. IMA levels could be associated with cardiometabolic risks and represent a possible indication of microvascular dysfunction in MS patients. Objective: To confirm this possible association, we evaluated the association between IMA levels and MS. Design: We performed a case-control study (32 healthy individuals and 74 subjects with MS) to evaluate the association between MS, IMA, and other biomarkers [high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (OxLDL), oxidized low-density lipoprotein autoantibodies (anti-OxLDL), IL-6, lipid profile, and glucose]. Results: The MS group showed higher levels of IMA (0.618 ± 0.1355) as well as higher levels of hs-CRP, OxLDL, anti-OxLDL, and IL-6 than did control subjects (IMA = 0.338 ± 0.0486) (P < 0.01). Multivariate analysis showed that IMA and MS association was independent of sex, age, diabetes mellitus 2, and hypercholesterolemia. Conclusion: We found an association between IMA and MS. Additional studies including prospective genetic variation approaches need to be performed to help elucidate this association between IMA and MS and its potential clinical role. PMID:20016051

  20. Peripheral serotonin enhances lipid metabolism by accelerating bile acid turnover.

    PubMed

    Watanabe, Hitoshi; Akasaka, Daisuke; Ogasawara, Hideki; Sato, Kan; Miyake, Masato; Saito, Kazuki; Takahashi, Yu; Kanaya, Takashi; Takakura, Ikuro; Hondo, Tetsuya; Chao, Guozheng; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Yamaguchi, Takahiro; Aso, Hisashi

    2010-10-01

    Serotonin is synthesized by two distinct tryptophan hydroxylases, one in the brain and one in the periphery. The latter is known to be unable to cross the blood-brain barrier. These two serotonin systems have apparently independent functions, although the functions of peripheral serotonin have yet to be fully elucidated. In this study, we have investigated the physiological effect of peripheral serotonin on the concentrations of metabolites in the circulation and in the liver. After fasting, mice were ip injected with 1 mg serotonin. The plasma glucose concentration was significantly elevated between 60 and 270 min after the injection. In contrast, plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations were decreased. The hepatic glycogen synthesis and concentrations were significantly higher at 240 min. At the same time, the hepatic triglyceride content was significantly lower than the basal levels noted before the serotonin injection, whereas the hepatic cholesterol content was significantly higher by 60 min after the injection. Furthermore, serotonin stimulated the contraction of the gallbladder and the excretion of bile. After the serotonin injection, there was a significant induction of apical sodium-dependent bile acid transporter expression, resulting in a decrease in the concentration of bile acids in the feces. Additionally, data are presented to show that the functions of serotonin are mediated through diverse serotonin receptor subtypes. These data indicate that peripheral serotonin accelerates the metabolism of lipid by increasing the concentration of bile acids in circulation.

  1. Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells

    PubMed Central

    DAKER, MAELINDA; BHUVANENDRAN, SAATHEEYAVAANE; AHMAD, MUNIRAH; TAKADA, KENZO; KHOO, ALAN SOO-BENG

    2012-01-01

    Nasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, closely associated with the Epstein-Barr virus (EBV). EBV-encoded RNAs (EBERs) are small non-polyadenylated RNAs that are abundantly expressed in latent EBV-infected NPC cells. To study the role of EBERs in NPC, we established stable expression of EBERs in HK1, an EBV-negative NPC cell line. Cells expressing EBERs consistently exhibited an increased growth rate. However, EBERs did not confer resistance towards cisplatin-induced apoptosis or promote migration or invasion ability in the cells tested. Using microarray gene expression profiling, we identified potential candidate genes that were deregulated in NPC cells expressing EBERs. Gene Ontology analysis of the data set revealed that EBERs upregulate the cellular lipid metabolic process. Upregulation of low-density lipoprotein receptor (LDLR) and fatty acid synthase (FASN) was observed in EBER-expressing cells. NPC cells exhibited LDL-dependent cell proliferation. In addition, a polyphenolic flavonoid compound, quercetin, known to inhibit FASN, was found to inhibit proliferation of NPC cells. PMID:23292678

  2. The role of lipid droplets in metabolic disease in rodents and humans

    PubMed Central

    Greenberg, Andrew S.; Coleman, Rosalind A.; Kraemer, Fredric B.; McManaman, James L.; Obin, Martin S.; Puri, Vishwajeet; Yan, Qing-Wu; Miyoshi, Hideaki; Mashek, Douglas G.

    2011-01-01

    Lipid droplets (LDs) are intracellular organelles that store neutral lipids within cells. Over the last two decades there has been a dramatic growth in our understanding of LD biology and, in parallel, our understanding of the role of LDs in health and disease. In its simplest form, the LD regulates the storage and hydrolysis of neutral lipids, including triacylglycerol and/or cholesterol esters. It is becoming increasingly evident that alterations in the regulation of LD physiology and metabolism influence the risk of developing metabolic diseases such as diabetes. In this review we provide an update on the role of LD-associated proteins and LDs in metabolic disease. PMID:21633178

  3. Acylcarnitines participate in developmental processes associated to lipid metabolism in plants.

    PubMed

    Nguyen, Phuong-Jean; Rippa, Sonia; Rossez, Yannick; Perrin, Yolande

    2016-04-01

    Plant acylcarnitines are present during anabolic processes of lipid metabolism. Their low contents relatively to the corresponding acyl-CoAs suggest that they are associated to specific pools of activated fatty acids. The non-proteinaceous amino acid carnitine exists in plants either as a free form or esterified to fatty acids. To clarify the biological significance of acylcarnitines in plant lipid metabolism, we have analyzed their content in plant extracts using an optimized tandem mass spectrometry coupled to liquid chromatography method. We have studied different developmental processes (post-germination, organogenesis, embryogenesis) targeted for their high requirement for lipid metabolism. The modulation of the acylcarnitine content was compared to that of the lipid composition and lipid biosynthetic gene expression level in the analyzed materials. Arabidopsis mutants were also studied based on their alteration in de novo fatty acid partitioning between the prokaryotic and eukaryotic pathways of lipid biosynthesis. We show that acylcarnitines cannot specifically be associated to triacylglycerol catabolism but that they are also associated to anabolic pathways of lipid metabolism. They are present during membrane and storage lipid biosynthesis processes. A great divergence in the relative contents of acylcarnitines as compared to the corresponding acyl-CoAs suggests that acylcarnitines are associated to very specific process(es) of lipid metabolism. The nature of their involvement as the transport form of activated fatty acids or in connection with the management of acyl-CoA pools is discussed. Also, the occurrence of medium-chain entities suggests that acylcarnitines are associated with additional lipid processes such as protein acylation for instance. This work strengthens the understanding of the role of acylcarnitines in plant lipid metabolism, probably in the management of specific acyl-CoA pools.

  4. Acyl-CoA N-acyltransferase influences fertility by regulating lipid metabolism and jasmonic acid biogenesis in cotton

    PubMed Central

    Fu, Wenfeng; Shen, Ying; Hao, Juan; Wu, Jianyong; Ke, Liping; Wu, Caiyun; Huang, Kai; Luo, Binglun; Xu, Mingfeng; Cheng, Xiaofei; Zhou, Xueping; Sun, Jie; Xing, Chaozhu; Sun, Yuqiang

    2015-01-01

    Cotton (Gossypium spp.) is an important economic crop and there is obvious heterosis in cotton, fertility has played an important role in this heterosis. However, the genes that exhibit critical roles in anther development and fertility are not well understood. Here, we report an acyl-CoA N-acyltransferase (EC2.3; GhACNAT) that plays a key role in anther development and fertility. Suppression of GhACNAT by virus-induced gene silencing in transgenic cotton (G. hirsutum L. cv. C312) resulted in indehiscent anthers that were full of pollen, diminished filaments and stamens, and plant sterility. We found GhACNAT was involved in lipid metabolism and jasmonic acid (JA) biosynthesis. The genes differentially expressed in GhACNAT-silenced plants and C312 were mainly involved in catalytic activity and transcription regulator activity in lipid metabolism. In GhACNAT-silenced plants, the expression levels of genes involved in lipid metabolism and jasmonic acid biosynthesis were significantly changed, the amount of JA in leaves and reproductive organs was significantly decreased compared with the amounts in C312. Treatments with exogenous methyl jasmonate rescued anther dehiscence and pollen release in GhACNAT-silenced plants and caused self-fertility. The GhACNAT gene may play an important role in controlling cotton fertility by regulating the pathways of lipid synthesis and JA biogenesis. PMID:26134787

  5. Acyl-CoA N-acyltransferase influences fertility by regulating lipid metabolism and jasmonic acid biogenesis in cotton.

    PubMed

    Fu, Wenfeng; Shen, Ying; Hao, Juan; Wu, Jianyong; Ke, Liping; Wu, Caiyun; Huang, Kai; Luo, Binglun; Xu, Mingfeng; Cheng, Xiaofei; Zhou, Xueping; Sun, Jie; Xing, Chaozhu; Sun, Yuqiang

    2015-07-02

    Cotton (Gossypium spp.) is an important economic crop and there is obvious heterosis in cotton, fertility has played an important role in this heterosis. However, the genes that exhibit critical roles in anther development and fertility are not well understood. Here, we report an acyl-CoA N-acyltransferase (EC2.3; GhACNAT) that plays a key role in anther development and fertility. Suppression of GhACNAT by virus-induced gene silencing in transgenic cotton (G. hirsutum L. cv. C312) resulted in indehiscent anthers that were full of pollen, diminished filaments and stamens, and plant sterility. We found GhACNAT was involved in lipid metabolism and jasmonic acid (JA) biosynthesis. The genes differentially expressed in GhACNAT-silenced plants and C312 were mainly involved in catalytic activity and transcription regulator activity in lipid metabolism. In GhACNAT-silenced plants, the expression levels of genes involved in lipid metabolism and jasmonic acid biosynthesis were significantly changed, the amount of JA in leaves and reproductive organs was significantly decreased compared with the amounts in C312. Treatments with exogenous methyl jasmonate rescued anther dehiscence and pollen release in GhACNAT-silenced plants and caused self-fertility. The GhACNAT gene may play an important role in controlling cotton fertility by regulating the pathways of lipid synthesis and JA biogenesis.

  6. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

    PubMed Central

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Yan, Zuoqin; Qian, Ruizhe

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation. PMID:27631008

  7. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition.

    PubMed

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Qian, Ruizhe; Lu, Chao

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  8. Integration of lipidomics and transcriptomics unravels aberrant lipid metabolism and defines cholesteryl oleate as potential biomarker of prostate cancer

    NASA Astrophysics Data System (ADS)

    Li, Jia; Ren, Shancheng; Piao, Hai-Long; Wang, Fubo; Yin, Peiyuan; Xu, Chuanliang; Lu, Xin; Ye, Guozhu; Shao, Yaping; Yan, Min; Zhao, Xinjie; Sun, Yinghao; Xu, Guowang

    2016-02-01

    In-depth delineation of lipid metabolism in prostate cancer (PCa) is significant to open new insights into prostate tumorigenesis and progression, and provide potential biomarkers with greater accuracy for improved diagnosis. Here, we performed lipidomics and transcriptomics in paired prostate cancer tumor (PCT) and adjacent nontumor (ANT) tissues, followed by external validation of biomarker candidates. We identified major dysregulated pathways involving lipogenesis, lipid uptake and phospholipids remodeling, correlated with widespread lipid accumulation and lipid compositional reprogramming in PCa. Specifically, cholesteryl esters (CEs) were most prominently accumulated in PCa, and significantly associated with cancer progression and metastasis. We showed that overexpressed scavenger receptor class B type I (SR-BI) may contribute to CEs accumulation. In discovery set, CEs robustly differentiated PCa from nontumor (area under curve (AUC) of receiver operating characteristics (ROC), 0.90-0.94). In validation set, CEs potently distinguished PCa and non-malignance (AUC, 0.84-0.91), and discriminated PCa and benign prostatic hyperplasia (BPH) (AUC, 0.90-0.96), superior to serum prostate-specific antigen (PSA) (AUC = 0.83). Cholesteryl oleate showed highest AUCs in distinguishing PCa from non-malignance or BPH (AUC = 0.91 and 0.96). Collectively, our results unravel the major lipid metabolic aberrations in PCa and imply the potential role of CEs, particularly, cholesteryl oleate, as molecular biomarker for PCa detection.

  9. Integration of lipidomics and transcriptomics unravels aberrant lipid metabolism and defines cholesteryl oleate as potential biomarker of prostate cancer

    PubMed Central

    Li, Jia; Ren, Shancheng; Piao, Hai-long; Wang, Fubo; Yin, Peiyuan; Xu, Chuanliang; Lu, Xin; Ye, Guozhu; Shao, Yaping; Yan, Min; Zhao, Xinjie; Sun, Yinghao; Xu, Guowang

    2016-01-01

    In-depth delineation of lipid metabolism in prostate cancer (PCa) is significant to open new insights into prostate tumorigenesis and progression, and provide potential biomarkers with greater accuracy for improved diagnosis. Here, we performed lipidomics and transcriptomics in paired prostate cancer tumor (PCT) and adjacent nontumor (ANT) tissues, followed by external validation of biomarker candidates. We identified major dysregulated pathways involving lipogenesis, lipid uptake and phospholipids remodeling, correlated with widespread lipid accumulation and lipid compositional reprogramming in PCa. Specifically, cholesteryl esters (CEs) were most prominently accumulated in PCa, and significantly associated with cancer progression and metastasis. We showed that overexpressed scavenger receptor class B type I (SR-BI) may contribute to CEs accumulation. In discovery set, CEs robustly differentiated PCa from nontumor (area under curve (AUC) of receiver operating characteristics (ROC), 0.90–0.94). In validation set, CEs potently distinguished PCa and non-malignance (AUC, 0.84–0.91), and discriminated PCa and benign prostatic hyperplasia (BPH) (AUC, 0.90–0.96), superior to serum prostate-specific antigen (PSA) (AUC = 0.83). Cholesteryl oleate showed highest AUCs in distinguishing PCa from non-malignance or BPH (AUC = 0.91 and 0.96). Collectively, our results unravel the major lipid metabolic aberrations in PCa and imply the potential role of CEs, particularly, cholesteryl oleate, as molecular biomarker for PCa detection. PMID:26865432

  10. Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

    PubMed

    Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

    2017-08-10

    One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism

    PubMed Central

    Duparc, Thibaut; Plovier, Hubert; Marrachelli, Vannina G; Van Hul, Matthias; Essaghir, Ahmed; Ståhlman, Marcus; Matamoros, Sébastien; Geurts, Lucie; Pardo-Tendero, Mercedes M; Druart, Céline; Delzenne, Nathalie M; Demoulin, Jean-Baptiste; van der Merwe, Schalk W; van Pelt, Jos; Bäckhed, Fredrik; Monleon, Daniel; Everard, Amandine; Cani, Patrice D

    2017-01-01

    Objective To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. Design To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non-alcoholic steatohepatitis (NASH). Results Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. Conclusions Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans. PMID

  12. Imaging and lipidomics methods for lipid analysis in metabolic and cardiovascular disease.

    PubMed

    Stevens, K G; Bader, C A; Sorvina, A; Brooks, D A; Plush, S E; Morrison, J L

    2017-07-12

    Cardiometabolic diseases exhibit changes in lipid biology, which is important as lipids have critical roles in membrane architecture, signalling, hormone synthesis, homoeostasis and metabolism. However, Developmental Origins of Health and Disease studies of cardiometabolic disease rarely include analysis of lipids. This short review highlights some examples of lipid pathology and then explores the technology available for analysing lipids, focussing on the need to develop imaging modalities for intracellular lipids. Analytical methods for studying interactions between the complex endocrine and intracellular signalling pathways that regulate lipid metabolism have been critical in expanding our understanding of how cardiometabolic diseases develop in association with obesity and dietary factors. Biochemical methods can be used to generate detailed lipid profiles to establish links between lifestyle factors and metabolic signalling pathways and determine how changes in specific lipid subtypes in plasma and homogenized tissue are associated with disease progression. New imaging modalities enable the specific visualization of intracellular lipid traffic and distribution in situ. These techniques provide a dynamic picture of the interactions between lipid storage, mobilization and signalling, which operate during normal cell function and are altered in many important diseases. The development of methods for imaging intracellular lipids can provide a dynamic real-time picture of how lipids are involved in complex signalling and other cell biology pathways; and how they ultimately regulate metabolic function/homoeostasis during early development. Some imaging modalities have the potential to be adapted for in vivo applications, and may enable the direct visualization of progression of pathogenesis of cardiometabolic disease after poor growth in early life.

  13. Cancer Cells Differentially Activate and Thrive on De Novo Lipid Synthesis Pathways in a Low-Lipid Environment

    PubMed Central

    Daniëls, Veerle W.; Smans, Karine; Royaux, Ines; Chypre, Melanie

    2014-01-01

    the cancer cell's lipid metabolism. PMID:25215509

  14. Sphingomyelin metabolism is involved in the differentiation of MDCK cells induced by environmental hypertonicity

    PubMed Central

    Favale, Nicolás Octavio; Santacreu, Bruno Jaime; Pescio, Lucila Gisele; Marquez, Maria Gabriela; Sterin-Speziale, Norma Beatriz

    2015-01-01

    Sphingolipids (SLs) are relevant lipid components of eukaryotic cells. Besides regulating various cellular processes, SLs provide the structural framework for plasma membrane organization. Particularly, SM is associated with detergent-resistant microdomains. We have previously shown that the adherens junction (AJ) complex, the relevant cell-cell adhesion structure involved in cell differentiation and tissue organization, is located in an SM-rich membrane lipid domain. We have also demonstrated that under hypertonic conditions, Madin-Darby canine kidney (MDCK) cells acquire a differentiated phenotype with changes in SL metabolism. For these reasons, we decided to evaluate whether SM metabolism is involved in the acquisition of the differentiated phenotype of MDCK cells. We found that SM synthesis mediated by SM synthase 1 is involved in hypertonicity-induced formation of mature AJs, necessary for correct epithelial cell differentiation. Inhibition of SM synthesis impaired the acquisition of mature AJs, evoking a disintegration-like process reflected by the dissipation of E-cadherin and β- and α-catenins from the AJ complex. As a consequence, MDCK cells did not develop the hypertonicity-induced differentiated epithelial cell phenotype. PMID:25670801

  15. Lipid droplets fusion in adipocyte differentiated 3T3-L1 cells: A Monte Carlo simulation

    SciTech Connect

    Boschi, Federico; Rizzatti, Vanni; Zamboni, Mauro; Sbarbati, Andrea

    2014-02-15

    Several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis, atherosclerosis and other metabolic pathologies are related to the excessive accumulation of lipids in cells. Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes. It has been suggested that LDs can grow in size due to a fusion process by which a larger LD is obtained with spherical shape and volume equal to the sum of the progenitors’ ones. In this study, the size distribution of two populations of LDs was analyzed in immature and mature (5-days differentiated) 3T3-L1 adipocytes (first and second populations, respectively) after Oil Red O staining. A Monte Carlo simulation of interaction between LDs has been developed in order to quantify the size distribution and the number of fusion events needed to obtain the distribution of the second population size starting from the first one. Four models are presented here based on different kinds of interaction: a surface weighted interaction (R2 Model), a volume weighted interaction (R3 Model), a random interaction (Random model) and an interaction related to the place where the LDs are born (Nearest Model). The last two models mimic quite well the behavior found in the experimental data. This work represents a first step in developing numerical simulations of the LDs growth process. Due to the complex phenomena involving LDs (absorption, growth through additional neutral lipid deposition in existing droplets, de novo formation and catabolism) the study focuses on the fusion process. The results suggest that, to obtain the observed size distribution, a number of fusion events comparable with the number of LDs themselves is needed. Moreover the MC approach results a powerful tool for investigating the LDs growth process. Highlights: • We evaluated the role of the fusion process in the synthesis of the lipid droplets. • We compared the

  16. Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis

    PubMed Central

    Lee, Sunjae; Mardinoglu, Adil; Zhang, Cheng; Lee, Doheon; Nielsen, Jens

    2016-01-01

    Hepatocellular carcinoma (HCC) has a high mortality rate and early detection of HCC is crucial for the application of effective treatment strategies. HCC is typically caused by either viral hepatitis infection or by fatty liver disease. To diagnose and treat HCC it is necessary to elucidate the underlying molecular mechanisms. As a major cause for development of HCC is fatty liver disease, we here investigated anomalies in regulation of lipid metabolism in the liver. We applied a tailored network-based approach to identify signaling hubs associated with regulation of this part of metabolism. Using transcriptomics data of HCC patients, we identified significant dysregulated expressions of lipid-regulated genes, across many different lipid metabolic pathways. Our findings, however, show that viral hepatitis causes HCC by a distinct mechanism, less likely involving lipid anomalies. Based on our analysis we suggest signaling hub genes governing overall catabolic or anabolic pathways, as novel drug targets for treatment of HCC that involves lipid anomalies. PMID:27216817

  17. Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses

    PubMed Central

    Villareal, Valerie A.; Rodgers, Mary A.; Costello, Deirdre A.; Yang, Priscilla L.

    2015-01-01

    Lipids are necessary for every step in the replication cycle of hepatitis C virus (HCV) and dengue virus (DENV), members of the family Flaviviridae. Recent studies have demonstrated that discrete steps in the replication cycles of these viruses can be inhibited by pharmacological agents that target host factors mediating lipid synthesis, metabolism, trafficking, and signal transduction. Despite this, targeting host lipid metabolism and trafficking as an antiviral strategy by blockade of entire pathways may be limited due to host toxicity. Knowledge of the molecular details of lipid structure and function in replication and the mechanisms whereby specific lipids are generated and trafficked to the relevant sites may enable more targeted antiviral strategies without global effects on the host cell. In this review, we discuss lipids demonstrated to be critical to the replication cycles of HCV and DENV and highlight potential areas for anti-viral development. This review article forms part of a symposium on flavivirus drug discovery in Antiviral Research. PMID:26526588

  18. Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses.

    PubMed

    Villareal, Valerie A; Rodgers, Mary A; Costello, Deirdre A; Yang, Priscilla L

    2015-12-01

    Lipids are necessary for every step in the replication cycle of hepatitis C virus (HCV) and dengue virus (DENV), members of the family Flaviviridae. Recent studies have demonstrated that discrete steps in the replication cycles of these viruses can be inhibited by pharmacological agents that target host factors mediating lipid synthesis, metabolism, trafficking, and signal transduction. Despite this, targeting host lipid metabolism and trafficking as an antiviral strategy by blockade of entire pathways may be limited due to host toxicity. Knowledge of the molecular details of lipid structure and function in replication and the mechanisms whereby specific lipids are generated and trafficked to the relevant sites may enable more targeted antiviral strategies without global effects on the host cell. In this review, we discuss lipids demonstrated to be critical to the replication cycles of HCV and DENV and highlight potential areas for anti-viral development. This review article forms part of a symposium on flavivirus drug discovery in Antiviral Research.

  19. Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells.

    PubMed

    Li, Junjie; Condello, Salvatore; Thomes-Pepin, Jessica; Ma, Xiaoxiao; Xia, Yu; Hurley, Thomas D; Matei, Daniela; Cheng, Ji-Xin

    2017-03-02

    Lack of sensitive single-cell analysis tools has limited the characterization of metabolic activity in cancer stem cells. By hyperspectral-stimulated Raman scattering imaging of single living cells and mass spectrometry analysis of extracted lipids, we report here significantly increased levels of unsaturated lipids in ovarian cancer stem cells (CSCs) as compared to non-CSCs. Higher lipid unsaturation levels were also detected in CSC-enriched spheroids compared to monolayer cultures of ovarian cancer cell lines or primary cells. Inhibition of lipid desaturases effectively eliminated CSCs, suppressed sphere formation in vitro, and blocked tumor initiation capacity in vivo. Mechanistically, we demonstrate that nuclear factor κB (NF-κB) directly regulates the expression levels of lipid desaturases, and inhibition of desaturases blocks NF-κB signaling. Collectively, our findings reveal that increased lipid unsaturation is a metabolic marker for ovarian CSCs and a target for CSC-specific therapy.

  20. Effects of gemfibrozil on lipid metabolism, steroidogenesis and reproduction in the fathead minnow (Pimephales promelas)

    EPA Science Inventory

    Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome proliferator-activated receptors (PPARs), which are transcriptional cofactors that regulate expression of genes related to lipid metabolism. Gemfibrozil is a fi...

  1. Effects of gemfibrozil on lipid metabolism, steroidogenesis and reproduction in the fathead minnow (Pimephales promelas)

    EPA Science Inventory

    Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome proliferator-activated receptors (PPARs), which are transcriptional cofactors that regulate expression of genes related to lipid metabolism. Gemfibrozil is a fi...

  2. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    PubMed Central

    Meng, Shengxi; Cao, Jianmei; Feng, Qin; Peng, Jinghua; Hu, Yiyang

    2013-01-01

    Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism. PMID:24062792

  3. Dynamics of human adipose lipid turnover in health and metabolic disease.

    PubMed

    Arner, Peter; Bernard, Samuel; Salehpour, Mehran; Possnert, Göran; Liebl, Jakob; Steier, Peter; Buchholz, Bruce A; Eriksson, Mats; Arner, Erik; Hauner, Hans; Skurk, Thomas; Rydén, Mikael; Frayn, Keith N; Spalding, Kirsty L

    2011-09-25

    Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.

  4. MALDI Mass Spectrometry Imaging of Lipids and Gene Expression Reveals Differences in Fatty Acid Metabolism between Follicular Compartments in Porcine Ovaries

    PubMed Central

    Uzbekova, Svetlana; Elis, Sebastien; Teixeira-Gomes, Ana-Paula; Desmarchais, Alice; Maillard, Virginie; Labas, Valerie

    2015-01-01

    In mammals, oocytes develop inside the ovarian follicles; this process is strongly supported by the surrounding follicular environment consisting of cumulus, granulosa and theca cells, and follicular fluid. In the antral follicle, the final stages of oogenesis require large amounts of energy that is produced by follicular cells from substrates including glucose, amino acids and fatty acids (FAs). Since lipid metabolism plays an important role in acquiring oocyte developmental competence, the aim of this study was to investigate site-specificity of lipid metabolism in ovaries by comparing lipid profiles and expression of FA metabolism-related genes in different ovarian compartments. Using MALDI Mass Spectrometry Imaging, images of porcine ovary sections were reconstructed from lipid ion signals for the first time. Cluster analysis of ion spectra revealed differences in spatial distribution of lipid species among ovarian compartments, notably between the follicles and interstitial tissue. Inside the follicles analysis differentiated follicular fluid, granulosa, theca and the oocyte-cumulus complex. Moreover, by transcript quantification using real time PCR, we showed that expression of five key genes in FA metabolism significantly varied between somatic follicular cells (theca, granulosa and cumulus) and the oocyte. In conclusion, lipid metabolism differs between ovarian and follicular compartments. PMID:25756245

  5. Effect of hepatoprotectors on lipid metabolism in hepatitis induced by carbon tetrachloride

    SciTech Connect

    Vengerovskii, A.I.; Chuchalin, V.S.; Paul's; O.V.; Saratikov, A.S.

    1987-09-01

    The authors study the effect of the widely used hepatoprotective agents- the flavonoid silybinin and the phosphatidylcholine-containing substance essentiale - on the combination of disturbances of lipid metabolism present in severe toxic hepatitis induced by carbon tetrachloride in rats. It was found that CCl/sub 4/ caused a profound disturbance of lipid metabolism. The hepatoprotective effect of silybinin and essentiale is due to their antioxidant action and to normalization of function of the liver phospholipids.

  6. Glucidic and lipidic metabolic changes in rats induced by irradiation and the effect of adrenalectomy.

    PubMed

    Groza, P; Ghizari, E; Butculescu, I; Ciontescu, L; Ciuntu, L

    1975-01-01

    In experiments on X-irradiated rats (1000 R) the hepatic glycogen, total lipids, phospholipids content, and plasma glucose, cholesterol and beta-lipoprotein concentration were determined in intact and adrenalectomized animals. It was confirmed that irradiation produces a hepatic glycogen and blood glucose increased concentration. The glucidic metabolic response on irradiation is diminished by adrenalectomy. The adrenalectomy-induced modifications in the lipid metabolism of irradiated rats are more inconstant, which corresponds with its relative independence from glucocorticoid hormones.

  7. [Impact of the use of alcoholic beverages on lipid metabolic parameters in Northern Water Basin workers].

    PubMed

    Petrova, T B; Bichkaeva, F A; Zhilina, L P; Tret'iakova, T V; Vlasova, O S

    2010-01-01

    The nature of changes in lipid metabolic parameters was studied in the sailors, river transport workers, and fishermen of the Northern Water Basin in relation to the specific features of their working conditions and the frequency of drinking alcoholic beverages. It was shown that there was imbalance in the levels of lipid parameters, which was more pronounced in sailors and river transport workers.

  8. Calcium and zinc differentially affect the structure of lipid membranes

    DOE PAGES

    Kučerka, Norbert; Dushanov, Ermuhammad; Kholmurodov, Kholmirzo T.; ...

    2017-03-09

    Interactions of calcium (Ca2+) and zinc (Zn2+) cations with biomimetic membranes made of dipalmitoylphosphatidylcholine (DPPC) were studied by small angle neutron diffraction (SAND). Experiments show that the structure of these lipid bilayers is differentially affected by the two divalent cations. Initially, both Ca2+ and Zn2+ cause DPPC bilayers to thicken, while further increases in Ca2+ concentration result in the bilayer thinning, eventually reverting to having the same thickness as pure DPPC. The binding of Zn2+, on the other hand, causes the bilayers to swell to a maximum thickness, and the addition of more Zn2+ does not result in a furthermore » thickening of the membrane. Agreement between our results obtained using oriented planar membranes and those from vesicular samples implies that the effect of cations on bilayer thickness is the result of electrostatic interactions, rather than geometrical constraints due to bilayer curvature. This notion is further reinforced by MD simulations. Lastly, the radial distribution functions reveal a strong interaction between Ca2+ and the phosphate oxygens, while Zn2+ shows a much weaker binding specificity.« less

  9. Differential serum proteomic analysis in a model of metabolic disease.

    PubMed

    Matsumura, Takayoshi; Suzuki, Toru; Kada, Nanae; Aizawa, Kenichi; Munemasa, Yoshiko; Nagai, Ryozo

    2006-12-29

    Protein profiling would aid in better understanding the pathophysiology of metabolic disease. Here, we report on differential proteomic analysis using an animal model of diabetes mellitus and associated metabolic disorders (Otsuka Long-Evans Tokushima Fatty rat). Serum was analyzed by a new two-dimensional liquid chromatography system which separated proteins by chromatofocusing and subsequent reversed-phase chromatography. This is the first application of this approach to differential serum proteomics. Differentially expressed proteins, identified with MALDI-TOF mass spectrometry, included apolipoproteins and alpha2-HS-glycoprotein. These findings add to our understanding of the underlying pathophysiology. This new proteomic analysis is a promising tool to elucidate disease mechanisms.

  10. Hormonal regulation of lipid metabolism in developing coho salmon, Oncorhynchus kisutch

    SciTech Connect

    Sheridan, M.A.

    1985-01-01

    Lipid metabolism in juvenile coho salmon is characterized, and adaptive changes in lipid mobilization are described in relation to development and hormonal influences. The rates of lipogenesis and lipolysis were determined in selected tissues of juvenile salmon during the period of seawater preadaptive development (smoltification). Neutral lipid (sterol) and fatty acid synthesis in the liver and mesenteric fat was measured by tritium incorporation. Fatty acid synthesis in the liver and mesenteric fat decreased by 88% and 81%, respectively, between late February (parr) and early June (smolt). To assess the role of hormones in smoltification-associated lipid depletion, growth hormone, prolactin, thyroxin and cortisol were administered in vivo early in development (parr) to determine if any of these factors could initiate the metabolic responses normally seen later in development (smolt). Growth hormone stimulated lipid mobilization from coho salmon parr. Prolactin strongly stimulated lipid mobilization in coho parr. Thyroxin and cortisol also stimulated lipid mobilization for coho salmon parr. The direct effect of hormones was studied by in vitro pH-stat incubation of liver slices. These data suggest that norepinephrine stimulates fatty acid release via ..beta..-adrenergic pathways. Somatostatin and its partial analogue from the fish caudal neurosecretory system, urotensin II, also affect lipid mobilization. These results establish the presence of hormone-sensitive lipase in salmon liver and suggest that the regulation of lipid metabolism in salmon involves both long-acting and short-acting hormonal agents.

  11. Aberrant Lipid Metabolism Promotes Prostate Cancer: Role in Cell Survival under Hypoxia and Extracellular Vesicles Biogenesis

    PubMed Central

    Deep, Gagan; Schlaepfer, Isabel R.

    2016-01-01

    Prostate cancer (PCa) is the leading malignancy among men in United States. Recent studies have focused on the identification of novel metabolic characteristics of PCa, aimed at devising better preventive and therapeutic approaches. PCa cells have revealed unique metabolic features such as higher expression of several enzymes associated with de novo lipogenesis, fatty acid up-take and β-oxidation. This aberrant lipid metabolism has been reported to be important for PCa growth, hormone-refractory progression and treatment resistance. Furthermore, PCa cells effectively use lipid metabolism under adverse environmental conditions for their survival advantage. Specifically, hypoxic cancer cells accumulate higher amount of lipids through a combination of metabolic alterations including high glutamine and fatty acid uptake, as well as decreased fatty acid oxidation. These stored lipids serve to protect cancer cells from oxidative and endoplasmic reticulum stress, and play important roles in fueling cancer cell proliferation following re-oxygenation. Lastly, cellular lipids have also been implicated in extracellular vesicle biogenesis, which play a vital role in intercellular communication. Overall, the new understanding of lipid metabolism in recent years has offered several novel targets to better target and manage clinical PCa. PMID:27384557

  12. Salivary composition in obese vs normal-weight subjects: towards a role in postprandial lipid metabolism?

    PubMed

    Vors, C; Drai, J; Gabert, L; Pineau, G; Laville, M; Vidal, H; Guichard, E; Michalski, M-C; Feron, G

    2015-09-01

    In the pathophysiological context of obesity, oral exposure to dietary fat can modulate lipid digestion and absorption, but underlying in-mouth mechanisms have not been clearly identified. Therefore, we tested the hypothesis that salivary components related to dietary fat sensitivity would differ according to body mass index (BMI) and postprandial lipid metabolism in young men. Saliva was collected from nine normal-weight (BMI=22.3±0.5 kg m(-2)) and nine non-morbid obese (BMI=31.7±0.3 kg m(-2)) men before an 8-h postprandial metabolic exploration test involving the consumption of a 40-g fat meal, in which obese subjects revealed a delayed postprandial lipid metabolism. Nine salivary characteristics (flow, protein content, lipolysis, amylase, proteolysis, total antioxidant status, lysozyme, lipocalin 1 and carbonic anhydrase-VI) were investigated. We show that, under fasting conditions, salivary lipolysis was lower in obese vs normal-weight subjects, whereas proteolysis and carbonic anhydrase VI were higher. We reveal through multivariate and Mann-Whitney analysis that differences in fasting salivary lipolysis and proteolysis between both groups are related to differences in postprandial lipid metabolism including exogenous fatty-acid absorption and β-oxidation. These results suggest a potential role of salivary composition on postprandial lipid metabolism and bring novel causal hypotheses on the links between salivary composition, sensitivity to dietary fat oral income and postprandial lipid metabolism according to BMI.

  13. [Response of arbuscular mycorrhizal fungal lipid metabolism to symbiotic signals in mycorrhiza].

    PubMed

    Tian, Lei; Li, Yuanjing; Tian, Chunjie

    2016-01-04

    Arbuscular mycorrhizal (AM) fungi play an important role in energy flow and nutrient cycling, besides their wide distribution in the cosystem. With a long co-evolution, AM fungi and host plant have formed a symbiotic relationship, and fungal lipid metabolism may be the key point to find the symbiotic mechanism in arbusculart mycorrhiza. Here, we reviewed the most recent progress on the interaction between AM fungal lipid metabolism and symbiotic signaling networks, especially the response of AM fungal lipid metabolism to symbiotic signals. Furthermore, we discussed the response of AM fungal lipid storage and release to symbiotic or non-symbiotic status, and the correlation between fungal lipid metabolism and nutrient transfer in mycorrhiza. In addition, we explored the feedback of the lipolysis process to molecular signals during the establishment of symbiosis, and the corresponding material conversion and energy metabolism besides the crosstalk of fungal lipid metabolism and signaling networks. This review will help understand symbiotic mechanism of arbuscular mycorrhiza fungi and further application in ecosystem.

  14. Role of lipid rafts in neuronal differentiation of dental pulp-derived stem cells.

    PubMed

    Mattei, Vincenzo; Santacroce, Costantino; Tasciotti, Vincenzo; Martellucci, Stefano; Santilli, Francesca; Manganelli, Valeria; Piccoli, Luca; Misasi, Roberta; Sorice, Maurizio; Garofalo, Tina

    2015-12-10

    Human dental pulp-derived stem cells (hDPSCs) are characterized by a typical fibroblast-like morphology. They express specific markers for mesenchymal stem cells and are capable of differentiation into osteoblasts, adipoblasts and neurons in vitro. Previous studies showed that gangliosides are involved in the induction of early neuronal differentiation of hDPSCs. This study was undertaken to investigate the role of lipid rafts in this process. Lipid rafts are signaling microdomains enriched in glycosphingolipids, cholesterol, tyrosine kinase receptors, mono- or heterotrimeric G proteins and GPI-anchored proteins. We preliminary showed that established cells expressed multipotent mesenchymal stromal-specific surface antigens. Then, we analyzed the distribution of lipid rafts, revealing plasma membrane microdomains with GM2 and EGF-R enrichment. Following stimulation with EGF/bFGF, neuronal differentiation was observed. To analyze the functional role of lipid rafts in EGF/bFGF-induced hDPSCs differentiation, cells were preincubated with lipid raft affecting agents, i.e. [D]-PDMP or methyl-β-cyclodextrin. These compounds significantly prevented neuronal-specific antigen expression, as well as Akt and ERK 1/2 phosphorylation, induced by EGF/bFGF, indicating that lipid raft integrity is essential for EGF/bFGF-induced hDPSCs differentiation. These results suggest that lipid rafts may represent specific chambers, where multimolecular signaling complexes, including lipids (gangliosides, cholesterol) and proteins (EGF-R), play a role in hDPSCs differentiation.

  15. Hexosamine Biosynthesis Is a Possible Mechanism Underlying Hypoxia’s Effects on Lipid Metabolism in Human Adipocytes

    PubMed Central

    O’Rourke, Robert W.; Meyer, Kevin A.; Gaston, Garen; White, Ashley E.; Lumeng, Carey N.; Marks, Daniel L.

    2013-01-01

    Introduction Hypoxia regulates adipocyte metabolism. Hexosamine biosynthesis is implicated in murine 3T3L1 adipocyte differentiation and is a possible underlying mechanism for hypoxia’s effects on adipocyte metabolism. Methods Lipid metabolism was studied in human visceral and subcutaneous adipocytes in in vitro hypoxic culture with adipophilic staining, glycerol release, and palmitate oxidation assays. Gene expression and hexosamine biosynthesis activation was studied with QRTPCR, immunofluorescence microscopy, and Western blotting. Results Hypoxia inhibits lipogenesis and induces basal lipolysis in visceral and subcutaneous human adipocytes. Hypoxia induces fatty acid oxidation in visceral adipocytes but had no effect on fatty acid oxidation in subcutaneous adipocytes. Hypoxia inhibits hexosamine biosynthesis in adipocytes. Inhibition of hexosamine biosynthesis with azaserine attenuates lipogenesis and induces lipolysis in adipocytes in normoxic conditions, while promotion of hexosamine biosynthesis with glucosamine in hypoxic conditions slightly increases lipogenesis. Conclusions Hypoxia’s net effect on human adipocyte lipid metabolism would be expected to impair adipocyte buffering capacity and contribute to systemic lipotoxicity. Our data suggest that hypoxia may mediate its effects on lipogenesis and lipolysis through inhibition of hexosamine biosynthesis. Hexosamine biosynthesis represents a target for manipulation of adipocyte metabolism. PMID:23967162

  16. Visualizing digestive organ morphology and function using differential fatty acid metabolism in live zebrafish

    PubMed Central

    Carten, Juliana Debrito; Bradford, Mary Katherine; Farber, Steven Arthur

    2012-01-01

    Lipids are essential for cellular function as sources of fuel, critical signaling molecules and membrane components. Deficiencies in lipid processing and transport underlie many metabolic diseases. To better understand metabolic function as it relates to disease etiology, a whole animal approach is advantageous, one in which multiple organs and cell types can be assessed simultaneously in vivo. Towards this end, we have developed an assay to visualize fatty acid (FA) metabolism in larval zebrafish (Danio rerio). The method utilizes egg yolk liposomes to deliver different chain length FA analogs (BODIPY-FL) to six day-old larvae. Following liposome incubation, larvae accumulate the analogs throughout their digestive organs, providing a comprehensive readout of organ structure and physiology. Using this assay we have observed that different chain length FAs are differentially transported and metabolized by the larval digestive system. We show that this assay can also reveal structural and metabolic defects in digestive mutants. Because this labeling technique can be used to investigate digestive organ morphology and function, we foresee its application in diverse studies of organ development and physiology. PMID:21968100

  17. Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat.

    PubMed

    Torres, Nimbe; Bautista, Claudia J; Tovar, Armando R; Ordáz, Guillermo; Rodríguez-Cruz, Maricela; Ortiz, Victor; Granados, Omar; Nathanielsz, Peter W; Larrea, Fernando; Zambrano, Elena

    2010-02-01

    Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.

  18. Assessing compartmentalized flux in lipid metabolism with isotopes

    USDA-ARS?s Scientific Manuscript database

    Metabolism in plants takes place across multiple cell types and subpopulations in distinct organelles. The distributions equate to spatial heterogeneity; though the limited means to experimentally asses metabolism frequently involve homogenizing tissues and mixing metabolites from different location...

  19. Zinc mediates the SREBP-SCD axis to regulate lipid metabolism in Caenorhabditis elegans.

    PubMed

    Zhang, Jing-Jing; Hao, Jun-Jun; Zhang, Yu-Ru; Wang, Yan-Li; Li, Ming-Yi; Miao, Hui-Lai; Zou, Xiao-Ju; Liang, Bin

    2017-09-01

    Maintenance of lipid homeostasis is crucial for cells in response to lipid requirements or surplus. The SREBP transcription factors play essential roles in regulating lipid metabolism and are associated with many metabolic diseases. However, SREBP regulation of lipid metabolism is still not completely understood. Here, we showed that reduction of SBP-1, the only homolog of SREBPs in Caenorhabditis elegans, surprisingly led to a high level of zinc. On the contrary, zinc reduction by mutation of sur-7, encoding a member of the cation diffusion facilitator (CDF) family, restored the fat accumulation and fatty acid profile of the sbp-1(ep79) mutant. Zinc reduction resulted in iron overload, which thereby directly activated the conversion activity of stearoyl-CoA desaturase (SCD), a main target of SREBP, to promote lipid biosynthesis and accumulation. However, zinc reduction reversely repressed SBP-1 nuclear translocation and further downregulated the transcription expression of SCD for compensation. Collectively, we revealed zinc-mediated regulation of the SREBP-SCD axis in lipid metabolism, distinct from the negative regulation of SREBP-1 or SREBP-2 by phosphatidylcholine or cholesterol, respectively, thereby providing novel insights into the regulation of lipid homeostasis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  20. Lipid profiling of in vitro cell models of adipogenic differentiation: relationships with mouse adipose tissues

    PubMed Central

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A.; Anunciado-Koza, Rea V.; Siviski, Matthew E.; Lindner, Volkhard; Friesel, Robert E.; Rosen, Clifford J.; Baker, Paul R.S.; Simons, Brigitte; Vary, Calvin P.H.

    2016-01-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MSALL. Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MSALL data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. PMID:26910604

  1. Effects of Quercetin Supplementation on Lipid and Protein Metabolism after Classic Boxing Training

    ERIC Educational Resources Information Center

    Demirci, Nevzat

    2017-01-01

    The metabolic fitness (MF) is a component of athletes' physical conditioning. This study aims to investigate the effects of quercetin supplementation on Turkish Junior athletes' lipid and protein metabolism relating to MF after one month classic boxing training. Totally 20 voluntary junior male athletes were separated into two equal groups as the…

  2. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    PubMed

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities.

  3. Cinnamon extract regulates intestinal lipid metabolism related gene expression in primary enterocytes of rats

    USDA-ARS?s Scientific Manuscript database

    Emerging evidence suggests that the small intestine is not a passive organ, but is actively involved in the regulation of lipid absorption, intracellular transport, and metabolism, and is closely linked to systemic lipoprotein metabolism. We have reported previously that the water-soluble components...

  4. A novel dual peroxisome proliferator-activated receptors alpha and gamma agonist with beneficial effects on insulin resistance and lipid metabolism.

    PubMed

    Xu, Cheng; Wang, Li-Li; Liu, Hong-Ying; Ruan, Cheng-Mai; Zhou, Xing-Bo; Cao, Ying-Lin; Li, Song

    2006-06-01

    Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are key regulators of lipid homeostasis and insulin resistance. In this study we show that a novel compound, 3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}- 2-[2-(2-nitro-phenoxy)-acetyl amino]-propionic acid (O325H), is an agonist with dual effect on PPARalpha/gamma by using dual-luciferase reporter gene assay. By activating PPARalpha and PPARgamma simultaneously, O325H promotes pre-adipocyte differentiation and up-regulates the expression of glucose and lipid metabolic target genes. In diabetic mice, administration of O325H at 10 mg/kg decreases the blood lipid and glucose levels. Therefore, O325H has dual action on PPARalpha and PPARgamma and is a promising agent for the amelioration of lipid metabolic disorders and diabetes associated with insulin resistance.

  5. Understanding the control of acyl flux through the lipid metabolic network of plant oil biosynthesis.

    PubMed

    Bates, Philip D

    2016-09-01

    Plant oil biosynthesis involves a complex metabolic network with multiple subcellular compartments, parallel pathways, cycles, and pathways that have a dual function to produce essential membrane lipids and triacylglycerol. Modern molecular biology techniques provide tools to alter plant oil compositions through bioengineering, however with few exceptions the final composition of triacylglycerol cannot be predicted. One reason for limited success in oilseed bioengineering is the inadequate understanding of how to control the flux of fatty acids through various fatty acid modification, and triacylglycerol assembly pathways of the lipid metabolic network. This review focuses on the mechanisms of acyl flux through the lipid metabolic network, and highlights where uncertainty resides in our understanding of seed oil biosynthesis. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner.

  6. Aberrant Schwann cell lipid metabolism linked to mitochondrial deficits leads to axon degeneration and neuropathy.

    PubMed

    Viader, Andreu; Sasaki, Yo; Kim, Sungsu; Strickland, Amy; Workman, Cayce S; Yang, Kui; Gross, Richard W; Milbrandt, Jeffrey

    2013-03-06

    Mitochondrial dysfunction is a common cause of peripheral neuropathy. Much effort has been devoted to examining the role played by neuronal/axonal mitochondria, but how mitochondrial deficits in peripheral nerve glia (Schwann cells [SCs]) contribute to peripheral nerve diseases remains unclear. Here, we investigate a mouse model of peripheral neuropathy secondary to SC mitochondrial dysfunction (Tfam-SCKOs). We show that disruption of SC mitochondria activates a maladaptive integrated stress response (ISR) through the actions of heme-regulated inhibitor (HRI) kinase, and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. These alterations in SC lipid metabolism result in depletion of important myelin lipid components as well as in accumulation of acylcarnitines (ACs), an intermediate of fatty acid β-oxidation. Importantly, we show that ACs are released from SCs and induce axonal degeneration. A maladaptive ISR as well as altered SC lipid metabolism are thus underlying pathological mechanisms in mitochondria-related peripheral neuropathies.

  7. Metabolic Crosstalk: Molecular Links Between Glycogen and Lipid Metabolism in Obesity

    PubMed Central

    Lu, Binbin; Bridges, Dave; Yang, Yemen; Fisher, Kaleigh; Cheng, Alan; Chang, Louise; Meng, Zhuo-Xian; Lin, Jiandie D.; Downes, Michael; Yu, Ruth T.; Liddle, Christopher; Evans, Ronald M.

    2014-01-01

    Glycogen and lipids are major storage forms of energy that are tightly regulated by hormones and metabolic signals. We demonstrate that feeding mice a high-fat diet (HFD) increases hepatic glycogen due to increased expression of the glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and glycogen levels were augmented in mice and cells after activation of the mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed mice and reduced the expression of numerous lipogenic genes. Additionally, PTG deletion reduced fasting glucose and insulin levels in obese mice while improving insulin sensitivity, a result of reduced hepatic glucose output. This metabolic crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or knockdown cells, suggesting a positive feedback loop in which once accumulated, glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to lipogenesis. Together, these data reveal a previously unappreciated broad role for glycogen in the control of energy homeostasis. PMID:24722244

  8. Metabolic crosstalk: molecular links between glycogen and lipid metabolism in obesity.

    PubMed

    Lu, Binbin; Bridges, Dave; Yang, Yemen; Fisher, Kaleigh; Cheng, Alan; Chang, Louise; Meng, Zhuo-Xian; Lin, Jiandie D; Downes, Michael; Yu, Ruth T; Liddle, Christopher; Evans, Ronald M; Saltiel, Alan R

    2014-09-01

    Glycogen and lipids are major storage forms of energy that are tightly regulated by hormones and metabolic signals. We demonstrate that feeding mice a high-fat diet (HFD) increases hepatic glycogen due to increased expression of the glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and glycogen levels were augmented in mice and cells after activation of the mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed mice and reduced the expression of numerous lipogenic genes. Additionally, PTG deletion reduced fasting glucose and insulin levels in obese mice while improving insulin sensitivity, a result of reduced hepatic glucose output. This metabolic crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or knockdown cells, suggesting a positive feedback loop in which once accumulated, glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to lipogenesis. Together, these data reveal a previously unappreciated broad role for glycogen in the control of energy homeostasis.

  9. Transcriptome-Wide Analysis Reveals the Role of PPARγ Controlling the Lipid Metabolism in Goat Mammary Epithelial Cells

    PubMed Central

    Zhao, Wangsheng; Zhang, Changhui

    2016-01-01

    To explore the large-scale effect of peroxisome proliferator-activated receptor γ (PPARG) in goat mammary epithelial cells (GMEC), an oligonucleotide microarray platform was used for transcriptome profiling in cells overexpressing PPARG and incubated with or without rosiglitazone (ROSI, a PPARγ agonist). A total of 1143 differentially expressed genes (DEG) due to treatment were detected. The Dynamic Impact Approach (DIA) analysis uncovered the most impacted and induced pathways “fatty acid elongation in mitochondria,” “glycosaminoglycan biosynthesis-keratan sulfate,” and “pentose phosphate pathway.” The data highlights the central role of PPARG in milk fatty acid metabolism via controlling fatty acid elongation, biosynthesis of unsaturated fatty acid, lipid formation, and lipid secretion; furthermore, its role related to carbohydrate metabolism promotes the production of intermediates required for milk fat synthesis. Analysis of upstream regulators indicated that PPARG participates in multiple physiological processes via controlling or cross talking with other key transcription factors such as PPARD and NR1H3 (also known as liver-X-receptor-α). This transcriptome-wide analysis represents the first attempt to better understand the biological relevance of PPARG expression in ruminant mammary cells. Overall, the data underscored the importance of PPARG in mammary lipid metabolism and transcription factor control. PMID:27818678

  10. Differential metabolic responses in three life stages of mussels Mytilus galloprovincialis exposed to cadmium.

    PubMed

    Wu, Huifeng; Xu, Lanlan; Yu, Deliang; Ji, Chenglong

    2017-01-01

    Cadmium (Cd) is one of the most important metal contaminants in the Bohai Sea. In this work, NMR-based metabolomics was used to investigate the toxicological effects of Cd at an environmentally relevant concentration (50 µg L(-1)) in three different life stages (D-shape larval, juvenile and adult) of mussels Mytilus galloprovincialis. Results indicated that the D-shape larval mussel was the most sensitive life stage to Cd. The significantly different metabolic profiles meant that Cd induced differential toxicological effects in three life stages of mussels. Basically, Cd caused osmotic stress in all the three life stages via different metabolic pathways. Cd exposure reduced the anaerobiosis in D-shape larval mussels and disturbed lipid metabolism in juvenile mussels, respectively. Compared with the D-shape larval and juvenile mussels, the adult mussels reduced energy consumption to deal with Cd stress.

  11. Lipid metabolism genes in contralateral unaffected breast and estrogen receptor status of breast cancer.

    PubMed

    Wang, Jun; Scholtens, Denise; Holko, Michelle; Ivancic, David; Lee, Oukseub; Hu, Hong; Chatterton, Robert T; Sullivan, Megan E; Hansen, Nora; Bethke, Kevin; Zalles, Carola M; Khan, Seema A

    2013-04-01

    Risk biomarkers that are specific to estrogen receptor (ER) subtypes of breast cancer would aid the development and implementation of distinct prevention strategies. The contralateral unaffected breast of women with unilateral breast cancer (cases) is a good model for defining subtype-specific risk because women with ER-negative (ER-) index primaries are at high risk for subsequent ER-negative primary cancers. We conducted random fine needle aspiration of the unaffected breasts of cases. Samples from 30 subjects [15 ER-positive (ER+) and 15 ER- cases matched for age, race and menopausal status] were used for Illumina expression array analysis. Findings were confirmed using quantitative real-time PCR (qRT-PCR) in the same samples. A validation set consisting of 36 subjects (12 ER+, 12 ER- and 12 standard-risk healthy controls) was used to compare gene expression across groups. ER- case samples displayed significantly higher expression of 18 genes/transcripts, 8 of which were associated with lipid metabolism on gene ontology analysis (GO: 0006629). This pattern was confirmed by qRT-PCR in the same samples, and in the 24 cases of the validation set. When compared to the healthy controls in the validation set, significant overexpression of 4 genes (DHRS2, HMGCS2, HPGD and ACSL3) was observed in ER- cases, with significantly lower expression of UGT2B11 and APOD in ER+ cases, and decreased expression of UGT2B7 in both subtypes. These data suggest that differential expression of lipid metabolism genes may be involved in the risk for subtypes of breast cancer, and are potential biomarkers of ER-specific breast cancer risk.

  12. Characterization of the sea bass melanocortin 5 receptor: a putative role in hepatic lipid metabolism.

    PubMed

    Sánchez, E; Rubio, V C; Cerdá-Reverter, J M

    2009-12-01

    The melanocortin 5 receptor (MC5R) plays a key role in the regulation of exocrine secretion in mammalian species. This receptor has also been characterized in some fish species but its function is unknown. We report the molecular and pharmacological characterization, as well as the tissue expression pattern, of sea bass MC5R. Cloning of five active alleles showing different levels of sensitivity to endogenous melanocortin and one non-functional allele demonstrate the allelic complexity of the MC5R locus. The sea bass receptor was activated by all the melanocortins tested, with ACTH and desacetyl-MSH and beta-MSH showing the lowest efficiency. The acetylation of the MSH isoforms seems to be critical for the effectiveness of the agonist. Agouti-related protein had no effect on basal or agonist-stimulated activation of the receptor. SbMC5R was mainly expressed in the brain but lower expression levels were found in several peripheral tissues, including liver. Progressive fasting did not induce up- or downregulation of hypothalamic MC5R expression, suggesting that central MC5R is not involved in the regulation of food intake in the sea bass. MTII, a sbMC5R agonist, stimulated hepatic lipolysis in vitro, measured as free fatty acid release into the culture medium after melanocortin agonist exposure of liver fragments, suggesting that MC5R is involved in the regulation of hepatic lipid metabolism. Taken together, the data suggest that different allelic combinations may confer differential sensitivity to endogenous melanocortin in tissues where MC5R is expressed and, by extension, in hepatic lipid metabolism.

  13. Metabolism of fatty acids and lipid hydroperoxides in human body monitoring with Fourier transform Infrared Spectroscopy.

    PubMed

    Yoshida, Satoshi; Zhang, Qin-Zeng; Sakuyama, Shu; Matsushima, Satoshi

    2009-07-24

    The metabolism of dietary fatty acids in human has been measured so far using human blood cells and stable-isotope labeled fatty acids, however, no direct data was available for human peripheral tissues and other major organs. To realize the role of dietary fatty acids in human health and diseases, it would be eager to develop convenient and suitable method to monitor fatty acid metabolism in human. We have developed the measurement system in situ for human lip surface lipids using the Fourier transform infrared spectroscopy (FTIR) - attenuated total reflection (ATR) detection system with special adaptor to monitor metabolic changes of lipids in human body. As human lip surface lipids may not be much affected by skin sebum constituents and may be affected directly by the lipid constituents of diet, we could detect changes of FTIR-ATR spectra, especially at 3005 to approximately 3015 cm(-1), of lip surface polyunsaturated fatty acids in a duration time-dependent manner after intake of the docosahexaenoic acid (DHA)-containing triglyceride diet. The ingested DHA appeared on the lip surface and was detected by FTIR-ATR directly and non-invasively. It was found that the metabolic rates of DHA for male volunteer subjects with age 60s were much lower than those with age 20s. Lipid hydroperoxides were found in lip lipids which were extracted from the lip surface using a mixture of ethanol/ethylpropionate/iso-octane solvents, and were the highest in the content just before noon. The changes of lipid hydroperoxides were detected also in situ with FTIR-ATR at 968 cm(-1). The measurements of lip surface lipids with FTIR-ATR technique may advance the investigation of human lipid metabolism in situ non-invasively.

  14. Metabolism of fatty acids and lipid hydroperoxides in human body monitoring with Fourier transform Infrared Spectroscopy

    PubMed Central

    Yoshida, Satoshi; Zhang, Qin-Zeng; Sakuyama, Shu; Matsushima, Satoshi

    2009-01-01

    Background The metabolism of dietary fatty acids in human has been measured so far using human blood cells and stable-isotope labeled fatty acids, however, no direct data was available for human peripheral tissues and other major organs. To realize the role of dietary fatty acids in human health and diseases, it would be eager to develop convenient and suitable method to monitor fatty acid metabolism in human. Results We have developed the measurement system in situ for human lip surface lipids using the Fourier transform infrared spectroscopy (FTIR) – attenuated total reflection (ATR) detection system with special adaptor to monitor metabolic changes of lipids in human body. As human lip surface lipids may not be much affected by skin sebum constituents and may be affected directly by the lipid constituents of diet, we could detect changes of FTIR-ATR spectra, especially at 3005~3015 cm-1, of lip surface polyunsaturated fatty acids in a duration time-dependent manner after intake of the docosahexaenoic acid (DHA)-containing triglyceride diet. The ingested DHA appeared on the lip surface and was detected by FTIR-ATR directly and non-invasively. It was found that the metabolic rates of DHA for male volunteer subjects with age 60s were much lower than those with age 20s. Lipid hydroperoxides were found in lip lipids which were extracted from the lip surface using a mixture of ethanol/ethylpropionate/iso-octane solvents, and were the highest in the content just before noon. The changes of lipid hydroperoxides were detected also in situ with FTIR-ATR at 968 cm-1. Conclusion The measurements of lip surface lipids with FTIR-ATR technique may advance the investigation of human lipid metabolism in situ non-invasively. PMID:19627618

  15. Lipidomics in situ: insights into plant lipid metabolism from high resolution spatial maps of metabolites.

    PubMed

    Horn, Patrick J; Chapman, Kent D

    2014-04-01

    The emergence of 'omics' technologies (i.e. genomics, proteomics, metabolomics, etc.) have revealed new avenues for exploring plant metabolism through data-rich experimentation and integration of complementary methodologies. Over the past decade, the lipidomics field has benefited from advances in instrumentation, especially mass spectrometry (MS)-based approaches that are well-suited for detailed lipid analysis. The broad classification of what constitutes a lipid lends itself to a structurally diverse range of molecules that contribute to a variety of biological processes in plants including membrane structure and transport, primary and secondary metabolism, abiotic and biotic stress tolerances, extracellular and intracellular signaling, and energy-rich storage of carbon. Progress in these research areas has been advanced in part through approaches analyzing chemical compositions of lipids in extracts from cells, tissues and/or whole organisms (e.g. shotgun lipidomics), and through visualization approaches primarily through microscopy-based methodologies (e.g. fluorescence, bright field, electron microscopy, etc.). While these techniques on their own provide rich biochemical and biological information, coordinated analyses of the complexity of lipid composition with the localization of these lipids at a high spatial resolution will help to develop a new level of understanding of lipid metabolism within the context of tissue/cellular compartmentation. This review will elaborate on recent advances of one such approach--mass spectrometry imaging (MSI)--that integrates in situ visualization with chemical-based lipidomics. We will illustrate, with an emphasis on oilseed lipid metabolism, how MS imaging can provide new insights and questions related to the spatial compartmentation of lipid metabolism in plants. Further it will be apparent that this MS imaging approach has broad application in plant metabolic research well beyond that of triacylglycerol biosynthesis in

  16. Transcriptome Analyses Reveal Lipid Metabolic Process in Liver Related to the Difference of Carcass Fat Content in Rainbow Trout (Oncorhynchus mykiss)

    PubMed Central

    Hu, Guo; Gu, Wei; Sun, Peng; Bai, Qingli

    2016-01-01

    Excessive accumulation of carcass fat in farm animals, including fish, has a significant impact on meat quality and on the cost of feeding. Similar to farmed animals and humans, the liver can be considered one of the most important organs involved in lipid metabolism in rainbow trout (Oncorhynchus mykiss). RNA-seq based whole transcriptome sequencing was performed to liver tissue of rainbow trout with high and low carcass fat content in this study. In total 1,694 differentially expressed transcripts were identified, including many genes involved in lipid metabolism, such as L-FABP, adiponectin, PPAR-α, PPAR-β, and IGFBP1a. Evidence presented in this study indicated that lipid metabolic process in liver may be related to the difference of carcass fat content. The relevance of PPAR-α and PPAR-β as molecular markers for fat storage in liver should be worthy of further investigation. PMID:27652256

  17. Differential distribution of lipids in epidermis, gastrodermis and hosted Symbiodinium in the sea anemone Anemonia viridis.

    PubMed

    Revel, Johana; Massi, Lionel; Mehiri, Mohamed; Boutoute, Marc; Mayzaud, Patrick; Capron, Laure; Sabourault, Cécile

    2016-01-01

    Cnidarian-dinoflagellate symbiosis mainly relies on nutrient recycling, thus providing both partners with a competitive advantage in nutrient-poor waters. Essential processes related to lipid metabolism can be influenced by various factors, including hyperthermal stress. This can affect the lipid content and distribution in both partners, while contributing to symbiosis disruption and bleaching. In order to gain further insight into the role and distribution of lipids in the cnidarian metabolism, we investigated the lipid composition of the sea anemone Anemonia viridis and its photosynthetic dinoflagellate endosymbionts (Symbiodinium). We compared the lipid content and fatty acid profiles of the host cellular layers, non-symbiotic epidermal and symbiont-containing gastrodermal cells, and those of Symbiodinium, in a mass spectrometry-based assessment. Lipids were more concentrated in Symbiodinium cells, and the lipid class distribution was dominated by polar lipids in all tissues. The fatty acid distribution between host cell layers and Symbiodinium cells suggested potential lipid transfers between the partners. The lipid composition and distribution was modified during short-term hyperthermal stress, mainly in Symbiodinium cells and gastrodermis. Exposure to elevated temperature rapidly caused a decrease in polar lipid C18 unsaturated fatty acids and a strong and rapid decrease in the abundance of polar lipid fatty acids relative to sterols. These lipid indicators could therefore be used as sensitive biomarkers to assess the physiology of symbiotic cnidarians, especially the effect of thermal stress at the onset of cnidarian bleaching. Overall, the findings of this study provide some insight on key lipids that may regulate maintenance of the symbiotic interaction. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Superovulation Induced Changes of Lipid Metabolism in Ovaries and Embryos and Its Probable Mechanism

    PubMed Central

    Wang, Li-Ya; Wang, Ning; Le, Fang; Li, Lei; Lou, Hang-Ying; Liu, Xiao-Zhen; Zheng, Ying-Ming; Qian, Ye-Qing; Chen, Yun-Long; Jiang, Xin-Hang; Huang, He-Feng; Jin, Fan

    2015-01-01

    This research was intended to investigate the fetal origins of changed birth weight of the offspring born through assisted reproductive technology (ART). The association between hormone and lipid metabolism or body weight has been generally accepted, and as the basic and specific treatment in ART procedure, gonadotropin stimulation might have potential effects on intrauterine lipid metabolism. In our studies, the mice were superovulated with two doses of gonadotropin. The cholesterol metabolism in ovaries and the triglyceride metabolism in embryos were analyzed. The results showed gonadotropin probably accelerated luteinization and induced a longer time follicle development and ovulation, which resulted in histological and morphological alteration of ovary, and increased the cholesterol content and the expressions of steroidogenesis-related genes. In embryos, gonadotropin increased lipid accumulation and decreased fatty acid synthesis in a dose-dependent manner. Moreover, the changes of fatty acid composition were also shown in superovulation groups. Our studies firstly provided the evidence that the superovulation might affect the maternal and fetal lipid metabolism. These variations of lipid metabolism in our results may be associated with birth weight of ART infants. PMID:26167919

  19. Superovulation Induced Changes of Lipid Metabolism in Ovaries and Embryos and Its Probable Mechanism.

    PubMed

    Wang, Li-Ya; Wang, Ning; Le, Fang; Li, Lei; Lou, Hang-Ying; Liu, Xiao-Zhen; Zheng, Ying-Ming; Qian, Ye-Qing; Chen, Yun-Long; Jiang, Xin-Hang; Huang, He-Feng; Jin, Fan

    2015-01-01

    This research was intended to investigate the fetal origins of changed birth weight of the offspring born through assisted reproductive technology (ART). The association between hormone and lipid metabolism or body weight has been generally accepted, and as the basic and specific treatment in ART procedure, gonadotropin stimulation might have potential effects on intrauterine lipid metabolism. In our studies, the mice were superovulated with two doses of gonadotropin. The cholesterol metabolism in ovaries and the triglyceride metabolism in embryos were analyzed. The results showed gonadotropin probably accelerated luteinization and induced a longer time follicle development and ovulation, which resulted in histological and morphological alteration of ovary, and increased the cholesterol content and the expressions of steroidogenesis-related genes. In embryos, gonadotropin increased lipid accumulation and decreased fatty acid synthesis in a dose-dependent manner. Moreover, the changes of fatty acid composition were also shown in superovulation groups. Our studies firstly provided the evidence that the superovulation might affect the maternal and fetal lipid metabolism. These variations of lipid metabolism in our results may be associated with birth weight of ART infants.

  20. Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism.

    PubMed

    Liao, Wenjuan; Liu, Hongbing; Zhang, Yiwei; Jung, Ji Hoon; Chen, Jiaxiang; Su, Xiaohua; Kim, Yeong C; Flores, Elsa R; Wang, San Ming; Czarny-Ratajczak, Malwina; Li, Wen; Zeng, Shelya X; Lu, Hua

    2017-08-21

    TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.

  1. Cell proliferation and progesterone synthesis depend on lipid metabolism in bovine granulosa cells.

    PubMed

    Elis, Sebastien; Desmarchais, Alice; Maillard, Virginie; Uzbekova, Svetlana; Monget, Philippe; Dupont, Joëlle

    2015-03-15

    In dairy cows, lipids are essential to support energy supplies for all biological functions, especially during early lactation. Lipid metabolism is crucial for sustaining proper reproductive function. Alteration of lipid metabolism impacts follicular development and affects oocyte developmental competence. Indeed, nonesterified fatty acids are able to decrease granulosa cell (GC) proliferation and affect estradiol synthesis, thus potentially affecting follicular growth and viability. The objective of this study was to assess the impact of lipid metabolism on bovine GCs, through the use of the lipid metabolism inhibitors etomoxir, an inhibitor of fatty acid (FA) oxidation through inhibition of carnitine palmitoyl transferase 1 (CPT1), and C75, an inhibitor of FA synthesis through inhibition of fatty acid synthase. We showed that etomoxir and C75 significantly inhibited DNA synthesis in vitro; C75 also significantly decreased progesterone synthesis. Both inhibitors significantly reduced AMPK (5' adenosine monophosphate-activated protein kinase) and acetyl-CoA carboxylase phosphorylation. Etomoxir also affected the AKT (protein kinase B) signaling pathway. Combined, these data suggest that both FA oxidation and synthesis are important for the bovine GCs to express a proliferative and steroidogenic phenotype and, thus, for sustaining follicular growth. Despite these findings, it is important to note that the changes caused by the inhibitors of FA metabolism on GCs in vitro are globally mild, suggesting that lipid metabolism is not as critical in GCs as was observed in the oocyte-cumulus complex. Further studies are needed to investigate the detailed mechanisms by which lipid metabolism interacts with GC functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Mammalian hibernation and regulation of lipid metabolism: a focus on non-coding RNAs.

    PubMed

    Lang-Ouellette, D; Richard, T G; Morin, P

    2014-11-01

    Numerous species will confront severe environmental conditions by undergoing significant metabolic rate reduction. Mammalian hibernation is one such natural model of hypometabolism. Hibernators experience considerable physiological, metabolic, and molecular changes to survive the harsh challenges associated with winter. Whether as fuel source or as key signaling molecules, lipids are of primary importance for a successful bout of hibernation and their careful regulation throughout this process is essential. In recent years, a plethora of non-coding RNAs has emerged as potential regulators of targets implicated in lipid metabolism in diverse models. In this review, we introduce the general characteristics associated with mammalian hibernation, present the importance of lipid metabolism prior to and during hibernation, as well as discuss the potential relevance of non-coding RNAs such as miRNAs and lncRNAs during this process.

  3. PPARγ Regulates Mouse Meibocyte Differentiation and Lipid Synthesis.

    PubMed

    Jester, James V; Potma, Eric; Brown, Donald J

    2016-10-01

    Previous reports suggest that age-related meibomian gland atrophy is associated with decreased expression of the lipid-sensitive nuclear receptor, PPARγ. The purpose of this study was to identify the role of PPARγ in modulating meibocyte lipid synthesis. Cytoplasmic and nuclear fractions from meibomian glands of young (2M) and old (2Y) C57Bl6 mice were probed using antibodies specific for PPARγ. Mouse meibocytes were cultured, immortalized using a SV40 lentiviral vector, and evaluated for lipid synthesis using LipidTox staining and CARS/Raman microspectroscopy. Lipid synthesizing clones were tested for effects of PPARγ agonist, rosiglitazone, on lipid synthesis and PPARγ localization, post-translational modification and induction of PPARγ response genes. The cytoplasmic fraction in young mice contained both 50 and 72 kDa PPARγ bands that were absent or reduced by 75% in older mice, respectively. Cultured meibocytes produced neutral lipid containing equal amounts of wax and cholesterol esters, similar to mouse meibum. Addition of rosiglitazone (10-50 μM) significantly increased lipid production (P<.05) in meibocytes, associated with SUMO1 sumoylation and cytoplasmic accumulation of the 72 kDa PPARγ. Rosiglitazone also increased the localization of PPARγ to the cytoplasm and up-regulated of PPARγ, ADP and ADFP mRNA. This study confirms the loss of cytoplasmic/vesicular PPARγ localization in older, atrophic mouse meibomian glands. Furthermore, PPARγ stimulates lipid synthesis in mouse meibocytes, associated with PPARγ sumoylation and translocation to the cytoplasm. Taken together these data suggest that lipid synthesis in older mice is down regulated by a PPARγ mediated pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. JAK and STAT members of yellow catfish Pelteobagrus fulvidraco and their roles in leptin affecting lipid metabolism.

    PubMed

    Wu, Kun; Tan, Xiao-Ying; Xu, Yi-Huan; Chen, Qi-Liang; Pan, Ya-Xiong

    2016-01-15

    The present study clones and characterizes the full-length cDNA sequences of members in JAK-STAT pathway, explores their mRNA tissue expression and the biological role in leptin influencing lipid metabolism in yellow catfish Pelteobagrus fulvidraco. Full-length cDNA sequences of five JAKs and seven STAT members, including some splicing variants, were obtained from yellow catfish. Compared to mammals, more members of the JAKs and STATs family were found in yellow catfish, which provided evidence that the JAK and STAT family members had arisen by the whole genome duplications during vertebrate evolution. All of these members were widely expressed across the eleven tissues (liver, white muscle, spleen, brain, gill, mesenteric fat, anterior intestine, heart, mid-kidney, testis and ovary) but at the variable levels. Intraperitoneal injection in vivo and incubation in vitro of recombinant human leptin changed triglyceride content and mRNA expression of several JAKs and STATs members, and genes involved in lipid metabolism. AG490, a specific inhibitor of JAK2-STAT pathway, partially reversed leptin-induced effects, indicating that the JAK2a/b-STAT3 pathway exerts main regulating actions of leptin on lipid metabolism at transcriptional level. Meanwhile, the different splicing variants were differentially regulated by leptin incubation. Thus, our data suggest that leptin activated the JAK/STAT pathway and increases the expression of target genes, which partially accounts for the leptin-induced changes in lipid metabolism in yellow catfish. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Docosahexaenoic acid modulates the enterocyte Caco-2 cell expression of microRNAs involved in lipid metabolism.

    PubMed

    Gil-Zamorano, Judit; Martin, Roberto; Daimiel, Lidia; Richardson, Kris; Giordano, Elena; Nicod, Nathalie; García-Carrasco, Belén; Soares, Sara M A; Iglesias-Gutiérrez, Eduardo; Lasunción, Miguel A; Sala-Vila, Aleix; Ros, Emilio; Ordovás, Jose M; Visioli, Francesco; Dávalos, Alberto

    2014-05-01

    Consumption of the long-chain ω-3 (n-3) polyunsaturated fatty acid docosahexaenoic acid (DHA) is associated with a reduced risk of cardiovascular disease and greater chemoprevention. However, the mechanisms underlying the biologic effects of DHA remain unknown. It is well known that microRNAs (miRNAs) are versatile regulators of gene expression. Therefore, we aimed to determine if the beneficial effects of DHA may be modulated in part through miRNAs. Loss of dicer 1 ribonuclease type III (DICER) in enterocyte Caco-2 cells supplemented with DHA suggested that several lipid metabolism genes are modulated by miRNAs. Analysis of miRNAs predicted to target these genes revealed several miRNA candidates that are differentially modulated by fatty acids. Among the miRNAs modulated by DHA were miR-192 and miR-30c. Overexpression of either miR-192 or miR-30c in enterocyte and hepatocyte cells suggested an effect on the expression of genes related to lipid metabolism, some of which were confirmed by endogenous inhibition of these miRNAs. Our results show in enterocytes that DHA exerts its biologic effect in part by regulating genes involved in lipid metabolism and cancer. Moreover, this response is mediated through miRNA activity. We validate novel targets of miR-30c and miR-192 related to lipid metabolism and cancer including nuclear receptor corepressor 2, isocitrate dehydrogenase 1, DICER, caveolin 1, ATP-binding cassette subfamily G (white) member 4, retinoic acid receptor β, and others. We also present evidence that in enterocytes DHA modulates the expression of regulatory factor X6 through these miRNAs. Alteration of miRNA levels by dietary components in support of their pharmacologic modulation might be valuable in adjunct therapy for dyslipidemia and other related diseases.

  6. Changes of lipidic and the immunological state at patients with a metabolic syndrome in Ukraine.

    PubMed

    Karlova, Olena O; Omelchuk, Sergei T; Kuzminska, Olena V; Melnyk, Valentyna V

    The metabolic syndrome has become pandemic nature and tends to rejuvenation in the world. Elucidation of the pathogenic mechanisms on membrane-cell level will optimize the treatment of patients with metabolic syndrome and prevention of metabolic syndrome on the level of pre-clinical manifestations. to study the immunological status and lipid metabolism in the patients with metabolic syndrome and the pathogenetic mechanisms of metabolic syndrome were established. There were 4 groups of pacients (110) with: metabolic syndrome, ischemic heart disease and hypertension, hypertention; control group. General clinical, instrumental, laboratory and statistical methods were used. The levels of immune factors - interleukin-6 in supernatants of mononuclear cells by 65%, sICAM-1 by 20% is elevated in patients with metabolic syndrome compared with the control group. The increasing of the content of saturated fatty acids by 9.4% and polyunsaturated fatty acid by 36.6% lead to fundamental breach of structural and functional properties of membranes. There is significant common carotid artery intima media thickness on average twice at the patients with metabolic syndrome and with ischemic heart disease and hypertension. The immunoinflammatory reactions were more revealed in the group of patients with metabolic syndrome than in other groups. The lipid state at patients with metabolic syndrome was changed more than in patients with hypertension or patients with ischemic heart disease and hypertension both. Moreover our data indicate the presence of structural changes in the vessel wall in patients with metabolic syndrome.

  7. Roles of leptin and ghrelin in adipogenesis and lipid metabolism of rainbow trout adipocytes in vitro.

    PubMed

    Salmerón, Cristina; Johansson, Marcus; Asaad, Maryam; Angotzi, Anna R; Rønnestad, Ivar; Stefansson, Sigurd O; Jönsson, Elisabeth; Björnsson, Björn Thrandur; Gutiérrez, Joaquim; Navarro, Isabel; Capilla, Encarnación

    2015-10-01

    Leptin and ghrelin are important regulators of energy homeostasis in mammals, whereas their physiological roles in fish have not been fully elucidated. In the present study, the effects of leptin and ghrelin on adipogenesis, lipolysis and on expression of lipid metabolism-related genes were examined in rainbow trout adipocytes in vitro. Leptin expression and release increased from preadipocytes to mature adipocytes in culture, but did not affect the process of adipogenesis. While ghrelin and its receptor were identified in cultured differentiated adipocytes, ghrelin did not influence either preadipocyte proliferation or differentiation, indicating that it may have other adipose-related roles. Leptin and ghrelin increased lipolysis in mature freshly isolated adipocytes, but mRNA expression of lipolysis markers was not significantly modified. Leptin significantly suppressed the fatty acid transporter-1 expression, suggesting a decrease in fatty acid uptake and storage, but did not affect expression of any of the lipogenesis or β-oxidation genes studied. Ghrelin significantly increased the mRNA levels of lipoprotein lipase, fatty acid synthase and peroxisome proliferator-activated receptor-β, and thus appears to stimulate synthesis of triglycerides as well as their mobilization. Overall, the study indicates that ghrelin, but not leptin seems to be an enhancer of lipid turn-over in adipose tissue of rainbow trout, and this regulation may at least partly be mediated through autocrine/paracrine mechanisms. The mode of action of both hormones needs to be further explored to better understand their roles in regulating adiposity in fish. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Membrane Lipid Metabolism in Germinating Castor Bean Endosperm 1

    PubMed Central

    Donaldson, Robert P.

    1976-01-01

    Castor bean (Ricinus communis L. var. Hale) endosperms, excised after 2 days germination at 30 C, were incubated 5 min to 8 hr with 14C-acetate and 3H-glycerol. Homogenates were fractionated by sucrose gradient centrifugation. Organelles found to be active in lipid synthesis were the lipid bodies and the endoplasmic reticulum. The products of incorporation in the lipid bodies were 3H-diglycerides containing 14C-fatty acids of more than 20 carbons. In contrast, the endoplasmic reticulum produced 3H-phospholipids as well as 3H-diglycerides rich in 14C-linoleate. The phospholipids synthesized and their acyl contents were of the types known to be the major components of organelle membranes in this tissue. Phospholipids and diglycerides containing 14C and 3H were found in the glyoxysomes and mitochondria subsequent to their appearance in the endoplasmic reticulum. The results show that germinating castor bean endosperm synthesizes membrane lipids de novo from acetate rather than reutilizing stored lipid components directly. It is also apparent that the endoplasmic reticulum is responsible for several steps in membrane lipid production. PMID:16659516

  9. Role of cystathionine beta synthase in lipid metabolism in ovarian cancer

    PubMed Central

    Chakraborty, Prabir K.; Xiong, Xunhao; Mustafi, Soumyajit Banerjee; Saha, Sounik; Dhanasekaran, Danny; Mandal, Nawajes A.; McMeekin, Scott; Bhattacharya, Resham; Mukherjee, Priyabrata

    2015-01-01

    Elevated lipid metabolism is implicated in poor survival in ovarian cancer (OC) and other cancers; however, current lipogenesis-targeting strategies lack cancer cell specificity. Here, we identify a novel role of cystathionine beta-synthase (CBS), a sulphur amino acid metabolizing enzyme highly expressed in several ovarian cancer cell lines, in driving deregulated lipid metabolism in OC. We examined the role of CBS in regulation of triglycerides, cholesterol and lipogenic enzymes via the lipogenic transcription factors SREBP1 and SREBP2. CBS silencing attenuated the expression of number of key enzymes involved in lipid synthesis (FASN and ACC1). Additionally CBS abrogates lipid uptake in OC cells. Gene silencing of CBS or SREBPs abrogated cellular migration and invasion in OC, while ectopic expression of SREBPs can rescue phenotypic effects of CBS silencing by restoring cell migration and invasion. Mechanistically, CBS represses SREBP1 and SREBP2 at the transcription levels by modulating the transcription factor Sp1. We further established the roles of both CBS and SREBPs in regulating ovarian tumor growth in vivo. In orthotopic tumor models, CBS or SREBP silencing resulted in reduced tumor cells proliferation, blood vessels formation and lipid content. Hence, cancer-selective disruption of the lipid metabolism pathway is possible by targeting CBS and, at least for OC, promises a profound benefit. PMID:26452259

  10. Serine dipeptide lipids of Porphyromonas gingivalis inhibit osteoblast differentiation: Relationship to Toll-like receptor 2.

    PubMed

    Wang, Yu-Hsiung; Nemati, Reza; Anstadt, Emily; Liu, Yaling; Son, Young; Zhu, Qiang; Yao, Xudong; Clark, Robert B; Rowe, David W; Nichols, Frank C

    2015-12-01

    Porphyromonas gingivalis is a periodontal pathogen strongly associated with loss of attachment and supporting bone for teeth. We have previously shown that the total lipid extract of P. gingivalis inhibits osteoblast differentiation through engagement of Toll-like receptor 2 (TLR2) and that serine dipeptide lipids of P. gingivalis engage both mouse and human TLR2. The purpose of the present investigation was to determine whether these serine lipids inhibit osteoblast differentiation in vitro and in vivo and whether TLR2 engagement is involved. Osteoblasts were obtained from calvaria of wild type or TLR2 knockout mouse pups that also express the Col2.3GFP transgene. Two classes of serine dipeptide lipids, termed Lipid 654 and Lipid 430, were tested. Osteoblast differentiation was monitored by cell GFP fluorescence and osteoblast gene expression and osteoblast function was monitored as von Kossa stained mineral deposits. Osteoblast differentiation and function were evaluated in calvarial cell cultures maintained for 21 days. Lipid 654 significantly inhibited GFP expression, osteoblast gene expression and mineral nodule formation and this inhibition was dependent on TLR2 engagement. Lipid 430 also significantly inhibited GFP expression, osteoblast gene expression and mineral nodule formation but these effects were only partially attributed to engagement of TLR2. More importantly, Lipid 430 stimulated TNF-α and RANKL gene expression in wild type cells but not in TLR2 knockout cells. Finally, osteoblast cultures were observed to hydrolyze Lipid 654 to Lipid 430 and this likely occurs through elevated PLA2 activity in the cultured cells. In conclusion, our results show that serine dipeptide lipids of P. gingivalis inhibit osteoblast differentiation and function at least in part through engagement of TLR2. The Lipid 430 serine class also increased the expression of genes that could increase osteoclast activity. We conclude that Lipid 654 and Lipid 430 have the potential

  11. Comparative transcriptome analysis of transporters, phytohormone and lipid metabolism pathways in response to arsenic stress in rice (Oryza sativa).

    PubMed

    Yu, Lu-jun; Luo, Ying-feng; Liao, Bin; Xie, Li-juan; Chen, Liang; Xiao, Shi; Li, Jin-tian; Hu, Song-nian; Shu, Wen-sheng

    2012-07-01

    • Arsenic (As) contamination of rice (Oryza sativa) is a worldwide concern and elucidating the molecular mechanisms of As accumulation in rice may provide promising solutions to the problem. Previous studies using microarray techniques to investigate transcriptional regulation of plant responses to As stress have identified numerous differentially expressed genes. However, little is known about the metabolic and regulatory network remodelings, or their interactions with microRNA (miRNA) in plants upon As(III) exposure. • We used Illumina sequencing to acquire global transcriptome alterations and miRNA regulation in rice under As(III) treatments of varying lengths of time and dosages. • We found that the response of roots was more distinct when the dosage was varied, whereas that of shoots was more distinct when the treatment time was varied. In particular, the genes involved in heavy metal transportation, jasmonate (JA) biosynthesis and signaling, and lipid metabolism were closely related to responses of rice under As(III) stress. Furthermore, we discovered 36 new As(III)-responsive miRNAs, 14 of which were likely involved in regulating gene expression in transportation, signaling, and metabolism. • Our findings highlight the significance of JA signaling and lipid metabolism in response to As(III) stress and their regulation by miRNA, which provides a foundation for subsequent functional research.

  12. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  13. Association of Polymorphisms of Genes Involved in Lipid Metabolism with Blood Pressure and Lipid Values in Mexican Hypertensive Individuals

    PubMed Central

    Ríos-González, Blanca Estela; Ibarra-Cortés, Bertha; Ramírez-López, Guadalupe; Sánchez-Corona, José; Magaña-Torres, María Teresa

    2014-01-01

    Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP). We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591) with blood pressure and lipid values in Mexican hypertensive (HT) patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC −514T, and MTTP −493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17–2.93; P = 0.001) under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients. PMID:25587205

  14. Association of polymorphisms of genes involved in lipid metabolism with blood pressure and lipid values in mexican hypertensive individuals.

    PubMed

    Ríos-González, Blanca Estela; Ibarra-Cortés, Bertha; Ramírez-López, Guadalupe; Sánchez-Corona, José; Magaña-Torres, María Teresa

    2014-01-01

    Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP). We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591) with blood pressure and lipid values in Mexican hypertensive (HT) patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC -514T, and MTTP -493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17-2.93; P = 0.001) under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients.

  15. Alteration of lipid status and lipid metabolism, induction of oxidative stress and lipid peroxidation by 2,4-dichlorophenoxyacetic herbicide in rat liver.

    PubMed

    Tayeb, Wafa; Nakbi, Amel; Cheraief, Imed; Miled, Abdelhedi; Hammami, Mohamed

    2013-07-01

    This study aims to investigate the effects of the 2,4-dichlorophenoxyacetic herbicide (2,4-D) on plasma lipids, lipoproteins concentrations, hepatic lipid peroxidation, fatty acid composition and antioxidant enzyme activities in rats. Animals were randomly divided into four groups of 10 each: control group and three 2,4-D-treated groups G1, G2 and G3 were administered 15, 75 and 150 mg/kg/BW/d 2,4-D by gavage for 28 d, respectively. Results showed that 2,4-D caused significant negative changes in the biochemical parameters investigated. The malondialdehyde level was significantly increased in 2,4-D-treated groups. Fatty acid composition of the liver was also significantly changed with 2,4-D exposure. Furthermore, the hepatic antioxidant enzyme activities were significantly affected. Finally, 2,4-D at the studied doses modifies lipidic status, disrupt lipid metabolism and induce hepatic oxidative stress. In conclusion, at higher doses, 2,4-D may play an important role in the development of vascular disease via metabolic disorder of lipoproteins, lipid peroxidation and oxidative stress.

  16. Effect of geraniol, a plant derived monoterpene on lipids and lipid metabolizing enzymes in experimental hyperlipidemic hamsters.

    PubMed

    Jayachandran, Muthukumaran; Chandrasekaran, Balaji; Namasivayam, Nalini

    2015-01-01

    Hyperlipidemia is a major, modifiable risk factor for atherosclerosis and cardiovascular disease. In the present study, we have focused on the effect of different doses of geraniol (GOH) on the lipid profile and lipid metabolizing enzymes in atherogenic diet (AD) fed hamsters. Male Syrian hamsters were grouped into seven: group 1 were control animals; group 2 were animals fed GOH alone (200 mg/kg b.w); group 3 were animals fed AD (10 % coconut oil, 0.25 % cholesterol, and 0.25 % cholic acid); group 4 were animals fed AD + corn oil (2.5 ml/kg b.w); and groups 5, 6, and 7 were fed AD as in group 3 + different doses of GOH (50, 100, and 200 mg/kg b.w), respectively, for 12 weeks. At the end of the experimental period, animals were sacrificed by cervical dislocation and various assays were performed in the plasma and tissues. The AD hamsters showed marked changes in lipid profile and lipid metabolizing enzymes. However, supplementation with GOH counteracted the hyperlipidemia by inhibiting HMG CoA reductase and suppressing lipogenesis. The antihyperlipidemic efficacy of GOH was found to be effective at the dose of 100 mg/kg b.w. This study illustrates that GOH is effective in lowering the risk of hyperlipidemia in AD fed hamsters.

  17. Resistin Regulates Pituitary Lipid Metabolism and Inflammation In Vivo and In Vitro

    PubMed Central

    Rodriguez-Pacheco, F.; Novelle, M. G.; Vazquez, M. J.; Garcia-Escobar, E.; Soriguer, F.; Rojo-Martinez, G.; García-Fuentes, E.; Malagon, M. M.; Dieguez, C.

    2013-01-01

    The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH) secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way) and in vitro (adenopituitary cell cultures treated with the adipokine). Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism. PMID:23710116

  18. Lipid metabolism-related gene expression pattern of Atlantic bluefin tuna (Thunnus thynnus L.) larvae fed on live prey.

    PubMed

    Betancor, Mónica B; Ortega, Aurelio; de la Gándara, Fernando; Tocher, Douglas R; Mourente, Gabriel

    2017-04-01

    The present study is the first to evaluate lipid metabolism in first-feeding Atlantic bluefin tuna (ABT; Thunnus thynnus L.) larvae fed different live prey including enriched rotifers Brachionus plicatilis and Acartia sp. copepod nauplii from 2 days after hatch. Understanding the molecular basis of lipid metabolism and regulation in ABT will provide insights to optimize diet formulations for this high-value species new to aquaculture. To this end, we investigated the effect of dietary lipid on whole larvae lipid class and fatty acid compositions and the expression of key genes involved in lipid metabolism in first feeding ABT larvae fed different live prey. Additionally, the expression of lipid metabolism genes in tissues of adult broodstock ABT was evaluated. Growth and survival data indicated that copepods were the best live prey for first feeding ABT and that differences in growth performance and lipid metabolism observed between larvae from different year classes could be a consequence of broodstock nutrition. In addition, expression patterns of lipid metabolic genes observed in ABT larvae in the trials could reflect differences in lipid class and fatty acid compositions of the live prey. The lipid nutritional requirements, including essential fatty acid requirements of larval ABT during the early feeding stages, are unknown, and the present study represents a first step in addressing these highly relevant issues. However, further studies are required to determine nutritional requirements and understand lipid metabolism during development of ABT larvae and to apply the knowledge to the commercial culture of this iconic species.

  19. Intracellular lipid content is a key intrinsic determinant for hepatocyte viability and metabolic and inflammatory states in mice

    PubMed Central

    Sheng, Liang; Jiang, Bijie

    2013-01-01

    The liver is an essential metabolic organ. In addition to metabolizing glucose and lipids, hepatocytes also secrete various cytokines that modulate both hepatocyte metabolism and liver inflammation. Hepatocyte injury and death and liver inflammation are the major contributors to liver diseases, including nonalcoholic steatohepatitis (NASH). Anatomic locations have a profound effect on hepatocyte metabolism, and liver zonation describes the metabolic heterogeneity of hepatocytes along the portovenous axis. However, it is unclear whether hepatocyte heterogeneity is affected by intrinsic factors and whether dietary fat, a risk factor for NASH, has distinct detrimental effects on different hepatocyte subpopulations. Here, we showed that mouse livers contained both high-lipid and low-lipid subpopulations of hepatocytes. The high-lipid subpopulation was more susceptible to injury and apoptosis and produced more proinflamatrory cytokines after treatment with endotoxin and saturated fatty acids. Dietary fat consumption further increased fatty acid uptake, intracellular lipid levels, hepatocyte injury and death, and the expression of proinflammatory cytokines in the high-lipid subpopulation. In contrast, dietary fat slightly increased lipid levels, cell death, and expression of proinflammatory cytokines in the low-lipid subpopulation. The low-lipid subpopulation produced more glucose. Fat consumption further activated the gluconeogenic program in the low-lipid, but not the high-lipid, subpopulations. These data suggest that intracellular lipid content is a key intrinsic determinant for hepatocyte heterogeneity of metabolic, inflammatory, and survival states. PMID:23982157

  20. Unraveling algal lipid metabolism: Recent advances in gene identification.

    PubMed

    Khozin-Goldberg, Inna; Cohen, Zvi

    2011-01-01

    Microalgae are now the focus of intensive research due to their potential as a renewable feedstock for biodiesel. This research requires a thorough understanding of the biochemistry and genetics of these organisms' lipid-biosynthesis pathways. Genes encoding lipid-biosynthesis enzymes can now be identified in the genomes of various eukaryotic microalgae. However, an examination of the predicted proteins at the biochemical and molecular levels is mandatory to verify their function. The essential molecular and genetic tools are now available for a comprehensive characterization of genes coding for enzymes of the lipid-biosynthesis pathways in some algal species. This review mainly summarizes the novel information emerging from recently obtained algal gene identification.

  1. Central ghrelin regulates peripheral lipid metabolism in a growth hormone-independent fashion.

    PubMed

    Sangiao-Alvarellos, Susana; Vázquez, María J; Varela, Luis; Nogueiras, Rubén; Saha, Asish K; Cordido, Fernando; López, Miguel; Diéguez, Carlos

    2009-10-01

    GH plays a major role in the regulation of lipid metabolism and alterations in GH axis elicit major changes in fat distribution and mobilization. For example, in patients with GH deficiency (GHD) or in mice lacking the GH receptor, the percentage of fat is increased. In addition to the direct actions of GH on lipid metabolism, current evidence indicates that ghrelin, a stomach-derived peptide hormone with potent GH secretagogue action, increases lipogenesis in white adipose tissue (WAT) through a hypothalamic-mediated mechanism. Still, the mechanism by which GH tone modulates ghrelin actions on WAT remains unclear. Here we investigated the effect of central ghrelin administration on lipid metabolism in lipogenic tissues (liver and WAT) in the absence of GH, by using a model for the study of GHD, namely the spontaneous dwarf rat, which shows increased body fat. Our data demonstrate that central chronic ghrelin administration regulates adipose lipid metabolism, mainly in a GH-independent fashion, as a result of increased mRNA, protein expression, and activity levels of fatty acid metabolism enzymes. On the contrary, central ghrelin regulates hepatic lipogenesis de novo in a GH-independent fashion but lipid mobilization in a GH-dependent fashion because carnitine palmitoyltransferase 1 was decreased only in wild-type Lewis rats. These findings suggest the existence of a new central nervous system-based neuroendocrine circuit, regulating metabolic homeostasis of adipose tissue. Understanding the molecular mechanism underlying the interplay between GH and ghrelin and their effects on lipid metabolism will provide new strategies for the design and development of suitable drugs for the treatment of GHD, obesity, and its comorbidities.

  2. RNA-seq based detection of differentially expressed genes in the skeletal muscle of Duroc pigs with distinct lipid profiles

    PubMed Central

    Cardoso, T. F.; Cánovas, A.; Canela-Xandri, O.; González-Prendes, R.; Amills, M.; Quintanilla, R.

    2017-01-01

    We have used a RNA-seq approach to investigate differential expression in the skeletal muscle of swine (N = 52) with divergent lipid profiles i.e. HIGH (increased intramuscular fat and muscle saturated and monounsaturated fatty acid contents, higher serum lipid concentrations and fatness) and LOW pigs (leaner and with an increased muscle polyunsaturated fatty acid content). The number of mRNAs and non-coding RNAs (ncRNAs) expressed in the porcine gluteus medius muscle were 18,104 and 1,558, respectively. At the nominal level of significance (P-value ≤ 0.05), we detected 1,430 mRNA and 12 non-coding RNA (ncRNA) transcripts as differentially expressed (DE) in the gluteus medius muscle of HIGH vs LOW pigs. This smaller contribution of ncRNAs to differential expression may have biological and technical reasons. We performed a second analysis, that was more stringent (P-value ≤ 0.01 and fold-change ≥ 1.5), and only 96 and 0 mRNA-and ncRNA-encoding genes happened to be DE, respectively. The subset of DE mRNA genes was enriched in pathways related with lipid (lipogenesis and triacylglycerol degradation) and glucose metabolism. Moreover, HIGH pigs showed a more lipogenic profile than their LOW counterparts. PMID:28195222

  3. Metabolic Inflammation-Differential Modulation by Dietary Constituents.

    PubMed

    Lyons, Claire L; Kennedy, Elaine B; Roche, Helen M

    2016-04-27

    Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin's action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review.

  4. Metabolic Inflammation-Differential Modulation by Dietary Constituents

    PubMed Central

    Lyons, Claire L.; Kennedy, Elaine B.; Roche, Helen M.

    2016-01-01

    Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin’s action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review. PMID:27128935

  5. PPARγ isoforms differentially regulate metabolic networks to mediate mouse prostatic epithelial differentiation.

    PubMed

    Strand, D W; Jiang, M; Murphy, T A; Yi, Y; Konvinse, K C; Franco, O E; Wang, Y; Young, J D; Hayward, S W

    2012-08-09

    Recent observations indicate prostatic diseases are comorbidities of systemic metabolic dysfunction. These discoveries revealed fundamental questions regarding the nature of prostate metabolism. We previously showed that prostate-specific ablation of PPARγ in mice resulted in tumorigenesis and active autophagy. Here, we demonstrate control of overlapping and distinct aspects of prostate epithelial metabolism by ectopic expression of individual PPARγ isoforms in PPARγ knockout prostate epithelial cells. Expression and activation of either PPARγ 1 or 2 reduced de novo lipogenesis and oxidative stress and mediated a switch from glucose to fatty acid oxidation through regulation of genes including Pdk4, Fabp4, Lpl, Acot1 and Cd36. Differential effects of PPARγ isoforms included decreased basal cell differentiation, Scd1 expression and triglyceride fatty acid desaturation and increased tumorigenicity by PPARγ1. In contrast, PPARγ2 expression significantly increased basal cell differentiation, Scd1 expression and AR expression and responsiveness. Finally, in confirmation of in vitro data, a PPARγ agonist versus high-fat diet (HFD) regimen in vivo confirmed that PPARγ agonization increased prostatic differentiation markers, whereas HFD downregulated PPARγ-regulated genes and decreased prostate differentiation. These data provide a rationale for pursuing a fundamental metabolic understanding of changes to glucose and fatty acid metabolism in benign and malignant prostatic diseases associated with systemic metabolic stress.

  6. The effects of time-restricted feeding on lipid metabolism and adiposity

    PubMed Central

    Chaix, Amandine; Zarrinpar, Amir

    2015-01-01

    Maintaining natural feeding rhythms with time-restricted feeding (TRF), without altering nutritional intake, prevents and reverses diet-induced obesity (DIO) and its associated metabolic disorders in mice. TRF has a direct effect on animal adiposity, causes an alteration of adipokine signaling, and diminishes white adipose tissue inflammation. Many genes involved in lipid metabolism are normally circadian, but their expression is perturbed with DIO; TRF restores their cyclical expression. One mechanism through which TRF could affect host metabolism is by altering the gut microbiome. Changes in the gut microbiome are coupled with an altered stool bile acid profile. Hence, TRF could affect lipid metabolism by altering bile acid signaling. TRF introduces many new possibilities in treating obesity and its associated metabolic disorders. However, further studies are needed to show whether these physiological findings in mice translate to humans. PMID:26451290

  7. Wolbachia Modulates Lipid Metabolism in Aedes albopictus Mosquito Cells

    PubMed Central

    Molloy, Jennifer C.; Sommer, Ulf; Viant, Mark R.

    2016-01-01

    ABSTRACT Certain strains of the intracellular endosymbiont Wolbachia can strongly inhibit or block the transmission of viruses such as dengue virus (DENV) by Aedes mosquitoes, and the mechanisms responsible are still not well understood. Direct infusion and liquid chromatography-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry-based lipidomics analyses were conducted using Aedes albopictus Aa23 cells that were infected with the wMel and wMelPop strains of Wolbachia in comparison to uninfected Aa23-T cells. Substantial shifts in the cellular lipid profile were apparent in the presence of Wolbachia. Most significantly, almost all sphingolipid classes were depleted, and some reductions in diacylglycerols and phosphatidylcholines were also observed. These lipid classes have previously been shown to be selectively enriched in DENV-infected mosquito cells, suggesting that Wolbachia may produce a cellular lipid environment that is antagonistic to viral replication. The data improve our understanding of the intracellular interactions between Wolbachia and mosquitoes. IMPORTANCE Mosquitoes transmit a variety of important viruses to humans, such as dengue virus and Zika virus. Certain strains of the intracellular bacterial genus called Wolbachia found in or introduced into mosquitoes can block the transmission of viruses, including dengue virus, but the mechanisms responsible are not well understood. We found substantial shifts in the cellular lipid profiles in the presence of these bacteria. Some lipid classes previously shown to be enriched in dengue virus-infected mosquito cells were depleted in the presence of Wolbachia, suggesting that Wolbachia may produce a cellular lipid environment that inhibits mosquito-borne viruses. PMID:26994075

  8. Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats.

    PubMed

    Choi, Joo Sun; Koh, In-Uk; Song, Jihyun

    2012-11-01

    Postmenopausal women are at higher risk for obesity and insulin resistance due to the decline of estrogen, but genistein, a phytoestrogen, may reduce the risks of these diet-related diseases. In this study, we hypothesized that supplemental genistein has beneficial effects on insulin resistance in an ovariectomized rat model by modulating lipid metabolism. Three weeks after a sham surgery (sham) or an ovariectomy (OVX), ovariectomized Sprague-Dawley rats were placed on a diet containing 0 (OVX group) or 0.1% genistein for 4 weeks. The sham rats were fed a high-fat diet containing 0% genistein and served as the control group (sham group). The ovariectomized rats showed increases in body weight and insulin resistance index, but genistein reduced insulin resistance index and the activity of hepatic fatty acid synthetase. Genistein was also associated with increased activity of succinate dehydrogenase and carnitine palmitoyltransferase and the rate of β-oxidation in the fat tissue of rats. The ovariectomized rats given genistein had smaller-sized adipocytes. Using gene-set enrichment analysis (GSEA) of microarray data, we found that a number of gene sets of fatty acid metabolism, insulin resistance, and oxidative stress were differentially expressed by OVX and reversed by genistein. This systemic approach of GSEA enables the identification of such consensus between the gene expression changes and phenotypic changes caused by OVX and genistein supplementation. Genistein treatment could help reduce insulin resistance through the amelioration of OVX-induced metabolic dysfunction, and the GSEA approach may be useful in proposing putative targets related to insulin resistance. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Muscle lipid metabolism in two rabbit lines divergently selected for intramuscular fat.

    PubMed

    Martínez-Álvaro, M; Agha, S; Blasco, A; Hernández, P

    2017-06-01

    A divergent selection experiment for intramuscular fat (IMF) of LM at 9 wk of age was performed in rabbits. The objective of this work was to compare the lipid metabolism in muscles and fat tissues of the high-IMF and low-IMF lines. Lipogenic, catabolic, and lipolytic activities were studied in 2 muscles with different oxidative patterns (LM and semimembranosus proprius) and in the perirenal fat depot at 2 ages, 9 and 13 wk. In addition, adipocytes were characterized in perirenal fat. In the fifth generation, direct response to selection was 0.26 g IMF/100 g muscle. Lines showed differences in their lipogenic activities of muscles and fat tissues at 13 wk but not at 9 wk. The high-IMF line showed greater glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (EM), and fatty acid synthase (FAS) activities in LM than the low-IMF line, with probabilities = 1.00, 0.93, and 0.90, respectively. Differences between lines were particularly great for G6PDH activity, representing 1.13 SD. The high-IMF line also showed greater G6PDH and FAS activities in semimembranosus proprius (P = 0.98 for G6PDH and 0.95 for FAS) and perirenal fat (P = 0.91 for G6PDH and 0.96 for FAS). However, in perirenal fat, EM activity was greater in the low-IMF line (P = 0.90). No differences between lines were found in almost any catabolic or lipolytic activities of muscles. Regarding adipocyte characteristics, the high-IMF line showed larger adipocytes in perirenal fat depot tissue (P = 0.97) compared to the low-IMF line, but no differences between lines were observed in the number of adipocytes. This study sheds light on the metabolic activities involved in the genetic differentiation of lipid deposition in rabbits. This study shows that lipogenic activities in muscles and fat tissues, in particular G6PDH in LM, are involved in the lipid accumulation in muscle and adipose tissues.

  10. Reversible Nuclear-Lipid-Droplet Morphology Induced by Oleic Acid: A Link to Cellular-Lipid Metabolism.

    PubMed

    Lagrutta, Lucía C; Montero-Villegas, Sandra; Layerenza, Juan P; Sisti, Martín S; García de Bravo, Margarita M; Ves-Losada, Ana

    2017-01-01

    Neutral lipids-involved in many cellular processes-are stored as lipid droplets (LD), those mainly cytosolic (cLD) along with a small nuclear population (nLD). nLD could be involved in nuclear-lipid homeostasis serving as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signalling pathways as transcription factors and as enzymes of lipid metabolism and nuclear processes. Our aim was to determine if nLD constituted a dynamic domain. Oleic-acid (OA) added to rat hepatocytes or HepG2 cells in culture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PL content and in cLD and nLD numbers and sizes. LD increments were reversed on exclusion of OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thus lipid biosynthesis. Under all conditions, nLD corresponded to a small population (2-10%) of total cellular LD. The anabolism triggered by OA, involving morphologic and size changes within the cLD and nLD populations, was reversed by a net balance of catabolism, upon eliminating OA. These catabolic processes included lipolysis and the mobilization of hydrolyzed FA from the LD to cytosolic-oxidation sites. These results would imply that nLD are actively involved in nuclear processes that include lipids. In conclusion, nLD are a dynamic nuclear domain since they are modified by OA through a reversible mechanism in combination with cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PL biosynthesis. Thus, liver nLD and cLD are both dynamic cellular organelles.

  11. The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells

    NASA Astrophysics Data System (ADS)

    Nunn, Abigail D. G.; Scopigno, Tullio; Pediconi, Natalia; Levrero, Massimo; Hagman, Henning; Kiskis, Juris; Enejder, Annika

    2016-06-01

    Dietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line. Specifically, we statistically quantify lipid droplet morphology at single cell level utilizing label-free microscopy, coherent anti-Stokes Raman scattering, supported by gene expression. We observe Entinostat efficiently rerouting carbohydrates and free-fatty acids into lipid droplets, upregulating lipid coat protein gene Plin4, and relocating droplets nearer to the nucleus. Our results demonstrate the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome.

  12. The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells

    PubMed Central

    Nunn, Abigail D. G.; Scopigno, Tullio; Pediconi, Natalia; Levrero, Massimo; Hagman, Henning; Kiskis, Juris; Enejder, Annika

    2016-01-01

    Dietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line. Specifically, we statistically quantify lipid droplet morphology at single cell level utilizing label-free microscopy, coherent anti-Stokes Raman scattering, supported by gene expression. We observe Entinostat efficiently rerouting carbohydrates and free-fatty acids into lipid droplets, upregulating lipid coat protein gene Plin4, and relocating droplets nearer to the nucleus. Our results demonstrate the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. PMID:27320682

  13. The effects of two Lactobacillus plantarum strains on rat lipid metabolism receiving a high fat diet.

    PubMed

    Salaj, Rastislav; Stofilová, Jana; Soltesová, Alena; Hertelyová, Zdenka; Hijová, Emília; Bertková, Izabela; Strojný, Ladislav; Kružliak, Peter; Bomba, Alojz

    2013-01-01

    The aim of our study was to evaluate the effects of the different probiotic strains, Lactobacillus plantarum LS/07 and Lactobacillus plantarum Biocenol LP96, on lipid metabolism and body weight in rats fed a high fat diet. Compared with the high fat diet group, the results showed that Lactobacillus plantarum LS/07 reduced serum cholesterol and LDL cholesterol, but Lactobacillus plantarum Biocenol LP96 decreased triglycerides and VLDL, while there was no change in the serum HDL level and liver lipids. Both probiotic strains lowered total bile acids in serum. Our strains have no significant change in body weight, gain weight, and body fat. These findings indicate that the effect of lactobacilli on lipid metabolism may differ among strains and that the Lactobacillus plantarum LS/07 and Lactobacillus plantarum Biocenol LP96 can be used to improve lipid profile and can contribute to a healthier bowel microbial balance.

  14. The Effects of Two Lactobacillus plantarum Strains on Rat Lipid Metabolism Receiving a High Fat Diet

    PubMed Central

    Salaj, Rastislav; Štofilová, Jana; Šoltesová, Alena; Hertelyová, Zdenka; Hijová, Emília; Bertková, Izabela; Strojný, Ladislav; Kružliak, Peter

    2013-01-01

    The aim of our study was to evaluate the effects of the different probiotic strains, Lactobacillus plantarum LS/07 and Lactobacillus plantarum Biocenol LP96, on lipid metabolism and body weight in rats fed a high fat diet. Compared with the high fat diet group, the results showed that Lactobacillus plantarum LS/07 reduced serum cholesterol and LDL cholesterol, but Lactobacillus plantarum Biocenol LP96 decreased triglycerides and VLDL, while there was no change in the serum HDL level and liver lipids. Both probiotic strains lowered total bile acids in serum. Our strains have no significant change in body weight, gain weight, and body fat. These findings indicate that the effect of lactobacilli on lipid metabolism may differ among strains and that the Lactobacillus plantarum LS/07 and Lactobacillus plantarum Biocenol LP96 can be used to improve lipid profile and can contribute to a healthier bowel microbial balance. PMID:24470789

  15. Identification of early transcriptome-based biomarkers related to lipid metabolism in peripheral blood mononuclear cells of rats nutritionally programmed for improved metabolic health.

    PubMed

    Konieczna, J; Sánchez, J; van Schothorst, E M; Torrens, J M; Bunschoten, A; Palou, M; Picó, C; Keijer, J; Palou, A

    2014-01-01

    Moderate maternal calorie restriction during lactation protects rat offspring against obesity development in adulthood, due to an improved ability to handle and store excess dietary fuel. We used this model to identify early transcriptome-based biomarkers of metabolic health using peripheral blood mononuclear cells (PBMCs), an easily accessible surrogate tissue, by focusing on molecular markers of lipid handling. Male and female offspring of control and 20 % calorie-restricted lactating dams (CR) were studied. At weaning, a set of pups was killed, and PBMCs were isolated for whole-genome microarray analysis. The remaining pups were killed at 6 months of age. CR gave lower body weight, food intake and fat accumulation, and improved levels of insulin and leptin throughout life, particularly in females. Microarray analysis of weaned rat PBMCs identified 278 genes significantly differentially expressed between control and CR. Among lipid metabolism-related genes, expression of Cpt1a, Lipe and Star was increased and Fasn, Lrp1 and Rxrb decreased in CR versus control, with changes fully confirmed by qPCR. Among them, Cpt1a, Fasn and Star emerged as particularly interesting. Transcript levels of Cpt1a in PBMCs correlated with their levels in WAT and liver at both ages examined; Fasn expression levels in PBMCs at an early age correlated with their expression levels in WAT; and early changes in Star expression levels in PBMCs correlated with their expression levels in liver and were sustained in adulthood. These findings reveal the possibility of using transcript levels of lipid metabolism-related genes in PBMCs as early biomarkers of metabolic health status.

  16. Kupffer cells facilitate the acute effects of leptin on hepatic lipid metabolism.

    PubMed

    Metlakunta, Anantha; Huang, Wan; Stefanovic-Racic, Maja; Dedousis, Nikolaos; Sipula, Ian; O'Doherty, Robert M

    2017-01-01

    Leptin has potent effects on lipid metabolism in a number of peripheral tissues. In liver, an acute leptin infusion (~120 min) stimulates hepatic fatty acid oxidation (~30%) and reduces triglycerides (TG, ~40%), effects that are dependent on phosphoinositol-3-kinase (PI3K) activity. In the current study we addressed the hypothesis that leptin actions on liver-resident immune cells are required for these metabolic effects. Myeloid cell-specific deletion of the leptin receptor (ObR) in mice or depletion of liver Kupffer cells (KC) in rats in vivo prevented the acute effects of leptin on liver lipid metabolism, while the metabolic effects of leptin were maintained in mice lacking ObR in hepatocytes. Notably, liver TG were elevated in both lean and obese myeloid cell ObR, but the degree of obesity and insulin resistance induced by a high-fat diet was similar to control mice. In isolated primary hepatocytes (HEP), leptin had no effects on HEP lipid metabolism and only weakly stimulated PI3K. However, the coculture of KC with HEP restored leptin action on HEP fatty acid metabolism and stimulation of HEP PI3K. Notably, leptin stimulated the release from KC of a number of cytokines. However, the exposure of HEP to these cytokines individually [granulocyte macrophage colony-stimulating factor, IL-1α, IL-1β, IL-6, IL-10, and IL-18] or in combination had no effects on HEP lipid metabolism. Together, these data demonstrate a role for liver mononuclear cells in the regulation of liver lipid metabolism by leptin. Copyright © 2017 the American Physiological Society.

  17. Metabolism of xenobiotic carboxylic acids: focus on coenzyme A conjugation, reactivity, and interference with lipid metabolism.

    PubMed

    Darnell, Malin; Weidolf, Lars

    2013-08-19

    While xenobiotic carboxylic acids (XCAs) have been studied extensively with respect to their enzymatic conversion to potentially reactive acyl glucuronides with implications to drug induced hepatotoxicity, the formation of xenobiotic-S-acyl-CoA thioesters (xenobiotic-CoAs) have been much less studied in spite of data indicating that such conjugates may be equally or more reactive than the corresponding acyl glucuronides. This review addresses enzymes and cell organelles involved in the formation of xenobiotic-CoAs, the reactivity of such conjugates toward biological macromolecules, and in vitro and in vivo methodology to assess consequences of such reactivity. Further, the propensity of xenobiotic-CoAs to interfere with endogenous lipid metabolism, e.g., inhibition of β-oxidation or depletion of the CoA or carnitine pools, adds to the complexity of the potential contribution of XCAs to hepatotoxicity by a number of mechanisms in addition to those in common with the corresponding acyl glucuronides. On the basis of our review of the literature on xenobiotic-CoA conjugates, there appear to be a number of gaps in our understanding of the bioactivation of XCA both with respect to the mechanisms involved and the experimental approaches to distinguish between the role of acyl glucuronides and xenobiotic-CoA conjugates. These aspects are focused upon and described in detail in this review.

  18. [Cadmium effects on lipid metabolism of rape (Brassica napus L.)].

    PubMed

    Ben Youssef, Nabil; Nouairi, Issam; Ben Temime, Sonia; Taamalli, Wael; Zarrouk, Mokhtar; Ghorbal, Mohamed Habib; Ben Miled Daoud, Douja

    2005-08-01

    Treatment of rape seedlings with increasing CdCl2 concentrations in the culture medium resulted in a cadmium accumulation within plant tissues, which increased with external metal dose; such accumulation was more important in roots than in leaves. Biomass production was severely inhibited, even at low cadmium concentration. In leaves, quantities of chloroplastic lipids, monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), sulfolipids (SL) and phosphatidylglycerol (PG) decreased sharply under metallic treatment. However, contents of extrachloroplastic lipids, mainly phosphatidylcholine (PC) and phosphatidylethanolamine (PE) increased significantly. In contrast to leaves, contents of root phospholipids decreased. Likewise, levels of tri-unsaturated fatty acids: linolenic (C18:3) and hexadecatrienoïc (C16:3) dropped in leaves of treated seedlings as compared to those of controls, suggesting that heavy metals induced an alteration in the fatty acid desaturation process or a stimulation of their peroxidation. Also, trans palmitoleic acid (C16:1-trans) level in PG decreased considerably. In roots, there was a slight decrease in C18:3 level, with a concomitant increase in the C18:2 percentage. Radioactive labelling of leaf lipids with (1-14C) acetate allowed to show that fatty acid biosynthesis was noticeably altered at the highest cadmium dose used (50 microM). Biosynthesis of tri-unsaturated fatty acids was also inhibited which may explain the decline in non-labelled lipid contents. Results showed that metallic ion seems to affect selectively chloroplastic membranes due to an inhibition of polyunsaturated fatty acid biosynthesis. Moreover, a lipid peroxidation occurred in our case because of the spectacular increase of malondialdehyde (MDA) content observed in cadmium treated leaves.

  19. Effect and mechanism of waterborne prolonged Zn exposure influencing hepatic lipid metabolism in javelin goby Synechogobius hasta.

    PubMed

    Huang, Chao; Luo, Zhi; Hogstrand, Christer; Chen, Feng; Shi, Xi; Chen, Qi-Liang; Song, Yu-Feng; Pan, Ya-Xiong

    2016-07-01

    The present study was conducted to determine the effect and mechanism of waterborne Zn exposure influencing hepatic lipid deposition and metabolism in javelin goby Synechogobius hasta. S. hasta were exposed to four waterborne Zn concentrations (Zn 0.005 [control], 0.18, 0.36 and 0.55 mg l(-1) , respectively) for 60 days. Sampling occurred at days 20, 40 and 60, respectively. Zn exposure increased Zn content, declined hepatic lipid content and reduced viscerosomatic and hepatosomatic indices and lipogenic enzyme activities, including 6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and fatty acid synthase (FAS). At days 20 and 60, Zn exposure decreased hepatic mRNA levels of 6PGD, G6PD, ME, FAS, acetyl-CoA carboxylase (ACC)α, ACCβ, hormone-sensitive lipase (HSL)a, HSLb, sterol-regulator element-binding protein (SREBP)-1, peroxisome proliferators-activated receptor (PPAR)α and PPARγ. However, the mRNA levels of CPT 1 and adipose triglyceride lipase increased following Zn exposure. On day 40, Zn exposure reduced hepatic mRNA expression of 6PGD, G6PD, ME, FAS, ACCα, ACCβ, HSLa, HSLb, SREBP-1 and PPARγ but increased mRNA expression of CPT 1, adipose triglyceride lipase and PPARα. General speaking, Zn exposure reduced hepatic lipid content by inhibiting lipogenesis and stimulating lipolysis. For the first time, the present study provided evidence that chronic Zn exposure differentially influenced mRNA expression and activities of genes and enzymes involved in lipogenic and lipolytic metabolism in a duration-dependent manner, and provided new insight into the relationship between metal elements and lipid metabolism. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    PubMed

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage.

  1. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage

    PubMed Central

    Liu, Fang; Rainosek, Shuo W.; Frisch-Daiello, Jessica L.; Patterson, Tucker A.; Paule, Merle G.; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-01-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. PMID:26206149

  2. Contaminant effect on cellular metabolic differential pressure curves.

    PubMed

    Milani, Marziale; Ballerini, Monica; Ferraro, L; Zabeo, M; Barberis, M; Cannone, M; Faraone, V

    2004-01-01

    The possibility of a pressure monitoring system by differential pressure sensors to detect contaminant effects on cellular cultures metabolic activity is discussed using Saccharomyces cerevisiae, lymphocyte, and AHH1 cell cultures. Metabolic (aerobic and anaerobic) processes in cells are accompanied by CO(2) production that induces changes in pressure values when cells are cultured in sealed vessels. These values are subsequently converted in voltage units and plotted pressure dynamics versus time. This procedure leads to a standard curve, typical of the cellular line, which characterizes cellular metabolism when all parameters are controlled, such as temperature and nutrients. Different phases appear in the S. cerevisiae differential pressure curve: an initial growth up to a maximum, followed by a decrement that leads to a typical "depression" (pressure values inside the test-tubes are lower than the initial one) after about 35 h from the beginning. The S. cerevisiae differential pressure curve is successfully used to test the effects of chemical (Amuchina, trieline) and physical (UV radiation, blue light, magnetic fields) contaminants. The same technique is applied to lymphocytes and AHH1 cultures to investigate the effects generated by a 72-h exposure to a 50-Hz, 60-microT electromagnetic field. Lymphocyte samples, cultured in a PHA medium, grow less than control ones, but exhibit a greater metabolic activity: changes in the exposure system configuration influence neither sample growth differences nor metabolic response variations between control and irradiated samples, while all the other irradiation parameters remain constant. Control and irradiated lymphocyte samples, without PHA in culture medium, show the same behavior both during irradiation and metabolic test. AHH1 control and irradiated samples show no difference both in growth percentage during irradiation and in metabolic activity. Different cell cultures respond to the same stimulus in different

  3. Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease.

    PubMed

    Mehlem, Annika; Hagberg, Carolina E; Muhl, Lars; Eriksson, Ulf; Falkevall, Annelie

    2013-06-01

    Excess lipid accumulation in peripheral tissues is a key feature of many metabolic diseases. Therefore, techniques for imaging and quantifying lipids in various tissues are important for understanding and evaluating the overall metabolic status of a research subject. Here we present a protocol that detects neutral lipids and lipid droplet (LD) morphology by oil red O (ORO) staining of sections from frozen tissues. The method allows for easy estimation of tissue lipid content and distribution using only basic laboratory and computer equipment. Furthermore, the procedure described here is well suited for the comparison of different metabolically challenged animal models. As an example, we include data on muscular and hepatic lipid accumulation in diet-induced and genetically induced diabetic mice. The experimental description presents details for optimal staining of lipids using ORO, including tissue collection, sectioning, staining, imaging and measurements of tissue lipids, in a time frame of less than 2 d.

  4. Inhibition of preadipocyte differentiation and lipid accumulation by Orengedokuto treatment of 3T3-L1 cultures.

    PubMed

    Ikarashi, Nobutomo; Tajima, Masataka; Suzuki, Kunihiro; Toda, Takahiro; Ito, Kiyomi; Ochiai, Wataru; Sugiyama, Kiyoshi

    2012-01-01

    Obesity is a major cause of metabolic syndrome and is due to an increase in the number and hypertrophy of adipocytes. Accordingly, inhibition of the differentiation and proliferation of adipocytes may be used in the treatment and prevention of metabolic syndrome. This study investigated the effects of 50 commonly used Kampo medicines on the differentiation of 3T3-L1 preadipocytes to search for a drug with an antiobesity effect. Kampo medicines were screened, and the strongest differentiation-inhibitory effect was noted with Orengedokuto. To explore the active ingredients in Orengedokuto, the effects of four crude drug components of Orengedokuto were investigated. It was found that the differentiation-inhibitory effect of Orengedokuto was accounted for by Coptidis rhizome and Phellodendri cortex. Furthermore, berberine, a principal ingredient common to Coptidis rhizome and Phellodendri cortex, showed a differentiation-inhibitory effect. The effect of berberine involves an inhibition of the mRNA and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). Moreover, berberine inhibited lipid accumulation in adipocytes. These findings suggest that an antiobesity effect could be a new indication for Orengedokuto and that its active ingredient is berberine, with a mechanism involving the inhibition of PPARγ and C/EBPα expression.

  5. Regulatory mechanisms underlying oil palm fruit mesocarp maturation, ripening, and functional specialization in lipid and carotenoid metabolism.

    PubMed

    Tranbarger, Timothy J; Dussert, Stéphane; Joët, Thierry; Argout, Xavier; Summo, Marilyne; Champion, Antony; Cros, David; Omore, Alphonse; Nouy, Bruno; Morcillo, Fabienne

    2011-06-01

    Fruit provide essential nutrients and vitamins for the human diet. Not only is the lipid-rich fleshy mesocarp tissue of the oil palm (Elaeis guineensis) fruit the main source of edible oil for the world, but it is also the richest dietary source of provitamin A. This study examines the transcriptional basis of these two outstanding metabolic characters in the oil palm mesocarp. Morphological, cellular, biochemical, and hormonal features defined key phases of mesocarp development. A 454 pyrosequencing-derived transcriptome was then assembled for the developmental phases preceding and during maturation and ripening, when high rates of lipid and carotenoid biosynthesis occur. A total of 2,629 contigs with differential representation revealed coordination of metabolic and regulatory components. Further analysis focused on the fatty acid and triacylglycerol assembly pathways and during carotenogenesis. Notably, a contig similar to the Arabidopsis (Arabidopsis thaliana) seed oil transcription factor WRINKLED1 was identified with a transcript profile coordinated with those of several fatty acid biosynthetic genes and the high rates of lipid accumulation, suggesting some common regulatory features between seeds and fruits. We also focused on transcriptional regulatory networks of the fruit, in particular those related to ethylene transcriptional and GLOBOSA/PISTILLATA-like proteins in the mesocarp and a central role for ethylene-coordinated transcriptional regulation of type VII ethylene response factors during ripening. Our results suggest that divergence has occurred in the regulatory components in this monocot fruit compared with those identified in the dicot tomato (Solanum lycopersicum) fleshy fruit model.

  6. Lipid metabolism as a target for brain cancer therapy: synergistic activity of lovastatin and sodium phenylacetate against human glioma cells.

    PubMed

    Prasanna, P; Thibault, A; Liu, L; Samid, D

    1996-02-01

    Malignant gliomas, the most common form of primary brain tumors, are highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical to cell replication. Human glioblastoma cells were found to be uniquely vulnerable to growth arrest by lovastatin, a competitive inhibitor of the enzyme regulating MVA synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. The sodium salt of phenylacetic acid (NaPA), an inhibitor of MVA-pyrophosphate decarboxylase, the enzyme that controls MVA use, acted synergistically with lovastatin to suppress malignant growth. When used at pharmacologically attainable concentrations, the two compounds induced profound cytostasis and loss of malignant properties such as invasiveness and expression of the transforming growth factor-beta 2 gene, coding for a potent immunosuppressive cytokine. Supplementation with exogenous ubiquinone, an end product of the MVA pathway, failed to rescue the cells, suggesting that decreased synthesis of intermediary products are responsible for the antitumor effects observed. In addition to blocking the MVA pathway, lovastatin alone and in combination with NaPA increased the expression of the peroxisome proliferator-activated receptor, a transcription factor implicated in the control of lipid metabolism, cell growth, and differentiation. Our results indicate that targeting lipid metabolism with lovastatin, used alone or in combination with the aromatic fatty acid NaPA, may offer a novel approach to the treatment of malignant gliomas.

  7. Effects of acute lipid overload on skeletal muscle insulin resistance, metabolic flexibility, and mitochondrial performance

    PubMed Central

    Coen, Paul M.; DiStefano, Giovanna; Chacon, Alexander C.; Helbling, Nicole L.; Desimone, Marisa E.; Stafanovic-Racic, Maja; Hames, Kazanna C.; Despines, Alex A.; Toledo, Frederico G. S.; Goodpaster, Bret H.

    2014-01-01

    We hypothesized that acute lipid-induced insulin resistance would be attenuated in high-oxidative muscle of lean trained (LT) endurance athletes due to their enhanced metabolic flexibility and mitochondrial capacity. Lean sedentary (LS), obese sedentary (OS), and LT participants completed two hyperinsulinemic euglycemic clamp studies with and without (glycerol control) the coinfusion of Intralipid. Metabolic flexibility was measured by indirect calorimetry as the oxidation of fatty acids and glucose during fasted and insulin-stimulated conditions, the latter with and without lipid oversupply. Muscle biopsies were obtained for mitochondrial and insulin-signaling studies. During hyperinsulinemia without lipid, glucose infusion rate (GIR) was lowest in OS due to lower rates of nonoxidative glucose disposal (NOGD), whereas state 4 respiration was increased in all groups. Lipid infusion reduced GIR similarly in all subjects and reduced state 4 respiration. However, in LT subjects, fat oxidation was higher with lipid oversupply, and although glucose oxidation was reduced, NOGD was better preserved compared with LS and OS subjects. Mitochondrial performance was positively associated with better NOGD and insulin sensitivity in both conditions. We conclude that enhanced mitochondrial performance with exercise is related to better metabolic flexibility and insulin sensitivity in response to lipid overload. PMID:25352435

  8. Effects of acute lipid overload on skeletal muscle insulin resistance, metabolic flexibility, and mitochondrial performance.

    PubMed

    Dubé, John J; Coen, Paul M; DiStefano, Giovanna; Chacon, Alexander C; Helbling, Nicole L; Desimone, Marisa E; Stafanovic-Racic, Maja; Hames, Kazanna C; Despines, Alex A; Toledo, Frederico G S; Goodpaster, Bret H

    2014-12-15

    We hypothesized that acute lipid-induced insulin resistance would be attenuated in high-oxidative muscle of lean trained (LT) endurance athletes due to their enhanced metabolic flexibility and mitochondrial capacity. Lean sedentary (LS), obese sedentary (OS), and LT participants completed two hyperinsulinemic euglycemic clamp studies with and without (glycerol control) the coinfusion of Intralipid. Metabolic flexibility was measured by indirect calorimetry as the oxidation of fatty acids and glucose during fasted and insulin-stimulated conditions, the latter with and without lipid oversupply. Muscle biopsies were obtained for mitochondrial and insulin-signaling studies. During hyperinsulinemia without lipid, glucose infusion rate (GIR) was lowest in OS due to lower rates of nonoxidative glucose disposal (NOGD), whereas state 4 respiration was increased in all groups. Lipid infusion reduced GIR similarly in all subjects and reduced state 4 respiration. However, in LT subjects, fat oxidation was higher with lipid oversupply, and although glucose oxidation was reduced, NOGD was better preserved compared with LS and OS subjects. Mitochondrial performance was positively associated with better NOGD and insulin sensitivity in both conditions. We conclude that enhanced mitochondrial performance with exercise is related to better metabolic flexibility and insulin sensitivity in response to lipid overload.

  9. Nutritional regulation of lipid metabolism in human adipose tissue.

    PubMed

    Coppack, S W; Patel, J N; Lawrence, V J

    2001-01-01

    Pfeiffer and colleagues years ago pointed out that different distributions and amounts of adipose tissue are associated with abnormalities of lipolysis and lipoprotein metabolism. Adipose tissue has several crucial roles including (i) mobilization from stores of fatty acids as an energy source, (ii) catabolism of lipoproteins such as very-low-density lipoprotein and (iii) synthesis and release of hormonal signals such as leptin and interleukin-6. These adipose tissue actions are crucially regulated by nutrition. The review considers the existence of metabolic pathways and modes of regulation within adipose tissue, and how such metabolic activity can be quantitated in humans. Nutrition can influence adipose tissue at several 'levels'. Firstly the level of obesity or malnutrition has important effects on many aspects of adipose tissue metabolism. Secondly short-term overfeeding, underfeeding and exercise have major impacts on adipose tissue behaviour. Lastly, specific nutrients are capable of regulating adipose tissue metabolism. Recently there have been considerable advances in understanding adipose tissue metabolism and in particular its regulation. This review discusses the behaviour of adipose tissue under various nutritional conditions. There is then a review of recent work examining the ways in which nutritional influences act via intra-cellular mechanisms, insulin and the sympathetic innervation of adipose tissue.

  10. Membrane lipid alterations in the metabolic syndrome and the role of dietary oils.

    PubMed

    Perona, Javier S

    2017-09-01

    The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue. Diet intervention has been proposed as a powerful tool to prevent the development of the metabolic syndrome, since healthy diets have been shown to have a protective role against the components of the metabolic syndrome. Particularly, dietary fatty acids are capable of modulating the deleterious effects of these conditions, among other mechanisms, by modifications of the lipid composition of the membranes in insulin-sensitive tissues. However, there is still scarce data based of high-level evidence on the effects of dietary oils on the effects of the metabolic syndrome and its components. This review summarizes the current knowledge on the effects of dietary oils on improving alterations of the components of the metabolic syndrome. It also examines their influence in the modulation of plasma membrane lipid composition and in the functionality of membrane proteins involved in insulin activity, like the insulin receptor, GLUT-4, CD36/FAT and ABCA-1, and their effect in the metabolism of glucose, fatty acids and cholesterol, and, in turn, the key features of the metabolic syndrome. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The effect of oral lipids and circulating lipoproteins on the metabolism of drugs.

    PubMed

    Patel, Jigar P; Brocks, Dion R

    2009-11-01

    The oral bioavailability of many lipophilic drugs is known to increase when coadministered with fatty meals. Although such a phenomenon is typically ascribed to increased solubilization and absorption of drug, in some cases this increase in systemic exposure may be in part due to the influence of lipids on the presystemic metabolism of the affected drug. Oral lipids on their absorption may interfere with the drug metabolizing enzymes expressed in the small intestine and/or liver. Fatty acids incorporated in dietary triglyceride can modulate the expression and activity of drug metabolizing enzymes within the small intestine. Lipoproteins, which are the major carriers of lipids in the systemic circulation, can become associated with lipophilic drugs. Such a combination may influence the metabolism of lipophilic drugs through limiting their uptake into the cells thereby decreasing their metabolism. In a contrary manner, an increased uptake and metabolism of lipoprotein-bound drug may be facilitated by lipoprotein receptors mediated uptake. The components of lipoproteins may also modulate the expression or activity of hepatic and extrahepatic drug metabolizing enzymes.

  12. Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer

    PubMed Central

    Swierczynski, Julian; Hebanowska, Areta; Sledzinski, Tomasz

    2014-01-01

    There is growing evidence that metabolic alterations play an important role in cancer development and progression. The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation. Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism. An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival, as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival. Based on the data that serum fatty acid synthase (FASN), also known as oncoantigen 519, is elevated in patients with certain types of cancer, its serum level was proposed as a marker of neoplasia. This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic neoplasm, characterized by high mortality. We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism. Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer. In particular, FASN is a viable candidate for indicator of pathologic state, marker of neoplasia, as well as, pharmacological treatment target in pancreatic cancer. Recent research showed that, in addition to lipogenesis, certain cancer cells can use fatty acids from circulation, derived from diet (chylomicrons), synthesized in liver, or released from adipose tissue for their growth. Thus, the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation. PMID:24605027

  13. Fluorometric biosniffer (biochemical gas sensor) for breath acetone as a volatile indicator of lipid metabolism

    NASA Astrophysics Data System (ADS)

    Mitsubayashi, Kohji; Chien, Po-Jen; Ye, Ming; Suzuki, Takuma; Toma, Koji; Arakawa, Takahiro

    2016-11-01

    A fluorometric acetone biosniffer (biochemical gas sensor) for assessment of lipid metabolism utilizing reverse reaction of secondary alcohol dehydrogenase was constructed and evaluated. The biosniffer showed highly sensitivity and selectivity for continuous monitoring of gaseous acetone. The measurement of breath acetone concentration during fasting and aerobic exercise were also investigated. The acetone biosniffer provides a novel analytical tool for noninvasive evaluation of human lipid metabolism and it is also expected to use for the clinical and physiological applications such as monitoring the progression of diabetes.

  14. Effect of copper and lead on lipid metabolism in bryophytes and lichens.

    PubMed

    Guschina, I A; Harwood, J L

    2000-12-01

    Bryophytes and lichens have a widespread occurrence and can survive under extreme environmental conditions, such as drought, low temperatures, continuous light or prolonged darkness. It has been shown that lipid metabolism is sensitive to both metal response and metal resistance mechanisms in many organisms, including yeast, Silene cucubalus, and in the marine brown algae Fucus spp. and Ascophyllum nodosum. In the present study, the effects of lead and copper on lipid metabolism have been studied in two moss species, Rhytidiadelphus squarrosus and Dicranum scoparium, and also in the lichen Peltigera horizontalis with a cyanobacterial Nostoc photobiont.

  15. Elevated CO2 improves lipid accumulation by increasing carbon metabolism in Chlorella sorokiniana.

    PubMed

    Sun, Zhilan; Chen, Yi-Feng; Du, Jianchang

    2016-02-01

    Supplying microalgae with extra CO2 is a promising means for improving lipid production. The molecular mechanisms involved in lipid accumulation under conditions of elevated CO2, however, remain to be fully elucidated. To understand how elevated CO2 improves lipid production, we performed sequencing of Chlorella sorokiniana LS-2 cellular transcripts during growth and compared transcriptional dynamics of genes involved in carbon flow from CO2 to triacylglycerol. These analyses identified the majority genes of carbohydrate metabolism and lipid biosynthesis pathways in C. sorokiniana LS-2. Under high doses of CO2 , despite down-regulation of most de novo fatty acid biosynthesis genes, genes involved in carbohydrate metabolic pathways including carbon fixation, chloroplastic glycolysis, components of the pyruvate dehydrogenase complex (PDHC) and chloroplastic membrane transporters were upexpressed at the prolonged lipid accumulation phase. The data indicate that lipid production is largely independent of de novo fatty acid synthesis. Elevated CO2 might push cells to channel photosynthetic carbon precursors into fatty acid synthesis pathways, resulting in an increase of overall triacylglycerol generation. In support of this notion, genes involved in triacylglycerol biosynthesis were substantially up-regulated. Thus, elevated CO2 may influence regulatory dynamics and result in increased carbon flow to triacylglycerol, thereby providing a feasible approach to increase lipid production in microalgae.

  16. The PPARα agonist fenofibrate suppresses B-cell lymphoma in mice by modulating lipid metabolism.

    PubMed

    Huang, Jianfeng; Das, Suman Kumar; Jha, Pooja; Al Zoughbi, Wael; Schauer, Silvia; Claudel, Thierry; Sexl, Veronika; Vesely, Paul; Birner-Gruenberger, Ruth; Kratky, Dagmar; Trauner, Michael; Hoefler, Gerald

    2013-10-01

    Obesity is associated with an increased risk for malignant lymphoma development. We used Bcr/Abl transformed B cells to determine the impact of aggressive lymphoma formation on systemic lipid mobilization and turnover. In wild-type mice, tumor size significantly correlated with depletion of white adipose tissues (WAT), resulting in increased serum free fatty acid (FFA) concentrations which promote B-cell proliferation in vitro. Moreover, B-cell tumor development induced hepatic lipid accumulation due to enhanced hepatic fatty acid (FA) uptake and impaired FA oxidation. Serum triglyceride, FFA, phospholipid and cholesterol levels were significantly elevated. Consistently, serum VLDL/LDL-cholesterol and apolipoprotein B levels were drastically increased. These findings suggest that B-cell tumors trigger systemic lipid mobilization from WAT to the liver and increase VLDL/LDL release from the liver to promote tumor growth. Further support for this concept stems from experiments where we used the peroxisome proliferator-activated receptor α (PPARα) agonist and lipid-lowering drug fenofibrate that significantly suppressed tumor growth independent of angiogenesis and inflammation. In addition to WAT depletion, fenofibrate further stimulated FFA uptake by the liver and restored hepatic FA oxidation capacity, thereby accelerating the clearance of lipids released from WAT. Furthermore, fenofibrate blocked hepatic lipid release induced by the tumors. In contrast, lipid utilization in the tumor tissue itself was not increased by fenofibrate which correlates with extremely low expression levels of PPARα in B-cells. Our data show that fenofibrate associated effects on hepatic lipid metabolism and deprivation of serum lipids are capable to suppress B-cell lymphoma growth which may direct novel treatment strategies. This article is part of a Special Issue entitled Lipid Metabolism in Cancer. Copyright © 2013 The Author. Published by Elsevier B.V. All rights reserved.

  17. Nuclear inositol lipid metabolism: more than just second messenger generation?

    PubMed

    Martelli, Alberto M; Follo, Matilde Yung; Evangelisti, Camilla; Falà, Federica; Fiume, Roberta; Billi, Anna Maria; Cocco, Lucio

    2005-10-01

    A distinct polyphosphoinositide cycle is present in the nucleus, and growing evidence suggests its importance in DNA replication, gene transcription, and apoptosis. Even though it was initially thought that nuclear inositol lipids would function as a source for second messengers, recent findings strongly indicate that lipids present in the nucleus also fulfil other roles. The scope of this review is to highlight the most intriguing advances made in the field over the last few years, such as the possibility that nuclear phosphatidylinositol (4,5) bisphosphate is involved in maintaining chromatin in a transcriptionally active conformation, the new emerging roles for intranuclear phosphatidylinositol (3,4,5) trisphosphate and phosphoinositide 3-kinase, and the evidence which suggests a tight relationship between a decreased level of nuclear phosphoinositide specific phospholipase C-beta1 and the evolution of myelodisplastic syndrome into acute myeloid leukemia.

  18. The effect of hypokinesia on lipid metabolism in adipose tissue

    NASA Astrophysics Data System (ADS)

    Macho, Ladislav; Kvetn̆anský, Richard; Ficková, Mária

    The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

  19. Effects of Maternal Chromium Restriction on the Long-Term Programming in MAPK Signaling Pathway of Lipid Metabolism in Mice

    PubMed Central

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2016-01-01

    It is now broadly accepted that the nutritional environment in early life is a key factor in susceptibility to metabolic diseases. In this study, we evaluated the effects of maternal chromium restriction in vivo on the modulation of lipid metabolism and the mechanisms involved in this process. Sixteen pregnant C57BL mice were randomly divided into two dietary treatments: a control (C) diet group and a low chromium (L) diet group. The diet treatment was maintained through gestation and lactation period. After weaning, some of the pups continued with either the control diet or low chromium diet (CC or LL), whereas other pups switched to another diet (CL or LC). At 32 weeks of age, serum lipid metabolism, proinflammatory indexes, oxidative stress and anti-oxidant markers, and DNA methylation status in adipose tissue were measured. The results indicated that the maternal low chromium diet increased body weight, fat pad weight, serum triglyceride (TG), low-density lipoprotein cholesterol (LDL), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and oxidized glutathione (GSSG). There was a decrease in serum reduced/oxidized glutathione (GSH/GSSG) ratio at 32 weeks of age in female offspring. From adipose tissue, we identified 1214 individual hypomethylated CpG sites and 411 individual hypermethylated CpG sites in the LC group when compared to the CC group. Pathway analysis of the differential methylation genes revealed a significant increase in hypomethylated genes in the mitogen-activated protein kinase (MAPK) signaling pathway in the LC group. Our study highlights the importance of the MAPK signaling pathway in epigenetic changes involved in the lipid metabolism of the offspring from chromium-restricted dams. PMID:27517955

  20. Effects of Maternal Chromium Restriction on the Long-Term Programming in MAPK Signaling Pathway of Lipid Metabolism in Mice.

    PubMed

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2016-08-10

    It is now broadly accepted that the nutritional environment in early life is a key factor in susceptibility to metabolic diseases. In this study, we evaluated the effects of maternal chromium restriction in vivo on the modulation of lipid metabolism and the mechanisms involved in this process. Sixteen pregnant C57BL mice were randomly divided into two dietary treatments: a control (C) diet group and a low chromium (L) diet group. The diet treatment was maintained through gestation and lactation period. After weaning, some of the pups continued with either the control diet or low chromium diet (CC or LL), whereas other pups switched to another diet (CL or LC). At 32 weeks of age, serum lipid metabolism, proinflammatory indexes, oxidative stress and anti-oxidant markers, and DNA methylation status in adipose tissue were measured. The results indicated that the maternal low chromium diet increased body weight, fat pad weight, serum triglyceride (TG), low-density lipoprotein cholesterol (LDL), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and oxidized glutathione (GSSG). There was a decrease in serum reduced/oxidized glutathione (GSH/GSSG) ratio at 32 weeks of age in female offspring. From adipose tissue, we identified 1214 individual hypomethylated CpG sites and 411 individual hypermethylated CpG sites in the LC group when compared to the CC group. Pathway analysis of the differential methylation genes revealed a significant increase in hypomethylated genes in the mitogen-activated protein kinase (MAPK) signaling pathway in the LC group. Our study highlights the importance of the MAPK signaling pathway in epigenetic changes involved in the lipid metabolism of the offspring from chromium-restricted dams.

  1. Mitochondria: A crossroads for lipid metabolism defect in neurodegeneration with brain iron accumulation diseases.

    PubMed

    Aoun, Manar; Tiranti, Valeria

    2015-06-01

    Neurodegeneration with brain iron accumulation (NBIA) comprises a group of brain iron deposition syndromes that lead to mixed extrapyramidal features and progressive dementia. Exact pathologic mechanism of iron deposition in NBIA remains unknown. However, it is becoming increasingly evident that many neurodegenerative diseases are hallmarked by metabolic dysfunction that often involves altered lipid profile. Among the identified disease genes, four encode for proteins localized in mitochondria, which are directly or indirectly implicated in lipid metabolism: PANK2, CoASY, PLA2G6 and C19orf12. Mutations in PANK2 and CoASY, both implicated in CoA biosynthesis that acts as a fatty acyl carrier, lead, respectively, to PKAN and CoPAN forms of NBIA. Mutations in PLA2G6, which plays a key role in the biosynthesis and remodeling of membrane phospholipids including cardiolipin, lead to PLAN. Mutations in C19orf12 lead to MPAN, a syndrome similar to that caused by mutations in PANK2 and PLA2G6. Although the function of C19orf12 is largely unknown, experimental data suggest its implication in mitochondrial homeostasis and lipid metabolism. Altogether, the identified mutated proteins localized in mitochondria and associated with different NBIA forms support the concept that dysfunctions in mitochondria and lipid metabolism play a crucial role in the pathogenesis of NBIA. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.

  2. Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate leptin and adiponectin secretion in 3T3-L1 adipocytes.

    PubMed

    Kowalska, Katarzyna; Olejnik, Anna; Rychlik, Joanna; Grajek, Włodzimierz

    2015-10-15

    It has previously been shown that lyophilized cranberries (LCB) decreased lipid accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down-regulation of the expression of key transcription factors (PPARγ, C/EBPα, SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti-lipogenic activity of LCB, the expression of several genes involved in lipid metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects of LCB on adiponectin and leptin expression and protein secretion were also investigated. LCB reduced lipid accumulation during preadipocyte differentiation by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover, LCB decreased leptin gene expression and increased adiponectin gene expression and protein secretion in a dose-dependent manner. Therefore cranberries could be considered as bioactive factors, which are effective in the inhibition of adipose tissue mass production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Potential of lipid metabolism in marine diatoms for biofuel production.

    PubMed

    d'Ippolito, Giuliana; Sardo, Angela; Paris, Debora; Vella, Filomena Monica; Adelfi, Maria Grazia; Botte, Pierpaolo; Gallo, Carmela; Fontana, Angelo

    2015-01-01

    Diatoms are an ecologically relevant group of microalgae that are not commonly considered for bio-oil production even if they are responsible for massive blooms at sea. Seventeen diatom species were screened for their capacity to produce biomass and lipids, in relation to their growth rate. Triglyceride levels were also assessed as a preferential source of biofuels. Using statistical analysis, two centric diatoms, Thalassiosira weissflogii and Cyclotella cryptica, were selected as good candidates for oil production. Lipid levels significantly increased when the two diatoms were cultivated in a two-stage process under nitrogen limitation. The effect was less pronounced in cultures where silicon was reduced to 20% of the standard supply. Nitrogen limitation did not affect growth rates but led to lipid remodeling and de novo synthesis of triacylglycerols. Triacylglycerols in T. weissflogii and C. cryptica can account for up to 82% and 88% of total glycerolipids, thereby suggesting that the two species are promising candidates for large-scale experimentation for biofuel production.

  4. Role of Lipid Metabolism in Plant Pollen Exine Development.

    PubMed

    Zhang, Dabing; Shi, Jianxin; Yang, Xijia

    2016-01-01

    Pollen plays important roles in the life cycle of angiosperms plants. It acts as not only a biological protector of male sperms but also a communicator between the male and the female reproductive organs, facilitating pollination and fertilization. Pollen is produced within the anther, and covered by the specialized outer envelope, pollen wall. Although the morphology of pollen varies among different plant species, the pollen wall is mainly comprised of three layers: the pollen coat, the outer exine layer, and the inner intine layer. Except the intine layer, the other two layers are basically of lipidic nature. Particularly, the outer pollen wall layer, the exine, is a highly resistant biopolymer of phenylpropanoid and lipidic monomers covalently coupled by ether and ester linkages. The precise molecular mechanisms underlying pollen coat formation and exine patterning remain largely elusive. Herein, we summarize the current genetic, phenotypic and biochemical studies regarding to the pollen exine development and underlying molecular regulatory mechanisms mainly obtained from monocot rice (Oryza sativa) and dicot Arabidopsis thaliana, aiming to extend our understandings of plant male reproductive biology. Genes, enzymes/proteins and regulatory factors that appear to play conserved and diversified roles in lipid biosynthesis, transportation and modification during pollen exine formation, were highlighted.

  5. Reversible Nuclear-Lipid-Droplet Morphology Induced by Oleic Acid: A Link to Cellular-Lipid Metabolism

    PubMed Central

    Lagrutta, Lucía C.; Montero-Villegas, Sandra; Layerenza, Juan P.; Sisti, Martín S.; García de Bravo, Margarita M.

    2017-01-01

    Neutral lipids—involved in many cellular processes—are stored as lipid droplets (LD), those mainly cytosolic (cLD) along with a small nuclear population (nLD). nLD could be involved in nuclear-lipid homeostasis serving as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signalling pathways as transcription factors and as enzymes of lipid metabolism and nuclear processes. Our aim was to determine if nLD constituted a dynamic domain. Oleic-acid (OA) added to rat hepatocytes or HepG2 cells in culture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PL content and in cLD and nLD numbers and sizes. LD increments were reversed on exclusion of OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thus lipid biosynthesis. Under all conditions, nLD corresponded to a small population (2–10%) of total cellular LD. The anabolism triggered by OA, involving morphologic and size changes within the cLD and nLD populations, was reversed by a net balance of catabolism, upon eliminating OA. These catabolic processes included lipolysis and the mobilization of hydrolyzed FA from the LD to cytosolic-oxidation sites. These results would imply that nLD are actively involved in nuclear processes that include lipids. In conclusion, nLD are a dynamic nuclear domain since they are modified by OA through a reversible mechanism in combination with cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PL biosynthesis. Thus, liver nLD and cLD are both dynamic cellular organelles. PMID:28125673

  6. Silencing of lipid metabolism genes through IRE1α-mediated mRNA decay lowers plasma lipids in mice

    PubMed Central

    So, Jae-Seon; Hur, Kyu Yeon; Tarrio, Margarite; Ruda, Vera; Frank-Kamenetsky, Maria; Fitzgerald, Kevin; Koteliansky, Victor; Lichtman, Andrew H.; Iwawaki, Takao; Glimcher, Laurie H.; Lee, Ann-Hwee

    2012-01-01

    XBP1 is a key regulator of the unfolded protein response (UPR), which is involved in a wide range of physiological and pathological processes. XBP1 ablation in liver causes profound hypolipidemia in mice, highlighting its critical role in lipid metabolism. XBP1 deficiency triggers feedback activation of its upstream enzyme IRE1α, instigating regulated IRE1-dependent decay (RIDD) of cytosolic mRNAs. Here, we identify RIDD as a crucial control mechanism of lipid homeostasis. Suppression of RIDD by RNA interference or genetic ablation of IRE1α reversed hypolipidemia in XBP1 deficient mice. Comprehensive microarray analysis of XBP1 and/or IRE1α deficient liver identified genes involved in lipogenesis and lipoprotein metabolism as RIDD substrates, which might contribute to the suppression of plasma lipid levels by activated IRE1α. Ablation of XBP1 ameliorated hepatosteatosis, liver damage and hypercholesterolemia in dyslipidemic animal models, suggesting that direct targeting of either IRE1α or XBP1 might be a feasible strategy to treat dyslipidemias. PMID:23040070

  7. Silencing of lipid metabolism genes through IRE1α-mediated mRNA decay lowers plasma lipids in mice.

    PubMed

    So, Jae-Seon; Hur, Kyu Yeon; Tarrio, Margarite; Ruda, Vera; Frank-Kamenetsky, Maria; Fitzgerald, Kevin; Koteliansky, Victor; Lichtman, Andrew H; Iwawaki, Takao; Glimcher, Laurie H; Lee, Ann-Hwee

    2012-10-03

    XBP1 is a key regulator of the unfolded protein response (UPR), which is involved in a wide range of physiological and pathological processes. XBP1 ablation in liver causes profound hypolipidemia in mice, highlighting its critical role in lipid metabolism. XBP1 deficiency triggers feedback activation of its upstream enzyme IRE1α, instigating regulated IRE1-dependent decay (RIDD) of cytosolic mRNAs. Here, we identify RIDD as a crucial control mechanism of lipid homeostasis. Suppression of RIDD by RNA interference or genetic ablation of IRE1α reversed hypolipidemia in XBP1-deficient mice. Comprehensive microarray analysis of XBP1 and/or IRE1α-deficient liver identified genes involved in lipogenesis and lipoprotein metabolism as RIDD substrates, which might contribute to the suppression of plasma lipid levels by activated IRE1α. Ablation of XBP1 ameliorated hepatosteatosis, liver damage, and hypercholesterolemia in dyslipidemic animal models, suggesting that direct targeting of either IRE1α or XBP1 might be a feasible strategy to treat dyslipidemias.

  8. [Lipid metabolism and insulin resistance--clinical aspects and pathobiochemistry].

    PubMed

    Gries, F A; Hübinger, A

    1994-01-01

    About 3 decades ago insulin resistance has been described as the pathogenetic factor leading from abnormal fat metabolism to diabetes mellitus. Within the metabolic syndrome insulin resistance is related to the upper body (android) type of obesity, hypertriglyceridaemia, hypertension, and diabetes mellitus ("deadly quartet"). It precedes the development of arterial hypertension and the metabolic disorders. The pathomechanisms leading from obesity and hypertriglyceridaemia to insulin resistance may be described by the glucose fatty acid cycle of Randle et al. According to their metabolic scheme increased supply of fatty acids results in reduced glucose oxidation. Concomittantly hepatic glucose production is increased. On the other hand insulin resistance combined with hyperinsulinaemia may lead to an elevation of VLDL-triglycerides and to a decrease of HDL-cholesterol in blood, thus creating a vicious cycle, in which elevated VLDL-triglycerides reinforce insulin resistance via the glucose fatty acid cycle. Interventions to improve insulin sensitivity and thereby lower plasma insulin should reduce obesity and hypertriglyceridaemia by dietary treatment. They usually improve promptly diabetic metabolism. New developments in pharmacological inhibition of fatty acid oxidation are discussed.

  9. Peroxisome Proliferator-Activated Receptor Alpha (PPARα), a Key Regulator of Lipid Metabolism in Avians.

    PubMed

    Navidshad, Bahman; Royan, M

    2016-01-01

    Dietary fatty acids have various effects on cellular metabolism, and many of these effects are carried out through the alteration of the gene expression. Fatty acids upregulate or downregulate the expression of different genes by acting both as agonists or antagonists for nuclear hormone receptors. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. To date, three PPAR subtypes, α, β, and γ, have been recognized. PPARs regulate various target genes with a role in intracellular and extracellular lipid metabolism, mainly those involved in peroxisomal β-oxidation. PPAR controls several genes involved in lipid metabolism, including Δ-5, Δ-6, and Δ-9 desaturases, acyl-coenzyme A oxidase, and carnitine palmitoyltransferase. The activation of PPARα might thus decrease fat deposits indirectly by raising hepatic fatty acid β-oxidation. PPARα is likely part of the regulating system of energy metabolism in peripheral tissues such as adipose tissue and skeletal muscles.

  10. Per-Arnt-Sim Kinase (PASK): An Emerging Regulator of Mammalian Glucose and Lipid Metabolism.

    PubMed

    Zhang, Dan-dan; Zhang, Ji-gang; Wang, Yu-zhu; Liu, Ying; Liu, Gao-lin; Li, Xiao-yu

    2015-09-07

    Per-Arnt-Sim Kinase (PASK) is an evolutionarily-conserved nutrient-responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, phosphorylation, and gene expression. Recent data suggests that mammalian PAS kinase is involved in glucose metabolism and acts on pancreatic islet α/β cells and glycogen synthase (GS), affecting insulin secretion and blood glucose levels. In addition, PASK knockout mice (PASK-/-) are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet, implying that PASK may be a new target for metabolic syndrome (MetS) treatment as well as the cellular nutrients and energy sensors-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the targets of rapamycin (m-TOR). In this review, we will briefly summarize the regulation of PASK on mammalian glucose and lipid metabolism and its possible mechanism, and further explore the potential targets for MetS therapy.

  11. Per-Arnt-Sim Kinase (PASK): An Emerging Regulator of Mammalian Glucose and Lipid Metabolism

    PubMed Central

    Zhang, Dan-dan; Zhang, Ji-gang; Wang, Yu-zhu; Liu, Ying; Liu, Gao-lin; Li, Xiao-yu

    2015-01-01

    Per-Arnt-Sim Kinase (PASK) is an evolutionarily-conserved nutrient-responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, phosphorylation, and gene expression. Recent data suggests that mammalian PAS kinase is involved in glucose metabolism and acts on pancreatic islet α/β cells and glycogen synthase (GS), affecting insulin secretion and blood glucose levels. In addition, PASK knockout mice (PASK-/-) are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet, implying that PASK may be a new target for metabolic syndrome (MetS) treatment as well as the cellular nutrients and energy sensors—adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the targets of rapamycin (m-TOR). In this review, we will briefly summarize the regulation of PASK on mammalian glucose and lipid metabolism and its possible mechanism, and further explore the potential targets for MetS therapy. PMID:26371032

  12. Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism.

    PubMed

    Duparc, Thibaut; Plovier, Hubert; Marrachelli, Vannina G; Van Hul, Matthias; Essaghir, Ahmed; Ståhlman, Marcus; Matamoros, Sébastien; Geurts, Lucie; Pardo-Tendero, Mercedes M; Druart, Céline; Delzenne, Nathalie M; Demoulin, Jean-Baptiste; van der Merwe, Schalk W; van Pelt, Jos; Bäckhed, Fredrik; Monleon, Daniel; Everard, Amandine; Cani, Patrice D

    2017-04-01

    To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non-alcoholic steatohepatitis (NASH). Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans. Published by the BMJ Publishing Group Limited

  13. Diets enriched in trans-11 vaccenic acid alleviate ectopic lipid accumulation in a rat model of NAFLD and metabolic syndrome.

    PubMed

    Jacome-Sosa, M Miriam; Borthwick, Faye; Mangat, Rabban; Uwiera, Richard; Reaney, Martin J; Shen, Jianheng; Quiroga, Ariel D; Jacobs, René L; Lehner, Richard; Proctor, Spencer D; Nelson, Randal C

    2014-07-01

    Trans11-18:1 (vaccenic acid, VA) is one of the most predominant naturally occurring trans fats in our food chain and has recently been shown to exert hypolipidemic effects in animal models. In this study, we reveal new mechanism(s) by which VA can alter body fat distribution, energy utilization and dysfunctional lipid metabolism in an animal model of obesity displaying features of the metabolic syndrome (MetS). Obese JCR:LA-cp rats were assigned to a control diet that included dairy-derived fat or the control diet supplemented with 1% VA. VA reduced total body fat (-6%), stimulated adipose tissue redistribution [reduced mesenteric fat (-17%) while increasing inguinal fat mass (29%)] and decreased adipocyte size (-44%) versus control rats. VA supplementation also increased metabolic rate (7%) concomitantly with an increased preference for whole-body glucose utilization for oxidation and increased insulin sensitivity [lower HOMA-IR (-59%)]. Further, VA decreased nonalcoholic fatty liver disease activity scores (-34%) and reduced hepatic (-27%) and intestinal (-39%) triglyceride secretion relative to control diet, while exerting differential transcriptional regulation of SREBP1 and FAS amongst other key genes in the liver and the intestine. Adding VA to dairy fat alleviates features of MetS potentially by remodeling adipose tissue and attenuating ectopic lipid accumulation in a rat model of obesity and MetS. Increasing VA content in the diet (naturally or by fortification) may be a useful approach to maximize the health value of dairy-derived fats.

  14. Lipids and Prostate Cancer

    PubMed Central

    Suburu, Janel; Chen, Yong Q.

    2012-01-01

    The role of lipid metabolism has gained particular interest in prostate cancer research. A large body of literature has outlined the unique upregulation of de novo lipid synthesis in prostate cancer. Concordant with this lipogenic phenotype is a metabolic shift, in which cancer cells use alternative enzymes and pathways to facilitate the production of fatty acids. These newly synthesized lipids may support a number of cellular processes to promote cancer cell proliferation and survival. Hence, de novo lipogenesis is under intense investigation as a therapeutic target. Epidemiologic studies suggest dietary fat may also contribute to prostate cancer; however, whether dietary lipids and de novo synthesized lipids are differentially metabolized remains unclear. Here, we highlight the lipogenic nature of prostate cancer, especially the promotion of de novo lipid synthesis, and the significance of various dietary lipids in prostate cancer development and progression. PMID:22503963

  15. Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

    PubMed Central

    2011-01-01

    Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC. PMID:21247503

  16. Quantification of Metabolic Rearrangements During Neural Stem Cells Differentiation into Astrocytes by Metabolic Flux Analysis.

    PubMed

    Sá, João V; Kleiderman, Susanne; Brito, Catarina; Sonnewald, Ursula; Leist, Marcel; Teixeira, Ana P; Alves, Paula M

    2017-01-01

    Proliferation and differentiation of neural stem cells (NSCs) have a crucial role to ensure neurogenesis and gliogenesis in the mammalian brain throughout life. As there is growing evidence for the significance of metabolism in regulating cell fate, knowledge on the metabolic programs in NSCs and how they evolve during differentiation into somatic cells may provide novel therapeutic approaches to address brain diseases. In this work, we applied a quantitative analysis to assess how the central carbon metabolism evolves upon differentiation of NSCs into astrocytes. Murine embryonic stem cell (mESC)-derived NSCs and astrocytes were incubated with labelled [1-(13)C]glucose and the label incorporation into intracellular metabolites was followed by GC-MS. The obtained (13)C labelling patterns, together with uptake/secretion rates determined from supernatant analysis, were integrated into an isotopic non-stationary metabolic flux analysis ((13)C-MFA) model to estimate intracellular flux maps. Significant metabolic differences between NSCs and astrocytes were identified, with a general downregulation of central carbon metabolism during astrocytic differentiation. While glucose uptake was 1.7-fold higher in NSCs (on a per cell basis), a high lactate-secreting phenotype was common to both cell types. Furthermore, NSCs consumed glutamine from the medium; the highly active reductive carboxylation of alpha-ketoglutarate indicates that this was converted to citrate and used for biosynthetic purposes. In astrocytes, pyruvate entered the TCA cycle mostly through pyruvate carboxylase (81%). This pathway supported glutamine and citrate secretion, recapitulating well described metabolic features of these cells in vivo. Overall, this fluxomics study allowed us to quantify the metabolic rewiring accompanying astrocytic lineage specification from NSCs.

  17. Ghrelin in the control of energy, lipid, and glucose metabolism.

    PubMed

    Heppner, Kristy M; Müller, Timo D; Tong, Jenny; Tschöp, Matthias H

    2012-01-01

    The discovery of ghrelin as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) led to subsequent studies characterizing the endogenous action of this gastrointestinal hormone. Accordingly, exogenous administration of ghrelin was found to increase food intake and adiposity in a variety of species, including rodents, nonhuman primates, and humans. Later work supported these findings and confirmed that ghrelin acts through hypothalamic neurons to mediate its effects on energy metabolism. Ghrelin acts specifically through GHS-R to promote a positive energy balance as demonstrated by loss of ghrelin action after pharmacological blockade or genetic deletion of GHS-R. More recently, ghrelin was found to be a mediator of glucose metabolism and acts to inhibit insulin secretion from pancreatic β-cells. Together, the literature highlights a predominant role of ghrelin in regulating energy and glucose metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals.

    PubMed

    Carmona-Antoñanzas, Greta; Tocher, Douglas R; Martinez-Rubio, Laura; Leaver, Michael J

    2014-01-15

    Lipid content and composition in aquafeeds have changed rapidly as a result of the recent drive to replace ecologically limited marine ingredients, fishmeal and fish oil (FO). Terrestrial plant products are the most economic and sustainable alternative; however, plant meals and oils are devoid of physiologically important cholesterol and long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acids. Although replacement of dietary FO with vegetable oil (VO) has little effect on growth in Atlantic salmon (Salmo salar), several studies have shown major effects on the activity and expression of genes involved in lipid homeostasis. In vertebrates, sterols and LC-PUFA play crucial roles in lipid metabolism by direct interaction with lipid-sensing transcription factors (TFs) and consequent regulation of target genes. The primary aim of the present study was to elucidate the role of key TFs in the transcriptional regulation of lipid metabolism in fish by transfection and overexpression of TFs. The results show that the expression of genes of LC-PUFA biosynthesis (elovl and fads2) and cholesterol metabolism (abca1) are regulated by Lxr and Srebp TFs in salmon, indicating highly conserved regulatory mechanism across vertebrates. In addition, srebp1 and srebp2 mRNA respond to replacement of dietary FO with VO. Thus, Atlantic salmon adjust lipid metabolism in response to dietary lipid composition through the transcriptional regulation of gene expression. It may be possible to further increase efficient and effective use of sustainable alternatives to marine products in aquaculture by considering these important molecular interactions when formulating diets. © 2013.

  19. Effect of hydrogen fluoride inhalation on lipid metabolism in guinea pigs

    SciTech Connect

    Philibert, C.; Dousset, J.C.; Rioufol, C.; Bourbon, P. )

    1991-01-01

    The action of fluoride in vivo (exposure 96 hrs to 7 mg/m3) on the metabolism of cyclic AMP and relationship between cAMP and lipid metabolism was investigated. The mean values for cAMP, non esterified fatty acids and cholesterol were significantly increased after hydrogen fluoride exposure. cAMP is directly responsible for the increased lipolysis. In animals exposed to HF, theophylline injection causes increases of non esterified fatty acids and not produces modification of cholesterol level.

  20. Rebamipide ameliorates atherosclerosis by controlling lipid metabolism and inflammation.

    PubMed

    Jhun, JooYeon; Kwon, Jeong-Eun; Kim, Se-Young; Jeong, Jeong-Hee; Na, Hyun Sik; Kim, Eun-Kyung; Lee, Seung Hoon; Jung, KyungAh; Min, Jun-Ki; Cho, Mi-La

    2017-01-01

    The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases.

  1. [Bone diseases caused by impaired glucose and lipid metabolism].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2013-11-01

    The number of patients with lifestyle-related diseases is rapidly increasing in Japan. Metabolic syndrome caused by abdominal fat accumulation induces diabetes mellitus, dyslipidemia, and hypertension, resulting in an increase in cardiovascular diseases. On the other hand, recent studies have shown that the lifestyle-related diseases are risk factors of osteoporotic fractures. Although it remains still unclear how metabolic disorders affect bone tissue, oxidative stress and/or glycation stress might directly have negative impacts on bone tissue and increase the risk of fractures. In this review, we describe the association of diabetes mellitus and dyslipidemia with the fracture risk through oxidative stress and glycation stress.

  2. The Effect of Sitagliptin on Lipid Metabolism of Fatty Liver Mice and Related Mechanisms

    PubMed Central

    Xu, Bilin; Shen, Tian; Chen, Lin; Xia, Juan; Zhang, Cuiping; Wang, Hongping; Yu, Ming; Lei, Tao

    2017-01-01

    Background In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. Material/Methods Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks. Blood lipid levels were measured and samples were stained with hematoxylin and eosin (H&E) and oil red staining for liver pathology and lipid deposition. Serum levels of fibroblast growth factor (FGF)-9 and FGF-21 were quantified by enzyme-linked immunosorbent assay (ELISA). Peroxisome proliferator-activated receptor (PPAR)-α, and cAMP reactive element binding homolog (CREBH) were measured by Western blotting, while fatty acid synthase and carnitine palmitoyltransferase 1 (CPT1) mRNA levels were assayed by RT-PCR. Results Compared to the control group, the NAFLD model mice had liver fatty disease, lower serum FGF-21 and FGF-19 levels, elevated serum lipid levels, depressed PPAR-α, CREBH, and CPT1 expression, and enhanced FAS expression (p<0.05). Sitagliptin treatment depressed blood lipid levels, increased serum FGF-21 and FGF-19 levels, PPAR-α, CREBH, and CPT1 expression, and suppressed FAS expression (p<0.05). Conclusions Sitagliptin can protect liver tissue and modulate lipid metabolism in NAFLD mice via elevating FGF-21 and FGF-19, upregulating liver PPAR-α and CREBH levels, and mediating expression levels of key enzymes for lipid metabolism. PMID:28315901

  3. The Effect of Sitagliptin on Lipid Metabolism of Fatty Liver Mice and Related Mechanisms.

    PubMed

    Xu, Bilin; Shen, Tian; Chen, Lin; Xia, Juan; Zhang, Cuiping; Wang, Hongping; Yu, Ming; Lei, Tao

    2017-03-19

    BACKGROUND In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. MATERIAL AND METHODS Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks. Blood lipid levels were measured and samples were stained with hematoxylin and eosin (H&E) and oil red staining for liver pathology and lipid deposition. Serum levels of fibroblast growth factor (FGF)-9 and FGF-21 were quantified by enzyme-linked immunosorbent assay (ELISA). Peroxisome proliferator-activated receptor (PPAR)-α, and cAMP reactive element binding homolog (CREBH) were measured by Western blotting, while fatty acid synthase and carnitine palmitoyltransferase 1 (CPT1) mRNA levels were assayed by RT-PCR. RESULTS Compared to the control group, the NAFLD model mice had liver fatty disease, lower serum FGF-21 and FGF-19 levels, elevated serum lipid levels, depressed PPAR-α, CREBH, and CPT1 expression, and enhanced FAS expression (p<0.05). Sitagliptin treatment depressed blood lipid levels, increased serum FGF-21 and FGF-19 levels, PPAR-α, CREBH, and CPT1 expression, and suppressed FAS expression (p<0.05). CONCLUSIONS Sitagliptin can protect liver tissue and modulate lipid metabolism in NAFLD mice via elevating FGF-21 and FGF-19, upregulating liver PPAR-a and CREBH levels, and mediating expression levels of key enzymes for lipid metabolism.

  4. The development and validation of a fast and robust dried blood spot based lipid profiling method to study infant metabolism.

    PubMed

    Koulman, Albert; Prentice, Philippa; Wong, Max C Y; Matthews, Lee; Bond, Nicholas J; Eiden, Michael; Griffin, Julian L; Dunger, David B

    2014-01-01

    Early life exposures and metabolic programming are associated with later disease risk. In particular lipid metabolism is thought to play a key role in the development of the metabolic syndrome and insulin resistance in later life. Investigative studies of metabolic programming are limited by the ethics and practicalities of sample collection in small infants. Dried blood spots on filter paper, derived from heel pricks are considered as the most suitable option for this age group. We validated a novel lipid profiling method, based on high resolution mass spectrometry to successfully determine the lipid composition of infants using dried blood spots. The spotting and air drying of blood on paper has noticeable effects on many of the lipids, leading to lipid oxidation and hydrolysis, which demand careful interpretation of the obtained data. We compared the lipid profiles from plasma or whole blood samples and the results from dried blood spots to determine if these revealed the same inter-subject differences. The results from dried blood spots were no less reproducible than other lipid profiling methods which required comparatively larger sample volumes. Therefore, lipid profiles obtained from dried blood spots can be successfully used to monitor infancy lipid metabolism and we show significant differences in the lipid metabolism of infants at age 3 versus 12 months.

  5. Identification of dual PPARα/γ agonists and their effects on lipid metabolism.

    PubMed

    Gao, Quanqing; Hanh, Jacky; Váradi, Linda; Cairns, Rose; Sjöström, Helena; Liao, Vivian W Y; Wood, Peta; Balaban, Seher; Ong, Jennifer Ai; Lin, Hsuan-Yu Jennifer; Lai, Felcia; Hoy, Andrew J; Grewal, Thomas; Groundwater, Paul W; Hibbs, David E

    2015-12-15

    The three peroxisome proliferator-activated receptor (PPAR) isoforms; PPARα, PPARγ and PPARδ, play central roles in lipid metabolism and glucose homeostasis. Dual PPARα/γ agonists, which stimulate both PPARα and PPARγ isoforms to similar extents, are gaining popularity as it is believed that they are able to ameliorate the unwanted side effects of selective PPARα and PPARγ agonists; and may also be used to treat dyslipidemia and type 2 diabetes mellitus simultaneously. In this study, virtual screening of natural product libraries, using both structure-based and ligand-based drug discovery approaches, identified ten potential dual PPARα/γ agonist lead compounds (9-13 and 16-20). In vitro assays confirmed these compounds to show no statistically significant toxicity to cells, with the exception of compound 12 which inhibited cell growth to 74.5%±3.5 and 54.1%±3.7 at 50μM and 100μM, respectively. In support of their potential as dual PPARα/γ agonists, all ten compounds upregulated the expression of cholesterol transporters ABCA1 and ABCG1 in THP-1 macrophages, with indoline derivative 16 producing the greatest elevation (2.3-fold; 3.3-fold, respectively). Furthermore, comparable to the activity of established PPARα and PPARγ agonists, compound 16 stimulated triacylglycerol accumulation during 3T3-L1 adipocyte differentiation as well as fatty acid β-oxidation in HuH7 hepatocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Diverse Roles of SIRT1 in Cancer Biology and Lipid Metabolism

    PubMed Central

    Simmons, Glenn E.; Pruitt, Wendy M.; Pruitt, Kevin

    2015-01-01

    SIRT1, an NAD+-dependent deacetylase, has been described in the literature as a major player in the regulation of cellular stress responses. Its expression has been shown to be altered in cancer cells, and it targets both histone and non-histone proteins for deacetylation and thereby alters metabolic programs in response to diverse physiological stress. Interestingly, many of the metabolic pathways that are influenced by SIRT1 are also altered in tumor development. Not only does SIRT1 have the potential to regulate oncogenic factors, it also orchestrates many aspects of metabolism and lipid regulation and recent reports are beginning to connect these areas. SIRT1 influences pathways that provide an alternative means of deriving energy (such as fatty acid oxidation and gluconeogenesis) when a cell encounters nutritive stress, and can therefore lead to altered lipid metabolism in various pathophysiological contexts. This review helps to show the various connections between SIRT1 and major pathways in cellular metabolism and the consequence of SIRT1 deregulation on carcinogenesis and lipid metabolism. PMID:25569080

  7. Differential CYP 2D6 metabolism alters primaquine pharmacokinetics.

    PubMed

    Potter, Brittney M J; Xie, Lisa H; Vuong, Chau; Zhang, Jing; Zhang, Ping; Duan, Dehui; Luong, Thu-Lan T; Bandara Herath, H M T; Dhammika Nanayakkara, N P; Tekwani, Babu L; Walker, Larry A; Nolan, Christina K; Sciotti, Richard J; Zottig, Victor E; Smith, Philip L; Paris, Robert M; Read, Lisa T; Li, Qigui; Pybus, Brandon S; Sousa, Jason C; Reichard, Gregory A; Marcsisin, Sean R

    2015-04-01

    Primaquine (PQ) metabolism by the cytochrome P450 (CYP) 2D family of enzymes is required for antimalarial activity in both humans (2D6) and mice (2D). Human CYP 2D6 is highly polymorphic, and decreased CYP 2D6 enzyme activity has been linked to decreased PQ antimalarial activity. Despite the importance of CYP 2D metabolism in PQ efficacy, the exact role that these enzymes play in PQ metabolism and pharmacokinetics has not been extensively studied in vivo. In this study, a series of PQ pharmacokinetic experiments were conducted in mice with differential CYP 2D metabolism characteristics, including wild-type (WT), CYP 2D knockout (KO), and humanized CYP 2D6 (KO/knock-in [KO/KI]) mice. Plasma and liver pharmacokinetic profiles from a single PQ dose (20 mg/kg of body weight) differed significantly among the strains for PQ and carboxy-PQ. Additionally, due to the suspected role of phenolic metabolites in PQ efficacy, these were probed using reference standards. Levels of phenolic metabolites were highest in mice capable of metabolizing CYP 2D6 substrates (WT and KO/KI 2D6 mice). PQ phenolic metabolites were present in different quantities in the two strains, illustrating species-specific differences in PQ metabolism between the human and mouse enzymes. Taking the data together, this report furthers understanding of PQ pharmacokinetics in the context of differential CYP 2D metabolism and has important implications for PQ administration in humans with different levels of CYP 2D6 enzyme activity.

  8. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

    PubMed

    Ayala, Antonio; Muñoz, Mario F; Argüelles, Sandro

    2014-01-01

    Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970-1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010-2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

  9. Effects of silicon deficiency on lipid composition and metabolism in the diatom Cyclotella cryptica

    SciTech Connect

    Roessler, P.G. )

    1988-09-01

    The effects of silicon deficiency on the metabolism and composition of lipids in Cyclotella cryptica T13L Reimann, Lewin, and Guillard were examined Silicon-deficient cells had higher levels of neutral lipids (primarily triacylglycerols) and higher proportions of saturated