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Sample records for affecting lipid metabolism

  1. Spastin Binds to Lipid Droplets and Affects Lipid Metabolism

    PubMed Central

    Papadopoulos, Chrisovalantis; Orso, Genny; Mancuso, Giuseppe; Herholz, Marija; Gumeni, Sentiljana; Tadepalle, Nimesha; Jüngst, Christian; Tzschichholz, Anne; Schauss, Astrid; Höning, Stefan; Trifunovic, Aleksandra; Daga, Andrea; Rugarli, Elena I.

    2015-01-01

    Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). HSP is characterized by weakness and spasticity of the lower limbs, owing to progressive retrograde degeneration of the long corticospinal axons. Spastin is a conserved microtubule (MT)-severing protein, involved in processes requiring rearrangement of the cytoskeleton in concert to membrane remodeling, such as neurite branching, axonal growth, midbody abscission, and endosome tubulation. Two isoforms of spastin are synthesized from alternative initiation codons (M1 and M87). We now show that spastin-M1 can sort from the endoplasmic reticulum (ER) to pre- and mature lipid droplets (LDs). A hydrophobic motif comprised of amino acids 57 through 86 of spastin was sufficient to direct a reporter protein to LDs, while mutation of arginine 65 to glycine abolished LD targeting. Increased levels of spastin-M1 expression reduced the number but increased the size of LDs. Expression of a mutant unable to bind and sever MTs caused clustering of LDs. Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels. In contrast, Dspastin overexpression increased LD number when expressed specifically in skeletal muscles or nerves. Downregulation of Dspastin and expression of a dominant-negative variant decreased LD number in Drosophila nerves, skeletal muscle and fat bodies, and reduced triacylglycerol levels in the larvae. Moreover, we found reduced amount of fat stores in intestinal cells of worms in which the spas-1 homologue was either depleted by RNA interference or deleted. Taken together, our data uncovers an evolutionarily conserved role of spastin as a positive regulator of LD metabolism and open up the possibility that dysfunction of LDs in axons may contribute to the pathogenesis of HSP. PMID:25875445

  2. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics.

    PubMed

    Zhang, Aihua; Qiu, Shi; Sun, Hui; Zhang, Tianlei; Guan, Yu; Han, Ying; Yan, Guangli; Wang, Xijun

    2016-01-01

    Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics. PMID:27306123

  3. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics

    PubMed Central

    Zhang, Aihua; Qiu, Shi; Sun, Hui; Zhang, Tianlei; Guan, Yu; Han, Ying; Yan, Guangli; Wang, Xijun

    2016-01-01

    Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics. PMID:27306123

  4. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.

    PubMed

    Abruzzese, Giselle Adriana; Heber, Maria Florencia; Ferreira, Silvana Rocio; Velez, Leandro Martin; Reynoso, Roxana; Pignataro, Omar Pedro; Motta, Alicia Beatriz

    2016-07-01

    Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. PMID:27179108

  5. 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.

  6. Environmentally Relevant Dose of Bisphenol A Does Not Affect Lipid Metabolism and Has No Synergetic or Antagonistic Effects on Genistein’s Beneficial Roles on Lipid Metabolism

    PubMed Central

    Fan, Ying; Li, Hongyu; Zhao, Nana; Yang, Huiqin; Ye, Xiaolei; He, Dongliang; Yang, Hui; Jin, Xin; Tian, Chong; Ying, Chenjiang

    2016-01-01

    Both bisphenol A (BPA, an endocrine disrupting chemicals) and genistein (a phytoestrogen mainly derived from leguminosae) are able to bind to estrogen receptors, but they are considered to have different effects on metabolic syndrome, surprisingly. We here investigate the effects of an environmentally relevant dose of BPA alone and the combined effects with genistein on lipid metabolism in rats. Eight groups of adult male Wistar rats, fed with either standard chow diet or high-fat diet, were treated with BPA (50μg/kg/day), genistein (10mg/kg/day), and BPA plus genistein for 35 weeks, respectively. Metabolic parameters in serum and liver were determined; the hematoxylin/eosin and oil Red O staining were used to observe liver histologically; gene expressions related to hepatic lipid metabolism were analyzed by Real-time PCR; protein expressions of PPARγ, PPARα and LC3 in liver were analyzed by western blotting. No difference of body weight gain, total energy intake, liver weight/body weight or body fat percentage in both STD- and HFD-fed sub-groups was observed after treatment with BPA, genistein, or BPA plus genistein (P>0.05). Genistein alleviated lipid metabolism disorder and decreased the mRNA and protein expression of PPARγ (P<0.05), and increased the protein expression of LC3II (P<0.05) in liver of HFD-fed rats. However, BPA treatment had no effect on lipid metabolism in rats alone (P>0.05) or combined with genistein. Our findings suggest that long-term environmentally relevant dose of BPA did not affect lipid metabolism, and had no synergetic or antagonistic roles on genistein’s beneficial function on hepatic lipid metabolism. PMID:27171397

  7. Disorders of Lipid Metabolism

    MedlinePlus

    ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Fats (lipids) are ... carbohydrates and low in fats. Supplements of the amino acid carnitine may be helpful. The long-term outcome ...

  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. PMID:23321473

  9. Drought stress affects chloroplast lipid metabolism in rape (Brassica napus) leaves.

    PubMed

    Benhassaine-Kesri, Ghouziel; Aid, Fatiha; Demandre, Chantal; Kader, Jean-Claude; Mazliak, Paul

    2002-06-01

    Rape (Brassica napus L. var. Bienvenue) is a 16:3 plant which contains predominantly prokaryotic species of monogalactosyldiacylglycerol i.e. sn-1 C18, sn-2 C16 (C18/C16 MGDG). Rape plants were exposed to a restricted water supply for 12 days. Under drought conditions, considerable changes in lipid metabolism were observed. Drought stress provoked a decline in leaf polar lipids, which is mainly due to a decrease in MGDG content. Determination of molecular species in phosphatidylcholine (PC) and MGDG indicated that the prokaryotic molecular species of MGDG (C18/C16) decreased after drought stress while the eukaryotic molecular species (C18/C18) remained stable. Drought stress had different effects on two key enzymes of PC and MGDG synthesis. The in vitro activity of MGDG synthase (EC. 2.4.1.46) was reduced in drought stressed plants whereas cholinephosphotransferase (EC. 2.7.8.2) activity was not affected. Altogether these results suggest that the prokaryotic pathway leading to MGDG synthesis was strongly affected by drought stress while the eukaryotic pathway was not. It was also observed that the molecular species of leaf PC became more saturated in drought stressed plants. This could be due to a specific decrease in oleate desaturase activity. PMID:12060239

  10. Lipid metabolism in mitochondrial membranes.

    PubMed

    Mayr, Johannes A

    2015-01-01

    Mitochondrial membranes have a unique lipid composition necessary for proper shape and function of the organelle. Mitochondrial lipid metabolism involves biosynthesis of the phospholipids phosphatidylethanolamine, cardiolipin and phosphatidylglycerol, the latter is a precursor of the late endosomal lipid bis(monoacylglycero)phosphate. It also includes mitochondrial fatty acid synthesis necessary for the formation of the lipid cofactor lipoic acid. Furthermore the synthesis of coenzyme Q takes place in mitochondria as well as essential parts of the steroid and vitamin D metabolism. Lipid transport and remodelling, which are necessary for tailoring and maintaining specific membrane properties, are just partially unravelled. Mitochondrial lipids are involved in organelle maintenance, fission and fusion, mitophagy and cytochrome c-mediated apoptosis. Mutations in TAZ, SERAC1 and AGK affect mitochondrial phospholipid metabolism and cause Barth syndrome, MEGDEL and Sengers syndrome, respectively. In these disorders an abnormal mitochondrial energy metabolism was found, which seems to be due to disturbed protein-lipid interactions, affecting especially enzymes of the oxidative phosphorylation. Since a growing number of enzymes and transport processes are recognised as parts of the mitochondrial lipid metabolism, a further increase of lipid-related disorders can be expected. PMID:25082432

  11. Lipid Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs ...

  12. 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)

  13. 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. PMID:26987021

  14. Lipid metabolism in prostate cancer

    PubMed Central

    Wu, Xinyu; Daniels, Garrett; Lee, Peng; Monaco, Marie E

    2014-01-01

    The malignant transformation of cells requires adaptations across multiple metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism has been a hallmark of the malignant phenotype; increased lipid accumulation secondary to changes in the levels of a variety of lipid metabolic enzymes has been documented in a variety of tumors, including prostate. Alterations in prostate lipid metabolism include upregulation of several lipogenic enzymes as well as of enzymes that function to oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid metabolism are also affected. With respect to lipogenesis, most studies have concentrated on increased expression and activity ofthe de novo fatty acid synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might function as an oncogene. A central role for fatty acid oxidation in supplying energy to the prostate cancer cell is supported by the observation that the peroxisomal enzyme, α-methylacyl-CoA racemase (AMACR), which facilitates the transformation of branched chain fatty acids to a form suitable for β-oxidation, is highly overexpressed in prostate cancer compared with normal prostate. Exploitation of the alterations in lipid metabolic pathways in prostate cancer could result in the development of new therapeutic modalities as well as provide candidates for new prognostic and predictive biomarkers. AMACR has already proven to be a valuable biomarker in distinguishing normal from malignant prostate tissue, and is used routinely in clinical practice. PMID:25374912

  15. Dasatinib improves insulin sensitivity and affects lipid metabolism in a patient with chronic myeloid leukaemia.

    PubMed

    Iizuka, Katsumi; Niwa, Hiroyuki; Kato, Takehiro; Takeda, Jun

    2016-01-01

    A 65-year-old woman had been visiting our department for the treatment of type-2 diabetes mellitus since December 2012. Her glycated haemoglobin levels were well controlled (≈5.8% (40 mmol/mol)) by metformin (500 mg). In July 2014, her white cell count increased suddenly to 33 530 cells/μL and she was diagnosed with Ph+ chronic myeloid leukaemia. She was started on dasatinib (100 mg), which immediately normalised plasma levels of WCC. Dasatinib improved the glycaemic index to <6.0% and also improved plasma levels of triglycerides (TGs) and high-density lipoprotein-cholesterol (HDL-c). Levels of low-density lipoprotein-cholesterol were increased but remained within the normal range. The TG:HDL-c ratio and Quantitative Insulin Sensitivity Check Index rapidly improved. Followed by an improvement in insulin sensitivity, plasma levels of adiponectin and leptin were increased. This case study suggests that dasatinib might have positive as well as negative effects on the metabolism of glucose and lipids. PMID:26873919

  16. Acyl-lipid metabolism.

    PubMed

    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

  17. Acyl-lipid metabolism.

    PubMed

    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

  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

    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

  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

    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

  20. Sitamaquine-resistance in Leishmania donovani affects drug accumulation and lipid metabolism.

    PubMed

    Imbert, L; Cojean, S; Libong, D; Chaminade, P; Loiseau, P M

    2014-09-01

    This study focuses on the mechanism of sitamaquine-resistance in Leishmania donovani. Sitamaquine accumulated 10 and 1.4 fold more in cytosol than in membranes of wild-type (WT) and of sitamaquine-resistant (Sita-R160) L. donovani promastigotes, respectively. The sitamaquine accumulation was a concentration-dependent process in WT whereas a saturation occurred in Sita-R160 suggesting a reduced uptake or an increase of the sitamaquine efflux. Membrane negative phospholipids being the main target for sitamaquine uptake, a lipidomic analysis showed that sitamaquine-resistance did not rely on a decrease of membrane negative phospholipid rate in Sita-R160, discarding the hypothesis of reduced uptake. However, sterol and phospholipid metabolisms were strongly affected in Sita-R160 suggesting that sitamaquine-resistance could be related to an alteration of phosphatidylethanolamine-N-methyl-transferase and choline kinase activities and to a decrease in cholesterol uptake and of ergosterol biosynthesis. Preliminary data of proteomics analysis exhibited different protein profiles between WT and Sita-160R remaining to be characterized. PMID:25201056

  1. Embryonic exposures of lithium and homocysteine and folate protection affect lipid metabolism during mouse cardiogenesis and placentation.

    PubMed

    Han, Mingda; Evsikov, Alexei V; Zhang, Lifeng; Lastra-Vicente, Rosana; Linask, Kersti K

    2016-06-01

    Embryonic exposures can increase the risk of congenital cardiac birth defects and adult disease. The present study identifies the predominant pathways modulated by an acute embryonic mouse exposure during gastrulation to lithium or homocysteine that induces cardiac defects. High dose periconceptional folate supplementation normalized development. Microarray bioinformatic analysis of gene expression demonstrated that primarily lipid metabolism is altered after the acute exposures. The lipid-related modulation demonstrated a gender bias with male embryos showing greater number of lipid-related Gene Ontology biological processes altered than in female embryos. RT-PCR analysis demonstrated significant change of the fatty acid oxidation gene Acadm with homocysteine exposure primarily in male embryos than in female. The perturbations resulting from the exposures resulted in growth-restricted placentas with disorganized cellular lipid droplet distribution indicating lipids have a critical role in cardiac-placental abnormal development. High folate supplementation protected normal heart-placental function, gene expression and lipid localization. PMID:26993217

  2. Potato tuber expression of Arabidopsis WRINKLED1 increase triacylglycerol and membrane lipids while affecting central carbohydrate metabolism.

    PubMed

    Hofvander, Per; Ischebeck, Till; Turesson, Helle; Kushwaha, Sandeep K; Feussner, Ivo; Carlsson, Anders S; Andersson, Mariette

    2016-09-01

    Tuber and root crops virtually exclusively accumulate storage products in the form of carbohydrates. An exception is yellow nutsedge (Cyperus esculentus) in which tubers have the capacity to store starch and triacylglycerols (TAG) in roughly equal amounts. This suggests that a tuber crop can efficiently handle accumulation of energy dense oil. From a nutritional as well as economic aspect, it would be of interest to utilize the high yield capacity of tuber or root crops for oil accumulation similar to yellow nutsedge. The transcription factor WRINKLED1 from Arabidopsis thaliana, which in seed embryos induce fatty acid synthesis, has been shown to be a major factor for oil accumulation. WRINKLED1 was expressed in potato (Solanum tuberosum) tubers to explore whether this factor could impact tuber metabolism. This study shows that a WRINKLED1 transcription factor could induce triacylglycerol accumulation in tubers of transformed potato plants grown in field (up to 12 nmol TAG/mg dry weight, 1% of dry weight) together with a large increase in polar membrane lipids. The changes in metabolism further affected starch accumulation and composition concomitant with massive increases in sugar content. PMID:26914183

  3. 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. PMID:26704851

  4. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis

    PubMed Central

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  5. Lipid metabolism and signaling in cardiac lipotoxicity.

    PubMed

    D'Souza, Kenneth; Nzirorera, Carine; Kienesberger, Petra C

    2016-10-01

    The heart balances uptake, metabolism and oxidation of fatty acids (FAs) to maintain ATP production, membrane biosynthesis and lipid signaling. Under conditions where FA uptake outpaces FA oxidation and FA sequestration as triacylglycerols in lipid droplets, toxic FA metabolites such as ceramides, diacylglycerols, long-chain acyl-CoAs, and acylcarnitines can accumulate in cardiomyocytes and cause cardiomyopathy. Moreover, studies using mutant mice have shown that dysregulation of enzymes involved in triacylglycerol, phospholipid, and sphingolipid metabolism in the heart can lead to the excess deposition of toxic lipid species that adversely affect cardiomyocyte function. This review summarizes our current understanding of lipid uptake, metabolism and signaling pathways that have been implicated in the development of lipotoxic cardiomyopathy under conditions including obesity, diabetes, aging, and myocardial ischemia-reperfusion. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26924249

  6. 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

  7. Isolation and Expression Analysis of STAT Members from Synechogobius hasta and Their Roles in Leptin Affecting Lipid Metabolism.

    PubMed

    Wu, Kun; Tan, Xiao-Ying; Wei, Chuan-Chuan; You, Wen-Jing; Zhuo, Mei-Qin; Song, Yu-Feng

    2016-01-01

    Signal transducers and activators of transcription proteins (STATs) act as important mediators in multiple biological processes induced by a large number of cytokines. In the present study, full-length cDNA sequences of seven STAT members, including some splicing variants different from those in mammals, were obtained from Synechogobius hasta. The phylogenetic analysis revealed that the seven STAT members were derived from paralogous genes that might have arisen by whole genome duplication (WGD) events during vertebrate evolution. All of these members share similar domain structure compared with those of mammals, and were widely expressed across the tested tissues (brain, gill, heart, intestine, liver, muscle and spleen), but at variable levels. Incubation in vitro of recombinant human leptin changed the intracellular triglyceride (TG) content and mRNA levels of several STATs members, as well as expressions and activities of genes involved in lipid metabolism. Furthermore, Tyrphostin B42 (AG490), a specific inhibitor of the Janus Kinase 2(JAK2)-STAT pathway, partially reversed leptin-induced change on STAT3 and its two spliced isoforms expression, as well as expressions and activities of genes involved in lipid metabolism. As a consequence, the decrease of TG content was also reversed. Thus, our study suggests that STAT3 is the requisite for the leptin signal and the activation of the STAT3 member may account for the leptin-induced changes in lipid metabolism in S. hasta. PMID:27011172

  8. Isolation and Expression Analysis of STAT Members from Synechogobius hasta and Their Roles in Leptin Affecting Lipid Metabolism

    PubMed Central

    Wu, Kun; Tan, Xiao-Ying; Wei, Chuan-Chuan; You, Wen-Jing; Zhuo, Mei-Qin; Song, Yu-Feng

    2016-01-01

    Signal transducers and activators of transcription proteins (STATs) act as important mediators in multiple biological processes induced by a large number of cytokines. In the present study, full-length cDNA sequences of seven STAT members, including some splicing variants different from those in mammals, were obtained from Synechogobius hasta. The phylogenetic analysis revealed that the seven STAT members were derived from paralogous genes that might have arisen by whole genome duplication (WGD) events during vertebrate evolution. All of these members share similar domain structure compared with those of mammals, and were widely expressed across the tested tissues (brain, gill, heart, intestine, liver, muscle and spleen), but at variable levels. Incubation in vitro of recombinant human leptin changed the intracellular triglyceride (TG) content and mRNA levels of several STATs members, as well as expressions and activities of genes involved in lipid metabolism. Furthermore, Tyrphostin B42 (AG490), a specific inhibitor of the Janus Kinase 2(JAK2)-STAT pathway, partially reversed leptin-induced change on STAT3 and its two spliced isoforms expression, as well as expressions and activities of genes involved in lipid metabolism. As a consequence, the decrease of TG content was also reversed. Thus, our study suggests that STAT3 is the requisite for the leptin signal and the activation of the STAT3 member may account for the leptin-induced changes in lipid metabolism in S. hasta. PMID:27011172

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Nuclear receptors, mitochondria and lipid metabolism.

    PubMed

    Alaynick, William A

    2008-09-01

    Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome-proliferator activated receptors (PPARs) and liver X receptors (LXRs), acting in concert with PPARgamma Coactivator 1alpha (PGC-1alpha), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia and obesity). Recently, additional partners of PGC-1alpha have moved to the forefront of metabolic research, the estrogen-related receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function. PMID:18375192

  11. Ubiquinol affects the expression of genes involved in PPARα signalling and lipid metabolism without changes in methylation of CpG promoter islands in the liver of mice

    PubMed Central

    Schmelzer, Constance; Kitano, Mitsuaki; Hosoe, Kazunori; Döring, Frank

    2012-01-01

    Coenzyme Q10 is an essential cofactor in the respiratory chain and serves as a potent antioxidant in biological membranes. Recent studies in vitro and in vivo provide evidence that Coenzyme Q10 is involved in inflammatory processes and lipid metabolism via gene expression. To study these effects at the epigenomic level, C57BL6J mice were supplemented for one week with reduced Coenzyme Q10 (ubiquinol). Afterwards, gene expression signatures and DNA promoter methylation patterns of selected genes were analysed. Genome-wide transcript profiling in the liver identified 1112 up-regulated and 571 down-regulated transcripts as differentially regulated between ubiquinol-treated and control animals. Text mining and GeneOntology analysis revealed that the ”top 20” ubiquinol-regulated genes play a role in lipid metabolism and are functionally connected by the PPARα signalling pathway. With regard to the ubiquinol-induced changes in gene expression of about +3.14-fold (p≤0.05), +2.18-fold (p≤0.01), and −2.13-fold (p≤0.05) for ABCA1, ACYP1, and ACSL1 genes, respectively, hepatic DNA methylation analysis of 282 (sense orientation) and 271 (antisense) CpG units in the respective promoter islands revealed no significant effect of ubiquinol. In conclusion, ubiquinol affects the expression of genes involved in PPARα signalling and lipid metabolism without changing the promoter DNA methylation status in the liver of mice. PMID:22448092

  12. Drugs affecting glycosaminoglycan metabolism.

    PubMed

    Ghiselli, Giancarlo; Maccarana, Marco

    2016-07-01

    Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu through pharmacological interventions. In this review, we provide a classification of small molecules affecting GAG metabolism based on their mechanism of action. Furthermore, we present evidence to show that clinically approved drugs affect GAG metabolism and that this could contribute to their therapeutic benefit. PMID:27217160

  13. Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum.

    PubMed

    Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M; Ametaj, Burim N

    2016-08-01

    The objective of this investigation was to search for alterations in blood variables related to innate immunity and carbohydrate and lipid metabolism during the transition period in cows affected by ketosis. One hundred multiparous Holstein dairy cows were involved in the study. Blood samples were collected at -8, -4, week of disease diagnosis (+1 to +3weeks), and +4weeks relative to parturition from 6 healthy cows (CON) and 6 cows with ketosis and were analyzed for serum variables. Results showed that cows with ketosis had greater concentrations of serum β-hydroxybutyric acid (BHBA), interleukin (IL)-6, tumor necrosis factor (TNF), serum amyloid A (SAA), and lactate in comparison with the CON animals. Serum concentrations of BHBA, IL-6, TNF, and lactate were greater starting at -8 and -4weeks prior to parturition in cows with ketosis vs those of CON group. Cows with ketosis also had lower DMI and milk production vs CON cows. Milk fat also was lower in ketotic cows at diagnosis of disease. Cows affected by ketosis showed an activated innate immunity and altered carbohydrate and lipid metabolism several weeks prior to diagnosis of disease. Serum IL-6 and lactate were the strongest discriminators between ketosis cows and CON ones before the occurrence of ketosis, which might be useful as predictive biomarkers of the disease state. PMID:27474003

  14. Dietary Fatty Acid Metabolism is Affected More by Lipid Level than Source in Senegalese Sole Juveniles: Interactions for Optimal Dietary Formulation.

    PubMed

    Bonacic, Kruno; Estévez, Alicia; Bellot, Olga; Conde-Sieira, Marta; Gisbert, Enric; Morais, Sofia

    2016-01-01

    This study analyses the effects of dietary lipid level and source on lipid absorption and metabolism in Senegalese sole (Solea senegalensis). Juvenile fish were fed 4 experimental diets containing either 100 % fish oil (FO) or 25 % FO and 75 % vegetable oil (VO; rapeseed, linseed and soybean oils) at two lipid levels (~8 or ~18 %). Effects were assessed on fish performance, body proximate composition and lipid accumulation, activity of hepatic lipogenic and fatty acid oxidative enzymes and, finally, on the expression of genes related to lipid metabolism in liver and intestine, and to intestinal absorption, both pre- and postprandially. Increased dietary lipid level had no major effects on growth and feeding performance (FCR), although fish fed FO had marginally better growth. Nevertheless, diets induced significant changes in lipid accumulation and metabolism. Hepatic lipid deposits were higher in fish fed VO, associated to increased hepatic ATP citrate lyase activity and up-regulated carnitine palmitoyltransferase 1 (cpt1) mRNA levels post-prandially. However, lipid level had a larger effect on gene expression of metabolic (lipogenesis and β-oxidation) genes than lipid source, mostly at fasting. High dietary lipid level down-regulated fatty acid synthase expression in liver and intestine, and increased cpt1 mRNA in liver. Large lipid accumulations were observed in the enterocytes of fish fed high lipid diets. This was possibly a result of a poor capacity to adapt to high dietary lipid level, as most genes involved in intestinal absorption were not regulated in response to the diet. PMID:26563870

  15. Cold exposure affects carbohydrates and lipid metabolism, and induces Hog1p phosphorylation in Dekkera bruxellensis strain CBS 2499.

    PubMed

    Galafassi, Silvia; Toscano, Marco; Vigentini, Ileana; Zambelli, Paolo; Simonetti, Paolo; Foschino, Roberto; Compagno, Concetta

    2015-05-01

    Dekkera bruxellensis is a yeast known to affect the quality of wine and beer. This species, due to its high ethanol and acid tolerance, has been reported also to compete with Saccharomyces cerevisiae in distilleries producing fuel ethanol. In order to understand how this species responds when exposed to low temperatures, some mechanisms like synthesis and accumulation of intracellular metabolites, changes in lipid composition and activation of the HOG-MAPK pathway were investigated in the genome sequenced strain CBS 2499. We show that cold stress caused intracellular accumulation of glycogen, but did not induce accumulation of trehalose and glycerol. The cellular fatty acid composition changed after the temperature downshift, and a significant increase of palmitoleic acid was observed. RT-PCR analysis revealed that OLE1 encoding for Δ9-fatty acid desaturase was up-regulated, whereas TPS1 and INO1 didn't show changes in their expression. In D. bruxellensis Hog1p was activated by phosphorylation, as described in S. cerevisiae, highlighting a conserved role of the HOG-MAP kinase signaling pathway in cold stress response. PMID:25697274

  16. Lipid metabolism, apoptosis and cancer therapy.

    PubMed

    Huang, Chunfa; Freter, Carl

    2015-01-01

    Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy. PMID:25561239

  17. 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

  18. 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

  19. Inhibition of Ceramide De Novo Synthesis with Myriocin Affects Lipid Metabolism in the Liver of Rats with Streptozotocin-Induced Type 1 Diabetes

    PubMed Central

    Wiesiołek-Kurek, Patrycja; Piotrowska, Dominika M.; Łukaszuk, Bartłomiej; Chabowski, Adrian; Żendzian-Piotrowska, Małgorzata

    2014-01-01

    Nowadays diabetes is one of the most common metabolic diseases. Sphingolipids, which are vitally important constituents of intracellular signal transduction pathways, may be among the most pathogenic lipid moieties intermingled in the origin and development of diabetes. It is now well established that inhibition of de novo ceramide synthesis with myriocin exerts positive effects on lipid metabolism and glucose homeostasis in type 2 diabetes mellitus animal models. However, its influence on type I diabetes still remains unknown. Therefore, the scope of this paper is to fulfill that particular gap in our knowledge. PMID:24701589

  20. Dietary strawberry seed oil affects metabolite formation in the distal intestine and ameliorates lipid metabolism in rats fed an obesogenic diet

    PubMed Central

    Jurgoński, Adam; Fotschki, Bartosz; Juśkiewicz, Jerzy

    2015-01-01

    Objective To answer the question whether dietary strawberry seed oil rich in α-linolenic acid and linoleic acid (29.3 and 47.2% of total fatty acids, respectively) can beneficially affect disorders induced by the consumption of an obesogenic diet. Design Thirty-two male Wistar rats were randomly assigned to four groups of eight animals each and fed with a basal or obesogenic (high in fat and low in fiber) diet that contained either strawberry seed oil or an edible rapeseed oil. A two-way analysis of variance was then applied to assess the effects of diet and oil and the interaction between them. Results After 8 weeks of feeding, the obesogenic diet increased the body weight and the liver mass and fat content, whereas decreased the cecal acetate and butyrate concentration. This diet also altered the plasma lipid profile and decreased the liver sterol regulatory element-binding protein 1c (SREBP-1c) content. However, the lowest liver SREBP-1c content was observed in rats fed an obesogenic diet containing strawberry seed oil. Moreover, dietary strawberry seed oil decreased the cecal short-chain fatty acid concentrations (acetate, propionate, and butyrate) regardless of the diet type, whereas the cecal β-glucuronidase activity was considerably increased only in rats fed an obesogenic diet containing strawberry seed oil. Dietary strawberry seed oil also lowered the liver fat content, the plasma triglyceride level and the atherogenic index of plasma. Conclusions Strawberry seed oil has a potent lipid-lowering activity but can unfavorably affect microbial metabolism in the distal intestine. The observed effects are partly due to the synergistic action of the oil and the obesogenic diet. PMID:25636326

  1. Green tea extract suppresses adiposity and affects the expression of lipid metabolism genes in diet-induced obese zebrafish

    PubMed Central

    2012-01-01

    Background Visceral fat accumulation is one of the most important predictors of mortality in obese populations. Administration of green tea extract (GTE) can reduce body fat and reduce the risk of obesity-related diseases in mammals. In this study, we investigated the effects and mechanisms of GTE on adiposity in diet-induced obese (DIO) zebrafish. Methods Zebrafish at 3.5 to 4.5 months post-fertilization were allocated to four groups: non-DIO, DIO, DIO + 0.0025%GTE, and DIO + 0.0050%GTE. The non-DIO group was fed freshly hatched Artemia once daily (5 mg cysts/fish daily) for 40 days. Zebrafish in the three DIO groups were fed freshly hatched Artemia three times daily (60 mg cysts/fish daily). Zebrafish in the DIO + 0.0025%GTE and DIO + 0.0050%GTE groups were exposed to GTE after the start of feeding three times daily for 40 days. Results Three-dimensional microcomputed tomography analysis showed that GTE exposure significantly decreased the volume of visceral but not subcutaneous fat tissue in DIO zebrafish. GTE exposure increased hepatic expression of the lipid catabolism genes ACOX1 (acyl-coenzyme A oxidase 1, palmitoyl), ACADM (acyl-coenzyme A dehydrogenase, c-4 to c-12 straight chain), and PPARA (peroxisome proliferator-activated receptor alpha). GTE exposure also significantly decreased the visceral fat expression of SOCS3 (suppressor of cytokine signaling 3b) which inhibits leptin signaling. Conclusions The present results are consistent with those seen in mammals treated with GTE, supporting the validity of studying the effects of GTE in DIO zebrafish. Our results suggest that GTE exerts beneficial effects on adiposity, possibly by altering the expression of lipid catabolism genes and SOCS3. PMID:22871059

  2. Factors Affecting Gender Differences in the Association between Health-Related Quality of Life and Metabolic Syndrome Components: Tehran Lipid and Glucose Study

    PubMed Central

    Amiri, Parisa; Deihim, Tina; Taherian, Reza; Karimi, Mehrdad; Gharibzadeh, Safoora; Asghari-Jafarabadi, Mohammad; Shiva, Niloofar; Azizi, Fereidoun

    2015-01-01

    Objective Using structural equation modeling, this study is one of the first efforts aimed at assessing influential factors causing gender differences in the association between health-related quality of life (HRQoL) and metabolic syndrome. Methods A sample of 950 adults, from Tehran Lipid and Glucose Study were recruited for this cross sectional study in 2005–2007. Health-related quality of life was assessed using the Iranian version of SF-36. Metabolic syndrome components (MetSCs) and physical and mental HRQoL were considered as continuous latent constructs explaining the variances of their observed components. Structural equation modeling was performed to examine the association between the constructs of MetSCs and the physical and mental HRQoL within the two gender groups. Results Based on the primary hypothesis, MetSCs and HRQoL were fitted in a model. The negative effect of MetSCs on HRQoL was found to be significant only in the physical domain and only in women. The proportion of all the cardio-metabolic risk factors as well as subscales of physical HRQoL that have been explained via the two constructs of MetSCs and HRQoL, respectively, were significantly higher in women. Physical activity in both men (β = 3.19, p<0.05) and women (β = 3.94, p<0.05), age (β = -3.28, p<0.05), education (β = 2.63, p<0.05) only in women and smoking (β = 2.28, p<0.05) just in men, directly affected physical HRQoL. Regarding the mental domain, physical activity (β = 3.37, p<0.05) and marital status (β = 3.44, p<0.05) in women and age (β = 2.01, p<0.05) in men were direct effective factors. Age and education in women as well as smoking in men indirectly affected physical HRQoL via MetSCs. Conclusion Gender differences in the association between MetSCs and physical HRQoL could mostly be attributed to the different structures of both MetSCs and physical HRQoL constructs in men and women. Age and smoking are the most important socio-behavioral factors which could affect this

  3. Lipid metabolism and nutrient partitioning strategies.

    PubMed

    Morris, A M; Calsbeek, D J; Eckel, R H

    2004-10-01

    The increasing prevalence of overweight and obesity worldwide is daunting and requires prompt attention by the affected, health care profession, government and the pharmaceutical industry. Because overweight/obesity are defined as an excess of adipose tissue mass, all approaches in prevention and treatment must consider redirecting lipid storage in adipose tissue to oxidative metabolism. Lipid partitioning is a complex process that involves interaction between fat and other macronutrients, particularly carbohydrate. In an isocaloric environment, when fat is stored carbohydrate is oxidized and vice versa. Processes that influence fat partitioning in a manner in which weight is maintained must be modified by changes in organ-specific fat transport and metabolism. When therapy is considered, however, changes in lipid partitioning alone will be ineffective unless a negative energy balance is also achieved, i.e. energy expenditure exceeds energy intake. The intent of this review is to focus on molecules including hormones, enzymes, cytokines, membrane transport proteins, and transcription factors directly involved in fat trafficking and partitioning that could be potential drug targets. Some examples of favorably altering body composition by systemic and/or tissue specific modification of these molecules have already been provided with gene knockout and/or transgenic approaches in mice. The translation of this science to humans remains a challenging task. PMID:15544448

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. 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

  6. Overnutrition, ectopic lipid and the metabolic syndrome.

    PubMed

    Grundy, Scott M

    2016-08-01

    The metabolic syndrome is a constellation of metabolic risk factors including atherogenic dyslipidemia (elevated serum triglycerides, reduced high-density lipoprotein (HDL) cholesterol), elevated blood pressure, dysglycemia (insulin resistance and elevated serum glucose), a pro-inflammatory state, and a prothrombotic state. Most persons with metabolic syndrome are obese, and usually have abdominal obesity. Generally, obesity is a reflection of overnutrition. A current view is that when adipose tissue fails to store all excess nutrients as triglyceride, lipid begins to accumulate in various tissues (eg, muscle, liver, pancreas, and heart). This accumulation is called ectopic lipid. Various mechanisms have been proposed whereby ectopic lipid is detrimental in different tissues; these derangements induce metabolic risk factors. The foundation of the metabolic syndrome thus appears to be overnutrition, that is, more nutrient intake than can be safely disposed by lipid oxidation. Excess dietary carbohydrate also induces ectopic lipid. Of interest, less than half of obese individuals develop metabolic syndrome. Through various mechanisms they adapt to overnutrition so as to minimize lipid overload in tissues, and consequently, prevent the syndrome. PMID:27194746

  7. Roles of lipid metabolism in keloid development

    PubMed Central

    2013-01-01

    Keloids are common cutaneous pathological scars that are characterised by the histological accumulation of fibroblasts, collagen fibres, and clinically significant invasive growth. Although increasing lines of research on keloids have revealed genetic and environmental factors that contribute to their formation, the etiology of these scars remains unclear. Several studies have suggested the involvement of lipid metabolism, from a nutritional point of view. However, the role that lipid metabolism plays in the pathogenesis and progression of keloids has not previously been reviewed. The progress that has been made in understanding the roles of the pro- and anti-inflammatory lipid mediators in inflammation, and how they relate to the formation and progression of keloids, is also outlined. In particular, the possible relationships between mechanotransduction and lipid metabolites in keloids are explored. Mechanotransduction is the process by which physical forces are converted into biochemical signals that are then integrated into cellular responses. It is possible that lipid rafts and caveolae provide the location of lipid signaling and interactions between these signaling pathways and mechanotransduction. Moreover, interactions between lipid signaling pathway molecules and mechanotransduction molecules have been observed. A better understanding of the lipid profile changes and the functional roles lipid metabolism plays in keloids will help to identify target molecules for the development of novel interventions that can prevent, reduce, or even reverse pathological scar formation and/or progression. PMID:23634948

  8. 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. PMID:26477910

  9. 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

  10. Hepatitis C Virus Hijacks Host Lipid Metabolism

    PubMed Central

    Syed, Gulam H; Amako, Yutaka; Siddiqui, Aleem

    2009-01-01

    Hepatitis C virus (HCV) modulates cellular lipid metabolism to enhance its replication. HCV circulates in the blood in association with lipoproteins. HCV infection is associated with enhanced lipogenesis, reduced secretion and β-oxidation of lipids. HCV-induced imbalance in lipid homeostasis leads to steatosis. Many lipids are crucial for viral life cycle, and inhibitors of cholesterol/fatty acid biosynthetic pathways inhibit viral replication, maturation and secretion. HCV negatively modulates the synthesis and secretion of very low-density lipoproteins (VLDL). The components involved in VLDL assembly are also required for HCV morphogenesis/secretion, suggesting that HCV coopts the VLDL secretory pathway for its own secretion. This review highlights HCV-altered lipid metabolic events that aid in the viral life cycle and ultimately promote liver disease pathogenesis. PMID:19854061

  11. Antiretroviral drug levels and interactions affect lipid, lipoprotein and glucose metabolism in HIV-1 seronegative subjects: A pharmacokinetic-pharmacodynamic analysis

    PubMed Central

    Rosenkranz, Susan L.; Yarasheski, Kevin E.; Para, Michael F.; Reichman, Richard C.; Morse, Gene D.

    2007-01-01

    Background: HIV-infected patients treated with antiretroviral medications (ARVs) develop undesirable changes in lipid and glucose metabolism that mimic the metabolic syndrome and may be proatherogenic. Antiretroviral drug levels and their interactions may contribute to these metabolic alterations. Methods: Fifty-six HIV-seronegative adults were enrolled in an open-label, randomized, pharmacokinetic interaction study, and received a non-nucleoside reverse transcriptase inhibitor (efavirenz on days 1-21) plus a protease inhibitor (PI; amprenavir on days 11-21), with a second PI on days 15-21 (saquinavir, nelfinavir, indinavir, or ritonavir). Fasting triglycerides, total, LDL- and HDL-cholesterol, glucose, insulin and C-peptide levels were measured on days 0, 14, 21, and 2-3 weeks after discontinuing drugs. Regression models were used to estimate changes in these parameters and associations between these changes and circulating levels of study drugs. Results: Short-term efavirenz and amprenavir administration significantly increased cholesterol, triglycerides and glucose levels. Addition of a second protease inhibitor further increased triglycerides, total- and LDL-cholesterol levels. Higher amprenavir levels predicted larger increases in triglycerides, total and LDL-cholesterol. Two weeks after all study drugs were stopped, total, LDL- and HDL-cholesterol remained elevated above baseline. Conclusions: ARV regimens that include a non-nucleoside reverse transcriptase inhibitor plus single or boosted PIs are becoming more common, but the pharmacodynamic interactions associated with these regimens can result in persistent, undesirable alterations in serum lipid/lipoprotein levels. Additional pharmacodynamic studies are needed to examine the metabolic effects of ritonavir-boosted regimens, with and without efavirenz. PMID:18007962

  12. Tamoxifen affects glucose and lipid metabolism parameters, causes browning of subcutaneous adipose tissue and transient body composition changes in C57BL/6NTac mice

    SciTech Connect

    Hesselbarth, Nico; Pettinelli, Chiara; Gericke, Martin; Berger, Claudia; Kunath, Anne; Stumvoll, Michael; Blüher, Matthias; Klöting, Nora

    2015-08-28

    Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects. - Highlights: • Tamoxifen treatment causes significantly increased HbA{sub 1c}, triglyceride and free fatty acid serum concentrations. • Tamoxifen induces browning of subcutaneous AT and increased UCP-1 expression. • Tamoxifen changes adipocyte size distribution, and transient body composition.

  13. 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

  14. Lipid Metabolism and Toxicity in the Heart

    PubMed Central

    Goldberg, Ira J.; Trent, Chad M.; Schulze, P. Christian

    2012-01-01

    The heart has both the greatest caloric needs and the most robust oxidation of fatty acids. Under pathological conditions such as obesity and type 2 diabetes, cardiac uptake and oxidation are not balanced and hearts accumulate lipid potentially leading to cardiac lipotoxicity. We will first review the pathways utilized by the heart to acquire fatty acids from the circulation and to store triglyceride intracellularly. Then we will describe mouse models in which excess lipid accumulation causes heart dysfunction and experiments performed to alleviate this toxicity. Finally, the known relationships between heart lipid metabolism and dysfunction in humans will be summarized. PMID:22682221

  15. Synthetic redesign of plant lipid metabolism.

    PubMed

    Haslam, Richard P; Sayanova, Olga; Kim, Hae Jin; Cahoon, Edgar B; Napier, Johnathan A

    2016-07-01

    Plant seed lipid metabolism is an area of intensive research, including many examples of transgenic events in which oil composition has been modified. In the selected examples described in this review, progress towards the predictive manipulation of metabolism and the reconstitution of desired traits in a non-native host is considered. The advantages of a particular oilseed crop, Camelina sativa, as a flexible and utilitarian chassis for advanced metabolic engineering and applied synthetic biology are considered, as are the issues that still represent gaps in our ability to predictably alter plant lipid biosynthesis. Opportunities to deliver useful bio-based products via transgenic plants are described, some of which represent the most complex genetic engineering in plants to date. Future prospects are considered, with a focus on the desire to transition to more (computationally) directed manipulations of metabolism. PMID:27483205

  16. 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.

  17. Autophagy and regulation of lipid metabolism.

    PubMed

    Singh, Rajat

    2010-01-01

    Macroautophagy (henceforth referred to as autophagy) is an in-bulk lysosomal degradative pathway that plays a crucial role in the maintenance of cellular homeostasis through the removal of damaged proteins and aged organelles. Following nutrient deprivation, a primary cellular response is the induction of autophagy that breaks down redundant cellular components and provides amino acids and additional precursor molecules for processes critical for cellular survival. In parallel, nutrient depletion leads to the mobilization of cellular lipid stores to supply free fatty acids for energy, thus pointing to regulatory and functional similarities between autophagy and lipid metabolism. The current chapter discusses the novel and mutually exclusive roles of autophagy in the regulation of lipid metabolism in the liver and of fat storage within the adipose tissue. Our studies in cultured hepatocytes and the murine liver have demonstrated that autophagy serves to degrade intracellular lipid stores through a process that we have termed "macrolipophagy" and that ablation of liver-specific autophagy leads to excessive hepatic lipid accumulation and the development of fatty liver. In contrast, preadipocytes in culture that lacked autophagy failed to differentiate into mature adipocytes and exhibited a reduction in fat storage that translated to decreased adipose tissue mass in an in vivo mouse model. These recent findings establish an association between autophagy and regulation of hepatic lipid metabolism and adipose tissue biology, thus providing new mechanistic insights into the regulation of these complex processes. These findings also highlight the possibility of novel therapeutic approaches, such as differential organ-specific regulation of autophagy to solve problems that arise from lipid over accumulation that occur in the metabolic syndrome and with aging. PMID:20865370

  18. Hepatic glucose and lipid metabolism.

    PubMed

    Jones, John G

    2016-06-01

    The liver has a central role in the regulation of systemic glucose and lipid fluxes during feeding and fasting and also relies on these substrates for its own energy needs. These parallel requirements are met by coordinated control of carbohydrate and lipid fluxes into and out of the Krebs cycle, which is highly tuned to nutrient availability and heavily regulated by insulin and glucagon. During progression of type 2 diabetes, hepatic carbohydrate and lipid biosynthesis fluxes become elevated, thus contributing to hyperglycaemia and hypertriacylglycerolaemia. Over this interval there are also significant fluctuations in hepatic energy state. To date, it is not known to what extent abnormal glucose and lipid fluxes are causally linked to altered energy states. Recent evidence that the glucose-lowering effects of metformin appear to be mediated by attenuation of hepatic energy generation places an additional spotlight on the interdependence of hepatic biosynthetic and oxidative fluxes. The transition from fasting to feeding results in a significant re-direction of hepatic glucose and lipid fluxes and may also incur a temporary hepatic energy deficit. At present, it is not known to what extent these variables are additionally modified by type 2 diabetes and/or non-alcoholic fatty liver disease. Thus, there is a compelling need to measure fluxes through oxidative, gluconeogenic and lipogenic pathways and determine their relationship with hepatic energy state in both fasting and fed conditions. New magnetic resonance-based technologies allow these variables to be non-invasively studied in animal models and humans. This review summarises a presentation given at the symposium entitled 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by Hannele Yki-Järvinen, DOI: 10.1007/s00125-016-3944-1 ) and a commentary by the Session Chair, Michael

  19. Role for Torsin in Lipid Metabolism.

    PubMed

    Teleman, Aurelio A

    2016-08-01

    DYT1 dystonia is a neurological disease that causes involuntary twisting movements, often caused by dysfunction of the TorsinA gene. In this issue of Developmental Cell, Grillet et al. (2016) use Drosophila to discover that TorsinA regulates lipid metabolism, opening up future directions of research into the causes of this disease. PMID:27505412

  20. Thermoneutrality modifies the impact of hypoxia on lipid metabolism.

    PubMed

    Jun, Jonathan C; Shin, Mi-Kyung; Yao, Qiaoling; Devera, Ronald; Fonti-Bevans, Shannon; Polotsky, Vsevolod Y

    2013-02-15

    Hypoxia has been shown to rapidly increase triglycerides in mice by decreasing plasma lipoprotein clearance. However, the usual temperature of hypoxic exposure is below thermoneutrality for mice, which may increase thermogenesis and energy requirements, resulting in higher tissue lipid uptake. We hypothesize that decreased lipid clearance and ensuing hyperlipidemia are caused by hypoxic suppression of metabolism at cold temperatures and, therefore, would not occur at thermoneutrality. Twelve-week-old, male C57BL6/J mice were exposed to 6 h of 10% O₂ at the usual temperature (22°C) or thermoneutrality (30°C). Acclimation to 22°C increased lipid uptake in the heart, lungs, and brown adipose tissue, resulting in lower plasma triglyceride and cholesterol levels. At this temperature, hypoxia attenuated lipid uptake in most tissues, thereby raising plasma triglycerides and LDL cholesterol. Thermoneutrality decreased tissue lipid uptake, and hypoxia did not cause a further reduction in lipid uptake in any organs. Consequently, hypoxia at thermoneutrality did not affect plasma triglyceride levels. Unexpectedly, plasma HDL cholesterol increased. The effect of hypoxia on white adipose tissue lipolysis was also modified by temperature. Independent of temperature, hypoxia increased heart rate and glucose and decreased activity, body temperature, and glucose sensitivity. Our study underscores the importance of ambient temperature for hypoxia research, especially in studies of lipid metabolism. PMID:23249698

  1. Thermoneutrality modifies the impact of hypoxia on lipid metabolism

    PubMed Central

    Shin, Mi-Kyung; Yao, Qiaoling; Devera, Ronald; Fonti-Bevans, Shannon; Polotsky, Vsevolod Y.

    2013-01-01

    Hypoxia has been shown to rapidly increase triglycerides in mice by decreasing plasma lipoprotein clearance. However, the usual temperature of hypoxic exposure is below thermoneutrality for mice, which may increase thermogenesis and energy requirements, resulting in higher tissue lipid uptake. We hypothesize that decreased lipid clearance and ensuing hyperlipidemia are caused by hypoxic suppression of metabolism at cold temperatures and, therefore, would not occur at thermoneutrality. Twelve-week-old, male C57BL6/J mice were exposed to 6 h of 10% O2 at the usual temperature (22°C) or thermoneutrality (30°C). Acclimation to 22°C increased lipid uptake in the heart, lungs, and brown adipose tissue, resulting in lower plasma triglyceride and cholesterol levels. At this temperature, hypoxia attenuated lipid uptake in most tissues, thereby raising plasma triglycerides and LDL cholesterol. Thermoneutrality decreased tissue lipid uptake, and hypoxia did not cause a further reduction in lipid uptake in any organs. Consequently, hypoxia at thermoneutrality did not affect plasma triglyceride levels. Unexpectedly, plasma HDL cholesterol increased. The effect of hypoxia on white adipose tissue lipolysis was also modified by temperature. Independent of temperature, hypoxia increased heart rate and glucose and decreased activity, body temperature, and glucose sensitivity. Our study underscores the importance of ambient temperature for hypoxia research, especially in studies of lipid metabolism. PMID:23249698

  2. Capsinoids suppress fat accumulation via lipid metabolism.

    PubMed

    Hong, Qin; Xia, Chen; Xiangying, Hu; Quan, Yuan

    2015-03-01

    Capsaicin, found in red peppers, has been reported to have anti‑obesity, anti‑hypertension, anti‑diabetes and anti‑inflammatory functions. In the present study, we determined the effect of non‑pungent capsinoids on the metabolism of adipocytes. We demonstrated that capsinoids suppressed fat accumulation in vivo and in vitro in mice. Liver, the main tissue of lipid metabolism, was treated by capsinoids, and HMG‑CoA reductase, CPT‑1, FAT/CD36 and GLUT4 were found to be increased significantly, which demonstrated promotion of the lipid metabolism in liver and adipose tissues. In addition, by adding capsinoids, the induced adipocytes also demonstrated significantly increased levels of HMG‑CoA reductase, CPT‑1, FAT/CD36 and GLUT4. Oil red O staining also demonstrated that capsinoids decreased fat accumulation in the adipocytes. In conclusion, these results indicate that capsinoids may be worth investigating as a potential cure for obesity. PMID:25421144

  3. [The effect of prebiotics on lipid metabolism].

    PubMed

    Marti del Moral, A; Moreno-Aliaga, M J; Martínez Hernández, J Alfredo

    2003-01-01

    Prebiotics were defined in 1995 as non-digestible food ingredients beneficially affecting the host by stimulating the growth and/or activity of one or more bacteria in the colon, thus improving health. The proliferation of certain bacteria by fermentation of non-digestible carbohydrates has been shown to be able to inhibit the colonization of the intestine by pathogens, thus giving a protective effect vis-à-vis acute or chronic intestinal disorders. The fermentation of prebiotics may promote some specific physiological functions through the release of metabolites from the bacteria, especially short chain fatty acids (acetate, propionate, butyrate, lactate, etc.) into the lumen of the intestine. Short chain fatty acids may act directly or indirectly (by modifying the pH) on intestinal cells and may be involved in the control of various processes such as the proliferation of mucosa, inflammation, colorectal carcinogenesis, mineral absorption and the elimination of nitrogenated compounds. Curiously, numerous papers have hinted at the possibility that prebiotics may have systemic physiological effects that are related to beneficial effects on lipid metabolism and various cardiovascular risk factors. PMID:12884473

  4. Dietary energy sources affect the partition of body lipids and the hierarchy of energy metabolic pathways in growing pigs differing in feed efficiency.

    PubMed

    Gondret, F; Louveau, I; Mourot, J; Duclos, M J; Lagarrigue, S; Gilbert, H; van Milgen, J

    2014-11-01

    The use and partition of feed energy are key elements in productive efficiency of pigs. This study aimed to determine whether dietary energy sources affect the partition of body lipids and tissue biochemical pathways of energy use between pigs differing in feed efficiency. Forty-eight barrows (pure Large White) from two divergent lines selected for residual feed intake (RFI), a measure of feed efficiency, were compared. From 74 d to 132 ± 0.5 d of age, pigs (n = 12 by line and by diet) were offered diets with equal protein and ME contents. A low fat, low fiber diet (LF) based on cereals and a high fat, high fiber diet (HF) where vegetal oils and wheat straw were used to partially substitute cereals, were compared. Irrespective of diet, gain to feed was 10% better (P < 0.001), and carcass yield was greater (+2.3%; P < 0.001) in the low RFI compared with the high RFI line; the most-efficient line was also leaner (+3.2% for loin proportion in the carcass, P < 0.001). In both lines, ADFI and ADG were lower when pigs were fed the HF diet (-12.3% and -15%, respectively, relatively to LF diet; P < 0.001). Feeding the HF diet reduced the perirenal fat weight and backfat proportion in the carcass to the same extent in both lines (-27% on average; P < 0.05). Lipid contents in backfat and LM also declined (-5% and -19%, respectively; P < 0.05) in pigs offered the HF diet. The proportion of saturated fatty acids (FA) was lower, but the percentage of PUFA, especially the EFA C18:2 and C18:3, was greater (P < 0.001) in backfat of HF-fed pigs. In both lines, these changes were associated with a marked decrease (P < 0.001) in the activities of two lipogenic enzymes, the fatty acid synthase (FASN) and the malic enzyme, in backfat. For the high RFI line, the hepatic lipid content was greater (P < 0.05) in pigs fed the HF diet than in pigs fed the LF diet, despite a reduced FASN activity (-32%; P < 0.001). In both lines, the HF diet also led to lower glycogen content (-70%) and

  5. Computationally Modeling Lipid Metabolism and Aging: A Mini-review.

    PubMed

    Mc Auley, Mark T; Mooney, Kathleen M

    2015-01-01

    One of the greatest challenges in biology is to improve the understanding of the mechanisms which underpin aging and how these affect health. The need to better understand aging is amplified by demographic changes, which have caused a gradual increase in the global population of older people. Aging western populations have resulted in a rise in the prevalence of age-related pathologies. Of these diseases, cardiovascular disease is the most common underlying condition in older people. The dysregulation of lipid metabolism due to aging impinges significantly on cardiovascular health. However, the multifaceted nature of lipid metabolism and the complexities of its interaction with aging make it challenging to understand by conventional means. To address this challenge computational modeling, a key component of the systems biology paradigm is being used to study the dynamics of lipid metabolism. This mini-review briefly outlines the key regulators of lipid metabolism, their dysregulation, and how computational modeling is being used to gain an increased insight into this system. PMID:25750699

  6. Computationally Modeling Lipid Metabolism and Aging: A Mini-review

    PubMed Central

    Mc Auley, Mark T.; Mooney, Kathleen M.

    2014-01-01

    One of the greatest challenges in biology is to improve the understanding of the mechanisms which underpin aging and how these affect health. The need to better understand aging is amplified by demographic changes, which have caused a gradual increase in the global population of older people. Aging western populations have resulted in a rise in the prevalence of age-related pathologies. Of these diseases, cardiovascular disease is the most common underlying condition in older people. The dysregulation of lipid metabolism due to aging impinges significantly on cardiovascular health. However, the multifaceted nature of lipid metabolism and the complexities of its interaction with aging make it challenging to understand by conventional means. To address this challenge computational modeling, a key component of the systems biology paradigm is being used to study the dynamics of lipid metabolism. This mini-review briefly outlines the key regulators of lipid metabolism, their dysregulation, and how computational modeling is being used to gain an increased insight into this system. PMID:25750699

  7. 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.

  8. TNFα Altered Inflammatory Responses, Impaired Health and Productivity, but Did Not Affect Glucose or Lipid Metabolism in Early-Lactation Dairy Cows

    PubMed Central

    Mamedova, Laman K.; Sordillo, Lorraine M.; Bradford, Barry J.

    2013-01-01

    Inflammation may be a major contributing factor to peripartum metabolic disorders in dairy cattle. We tested whether administering an inflammatory cytokine, recombinant bovine tumor necrosis factor-α (rbTNFα), affects milk production, metabolism, and health during this period. Thirty-three Holstein cows (9 primiparous and 24 multiparous) were randomly assigned to 1 of 3 treatments at parturition. Treatments were 0 (Control), 1.5, or 3.0 µg/kg body weight rbTNFα, which were administered once daily by subcutaneous injection for the first 7 days of lactation. Statistical contrasts were used to evaluate the treatment and dose effects of rbTNFα administration. Plasma TNFα concentrations at 16 h post-administration tended to be increased (P<0.10) by rbTNFα administration, but no dose effect (P>0.10) was detected; rbTNFα treatments increased (P<0.01) concentrations of plasma haptoglobin. Most plasma eicosanoids were not affected (P>0.10) by rbTNFα administration, but 6 out of 16 measured eicosanoids changed (P<0.05) over the first week of lactation, reflecting elevated inflammatory mediators in the days immediately following parturition. Dry matter and water intake, milk yield, and milk fat and protein yields were all decreased (P<0.05) by rbTNFα treatments by 15 to 18%. Concentrations of plasma glucose, insulin, β-hydroxybutyrate, non-esterified fatty acids, triglyceride, 3-methylhistidine, and liver triglyceride were unaffected (P>0.10) by rbTNFα treatment. Glucose turnover rate was unaffected (P = 0.18) by rbTNFα administration. The higher dose of rbTNFα tended to increase the risk of cows developing one or more health disorders (P = 0.08). Taken together, these results indicate that administration of rbTNFα daily for the first 7 days of lactation altered inflammatory responses, impaired milk production and health, but did not significantly affect liver triglyceride accumulation or nutrient metabolism in dairy cows. PMID:24260367

  9. Changes in lipid metabolism and β-adrenergic response of adipose tissues of periparturient dairy cows affected by an energy-dense diet and nicotinic acid supplementation.

    PubMed

    Kenéz, Á; Tienken, R; Locher, L; Meyer, U; Rizk, A; Rehage, J; Dänicke, S; Huber, K

    2015-08-01

    Dairy cattle will mobilize large amounts of body fat during early lactation as an effect of decreased lipogenesis and increased lipolysis. Regulation of lipid metabolism involves fatty acid synthesis from acetate and β-adrenergic-stimulated phosphorylation of hormone-sensitive lipase (HSL) and perilipin in adipocytes. Although basic mechanisms of mobilizing fat storage in transition cows are understood, we lack a sufficiently detailed understanding to declare the exact regulatory network of these in a broad range of dairy cattle. The objective of the present study was to quantify 1) protein abundance of fatty acid synthase (FAS), 2) extent of phosphorylation of HSL and perilipin in vivo, and 3) β-adrenergic stimulated lipolytic response of adipose tissues in vitro at different stages of the periparturient period. We fed 20 German Holstein cows an energy-dense or an energetically adequate diet prepartum and 0 or 24 g/d nicotinic acid (NA) supplementation. Biopsy samples of subcutaneous and retroperitoneal adipose tissue were obtained at d 42 prepartum (d -42) and at d 1, 21, and 100 postpartum (d +1, d +21, d +100, respectively). To assess β-adrenergic response, tissue samples were incubated with 1 μ isoproterenol for 90 min at 37°C. The NEFA and glycerol release, as well as HSL and perilipin phosphorylation, was measured as indicators of in vitro stimulated lipolysis. In addition, protein expression of FAS and extent of HSL and perilipin phosphorylation were measured in fresh, nonincubated samples. There was no effect of dietary energy density or NA on the observed variables. The extent of HSL and perilipin phosphorylation under isoproterenol stimulation was strongly correlated with the release of NEFA and glycerol, consistent with the functional link between β-adrenergic-stimulated protein phosphorylation and lipolysis. In the nonincubated samples, FAS protein expression was decreased at d +1 and d +21, whereas HSL and perilipin phosphorylation increased

  10. Gene Expression in Plant Lipid Metabolism in Arabidopsis Seedlings

    PubMed Central

    Hsiao, An-Shan; Haslam, Richard P.; Michaelson, Louise V.; Liao, Pan; Napier, Johnathan A.; Chye, Mee-Len

    2014-01-01

    Events in plant lipid metabolism are important during seedling establishment. As it has not been experimentally verified whether lipid metabolism in 2- and 5-day-old Arabidopsis thaliana seedlings is diurnally-controlled, quantitative real-time PCR analysis was used to investigate the expression of target genes in acyl-lipid transfer, β-oxidation and triacylglycerol (TAG) synthesis and hydrolysis in wild-type Arabidopsis WS and Col-0. In both WS and Col-0, ACYL-COA-BINDING PROTEIN3 (ACBP3), DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1) and DGAT3 showed diurnal control in 2- and 5-day-old seedlings. Also, COMATOSE (CTS) was diurnally regulated in 2-day-old seedlings and LONG-CHAIN ACYL-COA SYNTHETASE6 (LACS6) in 5-day-old seedlings in both WS and Col-0. Subsequently, the effect of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) from the core clock system was examined using the cca1lhy mutant and CCA1-overexpressing (CCA1-OX) lines versus wild-type WS and Col-0, respectively. Results revealed differential gene expression in lipid metabolism between 2- and 5-day-old mutant and wild-type WS seedlings, as well as between CCA1-OX and wild-type Col-0. Of the ACBPs, ACBP3 displayed the most significant changes between cca1lhy and WS and between CCA1-OX and Col-0, consistent with previous reports that ACBP3 is greatly affected by light/dark cycling. Evidence of oil body retention in 4- and 5-day-old seedlings of the cca1lhy mutant in comparison to WS indicated the effect of cca1lhy on storage lipid reserve mobilization. Lipid profiling revealed differences in primary lipid metabolism, namely in TAG, fatty acid methyl ester and acyl-CoA contents amongst cca1lhy, CCA1-OX, and wild-type seedlings. Taken together, this study demonstrates that lipid metabolism is subject to diurnal regulation in the early stages of seedling development in Arabidopsis. PMID:25264899

  11. Transfection of L6 myoblasts with adipocyte fatty acid-binding protein cDNA does not affect fatty acid uptake but disturbs lipid metabolism and fusion.

    PubMed Central

    Prinsen, C F; Veerkamp, J H

    1998-01-01

    We studied the involvement of fatty acid-binding protein (FABP) in growth, differentiation and fatty acid metabolism of muscle cells by lipofection of rat L6 myoblasts with rat heart (H) FABP cDNA or with rat adipocyte (A) FABP cDNA in a eukaryotic expression vector which contained a puromycin acetyltransferase cassette. Stable transfectants showed integration into the genome for all constructs and type-specific overexpression at the mRNA and protein level for the clones with H-FABP and A-FABP cDNA constructs. The rate of proliferation of myoblasts transfected with rat A-FABP cDNA was 2-fold higher compared with all other transfected cells. In addition, these myoblasts showed disturbed fusion and differentiation, as assessed by morphological examination and creatine kinase activity. Uptake rates of palmitate were equal for all clone types, in spite of different FABP content and composition. Palmitate oxidation over a 3 h period was similar in all clones from growth medium. After being cultured in differentiation medium, mock- and H-FABP-cDNA-transfected cells showed a lower fatty acid-oxidation rate, in contrast with A-FABP-cDNA-transfected clones. The ratio of [14C]palmitic acid incorporation into phosphatidylcholine and phosphatidylethanolamine of A-FABP-cDNA-transfected clones changed in the opposite direction in differentiation medium from that of mock- and H-FABP-cDNA-transfected clones. In conclusion, transfection of L6 myoblasts with A-FABP cDNA does not affect H-FABP content and fatty acid uptake, but changes fatty acid metabolism. The latter changes may be related to the observed fusion defect. PMID:9425108

  12. 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. PMID:26892119

  13. 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. PMID:26892120

  14. 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

  15. 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

  16. 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

    2015-01-01

    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

  17. 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

  18. 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. PMID:25967672

  19. Zebrafish Lipid Metabolism: From Mediating Early Patterning to the Metabolism of Dietary Fat and Cholesterol

    PubMed Central

    Anderson, Jennifer L.; Carten, Juliana D.; Farber, Steven A.

    2013-01-01

    Lipids serve essential functions in cells as signaling molecules, membrane components, and sources of energy. Defects in lipid metabolism are implicated in a number of pandemic human diseases, including diabetes, obesity, and hypercholesterolemia. approaches for disease prevention and treatment. Numerous studies have shown that the zebrafish is an excellent model for vertebrate lipid metabolism. In this chapter, we review studies that employ zebrafish to better understand lipid signaling and metabolism. PMID:21550441

  20. A conjugated fatty acid present at high levels in bitter melon seed favorably affects lipid metabolism in hepatocytes by increasing NAD(+)/NADH ratio and activating PPARα, AMPK and SIRT1 signaling pathway.

    PubMed

    Chen, Gou-Chun; Su, Hui-Min; Lin, Yu-Shun; Tsou, Po-Yen; Chyuan, Jong-Ho; Chao, Pei-Min

    2016-07-01

    α-Eleostearic acid (α-ESA), or the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid, is a special fatty acid present at high levels in bitter melon seed oil. The aim of this study was to examine the effect of α-ESA on hepatic lipid metabolism. Using H4IIEC3 hepatoma cell line, we showed that α-ESA significantly lowered intracellular triglyceride accumulation compared to α-linolenic acid (LN), used as a fatty acid control, in a dose- and time-dependent manner. The effects of α-ESA on enzyme activities and mRNA profiles in H4IIEC3 cells suggested that enhanced fatty acid oxidation and lowered lipogenesis were involved in α-ESA-mediated triglyceride lowering effects. In addition, α-ESA triggered AMP-activated protein kinase (AMPK) activation without altering sirtuin 1 (SIRT1) protein levels. When cells were treated with vehicle control (VC), LN alone (LN; 100μmol/L) or in combination with α-ESA (LN+α-ESA; 75+25μmol/L) for 24h, acetylation of forkhead box protein O1 was decreased, while the NAD(+)/NADH ratio, mRNA levels of NAMPT and PTGR1 and enzyme activity of nicotinamide phosphoribosyltransferase were increased by LN+α-ESA treatment compared to treatment with LN alone, suggesting that α-ESA activates SIRT1 by increasing NAD(+) synthesis and NAD(P)H consumption. The antisteatosis effect of α-ESA was confirmed in mice treated with a high-sucrose diet supplemented with 1% α-ESA for 5weeks. We conclude that α-ESA favorably affects hepatic lipid metabolism by increasing cellular NAD(+)/NADH ratio and activating PPARα, AMPK and SIRT1 signaling pathways. PMID:27260465

  1. Role of a liver fatty acid-binding protein gene in lipid metabolism in chicken hepatocytes.

    PubMed

    Gao, G L; Na, W; Wang, Y X; Zhang, H F; Li, H; Wang, Q G

    2015-01-01

    This study investigated the role of the chicken liver fatty acid-binding protein (L-FABP) gene in lipid metabolism in hepatocytes, and the regulatory relationships between L-FABP and genes related to lipid metabolism. The short hairpin RNA (shRNA) interference vector with L-FABP and an eukaryotic expression vector were used. Chicken hepatocytes were subjected to shRNA-mediated knockdown or L-FABP cDNA overexpression. Expression levels of lipid metabolism-related genes and biochemical parameters were detected 24, 36, 48, 60, and 72 h after transfection with the interference or overexpression plasmids for L-FABP, PPARα and L-BABP expression levels, and the total amount of cholesterol, were significantly affected by L-FABP expression. L-FABP may affect lipid metabolism by regulating PPARα and L-BABP in chicken hepatocytes. PMID:25966259

  2. Lipid signaling in adipose tissue: Connecting inflammation & metabolism.

    PubMed

    Masoodi, Mojgan; Kuda, Ondrej; Rossmeisl, Martin; Flachs, Pavel; Kopecky, Jan

    2015-04-01

    Obesity-associated low-grade inflammation of white adipose tissue (WAT) contributes to development of insulin resistance and other disorders. Accumulation of immune cells, especially macrophages, and macrophage polarization from M2 to M1 state, affect intrinsic WAT signaling, namely anti-inflammatory and proinflammatory cytokines, fatty acids (FA), and lipid mediators derived from both n-6 and n-3 long-chain PUFA such as (i) arachidonic acid (AA)-derived eicosanoids and endocannabinoids, and (ii) specialized pro-resolving lipid mediators including resolvins derived from both eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), lipoxins (AA metabolites), protectins and maresins (DHA metabolites). In this respect, potential differences in modulating adipocyte metabolism by various lipid mediators formed by inflammatory M1 macrophages typical of obese state, and non-inflammatory M2 macrophages typical of lean state remain to be established. Studies in mice suggest that (i) transient accumulation of M2 macrophages could be essential for the control of tissue FA levels during activation of lipolysis, (ii) currently unidentified M2 macrophage-borne signaling molecule(s) could inhibit lipolysis and re-esterification of lipolyzed FA back to triacylglycerols (TAG/FA cycle), and (iii) the egress of M2 macrophages from rebuilt WAT and removal of the negative feedback regulation could allow for a full unmasking of metabolic activities of adipocytes. Thus, M2 macrophages could support remodeling of WAT to a tissue containing metabolically flexible adipocytes endowed with a high capacity of both TAG/FA cycling and oxidative phosphorylation. This situation could be exemplified by a combined intervention using mild calorie restriction and dietary supplementation with EPA/DHA, which enhances the formation of "healthy" adipocytes. This article is part of a Special Issue entitled Oxygenated metabolism of PUFA: analysis and biological relevance." PMID:25311170

  3. New insights on glucosylated lipids: metabolism and functions.

    PubMed

    Ishibashi, Yohei; Kohyama-Koganeya, Ayako; Hirabayashi, Yoshio

    2013-09-01

    Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids. PMID:23770033

  4. 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. PMID:25660108

  5. [Review: plant polyphenols modulate lipid metabolism and related molecular mechanism].

    PubMed

    Dai, Yan-li; Zou, Yu-xiao; Liu, Fan; Li, Hong-zhi

    2015-11-01

    Lipid metabolism disorder is an important risk factor to obesity, hyperlipidemia and type 2 diabetes as well as other chronic metabolic disease. It is also a key target in preventing metabolic syndrome, chronic disease prevention. Plant polyphenol plays an important role in maintaining or improving lipid profile in a variety of ways. including regulating cholesterol absorption, inhibiting synthesis and secretion of triglyceride, and lowering plasma low density lipoprotein oxidation, etc. The purpose of this article is to review the lipid regulation effects of plant polyphenols and its related mechanisms. PMID:27071245

  6. 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. PMID:25583222

  7. Gemfibrozil disrupts the metabolism of circulating lipids in bobwhite quails.

    PubMed

    Bussière-Côté, Sophie; Omlin, Teye; de Càssia Pinheiro, Eliana; Weber, Jean-Michel

    2016-01-01

    The circulating lipids of birds play essential roles for egg production and as an energy source for flight and thermogenesis. How lipid-lowering pharmaceuticals geared to prevent heart disease in humans and that are routinely released in the environment affect their metabolism is unknown. This study assesses the impact of the popular drug gemfibrozil (GEM) on the plasma phospholipids (PL), neutral lipids (NL), and nonesterified fatty acids (NEFA) of bobwhite quails (Colinus virginianus). Results show that bird lipoproteins are rapidly altered by GEM, even at environmentally-relevant doses. After 4 days of exposure, pharmacological amounts cause an 83% increase in circulating PL levels, a major decrease in average lipoprotein size measured as a 56% drop in the NL/PL ratio, and important changes in the fatty acid composition of PL and NEFA (increases in fatty acid unsaturation). The levels of PL carrying all individual fatty acids except arachidonate are strongly stimulated. The large decrease in bird lipoprotein size may reflect the effects seen in humans: lowering of LDL that can cause atherosclerosis and stimulation of HDL that promote cholesterol disposal. Lower (environmental) doses of GEM cause a reduction of %palmitate in all the plasma lipid fractions of quails, but particularly in the core triacylglycerol of lipoproteins (NL). No changes in mRNA levels of bird peroxisome proliferator-activated receptor (PPAR) could be demonstrated. The disrupting effects of GEM on circulating lipids reported here suggest that the pervasive presence of this drug in the environment could jeopardize reproduction and migratory behaviours in wild birds. PMID:26432161

  8. Mechanisms by which botanical lipids affect inflammatory disorders.

    PubMed

    Chilton, Floyd H; Rudel, Lawrence L; Parks, John S; Arm, Jonathan P; Seeds, Michael C

    2008-02-01

    Changes in diet over the past century have markedly altered the consumption of fatty acids. The dramatic increase in the ingestion of saturated and n-6 fatty acids and concomitant decrease in n-3 fatty acids are thought to be a major driver of the increase in the incidence of inflammatory diseases such as asthma, allergy, and atherosclerosis. The central objective of the Center for Botanical Lipids at Wake Forest University School of Medicine and the Brigham and Women's Hospital is to delineate the mechanisms by which fatty acid-based dietary supplements inhibit inflammation leading to chronic human diseases such as cardiovascular disease and asthma. The key question that this center addresses is whether botanical n-6 and n-3 fatty acids directly block recognized biochemical pathways or the expression of critical genes that lead to asthma and atherosclerosis. Dietary supplementation with flaxseed oil, borage oil, and echium oil affects the biochemistry of fatty acid metabolism and thus the balance of proinflammatory mediators and atherogenic lipids. Supplementation studies have begun to identify key molecular and genetic mechanisms that regulate the production of lipid mediators involved in inflammatory and hyperlipidemic diseases. Echium oil and other oils containing stearidonic acid as well as botanical oil combinations (such as echium and borage oils) hold great promise for modulating inflammatory diseases. PMID:18258646

  9. Lipid metabolizing enzyme activities modulated by phospholipid substrate lateral distribution.

    PubMed

    Salinas, Dino G; Reyes, Juan G; De la Fuente, Milton

    2011-09-01

    Biological membranes contain many domains enriched in phospholipid lipids and there is not yet clear explanation about how these domains can control the activity of phospholipid metabolizing enzymes. Here we used the surface dilution kinetic theory to derive general equations describing how complex substrate distributions affect the activity of enzymes following either the phospholipid binding kinetic model (which assumes that the enzyme molecules directly bind the phospholipid substrate molecules), or the surface-binding kinetic model (which assumes that the enzyme molecules bind to the membrane before binding the phospholipid substrate). Our results strongly suggest that, if the enzyme follows the phospholipid binding kinetic model, any substrate redistribution would increase the enzyme activity over than observed for a homogeneous distribution of substrate. Besides, enzymes following the surface-binding model would be independent of the substrate distribution. Given that the distribution of substrate in a population of micelles (each of them a lipid domain) should follow a Poisson law, we demonstrate that the general equations give an excellent fit to experimental data of lipases acting on micelles, providing reasonable values for kinetic parameters--without invoking special effects such as cooperative phenomena. Our theory will allow a better understanding of the cellular-metabolism control in membranes, as well as a more simple analysis of the mechanisms of membrane acting enzymes. PMID:21108012

  10. 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. PMID:23685199

  11. Targeting SREBP-1-driven lipid metabolism to treat cancer.

    PubMed

    Guo, Deliang; Bell, Erica Hlavin; Mischel, Paul; Chakravarti, Arnab

    2014-01-01

    Metabolic reprogramming is a hallmark of cancer. Oncogenic growth signaling regulates glucose, glutamine and lipid metabolism to meet the bioenergetics and biosynthetic demands of rapidly proliferating tumor cells. Emerging evidence indicates that sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that controls lipid metabolism, is a critical link between oncogenic signaling and tumor metabolism. We recently demonstrated that SREBP-1 is required for the survival of mutant EGFR-containing glioblastoma, and that this pro-survival metabolic pathway is mediated, in part, by SREBP-1-dependent upregulation of the fatty acid synthesis and low density lipoprotein (LDL) receptor (LDLR). These results have identified EGFR/PI3K/Akt/SREBP-1 signaling pathway that promotes growth and survival in glioblastoma, and potentially other cancer types. Here, we summarize recent insights in the understanding of cancer lipid metabolism, and discuss the evidence linking SREBP-1 with PI3K/Akt signaling-controlled glycolysis and with Myc-regulated glutaminolysis to lipid metabolism. We also discuss the development of potential drugs targeting the SREBP-1- driven lipid metabolism as anti-cancer agents. PMID:23859617

  12. 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.

  13. Obesity-Related Chronic Kidney Disease—The Role of Lipid Metabolism

    PubMed Central

    Mount, Peter; Davies, Matthew; Choy, Suet-Wan; Cook, Natasha; Power, David

    2015-01-01

    Obesity is an independent risk factor for chronic kidney disease (CKD). The mechanisms linking obesity and CKD include systemic changes such as high blood pressure and hyperglycemia, and intrarenal effects relating to lipid accumulation. Normal lipid metabolism is integral to renal physiology and disturbances of renal lipid and energy metabolism are increasingly being linked with kidney disease. AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) are important regulators of fatty acid oxidation, which is frequently abnormal in the kidney with CKD. A high fat diet reduces renal AMPK activity, thereby contributing to reduced fatty acid oxidation and energy imbalance, and treatments to activate AMPK are beneficial in animal models of obesity-related CKD. Studies have found that the specific cell types affected by excessive lipid accumulation are proximal tubular cells, podocytes, and mesangial cells. Targeting disturbances of renal energy metabolism is a promising approach to addressing the current epidemic of obesity-related kidney disease. PMID:26690487

  14. 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

  15. 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. PMID:12738609

  16. Sortilin: A novel regulator in lipid metabolism and atherogenesis.

    PubMed

    Zhong, Li-Yuan; Cayabyab, Francisco S; Tang, Chao-Ke; Zheng, Xi-Long; Peng, Tian-Hong; Lv, Yun-Cheng

    2016-09-01

    Several lines of evidence have shown that SORT1 gene within 1p13.3 locus is an important modulator of the low-density lipoprotein-cholesterol (LDL-C) level and atherosclerosis risk. Here, we summarize the effects of SORT1, which codes for sortilin, on lipid metabolism and development of atherosclerosis and explore the mechanisms underlying sortilin effects on lipid metabolism especially in hepatocytes and macrophages. Recent epidemiological evidence demonstrated that sortilin has been implicated as the causative factor and regulates lipid metabolism in vivo. Hepatic sortilin overexpression leads to both increased and decreased LDL-C levels by several different mechanisms, suggesting the complex roles of sortilin in hepatic lipid metabolism. Macrophage sortilin causes internalization of LDL and probably a reduction in cholesterol efflux, resulting in the intracellular accumulation of excessive lipids. In addition, sortilin deficiency in an atherosclerotic mouse model results in decreased aortic atherosclerotic lesion. Sortilin involves in lipid metabolism, promotes the development of atherosclerosis, and possibly becomes a potential therapeutic target for atherosclerosis treatment. PMID:27312323

  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. Torsins Are Essential Regulators of Cellular Lipid Metabolism.

    PubMed

    Grillet, Micheline; Dominguez Gonzalez, Beatriz; Sicart, Adria; Pöttler, Maria; Cascalho, Ana; Billion, Karolien; Hernandez Diaz, Sergio; Swerts, Jef; Naismith, Teresa V; Gounko, Natalia V; Verstreken, Patrik; Hanson, Phyllis I; Goodchild, Rose E

    2016-08-01

    Torsins are developmentally essential AAA+ proteins, and mutation of human torsinA causes the neurological disease DYT1 dystonia. They localize in the ER membranes, but their cellular function remains unclear. We now show that dTorsin is required in Drosophila adipose tissue, where it suppresses triglyceride levels, promotes cell growth, and elevates membrane lipid content. We also see that human torsinA at the inner nuclear membrane is associated with membrane expansion and elevated cellular lipid content. Furthermore, the key lipid metabolizing enzyme, lipin, is mislocalized in dTorsin-KO cells, and dTorsin increases levels of the lipin substrate, phosphatidate, and reduces the product, diacylglycerol. Finally, genetic suppression of dLipin rescues dTorsin-KO defects, including adipose cell size, animal growth, and survival. These findings identify that torsins are essential regulators of cellular lipid metabolism and implicate disturbed lipid biology in childhood-onset DYT1 dystonia. PMID:27453503

  19. Imaging vertebrate digestive function and lipid metabolism in vivo

    PubMed Central

    Otis, Jessica P.; Farber, Steven A.

    2012-01-01

    Challenges in imaging lipid-processing events in live, intact vertebrate models have historically led to reliance on cultured cell studies, thus hampering our understanding of lipid metabolism and gastrointestinal physiology. Fluorescently-labeled molecules, such as BODIPY-labeled lipids, can reveal lipid-processing events in live zebrafish (Danio rerio) and has expanded our understanding of digestive physiology. This review will cover recent advances from the past two to three years in the use of fluorescence-based imaging techniques in live zebrafish to characterize gastrointestinal physiology in health and disease and to conduct small molecule screens to discover therapeutic compounds. PMID:24187571

  20. [Effects of essential oil on lipid peroxidation and lipid metabolism in patients with chronic bronchitis].

    PubMed

    Siurin, S A

    1997-01-01

    Natural concentrations of some essential oils were examined for effects on the system lipid peroxidation-antioxidant defense and lipid metabolism in 150 patients with chronic bronchitis. Lowering of plasm levels of dienic conjugates and ketons, activation of catalase in red cells characteristic of antioxidant effect were observed in exposure to essential oils of rosemary, basil, fir, eucalyptus. Lavender essential oil promotes normalization of the level of total lipids, ratio of total cholesterol to its alpha-fraction. PMID:9490339

  1. Sirtuin 1 Deacetylase: A Key Regulator of Hepatic Lipid Metabolism

    PubMed Central

    Kemper, Jongsook Kim; Choi, SungE; Kim, Dong Hyun

    2016-01-01

    Summary 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. PMID:23374725

  2. 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. PMID:26167919

  3. Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice.

    PubMed

    Iwata, Junichi; Suzuki, Akiko; Pelikan, Richard C; Ho, Thach-Vu; Sanchez-Lara, Pedro A; Chai, Yang

    2014-01-01

    Mutations in transforming growth factor beta (TGFβ) receptor type II (TGFBR2) cause Loeys-Dietz syndrome, characterized by craniofacial and cardiovascular abnormalities. Mice with a deletion of Tgfbr2 in cranial neural crest cells (Tgfbr2(fl/fl);Wnt1-Cre mice) develop cleft palate as the result of abnormal TGFβ signaling activation. However, little is known about metabolic processes downstream of TGFβ signaling during palatogenesis. Here, we show that Tgfbr2 mutant palatal mesenchymal cells spontaneously accumulate lipid droplets, resulting from reduced lipolysis activity. Tgfbr2 mutant palatal mesenchymal cells failed to respond to the cell proliferation stimulator sonic hedgehog, derived from the palatal epithelium. Treatment with p38 mitogen-activated protein kinase (MAPK) inhibitor or telmisartan, a modulator of p38 MAPK activation and lipid metabolism, blocked abnormal TGFβ-mediated p38 MAPK activation, restoring lipid metabolism and cell proliferation activity both in vitro and in vivo. Our results highlight the influence of alternative TGFβ signaling on lipid metabolic activities, as well as how lipid metabolic defects can affect cell proliferation and adversely impact palatogenesis. This discovery has broader implications for the understanding of metabolic defects and potential prevention of congenital birth defects. PMID:23975680

  4. 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

  5. Methionine restriction on lipid metabolism and its possible mechanisms.

    PubMed

    Zhou, Xihong; He, Liuqin; Wan, Dan; Yang, Huansheng; Yao, Kang; Wu, Guoyao; Wu, Xin; Yin, Yulong

    2016-07-01

    Methionine restriction (MR) exerts many beneficial effects, such as increasing longevity, decreasing oxidative damage and alleviating inflammatory responses. Much attention has been recently focused on the effects of MR on metabolic health, especially lipid metabolism, since the increasing incidence of obesity, insulin resistance and type 2 diabetes causes a worldwide health problem. In general, MR is considered to increase de novo lipogenesis, lipolysis and fatty acid oxidation, with a result of reduced fat accumulation. However, different responses in lipid metabolism between adipose tissue and liver are declared. Therefore, in this review, we will focus on the changes of lipid metabolism responses to dietary MR. Moreover, the comparison of alterations of fat metabolism responses to dietary MR between adipose tissue and liver, and the comparison of changes between rodents and pigs is made to illustrate the tissue- and species-specific responses. In addition, the possible mechanisms that might be engaged in the regulation of MR diet on lipid metabolism are also discussed. PMID:27156065

  6. 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.

  7. Novel insights on interactions between folate and lipid metabolism.

    PubMed

    da Silva, Robin P; Kelly, Karen B; Al Rajabi, Ala; Jacobs, René L

    2014-01-01

    Folate is an essential B vitamin required for the maintenance of AdoMet-dependent methylation. The liver is responsible for many methylation reactions that are used for post-translational modification of proteins, methylation of DNA, and the synthesis of hormones, creatine, carnitine, and phosphatidylcholine. Conditions where methylation capacity is compromised, including folate deficiency, are associated with impaired phosphatidylcholine synthesis resulting in non-alcoholic fatty liver disease and steatohepatitis. In addition, folate intake and folate status have been associated with changes in the expression of genes involved in lipid metabolism, obesity, and metabolic syndrome. In this review, we provide insight on the relationship between folate and lipid metabolism, and an outlook for the future of lipid-related folate research. PMID:24353111

  8. Sphingolipid metabolism and interorganellar transport: localization of sphingolipid enzymes and lipid transfer proteins.

    PubMed

    Yamaji, Toshiyuki; Hanada, Kentaro

    2015-02-01

    In recent decades, many sphingolipid enzymes, sphingolipid-metabolism regulators and sphingolipid transfer proteins have been isolated and characterized. This review will provide an overview of the intracellular localization and topology of sphingolipid enzymes in mammalian cells to highlight the locations where respective sphingolipid species are produced. Interestingly, three sphingolipids that reside or are synthesized in cytosolic leaflets of membranes (ceramide, glucosylceramide and ceramide-1-phosphate) all have cytosolic lipid transfer proteins (LTPs). These LTPs consist of ceramide transfer protein (CERT), four-phosphate adaptor protein 2 (FAPP2) and ceramide-1-phosphate transfer protein (CPTP), respectively. These LTPs execute functions that affect both the location and metabolism of the lipids they bind. Molecular details describing the mechanisms of regulation of LTPs continue to emerge and reveal a number of critical processes, including competing phosphorylation and dephosphorylation reactions and binding interactions with regulatory proteins and lipids that influence the transport, organelle distribution and metabolism of sphingolipids. PMID:25382749

  9. Effects of cadmium on lipid metabolism in female estuarine crab, Chiromantes dehaani.

    PubMed

    Liu, Zhiquan; Lv, Weiwei; Huang, Youhui; Fan, Bin; Li, Yiming; Zhao, Yunlong

    2016-10-01

    Due to the nature of their habitat, which contains a high level of pollutants, estuarine crabs are at great risk of exposure to contaminants such as cadmium. Thus, in this study, the effects of cadmium on lipid metabolism were investigated in estuarine crab Chiromantes dehaani. Adult female estuarine crabs were randomly exposed to 0.05, 0.1, 0.5, and 1mg/L of CdCl2 for 7, 14 and 21days, after which the lipid contents of the hepatopancreas and ovary were measured. Also, the substance contents and the activities of the enzyme in lipid digestion, lipid synthesis and lipid transport metabolism were analyzed. The results showed that the lipid contents in the hepatopancreas and ovary of the exposed crabs decreased after prolonged exposure to cadmium compared to the control. The lipase activity decreased while the activities of fatty acid synthase and acetyl coenzyme A in the hepatopancreas increased on day 7 but decreased on days 14 and 21. Moreover, the change in non-esterified fatty acid level was similar to fatty acid synthase. The level of low-density lipoprotein increased in the exposed crabs compared to the control group while the level of high-density lipoprotein and the activity of lipoprotein lipase decreased at a higher concentration of cadmium and longer exposure time. These observations suggest that cadmium decreases the lipid content by weakening the ability of digestion, transportation and synthase of lipid, thus affecting hepatopancreas and ovary indices. PMID:27276547

  10. Altered lipid metabolism in Drosophila model of Huntington's disease.

    PubMed

    Aditi, Kumari; Shakarad, Mallikarjun N; Agrawal, Namita

    2016-01-01

    Huntington's disease (HD) is late-onset, progressive neurodegenerative disorder caused by expansion of polyglutamine (polyQ) repeat within Huntingtin (Htt) protein. In HD patients, energy-related manifestations such as modulation of weight during entire course of disease with energy deficit at terminal stage have been reported, however, underlying reason remains elusive till date. Lipids, carbohydrate and protein constitute a predominant fraction of body's energy reservoir and perturbation in their homeostasis may influence weight. To discern role of these energy molecules in weight alteration, we quantified them in an in vivo transgenic Drosophila model of HD. We document that diseased flies exhibit change in weight due to an altered lipid metabolism, as evident from considerably high lipid levels at the time of disease onset followed by a pathologic decline at end-stage. An alteration in intracellular lipid droplet size suggested altered cellular lipid turnover. Furthermore, diseased flies displayed substantial changes in carbohydrate and protein content. Interestingly, alteration in weight and lipid levels are independent of the feeding pattern in diseased condition and exhibit weak correlation with insulin-like peptide or adipokinetic hormone producing cells. We propose that therapeutic intervention aimed at restoring lipid levels and associated metabolic pathways may improve longevity and quality of patient's life. PMID:27506601

  11. PPARβ/δ and lipid metabolism in the heart.

    PubMed

    Palomer, Xavier; Barroso, Emma; Zarei, Mohammad; Botteri, Gaia; Vázquez-Carrera, Manuel

    2016-10-01

    Cardiac lipid metabolism is the focus of attention due to its involvement in the development of cardiac disorders. Both a reduction and an increase in fatty acid utilization make the heart more prone to the development of lipotoxic cardiac dysfunction. The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR)β/δ modulates different aspects of cardiac fatty acid metabolism, and targeting this nuclear receptor can improve heart diseases caused by altered fatty acid metabolism. In addition, PPARβ/δ regulates glucose metabolism, the cardiac levels of endogenous antioxidants, mitochondrial biogenesis, cardiomyocyte apoptosis, the insulin signaling pathway and lipid-induced myocardial inflammatory responses. As a result, PPARβ/δ ligands can improve cardiac function and ameliorate the pathological progression of cardiac hypertrophy, heart failure, cardiac oxidative damage, ischemia-reperfusion injury, lipotoxic cardiac dysfunction and lipid-induced cardiac inflammation. Most of these findings have been observed in preclinical studies and it remains to be established to what extent these intriguing observations can be translated into clinical practice. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26825692

  12. 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

  13. 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.

  14. Lipid transfer and metabolism across the endolysosomal-mitochondrial boundary.

    PubMed

    Daniele, Tiziana; Schiaffino, Maria Vittoria

    2016-08-01

    Lysosomes and mitochondria occupy a central stage in the maintenance of cellular homeostasis, by playing complementary roles in nutrient sensing and energy metabolism. Specifically, these organelles function as signaling hubs that integrate environmental and endogenous stimuli with specific metabolic responses. In particular, they control various lipid biosynthetic and degradative pipelines, either directly or indirectly, by regulating major cellular metabolic pathways, and by physical and functional connections established with each other and with other organelles. Membrane contact sites allow the exchange of ions and molecules between organelles, even without membrane fusion, and are privileged routes for lipid transfer among different membrane compartments. These inter-organellar connections typically involve the endoplasmic reticulum. Direct membrane contacts have now been described also between lysosomes, autophagosomes, lipid droplets, and mitochondria. This review focuses on these recently identified membrane contact sites, and on their role in lipid biosynthesis, exchange, turnover and catabolism. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26852832

  15. Influence of difenoconazole on lipid metabolism in marine medaka (Oryzias melastigma).

    PubMed

    Dong, Xiaocui; Li, Yan; Zhang, Lemeng; Zuo, Zhenghong; Wang, Chonggang; Chen, Meng

    2016-07-01

    Difenoconazole (DFZ) is a triazole fungicide that inhibits the biosynthesis of sterols in cell membranes and is widely used in agriculture for effectively treating fungal infections. However, there are few studies available addressing the effects of DFZ on lipid metabolism in marine fishes. The present study was conducted to investigate the effects of DFZ on lipid metabolism in marine medaka (Oryzias melastigma). After exposure to 1, 10, 100 and 1000 ng/L DFZ for 180 days, an increase in condition factor (CF), total lipids and polyunsaturated fatty acids (PUFA) contents accompanied with a decrease in saturated fatty acids was observed in the muscle of DFZ-exposed fish. The expression of peroxisome proliferator-activated receptor γ as well as retinoid X receptors in the muscle was up-regulated, which would be responsible for the lipid accumulation in the muscle. The elevation of Δ6-desaturase (FADS2) and Δ9-desaturase (SCD) mRNA levels in the muscle and liver might result in the increase of PUFA content. The increased CF index and total lipid amounts indicated that DFZ exposure could affect the health of fish. ∑SFA (sum of saturated fatty acids) and DHA (docosahexaenoic acid; 22:6n-3) concentrations decreased, and the levels of ∑PUFA and ∑n-6PUFA increased in the muscle, which suggested that DFZ exposure could change lipid metabolism and profiles in fish. PMID:27112457

  16. [Indicators of lipid metabolism in patients in critical condition].

    PubMed

    Moroz, V V; Molchanova, L V; Shcherbakova, L N; Kravchenko-Berezhnaia, N R; Meshcheriakov, G N

    2001-01-01

    Plasma lipid metabolism was studied in critical patients with severe combined injuries. Decrease in cholesterol concentration and increase in triglyceride concentrations were more pronounced in patients with lethal outcomes. The authors conclude that plasma cholesterol and triglyceride concentrations can be used as prognostic signs in patients with severe combined injuries. PMID:11855061

  17. Hepatic drug metabolism and lipid peroxidation in thiamine deficient rats.

    PubMed

    Galdhar, N R; Pawar, S S

    1976-01-01

    In vitro metabolism of aminopyrene, ethylmorphine (Type I substrates), N-methylaniline and acetanilide (Type II substrates) in liver microsomal fraction from thiamine deficient male and female rats was studied. No significant change in microsomal protein content was noticed during the period of thiamine deficiency. However, a significant increase in the in vitro oxidation of aminopyrene, ethylmorphine, N-methylaniline and hydroxylation of acetanilide was observed. The NADPH linked and ascorbate induced lipid peroxidation was also increased during thiamine deficiency. The levels of NADPH cytochrome c-reductase, cytochrome b5 and heme were noticeably increased in thiamine deficient animals as compared to normal rats. Phenobarbital treatment induced the activities of all drug enzymes and inhibited the lipid peroxidation in either sex during the period of thiamine deficiency. It appears that thiamine intake is an important determination in drug metabolism and lipid peroxidation. PMID:816749

  18. Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism.

    PubMed

    Caesar, Robert; Nygren, Heli; Orešič, Matej; Bäckhed, Fredrik

    2016-03-01

    The gut microbiota influences many aspects of host metabolism. We have previously shown that the presence of a gut microbiota remodels lipid composition. Here we investigated how interaction between gut microbiota and dietary lipids regulates lipid composition in the liver and plasma, and gene expression in the liver. Germ-free and conventionally raised mice were fed a lard or fish oil diet for 11 weeks. We performed lipidomics analysis of the liver and serum and microarray analysis of the liver. As expected, most of the variation in the lipidomics dataset was induced by the diet, and abundance of most lipid classes differed between mice fed lard and fish oil. However, the gut microbiota also affected lipid composition. The gut microbiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl esters were not affected by the gut microbiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gut microbiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gut microbiota-induced regulation of hepatic cholesterol metabolism is dependent on dietary lipid composition. PMID:26783361

  19. Regulation of lipid metabolism: a tale of two yeasts

    PubMed Central

    Raychaudhuri, Sumana; Young, Barry P.; Espenshade, Peter J.; Loewen, Christopher J.R.

    2015-01-01

    Eukaryotic cells synthesize multiple classes of lipids by distinct metabolic pathways in order to generate membranes with optimal physical and chemical properties. As a result, complex regulatory networks are required in all organisms to maintain lipid and membrane homeostasis as well as to rapidly and efficiently respond to cellular stress. The unicellular nature of yeast makes it particularly vulnerable to environmental stress and yeast has evolved elaborate signaling pathways to maintain lipid homeostasis. In this article we highlight the recent advances that have been made using the budding and fission yeasts and we discuss potential roles for the unfolded protein response (UPR) and the SREBP-Scap pathways in coordinate regulation of multiple lipid classes. PMID:22694927

  20. Sexual Dimorphism in the Effects of Exercise on Metabolism of Lipids to Support Resting Metabolism

    PubMed Central

    Henderson, Gregory C.

    2014-01-01

    Exercise training is generally a healthful activity and an effective intervention for reducing the risk of numerous chronic diseases including cardiovascular disease and diabetes. This is likely both a result of prevention of weight gain over time and direct effects of exercise on metabolism of lipids and the other macronutrient classes. Importantly, a single bout of exercise can alter lipid metabolism and metabolic rate for hours and even into the day following exercise, so individuals who regularly exercise, even if not performed every single day, overall could experience a substantial change in their resting metabolism that would reduce risk for metabolic diseases. However, resting metabolism does not respond similarly in all individuals to exercise participation, and indeed gender or sex is a major determinant of the response of resting lipid metabolism to prior exercise. In order to fully appreciate the metabolic effects and health benefits of exercise, the differences between men and women must be considered. In this article, the differences in the effects of exercise on resting metabolic rate, fuel selection after exercise, as well as the shuttling of triglyceride and fatty acids between tissues are discussed. Furthermore, concepts related to sex differences in the precision of homeostatic control and sex differences in the integration of metabolism between various organs are considered. PMID:25339941

  1. Dysregulation of lipid metabolism in Tangier monocyte-derived macrophages.

    PubMed

    Schmitz, G; Fischer, H; Beuck, M; Hoecker, K P; Robenek, H

    1990-01-01

    The cellular defect in Tangier mononuclear phagocytes (MNP) was shown to be associated with significant abnormalities in cellular phospholipid, triglyceride, and cholesteryl ester metabolism by using various radiolabeled precursors (32Pi, 3H-serine, 3H-choline, 14C-acetate, and 14C-oleic acid). Tangier MNP expressed increased rates of synthesis for phospholipids (twofold), triglycerides (fivefold), and cholesteryl esters (threefold) as compared to normal MNP when incubated in McCoy's medium containing 0.2% human serum albumin. The turnover rate of cellular phospholipids was also enhanced, while the turnover rates for triglycerides and cholesteryl esters were normal, thus leading to the accumulation of a larger pool of labeled triglycerides and cholesteryl esters in Tangier MNP. The individual phospholipid classes, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine were similarly affected. Cholesterol loading led to approximately 30% down-regulation of phospholipid synthesis in normal cells, but Tangier MNP showed a smaller response. When nonloaded normal MNP were exposed to high density lipoprotein3 (HDL3), they diminished cellular cholesterol esterification mediated by acyl-CoA:cholesterol acyltransferase (ACAT); in Tangier MNP, ACAT activity increased in the presence of HDL3. When cholesterol-loaded normal and Tangier MNP were treated with HDL3, an up-regulation of phospholipid synthesis was observed in both cell types, but Tangier MNP showed a smaller response. We conclude that the defect in Tangier disease, which we recently described as a "disorder of intracellular traffic" (Schmitz et al. Proc Natl Acad Sci USA 1985;82:6305-6309), is associated with a dysregulation of cellular lipid metabolism, leading to an overproduction of triglycerides and esterified cholesterol and to enhanced synthesis and catabolism of phospholipids. PMID:2244850

  2. 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.

  3. 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

  4. Affective Disorders, Bone Metabolism, and Osteoporosis

    PubMed Central

    2013-01-01

    The nature of the relationship between affective disorders, bone mineral density (BMD), and bone metabolism is unresolved, although there is growing evidence that many medications used to treat affective disorders are associated with low BMD or alterations in neuroendocrine systems that influence bone turnover. The objective of this review is to describe the current evidence regarding the association of unipolar and bipolar depression with BMD and indicators of bone metabolism, and to explore potential mediating and confounding influences of those relationships. The majority of studies of unipolar depression and BMD indicate that depressive symptoms are associated with low BMD. In contrast, evidence regarding the relationship between bipolar depression and BMD is inconsistent. There is limited but suggestive evidence to support an association between affective disorders and some markers of bone turnover. Many medications used to treat affective disorders have effects on physiologic systems that influence bone metabolism, and these conditions are also associated with a range of health behaviors that can influence osteoporosis risk. Future research should focus on disentangling the pathways linking psychotropic medications and their clinical indications with BMD and fracture risk. PMID:23874147

  5. Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences.

    PubMed

    Vaziri, Nosratola D

    2016-07-01

    Nephrotic syndrome results in hyperlipidemia and profound alterations in lipid and lipoprotein metabolism. Serum cholesterol, triglycerides, apolipoprotein B (apoB)-containing lipoproteins (very low-density lipoprotein [VLDL], immediate-density lipoprotein [IDL], and low-density lipoprotein [LDL]), lipoprotein(a) (Lp[a]), and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are increased in nephrotic syndrome. This is accompanied by significant changes in the composition of various lipoproteins including their cholesterol-to-triglyceride, free cholesterol-to-cholesterol ester, and phospholipid-to-protein ratios. These abnormalities are mediated by changes in the expression and activities of the key proteins involved in the biosynthesis, transport, remodeling, and catabolism of lipids and lipoproteins including apoproteins A, B, C, and E; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; fatty acid synthase; LDL receptor; lecithin cholesteryl ester acyltransferase; acyl coenzyme A cholesterol acyltransferase; HDL docking receptor (scavenger receptor class B, type 1 [SR-B1]); HDL endocytic receptor; lipoprotein lipase; and hepatic lipase, among others. The disorders of lipid and lipoprotein metabolism in nephrotic syndrome contribute to the development and progression of cardiovascular and kidney disease. In addition, by limiting delivery of lipid fuel to the muscles for generation of energy and to the adipose tissues for storage of energy, changes in lipid metabolism contribute to the reduction of body mass and impaired exercise capacity. This article provides an overview of the mechanisms, consequences, and treatment of lipid disorders in nephrotic syndrome. PMID:27165836

  6. 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. PMID:26426396

  7. The role of ER stress in lipid metabolism and lipotoxicity.

    PubMed

    Han, Jaeseok; Kaufman, Randal J

    2016-08-01

    The endoplasmic reticulum (ER) is a cellular organelle important for regulating calcium homeostasis, lipid metabolism, protein synthesis, and posttranslational modification and trafficking. Numerous environmental, physiological, and pathological insults disturb ER homeostasis, referred to as ER stress, in which a collection of conserved intracellular signaling pathways, termed the unfolded protein response (UPR), are activated to maintain ER function for cell survival. However, excessive and/or prolonged UPR activation leads to initiation of self-destruction through apoptosis. Excessive accumulation of lipids and their intermediate products causes metabolic abnormalities and cell death, called lipotoxicity, in peripheral organs, including the pancreatic islets, liver, muscle, and heart. Because accumulating evidence links chronic ER stress and defects in UPR signaling to lipotoxicity in peripheral tissues, understanding the role of ER stress in cell physiology is a topic under intense investigation. In this review, we highlight recent findings that link ER stress and UPR signaling to the pathogenesis of peripheral organs due to lipotoxicity. PMID:27146479

  8. Studying Lipid Metabolism and Transport During Zebrafish Development.

    PubMed

    Zeituni, Erin M; Farber, Steven A

    2016-01-01

    The zebrafish model facilitates the study of lipid metabolism and transport during development. Here, we outline methods to introduce traceable fluorescent or radiolabeled fatty acids into zebrafish embryos and larvae at various developmental stages. Labeled fatty acids can be injected into the large yolk cell prior to the development of digestive organs when the larvae is entirely dependent on the yolk for its nutrition (lecithotrophic state). Once zebrafish are able to consume exogenous food, labeled fatty acids can be incorporated into their food. Our group and others have demonstrated that the transport and processing of these injected or ingested fatty acid analogs can be followed through microscopy and/or biochemical analysis. These techniques can be easily combined with targeted antisense approaches, transgenics, or drug treatments (see Note 1 ), allowing studies of lipid cell biology and metabolism that are exceedingly difficult or impossible in mammals. PMID:27464812

  9. Perturbations of Lipid Metabolism Indexed by Lipidomic Biomarkers

    PubMed Central

    Lamaziere, Antonin; Wolf, Claude; Quinn, Peter J.

    2012-01-01

    The lipidome of the liver and the secreted circulating lipoproteins can now be interrogated conveniently by automated mass spectrometric methods. Multivariate analysis of the liver and serum lipid composition in various animal modes or in human patients has pointed to specific molecular species markers. The perturbations of lipid metabolism can be categorized on the basis of three basic pathological mechanisms: (1) an accelerated rate of de novo lipogenesis; (2) perturbation of the peroxisome pathway of ether-lipid and very-long-chain fatty acid biosynthesis; (3) a change in the rate of interconversion of essential omega-3 and -6 polyunsaturated fatty acids. This review provides examples to illustrate the practicalities of lipidomic studies in biomedicine. PMID:24957365

  10. 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

  11. Sex-Specific Differences in Lipid and Glucose Metabolism

    PubMed Central

    Varlamov, Oleg; Bethea, Cynthia L.; Roberts, Charles T.

    2014-01-01

    Energy metabolism in humans is tuned to distinct sex-specific functions that potentially reflect the unique requirements in females for gestation and lactation, whereas male metabolism may represent a default state. These differences are the consequence of the action of sex chromosomes and sex-specific hormones, including estrogens and progesterone in females and androgens in males. In humans, sex-specific specialization is associated with distinct body-fat distribution and energy substrate-utilization patterns; i.e., females store more lipids and have higher whole-body insulin sensitivity than males, while males tend to oxidize more lipids than females. These patterns are influenced by the menstrual phase in females, and by nutritional status and exercise intensity in both sexes. This minireview focuses on sex-specific mechanisms in lipid and glucose metabolism and their regulation by sex hormones, with a primary emphasis on studies in humans and the most relevant pre-clinical model of human physiology, non-human primates. PMID:25646091

  12. Regulation of glucose and lipid metabolism by dietary carbohydrate levels and lipid sources in gilthead sea bream juveniles.

    PubMed

    Castro, Carolina; Corraze, Geneviève; Firmino-Diógenes, Alexandre; Larroquet, Laurence; Panserat, Stéphane; Oliva-Teles, Aires

    2016-07-01

    The long-term effects on growth performance, body composition, plasma metabolites, liver and intestine glucose and lipid metabolism were assessed in gilthead sea bream juveniles fed diets without carbohydrates (CH-) or carbohydrate-enriched (20 % gelatinised starch, CH+) combined with two lipid sources (fish oil; or vegetable oil (VO)). No differences in growth performance among treatments were observed. Carbohydrate intake was associated with increased hepatic transcripts of glucokinase but not of 6-phosphofructokinase. Expression of phosphoenolpyruvate carboxykinase was down-regulated by carbohydrate intake, whereas, unexpectedly, glucose 6-phosphatase was up-regulated. Lipogenic enzyme activities (glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthase) and ∆6 fatty acyl desaturase (FADS2) transcripts were increased in liver of fish fed CH+ diets, supporting an enhanced potential for lipogenesis and long-chain PUFA (LC-PUFA) biosynthesis. Despite the lower hepatic cholesterol content in CH+ groups, no influence on the expression of genes related to cholesterol efflux (ATP-binding cassette G5) and biosynthesis (lanosterol 14 α-demethylase, cytochrome P450 51 cytochrome P450 51 (CYP51A1); 7-dehydrocholesterol reductase) was recorded at the hepatic level. At the intestinal level, however, induction of CYP51A1 transcripts by carbohydrate intake was recorded. Dietary VO led to decreased plasma phospholipid and cholesterol concentrations but not on the transcripts of proteins involved in phospholipid biosynthesis (glycerol-3-phosphate acyltransferase) and cholesterol metabolism at intestinal and hepatic levels. Hepatic and muscular fatty acid profiles reflected that of diets, despite the up-regulation of FADS2 transcripts. Overall, this study demonstrated that dietary carbohydrates mainly affected carbohydrate metabolism, lipogenesis and LC-PUFA biosynthesis, whereas effects of dietary lipid source were mostly related with tissue fatty acid composition

  13. 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. PMID:20691590

  14. Altered Lipid Metabolism in Brain Injury and Disorders

    PubMed Central

    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-α 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-α 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

  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. 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. PMID:25141153

  17. Regulation of egg quality and lipids metabolism by Zinc Oxide Nanoparticles.

    PubMed

    Zhao, Yong; Li, Lan; Zhang, Peng-Fei; Liu, Xin-Qi; Zhang, Wei-Dong; Ding, Zhao-Peng; Wang, Shi-Wen; Shen, Wei; Min, Ling-Jiang; Hao, Zhi-Hui

    2016-04-01

    This investigation was designed to explore the effects of Zinc Oxide Nanoparticles (ZnO NP) on egg quality and the mechanism of decreasing of yolk lipids. Different concentration of ZnO NP and ZnSO4 were used to treat hens for 24 weeks. The body weight and egg laying frequency were recorded and analyzed. Albumen height, Haugh unit, and yolk color score were analyzed by an Egg Multi Tester. Breaking strength was determined by an Egg Force Reader. Egg shell thickness was measured using an Egg Shell Thickness Gouge. Shell color was detected by a spectrophotometer. Egg shape index was measured by Egg Form Coefficient Measuring Instrument. Albumen and yolk protein was determined by the Kjeldahl method. Amino acids were determined by an amino acids analyzer. Trace elements Zn, Fe, Cu, and P (mg/kg wet mass) were determined in digested solutions using Inductively Coupled Plasma-Optical Emission Spectrometry. TC and TG were measured using commercial analytical kits. Yolk triglyceride, total cholesterol, pancreatic lipase, and phospholipids were determined by appropriate kits. β-carotene was determined by spectrophotometry. Lipid metabolism was also investigated with liver, plasma, and ovary samples. ZnO NP did not change the body weight of hens during the treatment period. ZnO NP slowed down egg laying frequency at the beginning of egg laying period but not at later time. ZnO NP did not affect egg protein or water contents, slightly decreased egg physical parameters (12 to 30%) and trace elements (20 to 35%) after 24 weeks treatment. However, yolk lipids content were significantly decreased by ZnO NP (20 to 35%). The mechanism of Zinc oxide nanoparticles decreasing yolk lipids was that they decreased the synthesis of lipids and increased lipid digestion. These data suggested ZnO NP affected egg quality and specifically regulated lipids metabolism in hens through altering the function of hen's ovary and liver. PMID:26908885

  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. PMID:25562812

  19. Uric acid as a modulator of glucose and lipid metabolism.

    PubMed

    Lima, William Gustavo; Martins-Santos, Maria Emília Soares; Chaves, Valéria Ernestânia

    2015-09-01

    In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine. Uric acid is similarly produced in the liver, adipose tissue and muscle and is primarily excreted through the urinary tract. Several factors, including a high-fructose diet and the use of xenobiotics and alcohol, contribute to hyperuricaemia. Hyperuricaemia belongs to a cluster of metabolic and haemodynamic abnormalities, called metabolic syndrome, characterised by abdominal obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. Hyperuricaemia reduction in the Pound mouse or fructose-fed rats, as well as hyperuricaemia induction by uricase inhibition in rodents and studies using cell culture have suggested that uric acid plays an important role in the development of metabolic syndrome. These studies have shown that high uric acid levels regulate the oxidative stress, inflammation and enzymes associated with glucose and lipid metabolism, suggesting a mechanism for the impairment of metabolic homeostasis. Humans lacking uricase, the enzyme responsible for uric acid degradation, are susceptible to these effects. In this review, we summarise the current knowledge of the effects of uric acid on the regulation of metabolism, primarily focusing on liver, adipose tissue and skeletal muscle. PMID:26133655

  20. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1.

    PubMed

    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

    2016-04-01

    Tissues with high metabolic rates often use lipids, as well as glucose, for energy, conferring a survival advantage during feast and famine. Current dogma suggests that high-energy-consuming photoreceptors depend on glucose. Here we show that the retina also uses fatty acid β-oxidation for energy. Moreover, we identify a lipid sensor, free fatty acid receptor 1 (Ffar1), that curbs glucose uptake when fatty acids are available. Very-low-density lipoprotein receptor (Vldlr), which is present in photoreceptors and is expressed in other tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acid. In the retinas of Vldlr(-/-) mice with low fatty acid uptake but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1. Impaired glucose entry into photoreceptors results in a dual (lipid and glucose) fuel shortage and a reduction in the levels of the Krebs cycle intermediate α-ketoglutarate (α-KG). Low α-KG levels promotes stabilization of hypoxia-induced factor 1a (Hif1a) and secretion of vascular endothelial growth factor A (Vegfa) by starved Vldlr(-/-) photoreceptors, leading to neovascularization. The aberrant vessels in the Vldlr(-/-) retinas, which invade normally avascular photoreceptors, are reminiscent of the vascular defects in retinal angiomatous proliferation, a subset of neovascular age-related macular degeneration (AMD), which is associated with high vitreous VEGFA levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in macular telangiectasia, neovascular AMD and other retinal diseases. PMID:26974308

  1. Diacylglycerol kinase-δ regulates AMPK signaling, lipid metabolism, and skeletal muscle energetics.

    PubMed

    Jiang, Lake Q; de Castro Barbosa, Thais; Massart, Julie; Deshmukh, Atul S; Löfgren, Lars; Duque-Guimaraes, Daniella E; Ozilgen, Arda; Osler, Megan E; Chibalin, Alexander V; Zierath, Juleen R

    2016-01-01

    Decrease of AMPK-related signal transduction and insufficient lipid oxidation contributes to the pathogenesis of obesity and type 2 diabetes. Previously, we identified that diacylglycerol kinase-δ (DGKδ), an enzyme involved in triglyceride biosynthesis, is reduced in skeletal muscle from type 2 diabetic patients. Here, we tested the hypothesis that DGKδ plays a role in maintaining appropriate AMPK action in skeletal muscle and energetic aspects of contraction. Voluntary running activity was reduced in DGKδ(+/-) mice, but glycogen content and mitochondrial markers were unaltered, suggesting that DGKδ deficiency affects skeletal muscle energetics but not mitochondrial protein abundance. We next determined the role of DGKδ in AMPK-related signal transduction and lipid metabolism in isolated skeletal muscle. AMPK activation and signaling were reduced in DGKδ(+/-) mice, concomitant with impaired lipid oxidation and elevated incorporation of free fatty acids into triglycerides. Strikingly, DGKδ deficiency impaired work performance, as evident by altered force production and relaxation dynamics in response to repeated contractions. In conclusion, DGKδ deficiency impairs AMPK signaling and lipid metabolism, thereby highlighting the deleterious role of excessive lipid metabolites in the development of peripheral insulin resistance and type 2 diabetes pathogenesis. DGKδ deficiency also influences skeletal muscle energetics, which may lead to low physical activity levels in type 2 diabetes. PMID:26530149

  2. Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition

    PubMed Central

    Kishino, Shigenobu; Takeuchi, Michiki; Park, Si-Bum; Hirata, Akiko; Kitamura, Nahoko; Kunisawa, Jun; Kiyono, Hiroshi; Iwamoto, Ryo; Isobe, Yosuke; Arita, Makoto; Arai, Hiroyuki; Ueda, Kazumitsu; Shima, Jun; Takahashi, Satomi; Yokozeki, Kenzo; Shimizu, Sakayu; Ogawa, Jun

    2013-01-01

    In the representative gut bacterium Lactobacillus plantarum, we identified genes encoding the enzymes involved in a saturation metabolism of polyunsaturated fatty acids and revealed in detail the metabolic pathway that generates hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and partially saturated trans-fatty acids as intermediates. Furthermore, we observed these intermediates, especially hydroxy fatty acids, in host organs. Levels of hydroxy fatty acids were much higher in specific pathogen-free mice than in germ-free mice, indicating that these fatty acids are generated through polyunsaturated fatty acids metabolism of gastrointestinal microorganisms. These findings suggested that lipid metabolism by gastrointestinal microbes affects the health of the host by modifying fatty acid composition. PMID:24127592

  3. Silibinin Regulates Lipid Metabolism and Differentiation in Functional Human Adipocytes

    PubMed Central

    Barbagallo, Ignazio; Vanella, Luca; Cambria, Maria T.; Tibullo, Daniele; Godos, Justyna; Guarnaccia, Laura; Zappalà, Agata; Galvano, Fabio; Li Volti, Giovanni

    2016-01-01

    Silibinin, a natural plant flavonolignan is the main active constituent found in milk thistle (Silybum marianum). It is known to have hepatoprotective, anti-neoplastic effect, and suppresses lipid accumulation in adipocytes. Objective of this study was to investigate the effect of silibinin on adipogenic differentiation and thermogenic capacity of human adipose tissue derived mesenchymal stem cells. Silibinin (10 μM) treatment, either at the beginning or at the end of adipogenic differentiation, resulted in an increase of SIRT-1, PPARα, Pgc-1α, and UCPs gene expression. Moreover, silibinin administration resulted in a decrease of PPARγ, FABP4, FAS, and MEST/PEG1 gene expression during the differentiation, confirming that this compound is able to reduce fatty acid accumulation and adipocyte size. Our data showed that silibinin regulated adipocyte lipid metabolism, inducing thermogenesis and promoting a brown remodeling in adipocyte. Taken together, our findings suggest that silibinin increases UCPs expression by stimulation of SIRT1, PPARα, and Pgc-1α, improved metabolic parameters, decreased lipid mass leading to the formation of functional adipocytes. PMID:26834634

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. 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

  6. FADD is a key regulator of lipid metabolism.

    PubMed

    Zhuang, Hongqin; Wang, Xueshi; Zha, Daolong; Gan, Ziyi; Cai, Fangfang; Du, Pan; Yang, Yunwen; Yang, Bingya; Zhang, Xiangyu; Yao, Chun; Zhou, Yuqiang; Jiang, Chizhou; Guan, Shengwen; Zhang, Xuerui; Zhang, Jing; Jiang, Wenhui; Hu, Qingang; Hua, Zi-Chun

    2016-01-01

    FADD, a classical apoptotic signaling adaptor, was recently reported to have non-apoptotic functions. Here, we report the discovery that FADD regulates lipid metabolism. PPAR-α is a dietary lipid sensor, whose activation results in hypolipidemic effects. We show that FADD interacts with RIP140, which is a corepressor for PPAR-α, and FADD phosphorylation-mimic mutation (FADD-D) or FADD deficiency abolishes RIP140-mediated transcriptional repression, leading to the activation of PPAR-α. FADD-D-mutant mice exhibit significantly decreased adipose tissue mass and triglyceride accumulation. Also, they exhibit increased energy expenditure with enhanced fatty acid oxidation in adipocytes due to the activation of PPAR-α. Similar metabolic phenotypes, such as reduced fat formation, insulin resistance, and resistance to HFD-induced obesity, are shown in adipose-specific FADD knockout mice. Additionally, FADD-D mutation can reverse the severe genetic obesity phenotype of ob/ob mice, with elevated fatty acid oxidation and oxygen consumption in adipose tissue, improved insulin resistance, and decreased triglyceride storage. We conclude that FADD is a master regulator of glucose and fat metabolism with potential applications for treatment of insulin resistance and obesity. PMID:27357657

  7. In vitro effects of exogenous carbon monoxide on oxidative stress and lipid metabolism in macrophages.

    PubMed

    Petrick, Lauren; Rosenblat, Mira; Aviram, Michael

    2016-07-01

    Carbon monoxide (CO) is a major constituent of traffic-related air pollution and is also produced endogenously under conditions of oxygen-mediated stress. It has been shown to affect both oxidative stress and inflammation. However, its role in lipid metabolism has been neglected. Using short exposure times, the effect of CO on J774A.1 macrophage atherogenic functions was investigated up to 16 h after exposure. Exposure of macrophages was found to be pro-atherogenic as it significantly increased triglyceride mass, up to 60%, and decreased high-density lipoprotein-mediated cholesterol efflux, up to 27%. In contrast, paraoxonase 2 lactonase activity was increased, up to 65%, and cellular oxidative stress was attenuated by 29%, compared with the control cells. The above results on lipid metabolism may lead to arterial macrophage foam cell formation, the hallmark of early atherogenesis. PMID:25501254

  8. How Lipid Membranes Affect Pore Forming Toxin Activity.

    PubMed

    Rojko, Nejc; Anderluh, Gregor

    2015-12-15

    , events associated with pore formation can modulate properties of the lipid membrane and affect its organization. Model membranes do not necessarily reproduce the physicochemical properties of the native cellular membrane, and caution is needed when transferring results from model to native lipid membranes. In this context, the utilization of novel approaches that enable studying PFTs on living cells at a single molecule level should reveal complex protein-lipid membrane interactions in greater detail. PMID:26641659

  9. The effect of alkylresorcinol on lipid metabolism in Azotobacter chroococcum.

    PubMed

    Rejman, Joanna; Kozubek, Arkadiusz

    2004-01-01

    We studied the effect of exogenous alkylresorcinols on the lipid metabolism of Azotobacter chroococcum. We observed that when 5-n-pentadecylresorcinol was present in the growth medium, the more endogenous alkylresorcinols were synthesized. Concurrently, a drop in the amount of phospholipids was observed. These changes were associated with increasing numbers of dormant cysts, while the number of vegetative cells diminished. The chemical nature of the alkylresorcinols synthesized by Azotobacter chroococcum was dependent on the duration of exposure of the bacteria to exogenous alkylresorcinols. When the exposure time was prolonged to four days, 5-n-nonadecylresorcinol (C 19:0) was substituted by 5-n-heneicosylresorcinol (C 21:0) and 5-n-tricosylresorcinol (C 23:0). Two fluorescent membrane probes, NBD-PE and TMA-DPH, further revealed that the presence of alkylresorcinols in the lipid bilayer restrains the phospholipid rotational motion. PMID:18998408

  10. [Chloroquine influence on lipid metabolism and selected laboratory parameters].

    PubMed

    Woźniacka, Anna; Lesiak, Aleksandra; Smigielski, Janusz; Sysa-Jedrzejowska, Anna

    2005-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with complex pathogenesis, various clinical presentation and chronic course with relapses. Mode of treatment depends on the disease activity and kind of internal organ involvement. In most cases clinical remission could be obtained after antimalarials, nonsteroidal anti-inflammatory drugs, corticosteroids, and photoprotection use. Despite the approved antimalarials therapeutic value, the mechanisms by which they provide benefit in lupus, patients are not fully understood. Literature data indicate that they can influence lipid metabolism. The aim of the performed study was the objective evaluation of the influence of 3-month chloroquine treatment (Arechin, 250 mg/day) on lipid metabolism and selected laboratory parameters. In 34 patients with SLE clinical and laboratory evaluation was performed twice, before and after 3-month treatment. After 3 months significantly lower total cholesterol level was observed (mean value 184.91 mg%, 165.26 mg%, p < 0.001). Also LDL level was evidently lowered (111.27 mg%, 99.25 mg%). Similar tendency was noticed in triglycerides, which level after 3 months decreased from the average 152.38 mg% to 104.97 mg%, p < 0.001. Moreover the lowering of sedimentation rate, increasing hemoglobin level and lengthening coagulation time was perceived. The results of the study indicate the influence of chloroquine on decreasing of the disease activity, its anti-inflammatory properties and mainly the drug impact on lipid metabolism. Not only does antimalarials treatment reduce the risk of atherosclerosis development but it also minimizes corticosteroids side effects, which are considered to be the basic medication in lupus patients. PMID:16541717

  11. Mammalian alpha beta hydrolase domain (ABHD) proteins: lipid metabolizing enzymes at the interface of cell signaling and energy metabolism

    PubMed Central

    Brown, J. Mark

    2016-01-01

    Dysregulation of lipid metabolism underlies many chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Therefore, understanding enzymatic mechanisms controlling lipid synthesis and degradation is imperative for successful drug discovery for these human diseases. Genes encoding α/β hydrolase fold domain (ABHD) proteins are present in virtually all reported genomes, and conserved structural motifs shared by these proteins predict common roles in lipid synthesis and degradation. However, the physiological substrates and products for these lipid metabolizing enzymes and their broader role in metabolic pathways remain largely uncharacterized. Recently, mutations in several members of the ABHD protein family have been implicated in inherited inborn errors of lipid metabolism. Furthermore, studies in cell and animal models have revealed important roles for ABHD proteins in lipid metabolism, lipid signal transduction, and metabolic disease. The purpose of this review is to provide a comprehensive summary surrounding the current state of knowledge regarding mammalian ABHD protein family members. In particular, we will discuss how ABHD proteins are ideally suited to act at the interface of lipid metabolism and signal transduction. Although, the current state of knowledge regarding mammalian ABHD proteins is still in its infancy, this review highlights the potential for the ABHD enzymes as being attractive targets for novel therapies targeting metabolic disease. PMID:23328280

  12. Effect of dietary fibres on small intestine histomorphology and lipid metabolism in young broiler chickens.

    PubMed

    Rahmatnejad, E; Saki, A A

    2016-08-01

    Two experiments were conducted to determine the influence of dietary fibres on small intestine histomorphology and lipid metabolism in broilers from 1 to 21 day of age. In experiment 1, diets containing insoluble [cellulose (CEL); 2% and 4%] or soluble [carboxymethyl cellulose (CMC); 2% and 4%] fibre were fed to broilers from day 1 to 21 post-hatch and ileal tissue was collected at day 21 of age for histological evaluation. In experiment 2, broilers diet was supplemented with 0%, 1% or 2% insoluble fibre (Arbocel) during day 7 to 21 post-hatch and plasma and liver lipid metabolism were evaluated at day 21. In experiment 1, inclusion of CMC reduced body weight gain (BWG) and feed intake (FI) and increased feed conversion ratio (FCR) compared with others. Intestinal histomorphology was unaffected by CEL, but CMC led to an increase in crypt depth (CD) and serosa thickness and a decrease in villus height (VH), villus width (VW), VH:CD ratio and villus surface area (VSA), rather than control and CEL groups. Treatment did not affect goblet cell type. Moreover, the CMC-fed birds had greater total goblet cell count (GCC) as compared with others. In experiment 2, fibre inclusion was associated with increases in BWG from 7 to 14 day of age and an improvement in FCR, whereas FI was not influenced by treatments. Inclusion of fibre in the diet decreased the weight of the abdominal fat and cholesterol concentrations of liver and plasma. No significant effects on fatty acid composition of liver lipid were observed by fibre supplementation. These findings suggest dietary fibre affects performance, intestinal histomorphology and lipid metabolism in young chicks, which may directly affect poultry feeding strategies. PMID:26667363

  13. 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. PMID:27306343

  14. Effects of drinking water monochloramine on lipid and thyroid metabolism in healthy men.

    PubMed

    Wones, R G; Deck, C C; Stadler, B; Roark, S; Hogg, E; Frohman, L A

    1993-03-01

    The purpose of this study was to determine whether a 4-week consumption of 1.5L per day of drinking water containing monochloramine at a concentration of 2 ppm (ppm = mg/L) or 15 ppm under controlled conditions would alter parameters of lipid or thyroid metabolism in healthy men. Forty-eight men completed an 8-week protocol during which diet (600 mg cholesterol per day, 40% calories as fat) and other factors known to affect lipid metabolism were controlled. During the first 4 weeks of the protocol, all subjects consumed distilled water. During the second 4 weeks, one-third of the subjects were assigned randomly to drink 1.5 L per day of water containing 2 ppm of monochloramine, to drink 1.5 L per day of water containing 15 ppm monochloramine, or to continue drinking distilled water. Four blood samples were collected from each subject at the end of each 4-week study period. Subjects drinking monochloramine at a concentration of 2 ppm showed no significant changes in total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoproteins A1, A2, or B when compared to the distilled water group. Parameters of thyroid function also were unchanged by exposure to monochloramine at this concentration. However, subjects drinking monochloramine at a concentration of 15 ppm experienced an increase in the level of apolipoprotein B. Other parameters of lipid and thyroid metabolism did not change. We conclude that consumption of drinking water containing 2 ppm of monochloramine does not alter parameters of lipid and thyroid metabolism in healthy men. Consumption of water containing 15 ppm monochloramine may be associated with increased levels of plasma apolipoprotein B. PMID:8319653

  15. Lipids rule: resetting lipid metabolism restores T cell function in systemic lupus erythematosus

    PubMed Central

    Kidani, Yoko; Bensinger, Steven J.

    2014-01-01

    Systemic lupus erythematosus (SLE) is a devastating autoimmune disease characterized by chronic inflammation and systemic destruction of host organs or tissue. A key feature of SLE is T cell dysfunction characterized by hyperresponsive antigen receptor signaling. In this issue of the JCI, McDonald and colleagues provide evidence that homeostasis of a subset of lipids, the glycosphingolipids (GSLs), is severely perturbed in the membranes of T cells from SLE patients. Furthermore, normalization of GSLs restored TCR signaling and ameliorated T cell dysfunction. These data suggest that targeting host metabolism may be an effective means of reinforcing self-tolerance and attenuating autoimmunity. PMID:24463443

  16. Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer

    PubMed Central

    2014-01-01

    Background Loss of the endosulfatase HSulf-1 is common in ovarian cancer, upregulates heparin binding growth factor signaling and potentiates tumorigenesis and angiogenesis. However, metabolic differences between isogenic cells with and without HSulf-1 have not been characterized upon HSulf-1 suppression in vitro. Since growth factor signaling is closely tied to metabolic alterations, we determined the extent to which HSulf-1 loss affects cancer cell metabolism. Results Ingenuity pathway analysis of gene expression in HSulf-1 shRNA-silenced cells (Sh1 and Sh2 cells) compared to non-targeted control shRNA cells (NTC cells) and subsequent Kyoto Encyclopedia of Genes and Genomics (KEGG) database analysis showed altered metabolic pathways with changes in the lipid metabolism as one of the major pathways altered inSh1 and 2 cells. Untargeted global metabolomic profiling in these isogenic cell lines identified approximately 338 metabolites using GC/MS and LC/MS/MS platforms. Knockdown of HSulf-1 in OV202 cells induced significant changes in 156 metabolites associated with several metabolic pathways including amino acid, lipids, and nucleotides. Loss of HSulf-1 promoted overall fatty acid synthesis leading to enhance the metabolite levels of long chain, branched, and essential fatty acids along with sphingolipids. Furthermore, HSulf-1 loss induced the expression of lipogenic genes including FASN, SREBF1, PPARγ, and PLA2G3 stimulated lipid droplet accumulation. Conversely, re-expression of HSulf-1 in Sh1 cells reduced the lipid droplet formation. Additionally, HSulf-1 also enhanced CPT1A and fatty acid oxidation and augmented the protein expression of key lipolytic enzymes such as MAGL, DAGLA, HSL, and ASCL1. Overall, these findings suggest that loss of HSulf-1 by concomitantly enhancing fatty acid synthesis and oxidation confers a lipogenic phenotype leading to the metabolic alterations associated with the progression of ovarian cancer. Conclusions Taken together, these

  17. 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. PMID:26143618

  18. Genome-wide screen for inositol auxotrophy in Saccharomyces cerevisiae implicates lipid metabolism in stress response signaling

    PubMed Central

    Villa-García, Manuel J.; Choi, Myung Sun; Hinz, Flora I.; Gaspar, María L.; Jesch, Stephen A.

    2011-01-01

    Inositol auxotrophy (Ino− phenotype) in budding yeast has classically been associated with misregulation of INO1 and other genes involved in lipid metabolism. To identify all non-essential yeast genes that are necessary for growth in the absence of inositol, we carried out a genome-wide phenotypic screening for deletion mutants exhibiting Ino− phenotypes under one or more growth conditions. We report the identification of 419 genes, including 385 genes not previously reported, which exhibit this phenotype when deleted. The identified genes are involved in a wide range of cellular processes, but are particularly enriched in those affecting transcription, protein modification, membrane trafficking, diverse stress responses, and lipid metabolism. Among the Ino− mutants involved in stress response, many exhibited phenotypes that are strengthened at elevated temperature and/or when choline is present in the medium. The role of inositol in regulation of lipid metabolism and stress response signaling is discussed. PMID:21136082

  19. Optimal management of lipids in diabetes and metabolic syndrome.

    PubMed

    Brown, W Virgil; Clark, Luther; Falko, James M; Guyton, John R; Rees, Tomas J; Schonfeld, Gustav; Lopes-Virella, Maria F

    2008-10-01

    Patients with diabetes or metabolic syndrome frequently have higher triglycerides, lower high-density lipoprotein (HDL) cholesterol, and more particles containing apolipoprotein B (ApoB); this combination contributes significantly to their cardiovascular risk. Optimal management of dyslipidemia and increased atherosclerotic risk requires a fundamental understanding of diabetic dyslipidemia, the clinical evidence for different interventional strategies, and the potential benefit of achieving therapeutic targets. For this review, we considered guidelines, recent reviews, and clinical trial results. The features of dyslipidemia in type 2 diabetes and the metabolic syndrome are linked metabolically and are related to central adiposity and insulin resistance. Levels of ApoB and HDL cholesterol are particularly important markers of risk. Guidelines broadly agree that low-density lipoprotein (LDL) cholesterol should be reduced below population average levels. Additional or secondary strategies in patients with diabetes or the metabolic syndrome are to decrease non-HDL cholesterol, ApoB and/or LDL particle concentration, to increase HDL cholesterol, and to reduce triglycerides. Lifestyle changes and statins are the bedrock of treatment, although second-line treatment using fibrates or niacin will likely benefit many patients with residual risk. Ezetimibe, too, has a favorable effect on lipid profile and inflammatory biomarkers of risk. Dyslipidemia in type 2 diabetes and metabolic syndrome has a distinct profile, suggesting the need for a tailored therapy that targets the key features of lowered HDL cholesterol and raised triglycerides, in addition to the primary antiatherogenic strategy of lowering ApoB-containing lipoproteins, such as LDL. With the prominent failure of some recent intervention trials, new therapeutic strategies-particularly safe and effective means to raise HDL-are needed to manage dyslipidemia in this high-risk population. PMID:21291758

  20. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts

    PubMed Central

    Maldini, Mariateresa; Natella, Fausta; Baima, Simona; Morelli, Giorgio; Scaccini, Cristina; Langridge, James; Astarita, Giuseppe

    2015-01-01

    The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle). We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the potential of an

  1. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts.

    PubMed

    Maldini, Mariateresa; Natella, Fausta; Baima, Simona; Morelli, Giorgio; Scaccini, Cristina; Langridge, James; Astarita, Giuseppe

    2015-01-01

    The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird's-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle). We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant's developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the potential of an

  2. Identifying lipid metabolism genes in pig liver after clenbuterol administration.

    PubMed

    Liu, Qiuyue; Zhang, Jin; Guo, Wei; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2012-01-01

    Clenbuterol is a repartition agent (beta 2-adrenoceptor agonist) that can decrease fat deposition and increase skeletal muscle growth at manageable dose. To better understand the molecular mechanism of Clenbuterol's action, GeneChips and real-time PCR were used to compare the gene expression profiles of liver tissue in pigs with/without administration of Clenbuterol. Metabolism effects and the global gene expression profiles of liver tissue from Clenbuterol-treated and untreated pigs were conducted. Function enrichment tests showed that the differentially expressed genes are enriched in glycoprotein protein, plasma membrane, fatty acid and amino acid metabolic process, and cell differentiation and signal transduction groups. Pathway mining analysis revealed that physiological pathways such as MAPK, cell adhesion molecules, and the insulin signaling pathway, were remarkably regulated when Clenbuterol was administered. Gene prioritization algorithm was used to associate a number of important differentially expressed genes with lipid metabolism in response to Clenbuterol. Genes identified as differentially expressed in this study will be candidates for further investigation of the molecular mechanisms involved in Clenbuterol's effects on adipose and skeletal muscle tissue. PMID:22652664

  3. TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

    PubMed Central

    Du, Zhongkun; Zhang, Yan; Wang, Guowei; Peng, Jianbiao; Wang, Zunyao; Gao, Shixiang

    2016-01-01

    Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0.050 mg/L and 0.300 mg/L triphenyl phosphate for 7 days. Metabolomic analysis revealed significant changes in the contents of glucose, UDP-glucose, lactate, succinate, fumarate, choline, acetylcarnitine, and several fatty acids. Transcriptomic analysis revealed that related pathways, such as the glycosphingolipid biosynthesis, PPAR signaling pathway and fatty acid elongation, were significantly affected. These results suggest that triphenyl phosphate exposure markedly disturbs hepatic carbohydrate and lipid metabolism in zebrafish. Moreover, DNA replication, the cell cycle, and non-homologous end-joining and base excision repair were strongly affected, thus indicating that triphenyl phosphate hinders the DNA damage repair system in zebrafish liver cells. The present study provides a systematic analysis of the triphenyl phosphate-induced toxic effects in zebrafish liver and demonstrates that low concentrations of triphenyl phosphate affect normal metabolism and cell cycle. PMID:26898711

  4. TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

    NASA Astrophysics Data System (ADS)

    Du, Zhongkun; Zhang, Yan; Wang, Guowei; Peng, Jianbiao; Wang, Zunyao; Gao, Shixiang

    2016-02-01

    Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0.050 mg/L and 0.300 mg/L triphenyl phosphate for 7 days. Metabolomic analysis revealed significant changes in the contents of glucose, UDP-glucose, lactate, succinate, fumarate, choline, acetylcarnitine, and several fatty acids. Transcriptomic analysis revealed that related pathways, such as the glycosphingolipid biosynthesis, PPAR signaling pathway and fatty acid elongation, were significantly affected. These results suggest that triphenyl phosphate exposure markedly disturbs hepatic carbohydrate and lipid metabolism in zebrafish. Moreover, DNA replication, the cell cycle, and non-homologous end-joining and base excision repair were strongly affected, thus indicating that triphenyl phosphate hinders the DNA damage repair system in zebrafish liver cells. The present study provides a systematic analysis of the triphenyl phosphate-induced toxic effects in zebrafish liver and demonstrates that low concentrations of triphenyl phosphate affect normal metabolism and cell cycle.

  5. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids.

    PubMed

    Huang, Tom Hsun-Wei; Peng, Gang; Kota, Bhavani Prasad; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D; Li, Yuhao

    2005-07-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake. PMID:15880139

  6. 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. PMID:21146236

  7. 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.

  8. 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

  9. D/H Ratios in Lipids as a Tool to Elucidate Microbial Metabolism

    NASA Astrophysics Data System (ADS)

    Wijker, R. S.; Sessions, A. L.

    2015-12-01

    Large D/H fractionations have been observed in the lipids and growth water of most organisms studied today. These fractionations have generally been assumed to be constant across most biota because they originate solely from isotope effects imposed by the highly conserved lipid biosynthetic pathway. Recent data is illustrating this conclusion as incomplete. Lipids from field and laboratory samples exhibit huge variations in D/H fractionation. In environmental samples, lipids vary in δD by up to 300 ‰ and in laboratory cultures the documented variation is up to 500 ‰ within the same organism. Remarkably, the isotope fractionation appears to be correlated with the type of metabolism employed by the host organism. However, the underlying biochemical mechanisms leading to these isotopic variations are not yet fully understood. Because the largest proportion of H-bound C in fatty acids is derived directly from NADPH during biosynthesis, the original hypothesis was that large differences in the isotopic composition of NADPH, generated by different central metabolic pathways, were the primary source of D/H variation in lipids. However, recent observations indicate that this cannot be the whole story and lead us to the conclusion that additional processes must affect the isotope composition of NADPH. These processes may include the isotopic exchange of NADPH with water as well as fractionation of NADPH by transhydrogenases, interconverting NADH to NADPH by exhibiting large isotope effects. In this project, our objective is to ascertain whether D/H fractionation and these biochemical processes are correlated. We investigate correlations between cellular NADPH/NADP+ as well as NADH/NAD+ pool sizes and the D/H fractionation in a set of different microorganisms and will present the first trends here. Our results will contribute to a more comprehensive understanding of the basic biological regulations over D/H fractionation and potentially enables their use as tracers and

  10. D/H Ratios in Lipids as a Tool to Elucidate Microbial Metabolism

    NASA Astrophysics Data System (ADS)

    Wijker, Reto S.; Sessions, Alex L.

    2016-04-01

    Large D/H fractionations have been observed in the lipids and growth water of most organisms studied today. These fractionations have generally been assumed to be constant across most biota because they originate solely from isotope effects imposed by the highly conserved lipid biosynthetic pathway. Recent data is illustrating this conclusion as incomplete. Lipids from field and laboratory samples exhibit huge variations in D/H fractionation. In environmental samples, lipids vary in δD by up to 300 ‰ and in laboratory cultures the documented variation is up to 500 ‰ within the same organism. Remarkably, the isotope fractionation appears to be correlated with the type of metabolism employed by the host organism. However, the underlying biochemical mechanisms leading to these isotopic variations are not yet fully understood. Because the largest proportion of H-bound C in fatty acids is derived directly from NADPH during biosynthesis, the original hypothesis was that large differences in the isotopic composition of NADPH, generated by different central metabolic pathways, were the primary source of D/H variation in lipids. However, recent observations indicate that this cannot be the whole story and lead us to the conclusion that additional processes must affect the isotope composition of NADPH. These processes may include the isotopic exchange of NADPH with water as well as fractionation of NADPH by transhydrogenases, interconverting NADH to NADPH by exhibiting large isotope effects. In this project, our objective is to ascertain whether D/H fractionation and these biochemical processes are correlated. We investigate correlations between cellular NADPH/NADP+ as well as NADH/NAD+ pool sizes and the D/H fractionation in a set of different microorganisms and will present the trends here. Our results will contribute to a more comprehensive understanding of the basic biological regulations over D/H fractionation and potentially enables their use as tracers and

  11. The Role of Glucose and Lipid Metabolism in Growth and Survival of Cancer Cells.

    PubMed

    Brault, Charlene; Schulze, Almut

    2016-01-01

    One of the prerequisites for cell growth and proliferation is the synthesis of macromolecules, including proteins, nucleic acids and lipids. Cells have to alter their metabolism to allow the production of metabolic intermediates that are the precursors for biomass production. It is now evident that oncogenic signalling pathways target metabolic processes on several levels and metabolic reprogramming has emerged as a hallmark of cancer. The increased metabolic demand of cancer cells also produces selective dependencies that could be targeted for therapeutic intervention. Understanding the role of glucose and lipid metabolism in supporting cancer cell growth and survival is crucial to identify essential processes that could provide therapeutic windows for cancer therapy. PMID:27557532

  12. Leptin: a possible metabolic signal affecting reproduction.

    PubMed

    Spicer, L J

    2001-11-01

    Since its discovery in 1994, leptin, a protein hormone synthesized and secreted by adipose tissue, has been shown to regulate feed intake in several species including sheep and pigs. Although a nimiety of information exists regarding the physiological role of leptin in rodents and humans, the regulation and action of leptin in domestic animals is less certain. Emerging evidence in several species indicates that leptin may also affect the hypothalamo-pituitary-gonadal axis. Leptin receptor mRNA is present in the anterior pituitary and hypothalamus of several species, including sheep. In rats, effects of leptin on GnRH, LH and FSH secretion have been inconsistent, with leptin exhibiting both stimulatory and inhibitory action in vivo and in vitro. Evidence to support direct action of leptin at the level of the gonad indicates that the leptin receptor and its mRNA are present in ovarian tissue of several species, including cattle. These leptin receptors are functional, since leptin inhibits insulin-induced steroidogenesis of both granulosa and thecal cells of cattle in vitro. Leptin receptor mRNA is also found in the testes of rodents. As with the ovary, these receptors are functional, at least in rats, since leptin inhibits hCG-induced testosterone secretion by Leydig cells in vitro. During pregnancy, placental production of leptin may be a major contributor to the increase in maternal leptin in primates but not rodents. However, in both primates and rodents, leptin receptors exist in placental tissues and may regulate metabolism of the fetal-placental unit. As specific leptin immunoassays are developed for domestic animals, in vivo associations may then be made among leptin, body energy stores, dietary energy intake and reproductive function. This may lead to a more definitive role of leptin in domestic animal reproduction. PMID:11872320

  13. Effects on Liver Lipid Metabolism of the Naturally Occurring Dietary Flavone Luteolin-7-glucoside.

    PubMed

    Sá, Carla; Oliveira, Ana Rita; Machado, Cátia; Azevedo, Marisa; Pereira-Wilson, Cristina

    2015-01-01

    Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzyme's in vitro activity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables. PMID:26113868

  14. Effect of dietary phosphorus levels on meat quality and lipid metabolism in broiler chickens.

    PubMed

    Li, Xue-Ke; Wang, Jin-Zhi; Wang, Chun-Qing; Zhang, Chun-Hui; Li, Xia; Tang, Chun-Hong; Wei, Xiu-Li

    2016-08-15

    To analyze the influence of dietary phosphorus (P) levels on meat quality and lipid metabolism, a 42-day feeding experiment (P deficient group; normal group; high P level groups of H1 and H2, respectively) using 100 one-day-old broilers was conducted. Results demonstrated that the quality of broiler chicken meat in deficient or high P groups decreased relative to the normal group. High P diets resulted in increased lightness, redness values, shear forces and decreased fatty acid contents and intramuscular fat content in breast meat (p<0.01). Compared with normal group, lower malic enzyme activity, higher fatty acid synthase and AMP-activated protein kinase activities were observed in the treatment groups (p<0.05). Chickens fed with normal diets had the lowest serum total cholesterol and triglyceride levels which differed from that of other treatments (p<0.05). High-P diets significantly decreased the lipid accumulation in the liver (p<0.01), whereas phosphorus levels in breast meat increased significantly (p<0.01). It can be concluded that deficient or higher P levels could affect meat quality and expression of indicators on lipid metabolism of broiler chickens. PMID:27006242

  15. Effects on Liver Lipid Metabolism of the Naturally Occurring Dietary Flavone Luteolin-7-glucoside

    PubMed Central

    Sá, Carla; Oliveira, Ana Rita; Machado, Cátia; Azevedo, Marisa; Pereira-Wilson, Cristina

    2015-01-01

    Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzyme's in vitro activity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables. PMID:26113868

  16. [Lipids composition and speed of energy metabolism in gastropods].

    PubMed

    Arakelova, E S

    2008-01-01

    Lipid composition of digestive gland and pedal muscle of two northern freshwater pulmonate snails Lymnaea stagnalis and Lymnaea ovata and three marine prosobranch gastropods Littorina obtusata, Littorina littorea, Buccinum undatum from the White Sea was studied. The species differ in ecology, particularly in trophic nabits and motor activity. The content of triacilglycerides both in digestive gland and pedal was higher in littoral dwellers Littorina the activity of which depends on the tide level. The phospholipids content in digestive gland does not differ in quantity in all cases and does not relate to type of feeding or resource quality. In a pedal muscle of marine species the quantity of common phospholipids is higher in comparison with the freshwater ones. The amount of total phospholipids in pedal muscle correlates with mass of metabolic inert formation which constitutes a part of whole mass of snails. The presence of massive shell enhances demands in energy needed for supporting movement and activity. Because the intensity of energy metabolism is related to quantity of total phospholipids, mitochondria and activity of their oxidizing ferments, the presence of thick shell in marine snails together with motor activity costs more in terms of energy than in freshwater snails with thin shell. This hypothesis is supported by the higher specific rate of oxygen consumption in marine snails than in freshwaters. PMID:19140337

  17. Interaction between Glucose and Lipid Metabolism: More than Diabetic Dyslipidemia

    PubMed Central

    2015-01-01

    Glucose and lipid metabolism are linked to each other in many ways. The most important clinical manifestation of this interaction is diabetic dyslipidemia, characterized by elevated triglycerides, low high density lipoprotein cholesterol (HDL-C), and predominance of small-dense LDL particles. However, in the last decade we have learned that the interaction is much more complex. Hypertriglyceridemia and low HDL-C cannot only be the consequence but also the cause of a disturbed glucose metabolism. Furthermore, it is now well established that statins are associated with a small but significant increase in the risk for new onset diabetes. The underlying mechanisms are not completely understood but modulation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA)-reductase may play a central role as genetic data indicate that mutations resulting in lower HMG CoA-reductase activity are also associated with obesity, higher glucose concentrations and diabetes. Very interestingly, this statin induced increased risk for new onset type 2 diabetes is not detectable in subjects with familial hypercholesterolemia. Furthermore, patients with familial hypercholesterolemia seem to have a lower risk for type 2 diabetes, a phenomenon which seems to be dose-dependent (the higher the low density lipoprotein cholesterol, the lower the risk). Whether there is also an interaction between lipoprotein(a) and diabetes is still a matter of debate. PMID:26566492

  18. 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

  19. Lysine-Specific Demethylase 2 Suppresses Lipid Influx and Metabolism in Hepatic Cells

    PubMed Central

    Nagaoka, Katsuya; Sakamoto, Akihisa; Anan, Kotaro; Takase, Ryuta; Umehara, Takashi; Yokoyama, Shigeyuki; Sasaki, Yutaka

    2015-01-01

    Cells link environmental fluctuations, such as nutrition, to metabolic remodeling. Epigenetic factors are thought to be involved in such cellular processes, but the molecular basis remains unclear. Here we report that the lysine-specific demethylase 2 (LSD2) suppresses the flux and metabolism of lipids to maintain the energy balance in hepatic cells. Using transcriptome and chromatin immunoprecipitation-sequencing analyses, we revealed that LSD2 represses the genes involved in lipid influx and metabolism through demethylation of histone H3K4. Selective recruitment of LSD2 at lipid metabolism gene loci was mediated in part by a stress-responsive transcription factor, c-Jun. Intriguingly, LSD2 depletion increased the intracellular levels of many lipid metabolites, which was accompanied by an increased susceptibility to toxic cell damage in response to fatty acid exposure. Our data demonstrate that LSD2 maintains metabolic plasticity under fluctuating environment in hepatocytes by mediating the cross talk between the epigenome and metabolism. PMID:25624347

  20. Genetic variants in lipid metabolism are independently associated with multiple features of the metabolic syndrome

    PubMed Central

    2011-01-01

    Background Our objective was to find single nucleotide polymorphisms (SNPs), within transcriptional pathways of glucose and lipid metabolism, which are related to multiple features of the metabolic syndrome (MetS). Methods 373 SNPs were measured in 3575 subjects of the Doetinchem cohort. Prevalence of MetS features, i.e. hyperglycemia, abdominal obesity, decreased HDL-cholesterol levels and hypertension, were measured twice in 6 years. Associations between the SNPs and the individual MetS features were analyzed by log-linear models. For SNPs related to multiple MetS features (P < 0.01), we investigated whether these associations were independent of each other. Results Two SNPs, CETP Ile405Val and APOE Cys112Arg, were associated with both the prevalence of low HDL-cholesterol level (Ile405Val P = < .0001; Cys112Arg P = 0.001) and with the prevalence of abdominal obesity (Ile405Val P = 0.007; Cys112Arg P = 0.007). For both SNPs, the association with HDL-cholesterol was partly independent of the association with abdominal obesity and vice versa. Conclusion Two SNPs, mainly known for their role in lipid metabolism, were associated with two MetS features i.e., low HDL-cholesterol concentration, as well as, independent of this association, abdominal obesity. These SNPs may help to explain why low HDL-cholesterol levels and abdominal obesity frequently co-occur. PMID:21767357

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

    PubMed

    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. 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

  3. 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.

  4. Effect of alcohol consumption on hormones involved in carbohydrate and lipid metabolism in premenopausal women

    SciTech Connect

    Law, J.S.; Bhathena, S.J.; Kim, Y.C.; Berlin, E.; Judd, J.T.; Reichman, M.E.; Taylor, P.R.; Schatzkin, A. NCI, Bethesda, MD )

    1991-03-15

    Alcohol consumption alters carbohydrate and lipid metabolism which are in part regulated by pancreatic and adrenal hormones. The menstrual cycle per se produces changes in several peptide and steroid hormones besides the sex hormones. The authors investigated the effect of moderate alcohol consumption on plasma hormone levels in 40 premenopausal women. The subjects were fed controlled diets containing 35% of calories from fat. In a random crossover design women were given either alcohol or a soft-drink of equal caloric value for 3 menstrual cycles. Fasting blood samples were collected in the third cycle during follicular, ovulatory and luteal phases. Plasma dehydroepiandrosterone-sulphate (DHEA-S), insulin, glucagon and cortisol levels were measured by radioimmunoassay. Moderate alcohol consumption had no effect on plasma insulin and DHEA-S levels but significantly increased glucagon and cortisol levels. Menstrual cycle per se affected plasma glucagon level in that the levels were higher during follicular phase than luteal phase. Thus, changes in carbohydrate and lipid metabolism following alcohol consumption are mediated in part by alterations in hormones involved in their metabolism.

  5. 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

  6. Peroxisomes Are Required for Lipid Metabolism and Muscle Function in Drosophila melanogaster

    PubMed Central

    Faust, Joseph E.; Manisundaram, Arvind; Ivanova, Pavlina T.; Milne, Stephen B.; Summerville, James B.; Brown, H. Alex; Wangler, Michael; Stern, Michael; McNew, James A.

    2014-01-01

    Peroxisomes are ubiquitous organelles that perform lipid and reactive oxygen species metabolism. Defects in peroxisome biogenesis cause peroxisome biogenesis disorders (PBDs). The most severe PBD, Zellweger syndrome, is characterized in part by neuronal dysfunction, craniofacial malformations, and low muscle tone (hypotonia). These devastating diseases lack effective therapies and the development of animal models may reveal new drug targets. We have generated Drosophila mutants with impaired peroxisome biogenesis by disrupting the early peroxin gene pex3, which participates in budding of pre-peroxisomes from the ER and peroxisomal membrane protein localization. pex3 deletion mutants lack detectible peroxisomes and die before or during pupariation. At earlier stages of development, larvae lacking Pex3 display reduced size and impaired lipid metabolism. Selective loss of peroxisomes in muscles impairs muscle function and results in flightless animals. Although, hypotonia in PBD patients is thought to be a secondary effect of neuronal dysfunction, our results suggest that peroxisome loss directly affects muscle physiology, possibly by disrupting energy metabolism. Understanding the role of peroxisomes in Drosophila physiology, specifically in muscle cells may reveal novel aspects of PBD etiology. PMID:24945818

  7. Peroxisomes are required for lipid metabolism and muscle function in Drosophila melanogaster.

    PubMed

    Faust, Joseph E; Manisundaram, Arvind; Ivanova, Pavlina T; Milne, Stephen B; Summerville, James B; Brown, H Alex; Wangler, Michael; Stern, Michael; McNew, James A

    2014-01-01

    Peroxisomes are ubiquitous organelles that perform lipid and reactive oxygen species metabolism. Defects in peroxisome biogenesis cause peroxisome biogenesis disorders (PBDs). The most severe PBD, Zellweger syndrome, is characterized in part by neuronal dysfunction, craniofacial malformations, and low muscle tone (hypotonia). These devastating diseases lack effective therapies and the development of animal models may reveal new drug targets. We have generated Drosophila mutants with impaired peroxisome biogenesis by disrupting the early peroxin gene pex3, which participates in budding of pre-peroxisomes from the ER and peroxisomal membrane protein localization. pex3 deletion mutants lack detectible peroxisomes and die before or during pupariation. At earlier stages of development, larvae lacking Pex3 display reduced size and impaired lipid metabolism. Selective loss of peroxisomes in muscles impairs muscle function and results in flightless animals. Although, hypotonia in PBD patients is thought to be a secondary effect of neuronal dysfunction, our results suggest that peroxisome loss directly affects muscle physiology, possibly by disrupting energy metabolism. Understanding the role of peroxisomes in Drosophila physiology, specifically in muscle cells may reveal novel aspects of PBD etiology. PMID:24945818

  8. 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. PMID:26886165

  9. Influence of minor plant constituents on porcine hepatic lipid metabolism. Impact on serum lipids.

    PubMed

    Qureshi, A A; Crenshaw, T D; Abuirmeileh, N; Peterson, D M; Elson, C E

    1987-04-01

    The effects of plant constituents on lipid metabolism were examined in swine that had been fed for 4 weeks a standard diet containing, in addition, (per kg diet) 3.15 g of the methanol serial solvent fraction garlic bulbs or 3.5 g of the petroleum ether solubles high-protein barley flour or 5 mg of the plant growth regulator, AMO 1618. All treatments suppressed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase activities. Modest increases in serum triglycerides were associated with significantly increased hepatic lipogenic activities in response to all treatments except that of the barley extract. The methanol solubles of a second lot of garlic were fractionated by HPLC and tested in an avian hepatocyte system. One component, an isoprenoid metabolite, MW 358, suppressed HMG-CoA reductase. PMID:3606707

  10. Migratory refueling affects non-enzymatic antioxidant capacity, but does not increase lipid peroxidation.

    PubMed

    Eikenaar, Cas; Jönsson, Johanna; Fritzsch, Anna; Wang, Hong-Lei; Isaksson, Caroline

    2016-05-01

    All aerobic organisms are to some degree affected by oxidative stress, which is an imbalance between pro-oxidants and antioxidants in favor of the former. Pro-oxidants can damage DNA, proteins and lipids, and as such oxidative stress can carry considerably fitness costs. In mammals excessive calorie intake is a known cause of oxidative stress. We investigated whether in migrant birds, which typically engage in over-eating in between flights (refueling), high food intake causes oxidative stress. In an experiment we compared levels of plasmatic total non-enzymatic antioxidant capacity (AOX) and oxidative damage (lipid peroxidation) between migrants repeatedly fasted and refed (simulating the flight-refuel cycle of wild migrants), and migrants on ad libitum food. We found that refueling increased AOX, an effect mainly attributable to an increase in uric acid level, an antioxidant that is produced during protein metabolism. Accordingly, variation in AOX was mainly explained by the refueling birds' food intake. However, food intake in migrants on ad libitum food did not explain any variation in AOX. Refueling did not affect lipid peroxidation, nor were its levels explained by food intake. We propose that over-eating migrants retain uric acid, which might be a very low cost mechanism to forego oxidative damage. PMID:26921098

  11. Factors affecting metabolic syndrome by lifestyle

    PubMed Central

    Ki, Nam-Kyun; Lee, Hae-Kag; Cho, Jae-Hwan; Kim, Seon-Chil; Kim, Nak-Sang

    2016-01-01

    [Purpose] The aim of this study was to explore lifestyle factors in relation to metabolic syndrome so as to be able to utilize the results as baseline data for the furtherance of health-care and medical treatment. [Subjects and Methods] This study was conducted with patients who visited a health care center located in Seoul and had abdominal ultrasonography between 2 March 2013 and 28 February, 2014. Heights, weights, and blood pressures were measured by automatic devices. Three radiologists examined the patients using abdominal ultrasonography for gallstone diagnosis. The statuses of patients with regard to smoking, alcohol, coffee, and physical activities were explored for the lifestyle investigation. For investigating baseline demographics, we first used descriptive statistics. We then used the χ2 test to analyze lifestyles and gallstone prevalence with regard to the presence of metabolic syndrome. Lastly, logistic regression analysis was conducted to discover the risk factors of metabolic syndrome. [Results] For men, body mass index, maximum gallstone size, and waist circumference were revealed as risk factors for metabolic syndrome, in descending order of the degree of risk. For females, gallstone presence was the most significant risk factor, followed by waist circumference. [Conclusion] Metabolic disease mainly presents itself along with obesity, and we should become more focused on preventing and treating this disease. A large-scale prospective study is needed in the future, as the cause of nonalcoholic steatohepatitis remained unclear in this study. PMID:26957725

  12. 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. PMID:26807857

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

    PubMed Central

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L.; Black, Katherine

    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. PMID:26807857

  14. Hypolipidemic effect of dietary pea proteins: Impact on genes regulating hepatic lipid metabolism.

    PubMed

    Rigamonti, Elena; Parolini, Cinzia; Marchesi, Marta; Diani, Erika; Brambilla, Stefano; Sirtori, Cesare R; Chiesa, Giulia

    2010-05-01

    Controversial data on the lipid-lowering effect of dietary pea proteins have been provided and the mechanisms behind this effect are not completely understood. The aim of the study was to evaluate a possible hypolipidemic activity of a pea protein isolate and to determine whether pea proteins could affect the hepatic lipid metabolism through regulation of genes involved in cholesterol and fatty acid homeostasis. Rats were fed Nath's hypercholesterolemic diets for 28 days, the protein sources being casein or a pea protein isolate from Pisum sativum. After 14 and 28 days of dietary treatment, rats fed pea proteins had markedly lower plasma cholesterol and triglyceride levels than rats fed casein (p<0.05). Pea protein-fed rats displayed higher hepatic mRNA levels of LDL receptor versus those fed casein (p<0.05). Hepatic mRNA concentration of genes involved in fatty acids synthesis, such as fatty acid synthase and stearoyl-CoA desaturase, was lower in pea protein-fed rats than in rats fed casein (p<0.05). In conclusion, the present study demonstrates a marked cholesterol and triglyceride-lowering activity of pea proteins in rats. Moreover, pea proteins appear to affect cellular lipid homeostasis by upregulating genes involved in hepatic cholesterol uptake and by downregulating fatty acid synthesis genes. PMID:20077421

  15. Up-Regulation of the Cardiac Lipid Metabolism at the Onset of Heart Failure

    PubMed Central

    AbdAlla, Said; Fu, Xuebin; Elzahwy, Sherif S; Klaetschke, Kristin; Streichert, Thomas; Quitterer, Ursula

    2011-01-01

    Chronic pressure overload and atherosclerosis are primary etiologic factors for cardiac hypertrophy and failure. However, mechanisms underlying the transition from hypertrophy to heart failure are incompletely understood. We analyzed the development of heart failure in mice with chronic pressure overload induced by aortic constriction and compared the results with aged apolipoprotein E-deficient mice suffering from advanced atherosclerosis. We combined cardiac function analysis by echocardiography and invasive hemodynamics with a comprehensive microarray gene expression study (GSE25765-8). The microarray data showed that the onset of heart failure induced by pressure overload or advanced atherosclerosis was accompanied by a strong up-regulation of key lipid metabolizing enzymes involved in fat synthesis, storage and oxidation. Cardiac lipid overload may be involved in the progression of heart failure by enhancing cardiomyocyte death. Up-regulation of the cardiac lipid metabolism was related to oxygen and ATP depletion of failing hearts because anti-ischemic treatment with ranolazine normalized the cardiac lipid metabolism and improved cardiac function. Vice versa, inhibition of cellular respiration and ATP generation by mild thiol-blocking with cystamine triggered the cardiac lipid metabolism and caused signs of heart failure. Cardiac tissue specimens of patients with heart failure also showed high protein levels of key fat metabolizing enzymes as well as lipid accumulation. Taken together, our data strongly indicate that up-regulation of the cardiac lipid metabolism and myocardial lipid overload are underlying the development of heart failure. PMID:21711241

  16. Multiple dietary supplements do not affect metabolic and cardiovascular health.

    PubMed

    Soare, Andreea; Weiss, Edward P; Holloszy, John O; Fontana, Luigi

    2013-09-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24036417

  17. Multiple dietary supplements do not affect metabolic and cardiovascular health

    PubMed Central

    Holloszy, John O.; Fontana, Luigi

    2014-01-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

  18. Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis.

    PubMed

    Sharma, Monika; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Prasad, Rajendra

    2012-01-01

    This study shows that antifungal curcumin (CUR), significantly depletes ergosterol levels in Candida albicans. CUR while displaying synergy with fluconazole (FLC) lowers ergosterol. However, CUR alone at its synergistic concentration (lower than MIC50), could not affect ergosterol contents. For deeper insight of CUR effects on lipids, we performed high throughput mass spectroscopy (MS) based lipid profiling of C. albicans cells. The lipidome analysis revealed that there were no major changes in phosphoglycerides (PGLs) composition following CUR treatment of Candida, however, significant differences in molecular species of PGLs were detected. Among major SPLs, CUR treatment resulted in the reduction of ceramide and accumulation of IPCs levels. The lipidome of CUR treated cells confirmed a dramatic drop in the ergosterol levels with a simultaneous accumulation of its biosynthetic precursors. This was further supported by the fact that the mutants defective in ergosterol biosynthesis (ERG2 and ERG11) and those lacking the transcription factor regulating ergosterol biosynthesis, UPC2, were highly susceptible to CUR. Our study first time shows that CUR, for its antifungal activity, targets and down regulates delta 5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of reactive oxygen species (ROS) and cell death. PMID:22201946

  19. Plasma and Liver Lipid Profiles in Rats Exposed to Chronic Hypobaric Hypoxia: Changes in Metabolic Pathways

    PubMed Central

    Brito, Julio; Naveas, Nelson; Pulido, Ruth; De la Cruz, Juan José; Mamani, Maribel; León-Velarde, Fabiola

    2014-01-01

    Abstract Siques, Patricia, Julio Brito, Nelson Naveas, Ruth Pulido, Juan José De la Cruz, Maribel Mamani, and Fabiola León-Velarde. Plasma and liver lipid profiles in rats exposed to chronic hypobaric hypoxia: Changes in metabolic pathways. High Alt Med Biol 15:388–395, 2014.—Lipid metabolism under chronic hypoxia (CH) has not received equal attention as intermittent hypoxia (IH). To determine the CH-induced changes in plasma and liver, as well as the mRNA and protein expression of two key enzymes in the triglyceride and cholesterol biosynthesis pathways, SREBP-1 (HMG-CoA reductase) and SREBP-2 (SCD-1), we exposed adult male Wistar rats to CH (4600 m; n=15) for 30 days compared to normoxic rats (n=15). The CH rats exhibited weight loss (p<0.001), higher hematocrit (%), and higher hemoglobin (g/dL) (p<0.01). In the plasma of CH rats, total cholesterol and LDL-cholesterol increased at day 15. VLDL-cholesterol and triglycerides (p<0.01) greatly increased (35%), while HDL-cholesterol decreased (p<0.01). Triglycerides and VLDL-cholesterol remained elevated by 28% at day 30 (p<0.01). Hepatic triglycerides increased two-fold, while total cholesterol increased by 51% (p<0.001; p<0.05). Upregulation of SCD-1 mRNA and protein was observed in the CH rats (p<0.01); however, no differences were observed in HMG-CoA reductase mRNA or protein expression in both groups. In conclusion, CH, like IH, alters lipid profiles by increasing triglycerides in the plasma and liver and upregulating triglyceride biosynthesis without affecting the cholesterol biosynthetic pathway. Additional involved mechanisms require further study because of the importance of lipids in cardiovascular risk. PMID:25185022

  20. Unexpected roles of plastoglobules (plastid lipid droplets) in vitamin K1 and E metabolism.

    PubMed

    Spicher, Livia; Kessler, Felix

    2015-06-01

    Tocopherol (vitamin E) and phylloquinone (vitamin K1) are lipid-soluble antioxidants that can only be synthesized by photosynthetic organisms. These compounds function primarily at the thylakoid membrane but are also present in chloroplast lipid droplets, also known as plastoglobules (PG). Depending on environmental conditions and stage of plant development, changes in the content, number and size of PG occur. PG are directly connected to the thylakoid membrane via the outer lipid leaflet. Apart from storage, PG are active in metabolism and likely trafficking of diverse lipid species. This review presents recent advances on how plastoglobules are implicated in the biosynthesis and metabolism of vitamin E and K. PMID:26037391

  1. Transcription analysis of genes involved in lipid metabolism reveals the role of chromium in reducing body fat in animal models.

    PubMed

    Sadeghi, Mostafa; Najaf Panah, Mohammad Javad; Bakhtiarizadeh, Mohammad Reza; Emami, Ali

    2015-10-01

    Chromium was proposed to be an essential trace element over 50 years ago and has been accepted as an essential element for over 30 years. The recent studies indicated that the addition of supra nutritional amounts of chromium to the diet can only be considered as having pharmacological effects. However, the precise mechanism through which chromium acts on lipid, carbohydrate, protein and nucleic acid metabolism are relatively poor studied. To uncover, at least partially, the role of chromium in lipid metabolism, in this study, we evaluated the expression status of eight important genes, involved in fat biosynthesis and lipid metabolism, in four different tissue types (liver, subcutaneous fat, visceral fat, and longissimus muscle) in domestic goat kids feeding on three different chromium levels. The quantitative real-time PCR (RT-PCR) was established for expression analyses with HSP90 gene was used as reference gene. The results showed that supplementation of goats with 1.5mg/day chromium significantly decreases the expression of the ACC1, DGAT1, FABP4, FAS, HSL, LEP genes, but does not affect the expression of the LPL and SCD1 genes in all studied tissues. This study highlights, for the first time, the role of supra nutritional levels of chromium in lipid biosynthesis and metabolism. These findings are of especial importance for improving meat quality in domestic animals. PMID:26302911

  2. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age.

    PubMed

    Keith, Dove; Finlay, Liam; Butler, Judy; Gómez, Luis; Smith, Eric; Moreau, Régis; Hagen, Tory

    2014-07-18

    It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks. PMID:24944020

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

    PubMed

    Daker, Maelinda; Bhuvanendran, Saatheeyavaane; Ahmad, Munirah; Takada, Kenzo; Khoo, Alan Soo-Beng

    2013-03-01

    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

  4. Selected parameters of lipid metabolism in young vegetarians.

    PubMed

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Ondreicka, R; Klvanová, J

    1994-01-01

    Selected parameters of lipid metabolism (cholesterol, HDL cholesterol, LDL cholesterol, atherogenic index, triacylglycerols, vitamin C, vitamin E, vitamin E/cholesterol, plasma fatty acid profile) and pro-oxidative/anti-oxidative parameters (conjugated dienes of fatty acids, activity of catalase and glutathione peroxidase) were estimated in blood of 59 healthy vegetarians aged 19-30 years. When compared to non-vegetarians, no incidence of obesity, low levels of cholesterol, LDL cholesterol, atherogenic index or triacylglycerols, HDL cholesterol levels on the margin of 1.4 mmol/l (boundary level between standard and reduced risk) as well as a higher plasma content of polyunsaturated fatty acids and a higher 18:2/18:1 ratio were all favourable consequences of vegetarianism with respect to atherosclerosis prevention. These factors are completed by higher levels of protective compounds with antisclerotic activity (vitamin C, vitamin E/cholesterol--protecting LDL from lipoperoxidation) as well as by beneficial pro-oxidative/anti-oxidative parameters (low values of conjugated dienes, significantly higher activity of catalase, higher level of vitamin C). PMID:7702361

  5. Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation.

    PubMed

    Younis, Sidra; Blumenberg, Miroslav; Javed, Qamar

    2016-05-01

    Acne vu lgaris is a multifactorial inflammatory skin disease causing social stigma and psychological effect on patients. We hypothesized that the genes that can affect both lipid metabolism and inflammation may be central for acne formation and present targets for treatment. Pro-inflammatory adipokine resistin, one such likely target, activates NFkB and JNK pathways inducing TLR-2, IL-1, IL-6, and TNFα genes. The polymorphisms in promoter and intron region of the resistin gene affect its expression levels. Therefore, we explored the association of resistin polymorphisms (RETN +299G > A and -420C > G) with pathogenesis of acne vulgaris. We used PCR-RFLP method to genotype at the two single nucleotide polymorphisms at RETN promoter in 530 acne patients vs. 550 age- and sex-matched control subjects. We also measured serum lipid levels in acne patients and associated these with RETN genotypes. We found that the RETN gene polymorphisms are strongly associated with acne vulgaris and the severity of acne symptoms. In females the variant allele frequencies of both SNPs are statistically higher in patients than in controls; in males frequency distribution does not reach significance. The haplotype containing both variant alleles is significantly more common in patients than in controls. We find no association of RETN SNPs with the acne types. Importantly, we found that the levels of HDL-C were significantly decreased in variant genotype of RETN. Our results show that the RETN polymorphisms expected to boost resistin expression increase the risk of developing acne. We suggest that resistin may provide an attractive target for treatment. PMID:26858108

  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.

  7. Desorption Electrospray Ionization Mass Spectrometry Reveals Lipid Metabolism of Individual Oocytes and Embryos

    PubMed Central

    González-Serrano, Andrés Felipe; Pirro, Valentina; Ferreira, Christina R.; Oliveri, Paolo; Eberlin, Livia S.; Heinzmann, Julia; Lucas-Hahn, Andrea; Niemann, Heiner; Cooks, Robert Graham

    2013-01-01

    Alteration of maternal lipid metabolism early in development has been shown to trigger obesity, insulin resistance, type 2 diabetes and cardiovascular diseases later in life in humans and animal models. Here, we set out to determine (i) lipid composition dynamics in single oocytes and preimplantation embryos by high mass resolution desorption electrospray ionization mass spectrometry (DESI-MS), using the bovine species as biological model, (ii) the metabolically most relevant lipid compounds by multivariate data analysis and (iii) lipid upstream metabolism by quantitative real-time PCR (qRT-PCR) analysis of several target genes (ACAT1, CPT 1b, FASN, SREBP1 and SCAP). Bovine oocytes and blastocysts were individually analyzed by DESI-MS in both positive and negative ion modes, without lipid extraction and under ambient conditions, and were profiled for free fatty acids (FFA), phospholipids (PL), cholesterol-related molecules, and triacylglycerols (TAG). Principal component analysis (PCA) and linear discriminant analysis (LDA), performed for the first time on DESI-MS fused data, allowed unequivocal discrimination between oocytes and blastocysts based on specific lipid profiles. This analytical approach resulted in broad and detailed lipid annotation of single oocytes and blastocysts. Results of DESI-MS and transcript regulation analysis demonstrate that blastocysts produced in vitro and their in vivo counterparts differed significantly in the homeostasis of cholesterol and FFA metabolism. These results should assist in the production of viable and healthy embryos by elucidating in vivo embryonic lipid metabolism. PMID:24073231

  8. Swimming improves high-fat induced insulin resistance by regulating lipid and energy metabolism and the insulin pathway in rats.

    PubMed

    Song, An; Wang, Chao; Ren, Luping; Zhao, Jiajun

    2014-06-01

    muscle, energy metabolism in skeletal muscle and insulin signaling transduction were all markedly upregulated. In conclusion, swimming can effectively improve insulin sensitivity and even prevent insulin resistance by affecting the expression of proteins related to lipid metabolism, energy metabolism and insulin signaling transduction in rats fed a high-fat diet. PMID:24715199

  9. 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. PMID:17928741

  10. MicroRNAs and Noncoding RNAs in Hepatic Lipid and Lipoprotein Metabolism: Potential Therapeutic Targets of Metabolic Disorders

    PubMed Central

    Sud, Neetu; Taher, Jennifer; Su, Qiaozhu

    2015-01-01

    Noncoding RNAs and microRNAs (miRNAs) represent an important class of regulatory molecules that modulate gene expression. The role of miRNAs in diverse cellular processes such as cancer, apoptosis, cell differentiation, cardiac remodeling, and inflammation has been intensively explored. Recent studies further demonstrated the important roles of miRNAs and noncoding RNAs in modulating a broad spectrum of genes involved in lipid synthesis and metabolic pathways. This overview focuses on the role of miRNAs in hepatic lipid and lipoprotein metabolism and their potential as therapeutic targets for metabolic syndrome. This included recent advances made in the understanding of their target pathways and the clinical development of miRNAs in lipid metabolic disorders. PMID:26286650

  11. Mechanics of lipid bilayer junctions affecting the size of a connecting lipid nanotube

    NASA Astrophysics Data System (ADS)

    Karlsson, Roger; Kurczy, Michael; Grzhibovskis, Richards; Adams, Kelly L.; Ewing, Andrew G.; Cans, Ann-Sofie; Voinova, Marina V.

    2011-06-01

    In this study we report a physical analysis of the membrane mechanics affecting the size of the highly curved region of a lipid nanotube (LNT) that is either connected between a lipid bilayer vesicle and the tip of a glass microinjection pipette (tube-only) or between a lipid bilayer vesicle and a vesicle that is attached to the tip of a glass microinjection pipette (two-vesicle). For the tube-only configuration (TOC), a micropipette is used to pull a LNT into the interior of a surface-immobilized vesicle, where the length of the tube L is determined by the distance of the micropipette to the vesicle wall. For the two-vesicle configuration (TVC), a small vesicle is inflated at the tip of the micropipette tip and the length of the tube L is in this case determined by the distance between the two interconnected vesicles. An electrochemical method monitoring diffusion of electroactive molecules through the nanotube has been used to determine the radius of the nanotube R as a function of nanotube length L for the two configurations. The data show that the LNT connected in the TVC constricts to a smaller radius in comparison to the tube-only mode and that tube radius shrinks at shorter tube lengths. To explain these electrochemical data, we developed a theoretical model taking into account the free energy of the membrane regions of the vesicles, the LNT and the high curvature junctions. In particular, this model allows us to estimate the surface tension coefficients from R( L) measurements.

  12. Effect of different dietary levels of mangrove (Laguncularia racemosa) leaves and spice supplementation on productive performance, egg quality, lipid metabolism and metabolic profiles in laying hens.

    PubMed

    Al-Harthi, M A; El-Deek, A A; Attia, Y A; Bovera, F; Qota, E M

    2009-11-01

    In order to study the influence of white mangrove (Laguncularia racemosa) leaves on productive performance, egg quality, lipids metabolism and metabolic profiles, 180 Hy-line laying hens were randomly distributed to 6 dietary treatments each contained 6 replicates of 5 individually caged hens during the period from 50 to 60 weeks of age. 2. Three isoenergetic and isonitrogenous diets were formulated to contain 0, 50 and 100 g/kg of sun-dried mangrove leaves. Each diet was fed with or without supplementation of 2 g of cardamom, cumin, hot and black pepper mixture (1:1:1:1)/kg diet. 3. Mangrove leaves at either 50 or 100 g/kg adversely affect laying rate, egg mass and FCR, whilst increasing water intake and water to feed ratio. Mangrove leaves had no significant effect on dry matter, protein, lipid, cholesterol and ash content of liver, or on dry matter, protein and ash of yolk. 4. Plasma total protein, total lipids; liver enzymes AST and ALT and mortality rate were not significantly affected by mangrove leaves. On the other hand, yolk lipid, yolk cholesterol and plasma cholesterol significantly decreased, while yolk colour significantly increased with inclusion of 50 or 100 g/kg mangrove leaves, and Haugh unit score significantly increased with 100 g/kg mangrove leaves. 5. Spice mixture significantly increased egg weight by 2.2%. Yolk lipid content significantly decreased by 2.6%, while yolk colour and Haugh unit significantly increased with inclusion of spice mixtures. 6. In conclusion, mangrove leaves at 50 g/kg may be included in the laying hen diets as a means of decreasing lipid and cholesterol in yolk and plasma cholesterol and increasing yolk colour. Spice mixture at 2 g of cardamom, cumin, hot and black pepper mixture (1:1:1:1)/kg diet increased laying rate, egg mass, Haugh unit score and yolk colour while decreasing yolk lipids. PMID:19946823

  13. Factors affecting Archaeal Lipid Compositions of the Sulfolobus Species

    NASA Astrophysics Data System (ADS)

    He, L.; Han, J.; Wei, Y.; Lin, L.; Wei, Y.; Zhang, C.

    2010-12-01

    Temperature is the best known variable affecting the distribution of the archaeal glycerol dibiphytanyl glycerol tetraethers (GDGTs) in marine and freshwater systems. Other variables such as pH, ionic strength, or bicarbonate concentration may also affect archaeal GDGTs in terrestrial systems. Studies of pure cultures can help us pinpoint the specific effects these variables may have on archaeal lipid distribution in natural environments. In this study, three Sulfolobus species (HG4, HB5-2, HB9-6) isolated from Tengchong hot springs (pH 2-3, temperature 73-90°C) in China were used to investigate the effects of temperature, pH, substrate, and type of strain on the composition of GDGTs. Results showed that increase in temperature had negative effects on the relative contents of GDGT-0 (no cyclopentyl rings), GDGT-1 (one cyclopentyl ring), GDGT-2 and GDGT-3 but positive effects on GDGT-4, GDGT-4', GDGT-5 and GDGT-5'. Increase in pH, on the other hand, had negative effects on GDGT-0, GDGT-1, GDGT-4', GDGT-5 and GDGT-5', and positive effects on GDGT-3 and GDGT-4. GDGT-2 remained relatively constant with changing pH. When the HG4 was grown on different substrates, GDGT-5 was five time more abundant in sucrose-grown cultures than in yeast extract- or sulfur- grown cultures, suggesting that carbohydrates may stimulate the production of GDGT-5. For all three species, the ring index (average number of rings) of GDGTs correlated positively with incubation temperature. In HG4, ring index was much lower at optimal pH (3.5) than at other pH values. Ring index of HB5-2 or HB9-6 is higher than that of HG4, suggesting that speciation may affect the degree of cyclization of GDGT of the Sulfolobus. These results indicate that individual archaeal lipids respond differently to changes in environmental variables, which may be also species specific.

  14. Effect of Peripheral 5-HT on Glucose and Lipid Metabolism in Wether Sheep

    PubMed Central

    Watanabe, Hitoshi; Saito, Ryo; Nakano, Tatsuya; Takahashi, Hideyuki; Takahashi, Yu; Sumiyoshi, Keisuke; Sato, Katsuyoshi; Chen, Xiangning; Okada, Natsumi; Iwasaki, Shunsuke; Harjanti, Dian W.; Sekiguchi, Natsumi; Sano, Hiroaki; Kitazawa, Haruki; Rose, Michael T.; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

    2014-01-01

    In mice, peripheral 5-HT induces an increase in the plasma concentrations of glucose, insulin and bile acids, and a decrease in plasma triglyceride, NEFA and cholesterol concentrations. However, given the unique characteristics of the metabolism of ruminants relative to monogastric animals, the physiological role of peripheral 5-HT on glucose and lipid metabolism in sheep remains to be established. Therefore, in this study, we investigated the effect of 5-HT on the circulating concentrations of metabolites and insulin using five 5-HT receptor (5HTR) antagonists in sheep. After fasting for 24 h, sheep were intravenously injected with 5-HT, following which-, plasma glucose, insulin, triglyceride and NEFA concentrations were significantly elevated. In contrast, 5-HT did not affect the plasma cholesterol concentration, and it induced a decrease in bile acid concentrations. Increases in plasma glucose and insulin concentrations induced by 5-HT were attenuated by pre-treatment with Methysergide, a 5HTR 1, 2 and 7 antagonist. Additionally, decreased plasma bile acid concentrations induced by 5-HT were blocked by pre-treatment with Ketanserin, a 5HTR 2A antagonist. However, none of the 5HTR antagonists inhibited the increase in plasma triglyceride and NEFA levels induced by 5-HT. On the other hand, mRNA expressions of 5HTR1D and 1E were observed in the liver, pancreas and skeletal muscle. These results suggest that there are a number of differences in the physiological functions of peripheral 5-HT with respect to lipid metabolism between mice and sheep, though its effect on glucose metabolism appears to be similar between these species. PMID:24505376

  15. The essential functions of endoplasmic reticulum chaperones in hepatic lipid metabolism.

    PubMed

    Zhang, LiChun; Wang, Hong-Hui

    2016-07-01

    The endoplasmic reticulum (ER) is an essential organelle for protein and lipid synthesis in hepatocytes. ER homeostasis is vital to maintain normal hepatocyte physiology. Perturbed ER functions causes ER stress associated with accumulation of unfolded protein in the ER that activates a series of adaptive signalling pathways, termed unfolded protein response (UPR). The UPR regulates ER chaperone levels to preserve ER protein-folding environment to protect the cell from ER stress. Recent findings reveal an array of ER chaperones that alter the protein-folding environment in the ER of hepatocytes and contribute to dysregulation of hepatocyte lipid metabolism and liver disease. In this review, we will discuss the specific functions of these chaperones in regulation of lipid metabolism, especially de novo lipogenesis and lipid transport and demonstrate their homeostatic role not only for ER-protein synthesis but also for lipid metabolism in hepatocyte. PMID:27133206

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

    PubMed

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

    2016-07-01

    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. 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

  18. Oral MSG administration alters hepatic expression of genes for lipid and nitrogen metabolism in suckling piglets.

    PubMed

    Chen, Gang; Zhang, Jun; Zhang, Yuzhe; Liao, Peng; Li, Tiejun; Chen, Lixiang; Yin, Yulong; Wang, Jinquan; Wu, Guoyao

    2014-01-01

    This experiment was conducted to investigate the effects of oral administration of monosodium glutamate (MSG) on expression of genes for hepatic lipid and nitrogen metabolism in piglets. A total of 24 newborn pigs were assigned randomly into one of four treatments (n = 6/group). The doses of oral MSG administration, given at 8:00 and 18:00 to sow-reared piglets between 0 and 21 days of age, were 0 (control), 0.06 (low dose), 0.5 (intermediate dose), and 1 (high dose) g/kg body weight/day. At the end of the 3-week treatment, serum concentrations of total protein and high-density lipoprotein cholesterol in the intermediate dose group were elevated than those in the control group (P < 0.05). Hepatic mRNA levels for fatty acid synthase, acetyl-coA carboxylase, insulin-like growth factor-1, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase were higher in the middle-dose group (P < 0.05), compared with the control group. MSG administration did not affect hepatic mRNA levels for hormone-sensitive lipase or carnitine palmitoyl transferase-1. We conclude that oral MSG administration alters hepatic expression of certain genes for lipid and nitrogen metabolism in suckling piglets. PMID:24221354

  19. A Yeast Mutant Deleted of GPH1 Bears Defects in Lipid Metabolism

    PubMed Central

    Gsell, Martina; Fankl, Ariane; Klug, Lisa; Mascher, Gerald; Schmidt, Claudia; Hrastnik, Claudia; Zellnig, Günther; Daum, Günther

    2015-01-01

    In a previous study we demonstrated up-regulation of the yeast GPH1 gene under conditions of phosphatidylethanolamine (PE) depletion caused by deletion of the mitochondrial (M) phosphatidylserine decarboxylase 1 (PSD1) (Gsell et al., 2013, PLoS One. 8(10):e77380. doi: 10.1371/journal.pone.0077380). Gph1p has originally been identified as a glycogen phosphorylase catalyzing degradation of glycogen to glucose in the stationary growth phase of the yeast. Here we show that deletion of this gene also causes decreased levels of phosphatidylcholine (PC), triacylglycerols and steryl esters. Depletion of the two non-polar lipids in a Δgph1 strain leads to lack of lipid droplets, and decrease of the PC level results in instability of the plasma membrane. In vivo labeling experiments revealed that formation of PC via both pathways of biosynthesis, the cytidine diphosphate (CDP)-choline and the methylation route, is negatively affected by a Δgph1 mutation, although expression of genes involved is not down regulated. Altogether, Gph1p besides its function as a glycogen mobilizing enzyme appears to play a regulatory role in yeast lipid metabolism. PMID:26327557

  20. A Yeast Mutant Deleted of GPH1 Bears Defects in Lipid Metabolism.

    PubMed

    Gsell, Martina; Fankl, Ariane; Klug, Lisa; Mascher, Gerald; Schmidt, Claudia; Hrastnik, Claudia; Zellnig, Günther; Daum, Günther

    2015-01-01

    In a previous study we demonstrated up-regulation of the yeast GPH1 gene under conditions of phosphatidylethanolamine (PE) depletion caused by deletion of the mitochondrial (M) phosphatidylserine decarboxylase 1 (PSD1) (Gsell et al., 2013, PLoS One. 8(10):e77380. doi: 10.1371/journal.pone.0077380). Gph1p has originally been identified as a glycogen phosphorylase catalyzing degradation of glycogen to glucose in the stationary growth phase of the yeast. Here we show that deletion of this gene also causes decreased levels of phosphatidylcholine (PC), triacylglycerols and steryl esters. Depletion of the two non-polar lipids in a Δgph1 strain leads to lack of lipid droplets, and decrease of the PC level results in instability of the plasma membrane. In vivo labeling experiments revealed that formation of PC via both pathways of biosynthesis, the cytidine diphosphate (CDP)-choline and the methylation route, is negatively affected by a Δgph1 mutation, although expression of genes involved is not down regulated. Altogether, Gph1p besides its function as a glycogen mobilizing enzyme appears to play a regulatory role in yeast lipid metabolism. PMID:26327557

  1. Acute and chronic toxicity of endosulfan to crab: Effect on lipid metabolism

    SciTech Connect

    Rafi, G.Md.; Srinivas, T.; Reddy, S.J.; Reddy, D.C.; Ramamurthi, R. )

    1991-12-01

    Endosulfan is toxic to fish and its toxic effects have been studied in several freshwater fish. However, information regarding toxicity of endosulfan to many freshwater invertebrates is fragmentary. Few reports are available on the toxic effect of endosulfan on carbohydrate and protein metabolisms of freshwater field crab, Oziotelphusa senex senex, another nontarget organism of aquatic ecosystem. The work on lipid metabolism under organochloride insecticide (OCI) stress is scant. The OCI tend to accumulate in the lipid rich tissues of the biosystem due to their lipophilic nature. The changes in lipid profiles under OCI stress reported to cause profound changes in the metabolism and physiology of animals. Therefore, this paper presents the effects of endosulfan on lipid metabolism in O. senex senex.

  2. 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...

  3. 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

  4. Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans.

    PubMed

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Saraf, Manish K; Annamalai, Palam; Yfanti, Christina; Chao, Tony; Wong, Daniel; Shinoda, Kosaku; Labbė, Sebastien M; Hurren, Nicholas M; Cesani, Fernardo; Kajimura, Shingo; Sidossis, Labros S

    2016-06-14

    Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans. PMID:27238638

  5. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    SciTech Connect

    Keith, Dove; Finlay, Liam; Butler, Judy; Gómez, Luis; Smith, Eric; Moreau, Régis; Hagen, Tory

    2014-07-18

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.

  6. Sasa quelpaertensis leaf extract improves high fat diet-induced lipid abnormalities and regulation of lipid metabolism genes in rats.

    PubMed

    Kim, Jina; Kim, Yoo-Sun; Lee, Hyun Ah; Lim, Ji Ye; Kim, Mina; Kwon, Oran; Ko, Hee-Chul; Kim, Se-Jae; Shin, Jae-Ho; Kim, Yuri

    2014-05-01

    Sasa quelpaertensis is a bamboo leaf that is only grown on Jeju Island in South Korea. It is used as a bamboo tea that is consumed for therapeutic purposes, particularly for its anti-diabetic, diuretic, and anti-inflammatory effects. This study investigated the effect of S. quelpaertensis leaf extract (SQE) on high fat-induced lipid abnormalities and regulation of lipid metabolism-related gene expressions in rats. SQE supplementation significantly decreased the levels of plasma triglycerides, total cholesterol, and low-density lipoprotein cholesterol as well as the atherogenic index. SQE restored levels of plasma high-density lipoprotein cholesterol, which were lowered by a high fat diet. Plasma and cardiac resistin levels were also significantly decreased by SQE supplementation. In adipose tissue, mRNA levels of CAAT/enhancer-binding protein β (C/EBPβ) were suppressed in the SQE group. SQE supplementation decreased the accumulation of lipid droplets, inflammatory cell infiltrations, levels of triglycerides, and total lipids in the liver and effectively down-regulated expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), and uncoupling protein 2 (UCP-2). These results suggest that SQE may be a potential treatment for high fat-related disorders by improving lipid profiles and modulating lipid metabolism. PMID:24738745

  7. Effect of lipid source and oxidation level on metabolic oxidation status of young pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the effects of lipid source and oxidation level on metabolic oxidation status of young pigs, 108 barrows (~ 6.66 kg BW) were assigned to 1 of 13 dietary treatments in a 4 × 3 factorial design, including one control diet and 12 diets containing 10% lipid [corn oil (CN), canola oil (CA), p...

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

    PubMed

    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

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

    PubMed

    Tian, Lei; Li, Yuanjing; Tian, Chunjie

    2016-01-01

    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. PMID:27305777

  10. 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

  11. [Pathogenetic correction of metabolic disturbances in chronic liver affections].

    PubMed

    Romantsov, M G; Petrov, A Iu; Aleksandrova, L N; Sukhanov, D S; Kovalenko, A L

    2012-01-01

    The available drugs for the treatment of chronic liver affections (the adequate model is chronic hepatitis C) include agents of metabolic therapy, whose efficacy is not always enough, that required the search for original mitochondrial substrates on the basis of succinate. Such agents were composed as a pharmaceutical group named "Substrates of Energetic Metabolism" or "Substrate Antihypoxants". The review presents the description of the pharmacological effects of remaxole and cytoflavin, evident from lower levels of active metabolites of oxygen that increases the clinical efficacy of the therapy. Their role in the metabolic reactions in chronic liver affections is exclusive and rather actual. PMID:23700935

  12. Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in Blastomyces dermatitidis

    PubMed Central

    Marty, Amber J.; Broman, Aimee T.; Zarnowski, Robert; Dwyer, Teigan G.; Bond, Laura M.; Lounes-Hadj Sahraoui, Anissa; Fontaine, Joël; Ntambi, James M.; Keleş, Sündüz; Kendziorski, Christina; Gauthier, Gregory M.

    2015-01-01

    In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s) underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ) fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0–48 hours), gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C) and during the phase transition to mold (22°C). This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition. PMID:26114571

  13. Gut microbiome phenotypes driven by host genetics affect arsenic metabolism.

    PubMed

    Lu, Kun; Mahbub, Ridwan; Cable, Peter Hans; Ru, Hongyu; Parry, Nicola M A; Bodnar, Wanda M; Wishnok, John S; Styblo, Miroslav; Swenberg, James A; Fox, James G; Tannenbaum, Steven R

    2014-02-17

    Large individual differences in susceptibility to arsenic-induced diseases are well-documented and frequently associated with different patterns of arsenic metabolism. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that gut microbiome phenotypes affect the spectrum of metabolized arsenic species. However, it remains unclear how host genetics and the gut microbiome interact to affect the biotransformation of arsenic. Using an integrated approach combining 16S rRNA gene sequencing and HPLC-ICP-MS arsenic speciation, we demonstrate that IL-10 gene knockout leads to a significant taxonomic change of the gut microbiome, which in turn substantially affects arsenic metabolism. PMID:24490651

  14. Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death

    PubMed Central

    2016-01-01

    Little is known about the regulation of nonapoptotic cell death. Using massive insertional mutagenesis of haploid KBM7 cells we identified nine genes involved in small-molecule-induced nonapoptotic cell death, including mediators of fatty acid metabolism (ACSL4) and lipid remodeling (LPCAT3) in ferroptosis. One novel compound, CIL56, triggered cell death dependent upon the rate-limiting de novo lipid synthetic enzyme ACC1. These results provide insight into the genetic regulation of cell death and highlight the central role of lipid metabolism in nonapoptotic cell death. PMID:25965523

  15. Severe dietary lysine restriction affects growth and body composition and hepatic gene expression for nitrogen metabolism in growing rats.

    PubMed

    Kim, J; Lee, K S; Kwon, D-H; Bong, J J; Jeong, J Y; Nam, Y S; Lee, M S; Liu, X; Baik, M

    2014-02-01

    Dietary lysine restriction may differentially affect body growth and lipid and nitrogen metabolism, depending on the degree of lysine restriction. This study was conducted to examine the effect of dietary lysine restriction on growth and lipid and nitrogen metabolism with two different degree of lysine restriction. Isocaloric amino acid-defined diets containing 1.4% lysine (adequate), 0.70% lysine (50% moderate lysine restriction) and 0.35% lysine (75% severe lysine restriction) were fed from the age of 52 to 77 days for 25 days in male Sprague-Dawley rats. The 75% severe lysine restriction increased (p < 0.05) food intake, but retarded (p < 0.05) growth, increased (p < 0.05) liver and muscle lipid contents and abdominal fat accumulation, increased (p < 0.05) blood urea nitrogen levels and mRNA levels of the serine-synthesizing 3-phosphoglycerate dehydrogenase gene, but decreased (p < 0.05) urea cycle arginase gene mRNA levels. In contrast, the 50% lysine restriction did not significantly (p > 0.05) affect body growth and lipid and nitrogen metabolism. Our results demonstrate that severe 75% lysine restriction has detrimental effects on body growth and deregulate lipid and nitrogen metabolism. PMID:23441935

  16. Abnormal barrier function in the pathogenesis of ichthyosis: Therapeutic implications for lipid metabolic disorders☆

    PubMed Central

    Elias, Peter M.; Williams, Mary L.; Feingold, Kenneth R.

    2013-01-01

    Ichthyoses, including inherited disorders of lipid metabolism, display a permeability barrier abnormality in which the severity of the clinical phenotype parallels the prominence of the barrier defect. The pathogenesis of the cutaneous phenotype represents the consequences of the mutation for epidermal function, coupled with a “best attempt” by affected epidermis to generate a competent barrier in a terrestrial environment. A compromised barrier in normal epidermis triggers a vigorous set of metabolic responses that rapidly normalizes function, but ichthyotic epidermis, which is inherently compromised, only partially succeeds in this effort. Unraveling mechanisms that account for barrier dysfunction in the ichthyoses has identified multiple, subcellular, and biochemical processes that contribute to the clinical phenotype. Current treatment of the ichthyoses remains largely symptomatic: directed toward reducing scale or corrective gene therapy. Reducing scale is often minimally effective. Gene therapy is impeded by multiple pitfalls, including difficulties in transcutaneous drug delivery, high costs, and discomfort of injections. We have begun to use information about disease pathogenesis to identify novel, pathogenesis-based therapeutic strategies for the ichthyoses. The clinical phenotype often reflects not only a deficiency of pathway end product due to reduced-function mutations in key synthetic enzymes but often also accumulation of proximal, potentially toxic metabolites. As a result, depending upon the identified pathomechanism(s) for each disorder, the accompanying ichthyosis can be treated by topical provision of pathway product (eg, cholesterol), with or without a proximal enzyme inhibitor (eg, simvastatin), to block metabolite production. Among the disorders of distal cholesterol metabolism, the cutaneous phenotype in Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) and X-linked ichthyosis reflect metabolite

  17. Topics in Transcriptional Control of Lipid Metabolism: from Transcription Factors to Gene-Promoter Polymorphisms

    PubMed Central

    Bergen, Werner G.; Burnett, Derris D.

    2013-01-01

    The central dogma of biology (DNA>>RNA>>Protein) has remained as an extremely useful scaffold to guide the study of molecular regulation of cellular metabolism. Molecular regulation of cellular metabolism has been pursued from an individual enzyme to a global assessment of protein function at the genomic (DNA), transcriptomic (RNA) and translation (Protein) levels. Details of a key role by inhibitory small RNAs and post-translational processing of cellular proteins on a whole cell/global basis are now just emerging. Below we emphasize the role of transcription factors (TF) in regulation of adipogenesis and lipogenesis. Additionally we have also focused on emerging additional TF that may also have hitherto unrecognized roles in adipogenesis and lipogenesis as compared to our present understanding. It is generally recognized that SNPs in structural genes can affect the final structure/function of a given protein. The implications of SNPs located in the non-transcribed promoter region on transcription have not been examined as extensively at this time. Here we have also summarized some emerging results on promoter SNPs for lipid metabolism and related cellular processes. PMID:25031651

  18. 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. PMID:23180608

  19. Cinnamon extract regulates intestinal lipid metabolism related gene expression in primary enterocytes of rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Evidence of aberrant lipid metabolism in hepatitis C and hepatocellular carcinoma

    PubMed Central

    Wu, Jian-Min; Skill, Nicholas J; Maluccio, Mary A

    2010-01-01

    Objectives Lipids are linked to many pathological processes including hepatic steatosis and liver malignancy. This study aimed to explore lipid metabolism in hepatitis C virus (HCV) and HCV-related hepatocellular carcinoma (HCC). Methods Serum lipids were measured in normal, HCV and HCV-HCC patients. Whole-genome microarray was performed to identify potential signature genes involved in lipid metabolism characterizing normal vs. HCV vs. HCV-HCC conditions. Results Serum cholesterol was significantly reduced in HCV and HCV-HCC patients compared with normal controls, whereas there was no difference in glucose and triglycerides. Microarray analysis identified 224 probe sets with known functional roles in lipid metabolism (anova, 1.5-fold, P ≤ 0.001). Gene-mediated fatty acid (FA) de novo synthesis and uptake were upregulated in HCV and this upregulation was further enhanced in HCC. Genes involved in FA oxidation were downregulated in both the HCV and HCC groups. The abnormality of cholesterol metabolism in HCV was associated with downregulation of genes involved in cholesterol biosynthesis, absorption and transportation and bile acid synthesis; this abnormality was further intensified in HCC. Conclusions Our data support the notion that HCV-related lipid metabolic abnormalities may contribute to hepatic steatosis and the development of cancer. Identification of these aberrations would stratify patients and improve treatment algorithms. PMID:20961371

  1. 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. PMID:27003249

  2. 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

  3. Assessing compartmentalized flux in lipid metabolism with isotopes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression

    PubMed Central

    Osawa, Yosuke; Seki, Ekihiro; Kodama, Yuzo; Suetsugu, Atsushi; Miura, Kouichi; Adachi, Masayuki; Ito, Hiroyasu; Shiratori, Yoshimune; Banno, Yoshiko; Olefsky, Jerrold M.; Nagaki, Masahito; Moriwaki, Hisataka; Brenner, David A.; Seishima, Mitsuru

    2011-01-01

    Acid sphingomyelinase (ASM) regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate (S1P). Because sphingolipids regulate AKT activation, we investigated the role of ASM in hepatic glucose and lipid metabolism. Initially, we overexpressed ASM in the livers of wild-type and diabetic db/db mice by adenovirus vector (Ad5ASM). In these mice, glucose tolerance was improved, and glycogen and lipid accumulation in the liver were increased. Using primary cultured hepatocytes, we confirmed that ASM increased glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3β. In addition, ASM induced up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase (AMPK) phosphorylation. Loss of sphingosine kinase-1 (SphK1) diminished ASM-mediated AKT phosphorylation, but exogenous S1P induced AKT activation in hepatocytes. In contrast, SphK1 deficiency did not affect AMPK activation. These results suggest that the SphK/S1P pathway is required for ASM-mediated AKT activation but not for AMPK inactivation. Finally, we found that treatment with high-dose glucose increased glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM−/− cells. This result is consistent with glucose intolerance in ASM−/− mice. In conclusion, ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver.—Osawa, Y., Seki, E., Kodama, Y., Suetsugu, A., Miura, K., Adachi, M., Ito, H., Shiratori, Y., Banno, Y., Olefsky, J. M., Nagaki, M., Moriwaki, H., Brenner, D. A., Seishima, M. Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression. PMID:21163859

  5. Effects of soyabean meal- or whey-based diets on lipid metabolism in weaned piglets.

    PubMed

    Theodorou, G; Papadomichelakis, G; Tsiplakou, E; Lampidonis, A D; Chadio, S; Zervas, G; Politis, I

    2015-02-01

    The present study aimed to test the hypothesis that dietary protein source influences lipid metabolism-related parameters weaned piglets. The effects of soyabean meal (SB) and whey proteins (WP) on gene expression of several genes involved in the lipogenic process in liver, visceral (VAT) and subcutaneous (SAT) adipose tissues, plasma insulin concentration and fatty acid (FA) profile were investigated in 18 weaned piglets. Weaned piglets were fed one of two diets containing either SB or WP as the main protein source. Following a 10-h fasting period, plasma insulin concentration and FA profile were assessed at 56 and 72 days of age, whereas gene expression in liver, VAT and SAT was assessed at 72 days of age. Plasma insulin concentration was not affected by diet, although it was 40% lower in SB fed pigs. The SB pigs had lower 14:0 (p < 0.01) and higher 18:3n-3 (p < 0.001) levels in plasma in comparison with WP pigs. However, these changes were attributed to background differences in the dietary FA profile and not to a direct protein source effect. Gene expression of sterol regulatory element-binding protein 1 (SREBP-1) in liver and VAT were lower (p < 0.01 and p < 0.05, respectively) in SB compared to WP fed piglets, but no differences occurred in SAT. No changes were observed in sterol regulatory element-binding protein 2, liver X receptor, peroxisome proliferator-activated receptors α and γ and plasminogen activator inhibitor 1 mRNA levels, either in liver or in adipose tissues. In conclusion, dietary protein source, accompanied likely by side alterations in the dietary composition, affects lipid metabolism in pigs through the downregulation of SREBP-1, which is a crucial determinant of lipogenic process. PMID:24924522

  6. Dietary carbohydrate and lipid sources affect differently the oxidative status of European sea bass (Dicentrarchus labrax) juveniles.

    PubMed

    Castro, Carolina; Peréz-Jiménez, Amalia; Coutinho, Filipe; Díaz-Rosales, Patricia; Serra, Cláudia Alexandra Dos Reis; Panserat, Stéphane; Corraze, Geneviève; Peres, Helena; Oliva-Teles, Aires

    2015-11-28

    This study aimed to evaluate the effects of dietary lipid source and carbohydrate content on the oxidative status of European sea bass (Dicentrarchus labrax) juveniles. For that purpose, four diets were formulated with fish oil (FO) and vegetable oils (VO) as the lipid source and with 20 or 0 % gelatinised starch as the carbohydrate source, in a 2×2 factorial design. Liver and intestine antioxidant enzyme activities (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD)), hepatic and intestinal lipid peroxidation (LPO), as well as hepatic oxidative stress index (OSI), were measured in fish fed the experimental diets for 73 d (n 9 fish/diet). Carbohydrate-rich diets promoted a decrease in hepatic LPO and OSI, whereas the lipid source induced no changes. Inversely, dietary lipid source, but not dietary carbohydrate concentration, affected LPO in the intestine. Lower intestinal LPO was observed in VO groups. Enzymes responsive to dietary treatments were GR, G6PD and CAT in the liver and GR and GPX in the intestine. Dietary carbohydrate induced GR and G6PD activities and depressed CAT activity in the liver. GPX and GR activities were increased in the intestine of fish fed VO diets. Overall, effects of diet composition on oxidative status were tissue-related: the liver and intestine were strongly responsive to dietary carbohydrates and lipid sources, respectively. Furthermore, different metabolic routes were more active to deal with the oxidative stress in the two organs studied. PMID:26365262

  7. Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

    PubMed Central

    Salas, Anna; Noé, Véronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

    2007-01-01

    Background Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα) values showed overexpression (198%). Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism. PMID:17725831

  8. Lipid composition and metabolism in embryos of Brassica napus

    SciTech Connect

    Sparace, S.A. ); Pomroy, M.K. )

    1990-05-01

    Seven and 14-day old microspore-derived developing embryos of the low-erucate Brassica napus L. (cv. Topas) were analyzed for their acyl lipid composition and capacity to incorporate ({sup 14}C)acetate into lipid. The most significant changes in the lipid compositions of these ages of embryos are (1) increased total lipid from 2 to 5% of fresh weight; (2) increased proportion of TAG from 31 to 74%, and shifts in the fatty acid composition of TAG from 25 to 50% 18:1; 28 to 23% 18:2; and 24 to 13% 18:3. Lipids of 7-day embryos also consist of primarily 8% DAG, 2% MG, 12% FFA, 10% DGDG, 15% PA and approximately 5% each of PC, PE and PG. The levels of these lipids generally decrease as the embryos mature and accumulate TAG. ({sup 14}C)Acetate is incorporated into all lipids and fatty acids except 18:2 or 18:3. As much as 39, 59 and 34% of the fatty acid radioactivity of Mg was recovered in 20:0, 22:0 and 24:0, respectively.

  9. The orchestra of lipid-transfer proteins at the crossroads between metabolism and signaling.

    PubMed

    Chiapparino, Antonella; Maeda, Kenji; Turei, Denes; Saez-Rodriguez, Julio; Gavin, Anne-Claude

    2016-01-01

    Within the eukaryotic cell, more than 1000 species of lipids define a series of membranes essential for cell function. Tightly controlled systems of lipid transport underlie the proper spatiotemporal distribution of membrane lipids, the coordination of spatially separated lipid metabolic pathways, and lipid signaling mediated by soluble proteins that may be localized some distance away from membranes. Alongside the well-established vesicular transport of lipids, non-vesicular transport mediated by a group of proteins referred to as lipid-transfer proteins (LTPs) is emerging as a key mechanism of lipid transport in a broad range of biological processes. More than a hundred LTPs exist in humans and these can be divided into at least ten protein families. LTPs are widely distributed in tissues, organelles and membrane contact sites (MCSs), as well as in the extracellular space. They all possess a soluble and globular domain that encapsulates a lipid monomer and they specifically bind and transport a wide range of lipids. Here, we present the most recent discoveries in the functions and physiological roles of LTPs, which have expanded the playground of lipids into the aqueous spaces of cells. PMID:26658141

  10. Imaging Lipid Metabolism in Live Caenorhabditis elegans Using Fingerprint Vibrations**

    PubMed Central

    Wang, Ping; Liu, Bin; Zhang, Delong; Belew, Micah Y.; Cheng, Ji-Xin

    2015-01-01

    Quantitation of lipid storage, desaturation, and oxidation in live C. elegans has been a long-standing obstacle. By hyperspectral stimulated Raman scattering imaging and multivariate analysis in fingerprint vibration region, we present a platform that allows quantitative mapping of fat distribution, degree of fat unsaturation, lipid oxidation, and cholesterol storage in vivo in whole worm. Our results reveal for the first time that lysosome related organelles in intestinal cells are sites for storage of cholesterol in C. elegans. PMID:25195517

  11. Metabolic changes of starch and lipid triggered by nitrogen starvation in the microalga Chlorella zofingiensis.

    PubMed

    Zhu, Shunni; Huang, Wei; Xu, Jin; Wang, Zhongming; Xu, Jingliang; Yuan, Zhenhong

    2014-01-01

    The aim of this research was to study the metabolic changes of starch and lipid biosynthesis in the microalga Chlorella zofingiensis under nitrogen starvation in comparison to nitrogen abundant condition. C. zonfingiensis showed a rapid growth and kept stable chlorophyll content when grown in nitrogen-replete medium, while a severe inhibition of cell growth and a sharp degradation of chlorophyll occurred under nitrogen depletion. Nitrogen-replete C. zonfingiensis cells possessed basal levels of starch and lipid. Upon nitrogen starvation, both starch and lipid increased greatly within cells, but starch synthesis preceded lipid accumulation. After 2 days of stress condition, starch was partially degraded, possibly to support lipid synthesis. It was speculated that starch accumulation acted as a quick response to environmental stress, whereas lipid served as long-term energy storage. Additionally, C. zonfingiensis tends to lower the degree of unsaturation in response to nitrogen starvation which is desirable for biodiesel production. PMID:24308944

  12. 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

  13. 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

  14. Inositol lipid metabolism in vasopressin stimulated hepatocytes from rats infused with tumor necrosis factor

    SciTech Connect

    Spitzer, J.A.; Rodriguez de Turco, E.B. )

    1989-05-30

    We studied the effect of i.v. infusion of human recombinant tumor necrosis factor alpha (rHuTNF alpha, Cetus, 15 micrograms/100 g bw over 3 h) on vasopressin (VP)-stimulated {sup 32}P-inositol lipid turnover and the release of {sup 3}H-inositol phosphates in isolated rat hepatocytes. The early VP-induced decrease (within 30 s) in {sup 32}P-phosphatidylinositol 4-phosphate and {sup 32}P-phosphatidylinositol 4,5-bisphosphate labeling was significantly reduced (-40%) and at the same time the uptake of {sup 32}P into phosphatidic acid was 50% lower than in saline-infused (matched control) rats. Within 5 min of VP-stimulation, lower {sup 32}P phosphatidylinositol (-40%) and higher {sup 32}P-phosphatidic acid (+30%) labeling were observed in rHuTNF alpha-infused rats. Infusion of rHuTNF alpha also affected the VP-induced release of {sup 3}H-inositol phosphates. The accumulation of {sup 3}H-inositol-labeled water soluble products was decreased by 25% and 17% at 30 s and 10 min, respectively. These data show that rHuTNF alpha mimics early perturbations induced by Escherichia coli endotoxin infusion in VP-stimulated inositol lipid metabolism in rat hepatocytes.

  15. Effects of Pu-erh tea aqueous extract (PTAE) on blood lipid metabolism enzymes.

    PubMed

    Zeng, Liang; Yan, Jingna; Luo, Liyong; Zhang, Dongying

    2015-06-01

    Disorders of blood lipid metabolism are the primary risk factors for many diseases. Recently, the effect of Pu-erh tea on blood lipid metabolism has received increasing attention. However, the mechanism underlying its ability to regulate blood lipid metabolism is unclear. We set out to study this through assessing the effects of Pu-erh tea aqueous extract (PTAE) on the central enzymes of blood lipid metabolism, including lipoprotein-associated phospholipase A2 (Lp-PLA2), lecithin: cholesterol acyltransferase (LCAT), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and pancreatic lipase (PL). We find that the Lp-PLA2, HMRG and PL activities are inhibited by PTAE in a dose-dependent manner and that the LCAT activity tends to increase with increasing PTAE concentrations. Lineweaver-Burk plot analyses reveal that PTAE acts as a competitive inhibitor for HMGR and PL and as a noncompetitive inhibitor for Lp-PLA2. Moreover, we determine that its active ingredients include catechins, gallic acid, caffeine, free amino acids, and soluble sugar. However, the effect of each ingredient and whether any of them have synergistic effects are still unknown. The results suggest that Pu-erh tea has a potent ability to regulate blood lipid metabolism and knowledge of the mechanisms provides insights into its potential therapeutic application as an alternative hypolipidemic drug. PMID:26018873

  16. The role of feeding regimens in regulating metabolism of sexually mature broiler breeders: hepatic lipid metabolism, plasma hormones and metabolites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A trial was conducted to determine the effects of different rearing feed regimens on plasma hormone and metabolite levels and hepatic lipid metabolism on sexually mature broiler breeders. A flock of Cobb 500 birds was divided into two groups at 35 days of age and fed either everyday (ED) or skip-a-d...

  17. 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

  18. FGF21 as an Endocrine Regulator in Lipid Metabolism: From Molecular Evolution to Physiology and Pathophysiology

    PubMed Central

    Murata, Yusuke; Konishi, Morichika; Itoh, Nobuyuki

    2011-01-01

    The FGF family comprises twenty-two structurally related proteins with functions in development and metabolism. The Fgf21 gene was generated early in vertebrate evolution. FGF21 acts as an endocrine regulator in lipid metabolism. Hepatic Fgf21 expression is markedly induced in mice by fasting or a ketogenic diet. Experiments with Fgf21 transgenic mice and cultured cells indicate that FGF21 exerts pharmacological effects on glucose and lipid metabolism in hepatocytes and adipocytes via cell surface FGF receptors. However, experiments with Fgf21 knockout mice indicate that FGF21 inhibits lipolysis in adipocytes during fasting and attenuates torpor induced by a ketogenic diet but maybe not a physiological regulator for these hepatic functions. These findings suggest the pharmacological effects to be distinct from the physiological roles. Serum FGF21 levels are increased in patients with metabolic diseases having insulin resistance, indicating that FGF21 is a metabolic regulator and a biomarker for these diseases. PMID:21331285

  19. Lipid content and metabolism of human keratinocyte cultures grown at the air-medium interface.

    PubMed

    Williams, M L; Brown, B E; Monger, D J; Grayson, S; Elias, P M

    1988-07-01

    The differentiation of human keratinocytes in most culture systems is incomplete; e.g., lamellar bodies, the characteristic lipid-delivery organelles of epidermis, are not present. Moreover, their lipid profile does not reflect the distinctive composition found in cornifying epidermis. In contrast, keratinocytes that grow at an air-medium interface exhibit more complete differentiation. In this study, we compared the elaboration of lamellar bodies, the lipid content, and the lipid metabolism of human keratinocytes, cultured both under standard immersed conditions and after lifting to an air-medium interface. Whereas submerged cultures neither elaborated lamellar bodies nor displayed a lipid distribution characteristic of cornifying epidermis, lifted cultures displayed advanced cornification, elaborated lamellar bodies which were deposited in intercellular domains, and a lipid profile more typical of cornifying epidermis. Moreover, lipid biosynthesis was 5-10-fold more active in lifted than in immersed cultures, and was not inhibited by exogenous lipoproteins. These findings are consistent with recent studies that demonstrate both high rates of lipogenesis in differentiating layers of the epidermis as well as autonomy of lipogenesis from the influence of circulating lipoproteins. Thus, the lipid content and metabolism of human keratinocyte cultures, grown at an air-medium interface, demonstrate features that simulate the epidermis. PMID:2456290

  20. [COMPARATIVE ANALYSIS OF LIPID METABOLISM INDICES IN SOME PARASITES OF THE WHITE CHARR (SALVELINUS ALBUS) FROM THE LAKE KRINOTSKOE].

    PubMed

    Gordeev, I I; Mikryakov, D V; Silkina, N I

    2015-01-01

    Comparative study of lipid metabolism indices (total lipids, separate lipid fractions, level of the lipid peroxidation processes, and antioxidant protection) was carried out in three parasite species collected from the white char in the Lake Kronotskoe: Diphyllobothrium ditremum Crepin, 1825 (Cestoda), Philonema oncorhynchi Kuitunen-Ekbaum, 1933 (Nematoda) H Neoechinorhynchus salmonis Ching, 1984 (Acanthocephala). Acanthocephalans possessed significantly greater levels of total lipids, triacylglycerol, and malondialdehyde; nematodes, of cholesterol and sterol esters; and cestodes, in phospholipids and constants of the substrate oxidation. Dependence between lipid metabolism of helminths and their taxonomic affiliation, morpho-functional features, the stage of the life cycle, and the site of infection in the host are discussed. PMID:26314155

  1. In Vivo Metabolic Fingerprinting of Neutral Lipids with Hyperspectral Stimulated Raman Scattering Microscopy

    PubMed Central

    2015-01-01

    Metabolic fingerprinting provides valuable information on the physiopathological states of cells and tissues. Traditional imaging mass spectrometry and magnetic resonance imaging are unable to probe the spatial-temporal dynamics of metabolites at the subcellular level due to either lack of spatial resolution or inability to perform live cell imaging. Here we report a complementary metabolic imaging technique that is based on hyperspectral stimulated Raman scattering (hsSRS). We demonstrated the use of hsSRS imaging in quantifying two major neutral lipids: cholesteryl ester and triacylglycerol in cells and tissues. Our imaging results revealed previously unknown changes of lipid composition associated with obesity and steatohepatitis. We further used stable-isotope labeling to trace the metabolic dynamics of fatty acids in live cells and live Caenorhabditis elegans with hsSRS imaging. We found that unsaturated fatty acid has preferential uptake into lipid storage while saturated fatty acid exhibits toxicity in hepatic cells. Simultaneous metabolic fingerprinting of deuterium-labeled saturated and unsaturated fatty acids in living C. elegans revealed that there is a lack of interaction between the two, unlike previously hypothesized. Our findings provide new approaches for metabolic tracing of neutral lipids and their precursors in living cells and organisms, and could potentially serve as a general approach for metabolic fingerprinting of other metabolites. PMID:24869754

  2. Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice.

    PubMed

    Zhang, Xin-Ru; Fu, Xiu-Juan; Zhu, Da-Sheng; Zhang, Chao-Zai; Hou, Shi; Li, Min; Yang, Xiao-Hong

    2016-05-15

    Salidroside is known for its pharmacological properties and in particular its antioxidation effects. In recent years, it has been recognized that salidroside plays an important role in treating diabetes. Accumulated evidence suggests that microRNAs may be involved in diabetic lipid disorders. We investigated how salidroside regulates lipid metabolism through miR-370 in vivo and in vitro. After 4 weeks of a high-fat diet, and intraperitoneal injection of streptozotocin (100mg/kg), type 2 diabetes was induced in male C56BL/6J mice. After 4 weeks, mice with fasting blood glucose levels above 7.8mmol/l were divided into five groups: those with diabetes mellitus, and those treated with 40mg/kg, 80mg/kg, and 160mg/kg salidroside, and metformin (480mg/kg), for a further 4 weeks. The hypoglycemic effects of salidroside were consistently demonstrated when measuring fasting blood glucose levels, observing insulin-sensitizing effects, and testing oral glucose tolerance. In addition to this, the expressions of miR-370, and related lipid protein expression in primary hepatocytes, were examined in primary type 2 diabetic mice. The present study has shown that the expression levels of miR-370, SREBP-1 and FAS-1 were significantly elevated in the liver of type 2 diabetic mice. In contrast, the elevated expression levels were reversed by salidroside. The addition of salidroside attenuated the effect of miR-370, and reduced the expression of these lipid metabolism proteins in primary hepatocytes. These findings demonstrate that salidroside can directly decrease the expression of miR-370 in type 2 diabetic mice, and particularly in primary hepatocytes, affecting lipid metabolism in the liver. PMID:26948318

  3. 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. PMID:20709142

  4. 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

  5. Differential Expression of Lipid and Carbohydrate Metabolism Genes in Upper Airway versus Diaphragm Muscle

    PubMed Central

    van Lunteren, Erik; Spiegler, Sarah; Moyer, Michelle

    2010-01-01

    Study Objectives: Contractile properties of upper airway muscles influence upper airway patency, an issue of particular importance for subjects with obstructive sleep apnea. Expression of genes related to cellular energetics is, in turn, critical for the maintenance of contractile integrity over time during repetitive activation. We tested the hypothesis that sternohyoid has lower expression of genes related to lipid and carbohydrate energetic pathways than the diaphragm. Methods: Sternohyoid and diaphragm from normal adult rats were examined with gene expression arrays. Analysis focused on genes belonging to Gene Ontology (GO) groups carbohydrate metabolism and lipid metabolism. Results: There were 433 genes with at least ± 2-fold significant differential expression between sternohyoid and diaphragm, of which 192 had sternohyoid > diaphragm and 241 had diaphragm > sternohyoid expression. Among genes with higher sternohyoid expression, there was over-representation of the GO group carbohydrate metabolism (P = 0.0053, n = 13 genes, range of differential expression 2.1- to 6.2-fold) but not lipid metabolism (P = 0.44). Conversely, among genes with higher diaphragm expression, there was over-representation of the GO group lipid metabolism (P = 0.0000065, n = 32 genes, range of differential expression 2.0- to 37.9-fold) but not carbohydrate metabolism (P = 0.23). Nineteen genes with diaphragm > sternohyoid expression were related to fatty acid metabolism (P = 0.000000058), in particular fatty acid β oxidation and biosynthesis in the mitochondria. Conclusions: Sternohyoid has much lower gene expression than diaphragm for mitochondrial enzymes that participate in fatty acid oxidation and biosynthesis. This likely contributes to the lower fatigue resistance of pharyngeal upper airway muscles compared with the diaphragm. Citation: van Lunteren E; Spiegler S; Moyer M. Differential expression of lipid and carbohydrate metabolism genes in upper airway versus diaphragm

  6. Environmental factors affecting pregnancy: endocrine disrupters, nutrients and metabolic pathways.

    PubMed

    Bazer, Fuller W; Wu, Guoyao; Johnson, Gregory A; Wang, Xiaoqiu

    2014-12-01

    Uterine adenogenesis, a unique post-natal event in mammals, is vulnerable to endocrine disruption by estrogens and progestins resulting in infertility or reduced prolificacy. The absence of uterine glands results in insufficient transport of nutrients into the uterine lumen to support conceptus development. Arginine, a component of histotroph, is substrate for production of nitric oxide, polyamines and agmatine and, with secreted phosphoprotein 1, it affects cytoskeletal organization of trophectoderm. Arginine is critical for development of the conceptus, pregnancy recognition signaling, implantation and placentation. Conceptuses of ungulates and cetaceans convert glucose to fructose which is metabolized via multiple pathways to support growth and development. However, high fructose corn syrup in soft drinks and foods may increase risks for metabolic disorders and increase insulin resistance in adults. Understanding endocrine disrupters and dietary substances, and novel pathways for nutrient metabolism during pregnancy can improve survival and growth, and prevent chronic metabolic diseases in offspring. PMID:25224489

  7. Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

    PubMed

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  8. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    PubMed Central

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  9. Chloroplast lipid droplet type II NAD(P)H quinone oxidoreductase is essential for prenylquinone metabolism and vitamin K1 accumulation

    PubMed Central

    Eugeni Piller, Lucia; Besagni, Céline; Ksas, Brigitte; Rumeau, Dominique; Bréhélin, Claire; Glauser, Gaétan; Kessler, Felix; Havaux, Michel

    2011-01-01

    Lipid droplets are ubiquitous cellular structures in eukaryotes and are required for lipid metabolism. Little is currently known about plant lipid droplets other than oil bodies. Here, we define dual roles for chloroplast lipid droplets (plastoglobules) in energy and prenylquinone metabolism. The prenylquinones—plastoquinone, plastochromanol-8, phylloquinone (vitamin K1), and tocopherol (vitamin E)—are partly stored in plastoglobules. This work shows that NAD(P)H dehydrogenase C1 (NDC1) (At5g08740), a type II NAD(P)H quinone oxidoreductase, associates with plastoglobules. NDC1 reduces a plastoquinone analog in vitro and affects the overall redox state of the total plastoquinone pool in vivo by reducing the plastoquinone reservoir of plastoglobules. Finally, NDC1 is required for normal plastochromanol-8 accumulation and is essential for vitamin K1 production. PMID:21844348

  10. Mechanism of bile acid-regulated glucose and lipid metabolism in duodenal-jejunal bypass

    PubMed Central

    Chai, Jie; Zou, Lei; Li, Xirui; Han, Dali; Wang, Shan; Hu, Sanyuan; Guan, Jie

    2015-01-01

    Bile acid plays an important role in regulating blood glucose, lipid and energy metabolism. The present study was implemented to determine the effect of duodenal-jejunal bypass (DJB) on FXR, TGR-5expression in terminal ileum and its bile acid-related mechanism on glucose and lipid metabolism. Immunohistochemistry was used to detect relative gene or protein expression in liver and intestine. Firstly, we found that expression of FXR in liver and terminal ileum of DJB group was significantly higher than that in S-DJB group (P<0.05). In addition, DJB dramatically increased the activation of TGR-5 in the liver of rats. Furthermore, PEPCK, G6Pase, FBPase 1 and GLP-1 were up-regulated by DJB. In conclusion, these results showed that bile acid ameliorated glucose and lipid metabolism through bile acid-FXR and bile acid- TGR-5 signaling pathway. PMID:26884847

  11. 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. PMID:25352435

  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. Endogenous and dietary lipids influencing feed intake and energy metabolism of periparturient dairy cows.

    PubMed

    Kuhla, B; Metges, C C; Hammon, H M

    2016-07-01

    The high metabolic priority of the mammary gland for milk production, accompanied by limited feed intake around parturition results in a high propensity to mobilize body fat reserves. Under these conditions, fuel selection of many peripheral organs is switched, for example, from carbohydrate to fat utilization to spare glucose for milk production and to ensure partitioning of tissue- and dietary-derived nutrients toward the mammary gland. For example, muscle tissue uses nonesterified fatty acids (NEFA) but releases lactate and amino acids in a coordinated order, thereby providing precursors for milk synthesis or hepatic gluconeogenesis. Tissue metabolism and in concert, nutrient partitioning are controlled by the endocrine system involving a reduction in insulin secretion and systemic insulin sensitivity and orchestrated changes in plasma hormones such as insulin, adiponectin, insulin growth factor-I, growth hormone, glucagon, leptin, glucocorticoids, and catecholamines. However, the endocrine system is highly sensitive and responsive to an overload of fatty acids no matter if excessive NEFA supply originates from exogenous or endogenous sources. Feeding a diet containing rumen-protected fat from late lactation to calving and beyond exerts similar negative effects on energy intake, glucose and insulin concentrations as does a high extent of body fat mobilization around parturition in regard to the risk for ketosis and fatty liver development. High plasma NEFA concentrations are thought not to act directly at the brain level, but they increase the energy charge of the liver which is, signaled to the brain to diminish feed intake. Cows differing in fat mobilization during the transition phase differ in their hepatic energy charge, whole body fat oxidation, glucose metabolism, plasma ghrelin, and leptin concentrations and in feed intake several week before parturition. Hence, a high lipid load, no matter if stored, mobilized or fed, affects the endocrine system

  14. Effect of in vitro cultured Anoectochilus formosanus on lipid metabolism in clinical uses.

    PubMed

    Du, Xiao-Ming; Sun, Ning-Yi; Furusho, Norihiro; Hayashi, Jun; Shoyama, Yukihiro

    2007-01-01

    A clinical study was performed on the effect of in vitro cultured Anoectochilus formosanus HAYATA on lipid-metabolism. Sixty-six volunteers, including 36 healthy, 14 high-triglyceride-, 11 high-cholesterol- and 5 high-triglyceride- and high cholesterol- subjects, were administrated with A. formosanus (450 mg/day) for 6 months or 12 months. A. formosanus significantly decreased the concentrations of the serum levels of cholesterol, low density lipoprotein and very low density lipoprotein in all volunteers. The results of the present study suggested that A. formosanus might function as a liver activator resulting in improvement of lipid-metabolism. PMID:17963314

  15. Altered lipid metabolism in Drosophila model of Huntington’s disease

    PubMed Central

    Aditi, Kumari; Shakarad, Mallikarjun N.; Agrawal, Namita

    2016-01-01

    Huntington’s disease (HD) is late-onset, progressive neurodegenerative disorder caused by expansion of polyglutamine (polyQ) repeat within Huntingtin (Htt) protein. In HD patients, energy-related manifestations such as modulation of weight during entire course of disease with energy deficit at terminal stage have been reported, however, underlying reason remains elusive till date. Lipids, carbohydrate and protein constitute a predominant fraction of body’s energy reservoir and perturbation in their homeostasis may influence weight. To discern role of these energy molecules in weight alteration, we quantified them in an in vivo transgenic Drosophila model of HD. We document that diseased flies exhibit change in weight due to an altered lipid metabolism, as evident from considerably high lipid levels at the time of disease onset followed by a pathologic decline at end-stage. An alteration in intracellular lipid droplet size suggested altered cellular lipid turnover. Furthermore, diseased flies displayed substantial changes in carbohydrate and protein content. Interestingly, alteration in weight and lipid levels are independent of the feeding pattern in diseased condition and exhibit weak correlation with insulin-like peptide or adipokinetic hormone producing cells. We propose that therapeutic intervention aimed at restoring lipid levels and associated metabolic pathways may improve longevity and quality of patient’s life. PMID:27506601

  16. 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. PMID:25973988

  17. 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

    2016-09-01

    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. PMID:27208774

  18. A New Fluorescence-Based Method Identifies Protein Phosphatases Regulating Lipid Droplet Metabolism

    PubMed Central

    Bozaquel-Morais, Bruno L.; Madeira, Juliana B.; Maya-Monteiro, Clarissa M.; Masuda, Claudio A.; Montero-Lomeli, Mónica

    2010-01-01

    In virtually every cell, neutral lipids are stored in cytoplasmic structures called lipid droplets (LDs) and also referred to as lipid bodies or lipid particles. We developed a rapid high-throughput assay based on the recovery of quenched BODIPY-fluorescence that allows to quantify lipid droplets. The method was validated by monitoring lipid droplet turnover during growth of a yeast culture and by screening a group of strains deleted in genes known to be involved in lipid metabolism. In both tests, the fluorimetric assay showed high sensitivity and good agreement with previously reported data using microscopy. We used this method for high-throughput identification of protein phosphatases involved in lipid droplet metabolism. From 65 yeast knockout strains encoding protein phosphatases and its regulatory subunits, 13 strains revealed to have abnormal levels of lipid droplets, 10 of them having high lipid droplet content. Strains deleted for type I protein phosphatases and related regulators (ppz2, gac1, bni4), type 2A phosphatase and its related regulator (pph21 and sap185), type 2C protein phosphatases (ptc1, ptc4, ptc7) and dual phosphatases (pps1, msg5) were catalogued as high-lipid droplet content strains. Only reg1, a targeting subunit of the type 1 phosphatase Glc7p, and members of the nutrient-sensitive TOR pathway (sit4 and the regulatory subunit sap190) were catalogued as low-lipid droplet content strains, which were studied further. We show that Snf1, the homologue of the mammalian AMP-activated kinase, is constitutively phosphorylated (hyperactive) in sit4 and sap190 strains leading to a reduction of acetyl-CoA carboxylase activity. In conclusion, our fast and highly sensitive method permitted us to catalogue protein phosphatases involved in the regulation of LD metabolism and present evidence indicating that the TOR pathway and the SNF1/AMPK pathway are connected through the Sit4p-Sap190p pair in the control of lipid droplet biogenesis. PMID:21060891

  19. 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.

  20. Rapid Communication: Cholesterol deficiency-associated APOB mutation impacts lipid metabolism in Holstein calves and breeding bulls.

    PubMed

    Gross, J J; Schwinn, A-C; Schmitz-Hsu, F; Menzi, F; Drögemüller, C; Albrecht, C; Bruckmaier, R M

    2016-04-01

    During the last months, the number of reports on Holstein calves suffering from incurable idiopathic diarrhea dramatically increased. Affected calves showed severe hypocholesterolemia and mostly died within days up to a few months after birth. This new autosomal monogenic recessive inherited fat metabolism disorder, termed cholesterol deficiency (CD), is caused by a loss of function mutation of the bovine gene. The objective of the present study was to investigate specific components of lipid metabolism in 6 homozygous for the mutation (CDS) and 6 normal Holstein calves with different genotypes. Independent of sex, CDS had significantly lower plasma concentrations of total cholesterol (TC), free cholesterol (FC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triacylglycerides (TAG), and phospholipids (PL) compared with homozygous wild-type calves ( < 0.05). Furthermore, we studied the effect of the genotype on cholesterol metabolism in adult Holstein breeding bulls of Swissgenetics. Among a total of 254 adult males, the homozygous mutant genotype was absent, 36 bulls were heterozygous carriers (CDC), and 218 bulls were homozygous wild-type (CDF). In CDC bulls, plasma concentrations of TC, FC, HDL-C, LDL-C, VLDL-C, TAG, and PL were lower compared with CDF bulls ( < 0.05). The ratios of FC:cholesteryl esters (CE) and FC:TC were higher in CDC bulls compared with CDF bulls, whereas the ratio of CE:TC was lower in CDC bulls compared with CDF bulls ( < 0.01). In conclusion, the CD-associated mutation was shown to affect lipid metabolism in affected Holstein calves and adult breeding bulls. Besides cholesterol, the concentrations of PL, TAG, and lipoproteins also were distinctly reduced in homozygous and heterozygous carriers of the mutation. Beyond malabsorption of dietary lipids, deleterious effects of apolipoprotein B deficiency on hepatic lipid metabolism, steroid

  1. 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. PMID:27023241

  2. 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. PMID:24177230

  3. Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices.

    PubMed

    Szalowska, Ewa; van der Burg, Bart; Man, Hai-Yen; Hendriksen, Peter J M; Peijnenburg, Ad A C M

    2014-01-01

    Although drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS) as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24 h with the model steatogenic compounds: amiodarone (AMI), valproic acid (VA), and tetracycline (TET). Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. Furthermore, on the basis of the transcriptomics data it was hypothesized that all three compounds affect peroxisome proliferator activated-receptor (PPAR) signaling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/(β/δ)/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA) or compounds impairing mitochondrial functions (i.e. TET). Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify early mechanisms of action of compounds altering lipid metabolism. PMID:24489787

  4. DNA Methylation of Lipid-Related Genes Affects Blood Lipid Levels

    PubMed Central

    Pfeiffer, Liliane; Wahl, Simone; Pilling, Luke C.; Reischl, Eva; Sandling, Johanna K.; Kunze, Sonja; Holdt, Lesca M.; Kretschmer, Anja; Schramm, Katharina; Adamski, Jerzy; Klopp, Norman; Illig, Thomas; Hedman, Åsa K.; Roden, Michael; Hernandez, Dena G.; Singleton, Andrew B.; Thasler, Wolfgang E.; Grallert, Harald; Gieger, Christian; Herder, Christian; Teupser, Daniel; Meisinger, Christa; Spector, Timothy D.; Kronenberg, Florian; Prokisch, Holger; Melzer, David; Peters, Annette; Deloukas, Panos; Ferrucci, Luigi; Waldenberger, Melanie

    2016-01-01

    Background Epigenetic mechanisms might be involved in the regulation of interindividual lipid level variability and thus may contribute to the cardiovascular risk profile. The aim of this study was to investigate the association between genome-wide DNA methylation and blood lipid levels high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Observed DNA methylation changes were also further analyzed to examine their relationship with previous hospitalized myocardial infarction. Methods and Results Genome-wide DNA methylation patterns were determined in whole blood samples of 1776 subjects of the Cooperative Health Research in the Region of Augsburg F4 cohort using the Infinium HumanMethylation450 BeadChip (Illumina). Ten novel lipid-related CpG sites annotated to various genes including ABCG1, MIR33B/SREBF1, and TNIP1 were identified. CpG cg06500161, located in ABCG1, was associated in opposite directions with both high-density lipoprotein cholesterol (β coefficient=−0.049; P=8.26E-17) and triglyceride levels (β=0.070; P=1.21E-27). Eight associations were confirmed by replication in the Cooperative Health Research in the Region of Augsburg F3 study (n=499) and in the Invecchiare in Chianti, Aging in the Chianti Area study (n=472). Associations between triglyceride levels and SREBF1 and ABCG1 were also found in adipose tissue of the Multiple Tissue Human Expression Resource cohort (n=634). Expression analysis revealed an association between ABCG1 methylation and lipid levels that might be partly mediated by ABCG1 expression. DNA methylation of ABCG1 might also play a role in previous hospitalized myocardial infarction (odds ratio, 1.15; 95% confidence interval=1.06–1.25). Conclusions Epigenetic modifications of the newly identified loci might regulate disturbed blood lipid levels and thus contribute to the development of complex lipid-related diseases. PMID:25583993

  5. 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.

  6. Bromochloromethane, a Methane Analogue, Affects the Microbiota and Metabolic Profiles of the Rat Gastrointestinal Tract

    PubMed Central

    Yang, Yu-Xiang; Mu, Chun-Long; Luo, Zhen

    2015-01-01

    Bromochloromethane (BCM), an inhibitor of methanogenesis, has been used in animal production. However, little is known about its impact on the intestinal microbiota and metabolic patterns. The present study aimed to investigate the effect of BCM on the colonic bacterial community and metabolism by establishing a Wistar rat model. Twenty male Wistar rats were randomly divided into two groups (control and treated with BCM) and raised for 6 weeks. Bacterial fermentation products in the cecum were determined, and colonic methanogens and sulfate-reducing bacteria (SRB) were quantified. The colonic microbiota was analyzed by pyrosequencing of the 16S rRNA genes, and metabolites were profiled by gas chromatography and mass spectrometry. The results showed that BCM did not affect body weight and feed intake, but it did significantly change the intestinal metabolic profiles. Cecal protein fermentation was enhanced by BCM, as methylamine, putrescine, phenylethylamine, tyramine, and skatole were significantly increased. Colonic fatty acid and carbohydrate concentrations were significantly decreased, indicating the perturbation of lipid and carbohydrate metabolism by BCM. BCM treatment decreased the abundance of methanogen populations, while SRB were increased in the colon. BCM did not affect the total colonic bacterial counts but significantly altered the bacterial community composition by decreasing the abundance of actinobacteria, acidobacteria, and proteobacteria. The results demonstrated that BCM treatment significantly altered the microbiotic and metabolite profiles in the intestines, which may provide further information on the use of BCM in animal production. PMID:26567308

  7. 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

  8. Dietary fructose and glucose differentially affect lipid and glucose homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Absorbed glucose and fructose differ in that glucose largely escapes first pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these two monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial trig...

  9. Dietary fructose and glucose differentially affect lipid and glucose homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these 2 monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial trigly...

  10. Integrated analysis, transcriptome-lipidome, reveals the effects of INO-level (INO2 and INO4) on lipid metabolism in yeast

    PubMed Central

    2013-01-01

    Background In the yeast Saccharomyces cerevisiae, genes containing UASINO sequences are regulated by the Ino2/Ino4 and Opi1 transcription factors, and this regulation controls lipid biosynthesis. The expression level of INO2 and INO4 genes (INO-level) at different nutrient limited conditions might lead to various responses in yeast lipid metabolism. Methods In this study, we undertook a global study on how INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in yeast and we also studied the effects of single and double deletions of the two INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h-1 and strains having different INO-level, we were able to see the effect on expression level of the genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through combined measurements of the transcriptome, metabolome, and lipidome it was possible to obtain a large dataset that could be used to identify how the INO-level controls lipid metabolism and also establish correlations between the different components. Results In this study, we undertook a global study on how INO-levels (transcription level of INO2 and INO4) affect lipid metabolism in yeast and we also studied the effects of single and double deletions of the two INO-genes (deficient effect). Using 2 types of nutrient limitations (carbon and nitrogen) in chemostat cultures operated at a fixed specific growth rate of 0.1 h-1 and strains having different INO-level, we were able to see the effect on expression level of the genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through combined measurements of the transcriptome, metabolome, and lipidome it was possible to obtain a large dataset that could be used to identify how the INO-level controls lipid metabolism and also establish correlations between the different

  11. Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal

    PubMed Central

    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. PMID:24999379

  12. Lipidomics reveals control of Mycobacterium tuberculosis virulence lipids via metabolic coupling.

    PubMed

    Jain, Madhulika; Petzold, Christopher J; Schelle, Michael W; Leavell, Michael D; Mougous, Joseph D; Bertozzi, Carolyn R; Leary, Julie A; Cox, Jeffery S

    2007-03-20

    Mycobacterium tuberculosis synthesizes specific polyketide lipids that interact with the host and are required for virulence. Using a mass spectrometric approach to simultaneously monitor hundreds of lipids, we discovered that the size and abundance of two lipid virulence factors, phthiocerol dimycocerosate (PDIM) and sulfolipid-1 (SL-1), are controlled by the availability of a common precursor, methyl malonyl CoA (MMCoA). Consistent with this view, increased levels of MMCoA led to increased abundance and mass of both PDIM and SL-1. Furthermore, perturbation of MMCoA metabolism attenuated pathogen replication in mice. Importantly, we detected increased PDIM synthesis in bacteria growing within host tissues and in bacteria grown in culture on odd-chain fatty acids. Because M. tuberculosis catabolizes host lipids to grow during infection, we propose that growth of M. tuberculosis on fatty acids in vivo leads to increased flux of MMCoA through lipid biosynthetic pathways, resulting in increased virulence lipid synthesis. Our results suggest that the shift to host lipid catabolism during infection allows for increased virulence lipid anabolism by the bacterium. PMID:17360366

  13. The Relationship of Ectopic Lipid Accumulation to Cardiac and Vascular Function in Obesity and Metabolic Syndrome

    PubMed Central

    Ruberg, Frederick L.; Chen, Zhongjing; Hua, Ning; Bigornia, Sherman; Guo, Zifang; Hallock, Kevin; Jara, Hernan; LaValley, Michael; Phinikaridou, Alkystis; Qiao, Ye; Viereck, Jason; Apovian, Caroline M.; Hamilton, James A.

    2010-01-01

    Storage of lipid in ectopic depots outside of abdominal visceral and subcutaneous stores, including within the pericardium and liver, has been associated with obesity, insulin resistance, and cardiovascular risk. We sought to determine whether anatomically distinct ectopic depots were physiologically correlated and site-specific effects upon cardiovascular function could be identified. Obese subjects (n = 28) with metabolic syndrome but without known atherosclerotic disease and healthy controls (n = 18) underwent magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) to quantify pericardial and periaortic lipid volumes, cardiac function, aortic compliance, and intrahepatic lipid content. Fasting plasma lipoproteins, glucose, insulin, and free-fatty acids were measured. Pericardial and intrahepatic (P < 0.01) and periaortic (P < 0.05) lipid volumes were increased in obese subjects vs. controls and were strongly and positively correlated (P ≤ 0.01) but independent of BMI (P = NS) among obese subjects. Intrahepatic lipid was associated with insulin resistance (P < 0.01) and triglycerides (P < 0.05), whereas pericardial and periaortic lipid were not (P = NS). Periaortic and pericardial lipid positively correlated to free-fatty acids (P ≤ 0.01) and negatively correlated to high-density lipoprotein (HDL) cholesterol (P < 0.05). Pericardial lipid negatively correlated to cardiac output (P = 0.03) and stroke volume (P = 0.01) but not to left ventricular ejection fraction (P = 0.46). None of the ectopic depots correlated to aortic compliance. In conclusion, ectopic storage of lipid in anatomically distinct depots appeared tightly correlated but independent of body size. Site-specific functional abnormalities were observed for pericardial but not periaortic lipid. These findings underscore the utility of MRI to assess individual differences in ectopic lipid that are not predictable from BMI. PMID:19875992

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

    PubMed Central

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

    2015-01-01

    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. PMID:25535344

  15. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

    PubMed Central

    Elias, Peter M.; Williams, Mary L.; Holleran, Walter M.; Jiang, Yan J.; Schmuth, Matthias

    2010-01-01

    Many of the ichthyoses are associated with inherited disorders of lipid metabolism. These disorders have provided unique models to dissect physiologic processes in normal epidermis and the pathophysiology of more common scaling conditions. In most of these disorders, a permeability barrier abnormality “drives” pathophysiology through stimulation of epidermal hyperplasia. Among primary abnormalities of nonpolar lipid metabolism, triglyceride accumulation in neutral lipid storage disease as a result of a lipase mutation provokes a barrier abnormality via lamellar/nonlamellar phase separation within the extracellular matrix of the stratum corneum (SC). Similar mechanisms account for the barrier abnormalities (and subsequent ichthyosis) in inherited disorders of polar lipid metabolism. For example, in recessive X-linked ichthyosis (RXLI), cholesterol sulfate (CSO4) accumulation also produces a permeability barrier defect through lamellar/nonlamellar phase separation. However, in RXLI, the desquamation abnormality is in part attributable to the plurifunctional roles of CSO4 as a regulator of both epidermal differentiation and corneodesmosome degradation. Phase separation also occurs in type II Gaucher disease (GD; from accumulation of glucosylceramides as a result of to β-glucocerebrosidase deficiency). Finally, failure to assemble both lipids and desquamatory enzymes into nascent epidermal lamellar bodies (LBs) accounts for both the permeability barrier and desquamation abnormalities in Harlequin ichthyosis (HI). The barrier abnormality provokes the clinical phenotype in these disorders not only by stimulating epidermal proliferation, but also by inducing inflammation. PMID:18245815

  16. Modulation of host lipid metabolism by hepatitis C virus: Role of new therapies

    PubMed Central

    Del Campo, José A; Romero-Gómez, Manuel

    2015-01-01

    It is well established that hepatitis C virus (HCV) infection and replication relies on host lipid metabolism. HCV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides, circulating infective particles are associated with very low-density lipoprotein. On the other hand, higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HCV infection, suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy (> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HCV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review, host genetic factors, viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism. PMID:26478669

  17. Depletion of Myostatin b Promotes Somatic Growth and Lipid Metabolism in Zebrafish.

    PubMed

    Gao, Yanping; Dai, Ziru; Shi, Chuang; Zhai, Gang; Jin, Xia; He, Jiangyan; Lou, Qiyong; Yin, Zhan

    2016-01-01

    Myostatin (MSTN) is a negative regulator of myogenesis in vertebrates. Depletion of mstn resulted in elevated muscle growth in several animal species. However, the report on the complete ablation of mstn in teleost fish has not yet become available. In this study, two independent mstnb-deficient mutant lines in zebrafish were generated with the TALENs technique. In the mstnb-deficient zebrafish, enhanced muscle growth with muscle fiber hyperplasia was achieved. Beginning at the adult stage (80 days postfertilization), the mstnb-deficient zebrafish exhibited increased circumferences and body weights compared with the wild-type sibling control fish. Although the overall total lipid/body weight ratios remained similar between the mstnb-deficient zebrafish and the control fish, the distribution of lipids was altered. The size of the visceral adipose tissues became smaller while more lipids accumulated in skeletal muscle in the mstnb-deficient zebrafish than in the wild-type control fish. Based on the transcriptional expression profiles, our results revealed that lipid metabolism, including lipolysis and lipogenesis processes, was highly activated in the mstnb-deficient zebrafish, which indicated the transition of energy metabolism from protein-dependent to lipid-dependent in mstnb-deficient zebrafish. Our mstnb-deficient model could be valuable in understanding not only the growth trait regulation in teleosts but also the mechanisms of teleost energy metabolism. PMID:27458428

  18. Depletion of Myostatin b Promotes Somatic Growth and Lipid Metabolism in Zebrafish

    PubMed Central

    Gao, Yanping; Dai, Ziru; Shi, Chuang; Zhai, Gang; Jin, Xia; He, Jiangyan; Lou, Qiyong; Yin, Zhan

    2016-01-01

    Myostatin (MSTN) is a negative regulator of myogenesis in vertebrates. Depletion of mstn resulted in elevated muscle growth in several animal species. However, the report on the complete ablation of mstn in teleost fish has not yet become available. In this study, two independent mstnb-deficient mutant lines in zebrafish were generated with the TALENs technique. In the mstnb-deficient zebrafish, enhanced muscle growth with muscle fiber hyperplasia was achieved. Beginning at the adult stage (80 days postfertilization), the mstnb-deficient zebrafish exhibited increased circumferences and body weights compared with the wild-type sibling control fish. Although the overall total lipid/body weight ratios remained similar between the mstnb-deficient zebrafish and the control fish, the distribution of lipids was altered. The size of the visceral adipose tissues became smaller while more lipids accumulated in skeletal muscle in the mstnb-deficient zebrafish than in the wild-type control fish. Based on the transcriptional expression profiles, our results revealed that lipid metabolism, including lipolysis and lipogenesis processes, was highly activated in the mstnb-deficient zebrafish, which indicated the transition of energy metabolism from protein-dependent to lipid-dependent in mstnb-deficient zebrafish. Our mstnb-deficient model could be valuable in understanding not only the growth trait regulation in teleosts but also the mechanisms of teleost energy metabolism. PMID:27458428

  19. Tribbles-1: a novel regulator of hepatic lipid metabolism in humans

    PubMed Central

    Bauer, Robert C.; Yenilmez, Batuhan O.; Rader, Daniel J.

    2015-01-01

    The protein tribbles-1, encoded by the gene TRIB1, is increasingly recognized as a major regulator of multiple cellular and physiological processes in humans. Recent human genetic studies, as well as molecular biological approaches, have implicated this intriguing protein in the aetiology of multiple human diseases, including myeloid leukaemia, Crohn's disease, non-alcoholic fatty liver disease (NAFLD), dyslipidaemia and coronary artery disease (CAD). Genome-wide association studies (GWAS) have repeatedly identified variants at the genomic TRIB1 locus as being significantly associated with multiple plasma lipid traits and cardiovascular disease (CVD) in humans. The involvement of TRIB1 in hepatic lipid metabolism has been validated through viral-mediated hepatic overexpression of the gene in mice; increasing levels of TRIB1 decreased plasma lipids in a dose-dependent manner. Additional studies have implicated TRIB1 in the regulation of hepatic lipogenesis and NAFLD. The exact mechanisms of TRIB1 regulation of both plasma lipids and hepatic lipogenesis remain undetermined, although multiple signalling pathways and transcription factors have been implicated in tribbles-1 function. Recent reports have been aimed at developing TRIB1-based lipid therapeutics. In summary, tribbles-1 is an important modulator of human energy metabolism and metabolic syndromes and worthy of future studies aimed at investigating its potential as a therapeutic target. PMID:26517927

  20. Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    HIV infection is associated with abnormal lipid metabolism, body fat redistribution, and altered energy expenditure. The pathogenesis of these complex abnormalities is unclear. Viral protein R (Vpr), an HIV-1 accessory protein, can regulate gene transcription mediated by the glucocorticoid receptor ...

  1. Chromium supplementation alters the glucose and lipid metabolism of feedlot cattle during the receiving period

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crossbreed steers (n = 20; 235 ± 4 kg) were fed 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brand Chromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (C...

  2. Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crossbred steers (n = 20; 235 +/- 4 kg) were fed 53 days during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brandChromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0...

  3. Identification of regulatory network hubs that control lipid metabolism in Chlamydomonas reinhardtii.

    PubMed

    Gargouri, Mahmoud; Park, Jeong-Jin; Holguin, F Omar; Kim, Min-Jeong; Wang, Hongxia; Deshpande, Rahul R; Shachar-Hill, Yair; Hicks, Leslie M; Gang, David R

    2015-08-01

    Microalgae-based biofuels are promising sources of alternative energy, but improvements throughout the production process are required to establish them as economically feasible. One of the most influential improvements would be a significant increase in lipid yields, which could be achieved by altering the regulation of lipid biosynthesis and accumulation. Chlamydomonas reinhardtii accumulates oil (triacylglycerols, TAG) in response to nitrogen (N) deprivation. Although a few important regulatory genes have been identified that are involved in controlling this process, a global understanding of the larger regulatory network has not been developed. In order to uncover this network in this species, a combined omics (transcriptomic, proteomic and metabolomic) analysis was applied to cells grown in a time course experiment after a shift from N-replete to N-depleted conditions. Changes in transcript and protein levels of 414 predicted transcription factors (TFs) and transcriptional regulators (TRs) were monitored relative to other genes. The TF and TR genes were thus classified by two separate measures: up-regulated versus down-regulated and early response versus late response relative to two phases of polar lipid synthesis (before and after TAG biosynthesis initiation). Lipidomic and primary metabolite profiling generated compound accumulation levels that were integrated with the transcript dataset and TF profiling to produce a transcriptional regulatory network. Evaluation of this proposed regulatory network led to the identification of several regulatory hubs that control many aspects of cellular metabolism, from N assimilation and metabolism, to central metabolism, photosynthesis and lipid metabolism. PMID:26022256

  4. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

    SciTech Connect

    Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In; Park, Sang-Joon; Lee, Sang Gyu; Lee, Inkyu; Kim, Myoung Ok; Yoon, Duhak; Ryoo, Zae Young

    2014-02-14

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.

  5. DIETARY LIPID AS A FACTOR MODULATING XENOBIOTIC METABOLISM IN CHANNEL CATFISH (ICTALURUS PUNCTATUS)

    EPA Science Inventory

    Adult channel catfish (Ictaiurus punctatus) were fed diets containing menhaden oil (MHO), soybean oil (SBO), or beef tallow (BFT) as lipid sources for 116 d. The effects of these diets on two important hepatic xenobiotic-metabolizing enzyme systems, cytochrome p-45O-dependent mon...

  6. Identification of regulatory network hubs that control lipid metabolism in Chlamydomonas reinhardtii

    PubMed Central

    Gargouri, Mahmoud; Park, Jeong-Jin; Holguin, F. Omar; Kim, Min-Jeong; Wang, Hongxia; Deshpande, Rahul R.; Shachar-Hill, Yair; Hicks, Leslie M.; Gang, David R.

    2015-01-01

    Microalgae-based biofuels are promising sources of alternative energy, but improvements throughout the production process are required to establish them as economically feasible. One of the most influential improvements would be a significant increase in lipid yields, which could be achieved by altering the regulation of lipid biosynthesis and accumulation. Chlamydomonas reinhardtii accumulates oil (triacylglycerols, TAG) in response to nitrogen (N) deprivation. Although a few important regulatory genes have been identified that are involved in controlling this process, a global understanding of the larger regulatory network has not been developed. In order to uncover this network in this species, a combined omics (transcriptomic, proteomic and metabolomic) analysis was applied to cells grown in a time course experiment after a shift from N-replete to N-depleted conditions. Changes in transcript and protein levels of 414 predicted transcription factors (TFs) and transcriptional regulators (TRs) were monitored relative to other genes. The TF and TR genes were thus classified by two separate measures: up-regulated versus down-regulated and early response versus late response relative to two phases of polar lipid synthesis (before and after TAG biosynthesis initiation). Lipidomic and primary metabolite profiling generated compound accumulation levels that were integrated with the transcript dataset and TF profiling to produce a transcriptional regulatory network. Evaluation of this proposed regulatory network led to the identification of several regulatory hubs that control many aspects of cellular metabolism, from N assimilation and metabolism, to central metabolism, photosynthesis and lipid metabolism. PMID:26022256

  7. Cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that curcumin (CUR) may increase lipid accumulation in cultured THP-1 monocytes/macrophages, but tetrahydrocurcumin (THC), an in vivo metabolite of CUR, had no such effect. In the present study, we have hypothesized that different cellular uptake and/or metabolism of CUR and THC...

  8. Lipid Metabolism Predicts Changes in Body Composition during Energy Restriction in Overweight Humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary weight loss regimens could be more effective by selectively targeting adipose while sparing lean mass if predictive information about individuals’ lipid metabolic responses to a intervention were available. The objective of this study was to examine the relationships among changes in four an...

  9. Nuclear receptors and their relevance to diseases related to lipid metabolism.

    PubMed

    Berkenstam, Anders; Gustafsson, Jan-Ake

    2005-04-01

    Drugs that target the nuclear hormone receptor family constitute one of the largest and most potent groups of pharmaceuticals currently in use. However, although many of these human nuclear receptors have been clearly demonstrated to be key sensors and regulators of lipid metabolism, the full pharmacological potential of this drug target class has not been fully explored. There are two main reasons for this. First, a rationale approach is needed to identify pharmacologically selective drug candidates to nuclear receptors that have a large therapeutic window between the beneficial effects and the unwanted side effects. This appears to apply to all ligand-regulated nuclear receptors, including those nuclear receptors more recently proposed as novel targets for diseases related to lipid metabolism such as the peroxisome proliferator-activated receptors, liver X receptors and farnesoid X-activated receptor. The second reason is that any sub-group of nuclear receptors important for the regulation of lipid metabolism might be pharmacologically inaccessible by conventional low molecular weight compounds, owing to the lack of a classical ligand-binding-pocket, as recently revealed by X-ray crystallography. Accordingly, targeting of classical nuclear receptor family members with better characterized endocrinology and roles in lipid metabolism, such as the thyroid and steroid hormone receptors, could become of renewed pharmacological interest, as these targets provide well-characterized alternatives to the more recently discovered nuclear receptors. PMID:15780827

  10. Monitoring intra-cellular lipid metabolism in macrophages by Raman- and CARS-microscopy

    NASA Astrophysics Data System (ADS)

    Matthäus, Christian; Bergner, Gero; Krafft, Christoph; Dietzek, Benjamin; Lorkowski, Stefan; Popp, Jürgen

    2010-04-01

    Monocyte-derived macrophages play a key role in lipid metabolism in vessel wall tissues. Macrophages can take up lipids by various mechanisms. As phagocytes, macrophages are important for the decomposition of lipid plaques within arterial walls that contribute to arteriosclerosis. Of special interest are uptake dynamics and intra-cellular fate of different individual types of lipids as, for example, fatty acids, triglycerides or free and esterified cholesterol. Here we utilize Raman microscopy to image the metabolism of such lipids and follow subsequent storage or degradation patterns. The combination of optical microscopy with Raman spectroscopy allows visualization at the diffraction limit of the employed laser light and biochemical characterization through the associated spectral information. Relatively long measuring times, due to the weakness of Raman scattering can be overcome by non-linear effects such as coherent anti-Stokes Raman scattering (CARS). With this contribution we introduce first results to monitor the incorporation of lipid components into individual cells employing Raman and CARS microscopy.

  11. The Sheep Genome Illuminates Biology of the Rumen and Lipid Metabolism

    PubMed Central

    Talbot, Richard; Maddox, Jillian F.; Faraut, Thomas; Wu, Chunhua; Muzny, Donna M.; Li, Yuxiang; Zhang, Wenguang; Stanton, Jo-Ann; Brauning, Rudiger; Barris, Wesley C.; Hourlier, Thibaut; Aken, Bronwen L.; Searle, Stephen M.J.; Adelson, David L.; Bian, Chao; Cam, Graham R.; Chen, Yulin; Cheng, Shifeng; DeSilva, Udaya; Dixen, Karen; Dong, Yang; Fan, Guangyi; Franklin, Ian R.; Fu, Shaoyin; Guan, Rui; Highland, Margaret A.; Holder, Michael E.; Huang, Guodong; Ingham, Aaron B.; Jhangiani, Shalini N.; Kalra, Divya; Kovar, Christie L.; Lee, Sandra L.; Liu, Weiqing; Liu, Xin; Lu, Changxin; Lv, Tian; Mathew, Tittu; McWilliam, Sean; Menzies, Moira; Pan, Shengkai; Robelin, David; Servin, Bertrand; Townley, David; Wang, Wenliang; Wei, Bin; White, Stephen N.; Yang, Xinhua; Ye, Chen; Yue, Yaojing; Zeng, Peng; Zhou, Qing; Hansen, Jacob B.; Kristensen, Karsten; Gibbs, Richard A.; Flicek, Paul; Warkup, Christopher C.; Jones, Huw E.; Oddy, V. Hutton; Nicholas, Frank W.; McEwan, John C.; Kijas, James; Wang, Jun; Worley, Kim C.; Archibald, Alan L.; Cockett, Noelle; Xu, Xun; Wang, Wen; Dalrymple, Brian P.

    2014-01-01

    Sheep (Ovis aries) are a major source of meat, milk and fiber in the form of wool, and represent a distinct class of animals that have a specialized digestive organ, the rumen, which carries out the initial digestion of plant material. We have developed and analyzed a high quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants, compared to non-ruminant animals. PMID:24904168

  12. The sheep genome illuminates biology of the rumen and lipid metabolism.

    PubMed

    Jiang, Yu; Xie, Min; Chen, Wenbin; Talbot, Richard; Maddox, Jillian F; Faraut, Thomas; Wu, Chunhua; Muzny, Donna M; Li, Yuxiang; Zhang, Wenguang; Stanton, Jo-Ann; Brauning, Rudiger; Barris, Wesley C; Hourlier, Thibaut; Aken, Bronwen L; Searle, Stephen M J; Adelson, David L; Bian, Chao; Cam, Graham R; Chen, Yulin; Cheng, Shifeng; DeSilva, Udaya; Dixen, Karen; Dong, Yang; Fan, Guangyi; Franklin, Ian R; Fu, Shaoyin; Fuentes-Utrilla, Pablo; Guan, Rui; Highland, Margaret A; Holder, Michael E; Huang, Guodong; Ingham, Aaron B; Jhangiani, Shalini N; Kalra, Divya; Kovar, Christie L; Lee, Sandra L; Liu, Weiqing; Liu, Xin; Lu, Changxin; Lv, Tian; Mathew, Tittu; McWilliam, Sean; Menzies, Moira; Pan, Shengkai; Robelin, David; Servin, Bertrand; Townley, David; Wang, Wenliang; Wei, Bin; White, Stephen N; Yang, Xinhua; Ye, Chen; Yue, Yaojing; Zeng, Peng; Zhou, Qing; Hansen, Jacob B; Kristiansen, Karsten; Gibbs, Richard A; Flicek, Paul; Warkup, Christopher C; Jones, Huw E; Oddy, V Hutton; Nicholas, Frank W; McEwan, John C; Kijas, James W; Wang, Jun; Worley, Kim C; Archibald, Alan L; Cockett, Noelle; Xu, Xun; Wang, Wen; Dalrymple, Brian P

    2014-06-01

    Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals. PMID:24904168

  13. Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice

    PubMed Central

    Skarpengland, Tonje; Holm, Sverre; Scheffler, Katja; Gregersen, Ida; Dahl, Tuva B.; Suganthan, Rajikala; Segers, Filip M.; Østlie, Ingunn; Otten, Jeroen J. T.; Luna, Luisa; Ketelhuth, Daniel F. J.; Lundberg, Anna M.; Neurauter, Christine G.; Hildrestrand, Gunn; Skjelland, Mona; Bjørndal, Bodil; Svardal, Asbjørn M.; Iversen, Per O.; Hedin, Ulf; Nygård, Ståle; Olstad, Ole K.; Krohg-Sørensen, Kirsten; Slupphaug, Geir; Eide, Lars; Kuśnierczyk, Anna; Folkersen, Lasse; Ueland, Thor; Berge, Rolf K.; Hansson, Göran K.; Biessen, Erik A. L.; Halvorsen, Bente; Bjørås, Magnar; Aukrust, Pål

    2016-01-01

    Increasing evidence suggests that oxidative DNA damage accumulates in atherosclerosis. Recently, we showed that a genetic variant in the human DNA repair enzyme NEIL3 was associated with increased risk of myocardial infarction. Here, we explored the role of Neil3/NEIL3 in atherogenesis by both clinical and experimental approaches. Human carotid plaques revealed increased NEIL3 mRNA expression which significantly correlated with mRNA levels of the macrophage marker CD68. Apoe−/−Neil3−/− mice on high-fat diet showed accelerated plaque formation as compared to Apoe−/− mice, reflecting an atherogenic lipid profile, increased hepatic triglyceride levels and attenuated macrophage cholesterol efflux capacity. Apoe−/−Neil3−/− mice showed marked alterations in several pathways affecting hepatic lipid metabolism, but no genotypic alterations in genome integrity or genome-wide accumulation of oxidative DNA damage. These results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage. PMID:27328939

  14. Insights from human congenital disorders of intestinal lipid metabolism

    PubMed Central

    Levy, Emile

    2015-01-01

    The intestine must challenge the profuse daily flux of dietary fat that serves as a vital source of energy and as an essential component of cell membranes. The fat absorption process takes place in a series of orderly and interrelated steps, including the uptake and translocation of lipolytic products from the brush border membrane to the endoplasmic reticulum, lipid esterification, Apo synthesis, and ultimately the packaging of lipid and Apo components into chylomicrons (CMs). Deciphering inherited disorders of intracellular CM elaboration afforded new insight into the key functions of crucial intracellular proteins, such as Apo B, microsomal TG transfer protein, and Sar1b GTPase, the defects of which lead to hypobetalipoproteinemia, abetalipoproteinemia, and CM retention disease, respectively. These “experiments of nature” are characterized by fat malabsorption, steatorrhea, failure to thrive, low plasma levels of TGs and cholesterol, and deficiency of liposoluble vitamins and essential FAs. After summarizing and discussing the functions and regulation of these proteins for reader’s comprehension, the current review focuses on their specific roles in malabsorptions and dyslipidemia-related intestinal fat hyperabsorption while dissecting the spectrum of clinical manifestations and managements. The influence of newly discovered proteins (proprotein convertase subtilisin/kexin type 9 and angiopoietin-like 3 protein) on fat absorption has also been provided. Finally, it is stressed how the overexpression or polymorphism status of the critical intracellular proteins promotes dyslipidemia and cardiometabolic disorders. PMID:25387865

  15. Effects of forsythia fruit extracts and lignan on lipid metabolism.

    PubMed

    Cho, Sung-Hee; Rhee, Soon-Jae; Choi, Sang-Won; Choi, Youngsun

    2004-01-01

    A primary methanol extract (F-ME), secondary butanol-soluble fraction (F-BU), and lignans were prepared from forsythia fruit (Forsythia viridissima L.) and added to 0.5% (w/w) cholesterol diets for male Sprague-Dawley rats weighing 121 +/- 12 g. There were six experimental groups: a control group, 0.2%, 0.4% F-ME supplemented groups, 0.1%, 0.02% F-BU groups and 0.02% lignan group. After 3 weeks of feeding, body weight gains, serum GOT and GPT levels were not different among the groups. HDL-/total cholesterol ratios increased in the 0.2% F-BU and lignan groups compared with the control groups. Liver triglyceride level lowered in most of forsythia groups. Fecal cholesterol excretions increased in the lignan group. Arctiin isolated from the forsythia fruit reduced cholesterol and triglyceride contents in cultured HepG2 cells at 0.01-0.1 microM. These results indicated that the forsythia lignan, arctiin is effective on improving blood lipid status without a significant hepatotoxicity and is to be utilized for the functional foods for lipid-lowering action. PMID:15630274

  16. Resolvins, Specialized Pro-Resolving Lipid Mediators and their Potential Roles in Metabolic Diseases

    PubMed Central

    Spite, Matthew; Clària, Joan; Serhan, Charles N.

    2013-01-01

    Inflammation is associated with development of diseases characterized by altered nutrient metabolism. While an acute inflammatory response is host-protective and normally self-limited, chronic low-grade inflammation associated with metabolic diseases is sustained and detrimental. Resolution of inflammation involves termination of neutrophil recruitment, counter-regulation of pro-inflammatory mediators, stimulation of macrophage-mediated clearance and tissue remodeling. Specialized pro-resolving lipid mediators (SPM) -- resolvins, protectins and maresins -- are novel autacoids that resolve inflammation, protect organs, and stimulate tissue regeneration. Here, we review evidence that failure of resolution programs contributes to metabolic diseases and that SPM may play pivotal roles in their resolution. PMID:24239568

  17. Effects of waterborne Cu exposure on intestinal copper transport and lipid metabolism of Synechogobius hasta.

    PubMed

    Chen, Feng; Luo, Zhi; Chen, Guang-Hui; Shi, Xi; Liu, Xu; Song, Yu-Feng; Pan, Ya-Xiong

    2016-09-01

    The present study was conducted to explore the effects of waterborne Cu exposure on intestinal Cu transport and lipid metabolism of Synechogobius hasta. S. hasta were exposed to 0, 0.4721 and 0.9442μM Cu, respectively. Sampling occurred on days 0, 21 and 42, respectively. Growth performance, intestinal lipid deposition, Cu content, and activities and mRNA expression of enzymes and genes involved in Cu transport and lipid metabolism were analyzed. Cu exposure decreased WG and SGR on days 21 and 42. Cu exposure increased intestinal Cu and lipid contents. Increased Cu accumulation was attributable to increased enzymatic activities (Cu-ATPase and Cu, Zn-SOD) and genes' (CTR1, CTR2, DMT1, ATP7a, ATP7b, MT1 and MT2) expression involved in Cu transport. Waterborne Cu exposure also increased activities of lipogenic enzymes (6PGD and ICDH on both days 21 and 42, ME on day 42), up-regulated mRNA levels of lipogenic genes (G6PD, 6PGD, ME, ICDH, FAS and ACCa), lipolytic genes (ACCb, CPT I and HSLa) and genes involved in intestinal fatty acid uptake (IFABP and FATP4) on both days 21 and 42. The up-regulation of lipolysis may result from the increased metabolic expenditure for detoxification and maintenance of the normal body functions in a response to Cu exposure. Meantime, Cu exposure increased lipogenesis and fatty acid uptake, leading to net lipid accumulation in the intestine despite increased lipolysis. To our knowledge, this is the first report involved in intestinal lipid metabolism in combination with intestinal Cu absorption following waterborne Cu exposure, which provides new insights and evidence into Cu toxicity in fish. PMID:27509383

  18. Lipid Biosynthetic Genes Affect Candida albicans Extracellular Vesicle Morphology, Cargo, and Immunostimulatory Properties

    PubMed Central

    Wolf, Julie M.; Espadas, Javier; Luque-Garcia, Jose; Reynolds, Todd

    2015-01-01

    Microbial secretion is integral for regulating cell homeostasis as well as releasing virulence factors during infection. The genes encoding phosphatidylserine synthase (CHO1) and phosphatidylserine decarboxylase (PSD1 and PSD2) are Candida albicans genes involved in phospholipid biosynthesis, and mutations in these genes affect mitochondrial function, cell wall thickness, and virulence in mice. We tested the roles of these genes in several agar-based secretion assays and observed that the cho1Δ/Δ and psd1Δ/Δ psd2Δ/Δ strains manifested less protease and phospholipase activity. Since extracellular vesicles (EVs) are surrounded by a lipid membrane, we investigated the effects of these mutations on EV structure, composition, and biological activity. The cho1Δ/Δ mutant releases EVs comparable in size to wild-type EVs, but EVs from the psd1Δ/Δ psd2Δ/Δ strain are much larger than those from the wild type, including a population of >100-nm EVs not observed in the EVs from the wild type. Proteomic analysis revealed that EVs from both mutants had a significantly different protein cargo than that of EVs from the wild type. EVs were tested for their ability to activate NF-κB in bone marrow-derived macrophage cells. While wild-type and psd1Δ/Δ psd2Δ/Δ mutant-derived EVs activated NF-κB, the cho1Δ/Δ mutant-derived EV did not. These studies indicate that the presence and absence of these C. albicans genes have qualitative and quantitative effects on EV size, composition, and immunostimulatory phenotypes that highlight a complex interplay between lipid metabolism and vesicle production. PMID:26024904

  19. Polydatin improves glucose and lipid metabolism in experimental diabetes through activating the Akt signaling pathway.

    PubMed

    Hao, Jie; Chen, Cheng; Huang, Kaipeng; Huang, Junying; Li, Jie; Liu, Peiqing; Huang, Heqing

    2014-12-15

    Recently, the effect of polydatin on lipid regulation has gained considerable attention. And previous study has demonstrated that polydatin has hypoglycemic effect on experimental diabetic rats. Repressed Akt pathway contributes to glucose and lipid disorders in diabetes. Thus, whether polydatin regulates glucose and lipid metabolism in experimental diabetic models through the Akt pathway arouses interest. The purpose was to explore the regulatory mechanism of polydain on glucose and lipid through Akt pathway. We used a diabetic rat model induced by high-fat and -sugar diet with low-dose of streptozocin and an insulin resistant HepG2 cell model induced by palmitic acid to clarify the role of polydatin on glucose and lipid metabolism. Here, we found that polydatin significantly attenuated fasting blood–glucose, glycosylated hemoglobin, glycosylated serum protein, total cholesterol, triglyceride, and low-density lipoprotein cholesterol in diabetic rats. Furthermore, polydatin significantly increased glucose uptake and consumption and decreased lipid accumulation in insulin resistant HepG2 cells. Polydatin markedly increased serum insulin levels in diabetic rats, and obviously activated the Akt signaling pathway in diabetic rat livers and insulin resistant HepG2 cells. Polydatin markedly increased phosphorylated GSK-3β, decreased the protein levels of G6Pase and SREBP-1c, and increased protein levels of GCK, LDLR, and phosphorylated IRS in livers and HepG2 cells. Overall, the results indicate that polydatin regulates glucose and lipid metabolism in experimental diabetic models, the underlying mechanism is probably associated with regulating the Akt pathway. The effect of polydatin on increased Akt phosphorylation is independent of prompting insulin secretion, but dependent of increasing IRS phosphorylation. PMID:25310908

  20. Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders

    PubMed Central

    Berger, Hannah S.; Do, Kieu Trinh; Kastenmüller, Gabi; Wahl, Simone; Adamski, Jerzy; Peters, Annette; Krumsiek, Jan; Suhre, Karsten; Haslinger, Bernhard; Ceballos-Baumann, Andres; Gieger, Christian; Winkelmann, Juliane

    2016-01-01

    Background Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS) and Parkinson`s disease (PD) represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases. Methods 456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls. Results After stringent quality control, we identified decreased levels of long-chain (polyunsaturated) fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9) and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32). In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7). The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD. Conclusions A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention. PMID:26808974

  1. The role of CD36 in the regulation of myocardial lipid metabolism.

    PubMed

    Kim, Ty T; Dyck, Jason R B

    2016-10-01

    Since the heart has one of the highest energy requirements of all organs in the body, it requires a constant and plentiful supply of fuel to function properly. Mitochondrial oxidation of lipids provides a major source of ATP for the heart, and the cellular processes that regulate lipid uptake and utilization are important contributors to maintaining proper myocardial energetic status. Although numerous proteins are coordinately regulated in order to ensure proper fatty acid utilization in the cardiomyocyte, a key first step in this process is the entry of fatty acids into the cell. An important protein involved in the transport of fatty acids into the cardiomyocyte is the plasma membrane-associated protein known as fatty acid translocase (FAT; also known as CD36). While multiple proteins are involved in facilitating fatty acid uptake in the heart, CD36 accounts for approximately 50-70% of the total fatty acid taken up in cardiomyocytes. As such, myocardial metabolism of fatty acids may depend upon proper CD36 function. Consistent with this, changes in CD36 levels/function have been implicated in the alteration of myocardial metabolism in the pathophysiology of certain cardiovascular diseases. As such, a better understanding of the role and function of CD36 in the heart may provide important insights for the development of new treatments for specific cardiovascular diseases. Herein, we review the role of CD36 in myocardial lipid metabolism in the healthy heart and describe how CD36-mediated alterations in lipid metabolism may contribute to cardiovascular disease. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26995462

  2. Impaired glucose and lipid metabolism in ageing aryl hydrocarbon receptor deficient mice

    PubMed Central

    Biljes, Daniel; Hammerschmidt-Kamper, Christiane; Kadow, Stephanie; Diel, Patrick; Weigt, Carmen; Burkart, Volker; Esser, Charlotte

    2015-01-01

    Disturbed homeostasis of glucose and lipid metabolism are dominant features of the so-called metabolic syndrome (MetS) and can increase the risk for the development of type 2 diabetes (T2D), a severe metabolic disease. T2D prevalence increases with age. The aryl hydrocarbon receptor (AHR) is a sensor of small molecules including dietary components. AHR has been identified as potential regulator of glucose homeostasis and lipid metabolism. Epidemiologically, exposure to xenobiotic AHR ligands such as polycyclic aromatic hydrocarbons is linked to T2D. We assess here the potential role of the AHR in disturbances of glucose and lipid metabolism in young (age 2-5 months) and old (age > 1,5 years) AHR-deficient (AHR KO) mice. Fasted young wildtype (WT) and AHR-KO mice displayed similar blood glucose kinetics after challenge with intra-peritoneal glucose injection. However, old AHR-KO mice showed lower tolerance than WT to i.p. administered glucose, i.e. glucose levels rose higher and returned more slowly to normal levels. Old mice had overall higher insulin levels than young mice, and old AHR-KO had a somewhat disturbed insulin kinetic in the serum after glucose challenge. Surprisingly, young AHR-KO mice had significantly lower triglycerides, cholesterol, high density lipoprotein values than WT, i.e., a dyslipidemic profile. With ageing, AHR-KO and WT mice did not differ in these lipid levels, except for slightly reduced levels of triglycerides and cholesterol. In conclusion, our findings in AHR KO mice suggest that AHR expression is relevant for the maintenance of glucose and lipid homeostasis in old mice. PMID:26664351

  3. Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

    PubMed Central

    Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

    2014-01-01

    Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain. PMID:24765590

  4. Role of BAF60a/BAF60c in chromatin remodeling and hepatic lipid metabolism.

    PubMed

    Zhang, Ping; Li, Lulu; Bao, Zhengxi; Huang, Feiruo

    2016-01-01

    The switching defective/sucrose non-fermenting (SWI/SNF) complexes play an important role in hepatic lipid metabolism regulating both transcriptional activation and repression. BAF60a is a core subunit of the SWI/SNF chromatin-remodeling complexes that activates the transcription of fatty acid oxidation genes during fasting/glucagon. BAF60c, another subunit of SWI/SNF complexes, is recruited to form the lipoBAF complex that activates lipogenic genes, promoting lipogenesis and increasing the triglyceride level in response to feeding/insulin. Interestingly, hepatocytes located in the periportal and perivenous zones of the liver display a remarkable heterogeneity in the activity of various enzymes, metabolic functions and gene expression. Especially, fatty-acid oxidation was shown to be mostly periportal, whereas lipogenesis was mostly perivenous. Therefore, the present review highlights the role of of SWI/SNF regulating lipid metabolism under nutritional and hormonal control, which may be associated with hepatocyte heterogeneity. PMID:27127533

  5. Characterizing the Network of Drugs and Their Affected Metabolic Subpathways

    PubMed Central

    Li, Jing; Han, Junwei; Wang, Shuyuan; Yao, Qianlan; Wang, Yingying; Zhang, Yunpeng; Zhang, Chunlong; Xu, Yanjun; Jiang, Wei; Li, Xia

    2012-01-01

    A fundamental issue in biology and medicine is illustration of the overall drug impact which is always the consequence of changes in local regions of metabolic pathways (subpathways). To gain insights into the global relationship between drugs and their affected metabolic subpathways, we constructed a drug–metabolic subpathway network (DRSN). This network included 3925 significant drug–metabolic subpathway associations representing drug dual effects. Through analyses based on network biology, we found that if drugs were linked to the same subpathways in the DRSN, they tended to share the same indications and side effects. Furthermore, if drugs shared more subpathways, they tended to share more side effects. We then calculated the association score by integrating drug-affected subpathways and disease-related subpathways to quantify the extent of the associations between each drug class and disease class. The results showed some close drug–disease associations such as sex hormone drugs and cancer suggesting drug dual effects. Surprisingly, most drugs displayed close associations with their side effects rather than their indications. To further investigate the mechanism of drug dual effects, we classified all the subpathways in the DRSN into therapeutic and non-therapeutic subpathways representing drug therapeutic effects and side effects. Compared to drug side effects, the therapeutic effects tended to work through tissue-specific genes and these genes tend to be expressed in the adrenal gland, liver and kidney; while drug side effects always occurred in the liver, bone marrow and trachea. Taken together, the DRSN could provide great insights into understanding the global relationship between drugs and metabolic subpathways. PMID:23112813

  6. Temperature-dependent lipid metabolism in the blow fly Lucilia sericata.

    PubMed

    Muntzer, A; Montagne, C; Ellse, L; Wall, R

    2015-09-01

    An understanding of how arthropods use energy is fundamental to explaining their diverse life histories and adaptation to specific environments. It is also of importance when attempting to predict the impacts of environmental change on patterns of development and phenology. Here, lipid use by the economically important agent of ovine myiasis, Lucilia sericata (Diptera: Calliphoridae), was quantified at a range of temperatures. During pupation, at temperatures above the minimum temperature required for development (9 °C), pupae depleted an average of 30% of their total lipid over the course of pupation regardless of temperature. There was no detectable loss of lipid during pupation at temperatures below 9 °C. In general, larger individuals had the same relative amounts of lipid as smaller individuals. Newly emerged adults metabolized about 16% of the lipid reserves with which they emerged in the first 24 h during flight-related activity. Starved adults, with access to water but without sucrose or protein, depleted their lipid reserves and died within about 4 days of emergence. However, adults with access to protein and/or carbohydrate were able to maintain a stored lipid content of about 2.38% of their total body mass for at least 14 days after emergence, irrespective of sex. This finding is similar to that in field-caught individuals, in which lipid content was found to be a mean of 3% of body mass. The data suggest that warmer environmental conditions, within the temperature limits tested here, although shortening the time required for development and altering the patterns of seasonal abundance of L. sericata, are unlikely to impact on fly survival because of greater metabolic demands during non-feeding stages of the lifecycle. PMID:25753336

  7. Octopamine connects nutrient cues to lipid metabolism upon nutrient deprivation

    PubMed Central

    Tao, Jun; Ma, Yi-Cheng; Yang, Zhong-Shan; Zou, Cheng-Gang; Zhang, Ke-Qin

    2016-01-01

    Starvation is probably the most common stressful situation in nature. In vertebrates, elevation of the biogenic amine norepinephrine levels is common during starvation. However, the precise role of norepinephrine in nutrient deprivation remains largely unknown. We report that in the free-living nematode Caenorhabditis elegans, up-regulation of the biosynthesis of octopamine, the invertebrate counterpart of norepinephrine, serves as a mechanism to adapt to starvation. During nutrient deprivation, the nuclear receptor DAF-12, known to sense nutritional cues, up-regulates the expression of tbh-1 that encodes tyramine β-hydroxylase, a key enzyme for octopamine biosynthesis, in the RIC neurons. Octopamine induces the expression of the lipase gene lips-6 via its receptor SER-3 in the intestine. LIPS-6, in turn, elicits lipid mobilization. Our findings reveal that octopamine acts as an endocrine regulator linking nutrient cues to lipolysis to maintain energy homeostasis, and suggest that such a mechanism may be evolutionally conserved in diverse organisms. PMID:27386520

  8. The Role of Gastrointestinal Hormones in Hepatic Lipid Metabolism

    PubMed Central

    Mells, Jamie Eugene; Anania, Frank A.

    2014-01-01

    Hepatocellular accumulation of free fatty acids (FFAs) in the form of triglycerides constitutes the metabolic basis for the development of nonalcoholic fatty liver disease (NAFLD). Recent data demonstrate that excess FFA hepatocyte storage is likely to lead to lipotoxicity and hepatocyte apoptosis. Hence, FFA-mediated hepatocyte injury is a key contributor to the pathogenesis of nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis, obesity, type 2 diabetes, essential hypertension, and other common medical problems together comprise metabolic syndrome. Evidence suggests that peptide hormones from the L cells of the distal small intestine, which comprise the core of the enteroendocrine system (EES), play two key roles, serving either as incretins, or as mediators of appetite and satiety in the central nervous system. Recent data related to glucagon-like peptide-1 (GLP-1) and other known L-cell hormones have accumulated due to the increasing frequency of bariatric surgery, which increase delivery of bile salts to the hindgut. Bile acids are a key stimulus for the TGR5 receptor of the L cells. Enhanced bile-salt flow and subsequent EES stimulation may be central to elimination of hepatic steatosis following bariatric surgery. Although GLP-1 is a clinically relevant pharmacological analogue that drives pancreatic β-cell insulin output, GLP-1 analogues also have independent benefits via their effects on hepatocellular FFA metabolism. The authors also discuss recent data regarding the role of the major peptides released by the EES, which promote satiety and modulate energy homeostasis and utilization, as well as those that control fat absorption and intestinal permeability. Taken together, elucidating novel functions for EES-related peptides and pharmacologic development of peptide analogues offer potential far-ranging treatment for obesity-related human disease. PMID:24222092

  9. Insulin signalling and the regulation of glucose and lipid metabolism

    NASA Astrophysics Data System (ADS)

    Saltiel, Alan R.; Kahn, C. Ronald

    2001-12-01

    The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.

  10. HNF6 and Rev-erbα integrate hepatic lipid metabolism by overlapping and distinct transcriptional mechanisms.

    PubMed

    Zhang, Yuxiang; Fang, Bin; Damle, Manashree; Guan, Dongyin; Li, Zhenghui; Kim, Yong Hoon; Gannon, Maureen; Lazar, Mitchell A

    2016-07-15

    Hepatocyte nuclear factor 6 (HNF6) is required for liver development, but its role in adult liver metabolism is not known. Here we show that deletion of HNF6 in livers of adult C57Bl/6 mice leads to hepatic steatosis in mice fed normal laboratory chow. Although HNF6 is known mainly as a transcriptional activator, hepatic loss of HNF6 up-regulated many lipogenic genes bound directly by HNF6. Many of these genes are targets of the circadian nuclear receptor Rev-erbα, and binding of Rev-erbα at these sites was lost when HNF6 was ablated in the liver. While HNF6 and Rev-erbα coordinately regulate hepatic lipid metabolism, each factor also affects additional gene sets independently. These findings highlight a novel mechanism of transcriptional repression by HNF6 and demonstrate how overlapping and distinct mechanisms of transcription factor function contribute to the integrated physiology of the liver. PMID:27445394

  11. 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

    2015-11-01

    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. PMID:26463554

  12. Serotonergic agonists stimulate inositol lipid metabolism in rabbit platelets

    SciTech Connect

    Schaechter, M.; Godfrey, P.P.; Minchin, M.C.W.; McClue, S.J.; Young, M.M.

    1985-10-28

    The metabolism of inositol phospholipids in response to serotonergic agonists was investigated in rabbit platelets. In platelets prelabelled with (/sup 3/H)-inositol, in a medium containing 10 mM LiCl which blocks the enzyme inositol-1-phosphatase, 5-hydroxytryptamine (5-HT) caused a dose-dependent accumulation of inositol phosphates (IP). This suggests a phospholipase-C-mediated breakdown of phosphoinositides. Ketanserin, a selective 5-HT/sub 2/ antagonist, was a potent inhibitor of the 5-HT response, with a Ki of 28 nM, indicating that 5-HT is activating receptors of the 5-HT/sub 2/ type in the platelet. Lysergic acid diethylamide (LSD) and quipazine also caused dose-related increases in inositol phosphate levels, though these were considerably less than those produced by 5-HT. These results show that relatively small changes in phosphoinositide metabolism induced by serotonergic agonists can be investigated in the rabbit platelet, and this cell may therefore be a useful model for the study of some 5-HT receptors. 30 references, 4 figures.

  13. Gene expression profiling reveals Nef induced deregulation of lipid metabolism in HIV-1 infected T cells.

    PubMed

    Shrivastava, Surya; Trivedi, Jay; Mitra, Debashis

    2016-03-25

    Human Immunodeficiency Virus-1 (HIV-1) encodes a 27 kDa Negative Factor or Nef protein, which is increasingly proving to be a misnomer. Nef seems to be crucial for AIDS progression as individuals infected with nef-deleted strain of HIV were reported to become Long Term Non Progressors (LTNP). These findings necessitate tracing of Nef's footprint on landscape of cellular transcriptome favoring HIV-1 pathogenesis. We have tried to explore effect of Nef on cellular gene expression profile in conjunction with rest of HIV-1 proteins. Our results show that 237 genes are differentially regulated due to the presence of Nef during infection, which belong to several broad categories like "signaling", "apoptosis", "transcription" and "lipid metabolism" in gene ontology analysis. Furthermore, our results show that Nef causes disruption of lipid content in HIV-1 infected T cells. Molecular inhibitors of lipid metabolism like Atorvastatin and Ranolazine were found to have profound effect on wild type virus as compared to nef-deleted HIV-1. Thus our results suggest that interference in lipid metabolism is a potential mechanism through which Nef contributes in enhancing HIV-1 pathogenesis. PMID:26915805

  14. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

    SciTech Connect

    Pols, Thijs W.H.; Ottenhoff, Roelof; Vos, Mariska; Levels, Johannes H.M.; Quax, Paul H.A.; Meijers, Joost C.M.; Pannekoek, Hans; Groen, Albert K.; Vries, Carlie J.M. de

    2008-02-22

    NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity.

  15. Subcellular distribution of key enzymes of lipid metabolism during the euthermia-hibernation-arousal cycle

    PubMed Central

    Suozzi, Anna; Malatesta, Manuela; Zancanaro, Carlo

    2009-01-01

    Mammalian hibernation is a natural, fully reversible hypometabolic state characterized by a drastic reduction of body temperature and metabolic activity, which ensures survival to many species under adverse environmental conditions. During hibernation, many hibernators rely for energy supply almost exclusively on lipid reserves; the shift from carbohydrate to lipid metabolism implies profound rearrangement of the anabolic and catabolic pathways of energetic substrates. However, the structural counterpart of such adaptation is not known. In this study we investigated, by using immunoelectron microscopy, the fine intracellular distribution of two key enzymes involved in lipid metabolism, namely, the fatty acid synthase (FAS) and the long-chain fatty acyl-CoA synthetase (ACSL), in hepatocytes of euthermic, hibernating and arousing hazel dormice. Our results show that the two enzymes are differentially distributed in cellular compartments (cytoplasm, mitochondria and cell nuclei) of hepatocytes during euthermia. Quantitative redistribution of both enzymes among cellular compartments takes place during hibernation and arousal, in accordance with the physiological changes. Interestingly, this redistribution follows different seasonal patterns in cytoplasm, mitochondria and nuclei. In conclusion, our data represent the first quantitative morphological evidence of lipid enzyme distribution in a true hibernator throughout the year cycle, thus providing a structural framework to biochemical changes associated with the hypometabolism of hibernation. PMID:19538638

  16. The epigenetic drug 5-azacytidine interferes with cholesterol and lipid metabolism.

    PubMed

    Poirier, Steve; Samami, Samaneh; Mamarbachi, Maya; Demers, Annie; Chang, Ta Yuan; Vance, Dennis E; Hatch, Grant M; Mayer, Gaétan

    2014-07-01

    DNA methylation and histone acetylation inhibitors are widely used to study the role of epigenetic marks in the regulation of gene expression. In addition, several of these molecules are being tested in clinical trials or already in use in the clinic. Antimetabolites, such as the DNA-hypomethylating agent 5-azacytidine (5-AzaC), have been shown to lower malignant progression to acute myeloid leukemia and to prolong survival in patients with myelodysplastic syndromes. Here we examined the effects of DNA methylation inhibitors on the expression of lipid biosynthetic and uptake genes. Our data demonstrate that, independently of DNA methylation, 5-AzaC selectively and very potently reduces expression of key genes involved in cholesterol and lipid metabolism (e.g. PCSK9, HMGCR, and FASN) in all tested cell lines and in vivo in mouse liver. Treatment with 5-AzaC disturbed subcellular cholesterol homeostasis, thereby impeding activation of sterol regulatory element-binding proteins (key regulators of lipid metabolism). Through inhibition of UMP synthase, 5-AzaC also strongly induced expression of 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) and promoted triacylglycerol synthesis and cytosolic lipid droplet formation. Remarkably, complete reversal was obtained by the co-addition of either UMP or cytidine. Therefore, this study provides the first evidence that inhibition of the de novo pyrimidine synthesis by 5-AzaC disturbs cholesterol and lipid homeostasis, probably through the glycerolipid biosynthesis pathway, which may contribute mechanistically to its beneficial cytostatic properties. PMID:24855646

  17. The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism*

    PubMed Central

    Poirier, Steve; Samami, Samaneh; Mamarbachi, Maya; Demers, Annie; Chang, Ta Yuan; Vance, Dennis E.; Hatch, Grant M.; Mayer, Gaétan

    2014-01-01

    DNA methylation and histone acetylation inhibitors are widely used to study the role of epigenetic marks in the regulation of gene expression. In addition, several of these molecules are being tested in clinical trials or already in use in the clinic. Antimetabolites, such as the DNA-hypomethylating agent 5-azacytidine (5-AzaC), have been shown to lower malignant progression to acute myeloid leukemia and to prolong survival in patients with myelodysplastic syndromes. Here we examined the effects of DNA methylation inhibitors on the expression of lipid biosynthetic and uptake genes. Our data demonstrate that, independently of DNA methylation, 5-AzaC selectively and very potently reduces expression of key genes involved in cholesterol and lipid metabolism (e.g. PCSK9, HMGCR, and FASN) in all tested cell lines and in vivo in mouse liver. Treatment with 5-AzaC disturbed subcellular cholesterol homeostasis, thereby impeding activation of sterol regulatory element-binding proteins (key regulators of lipid metabolism). Through inhibition of UMP synthase, 5-AzaC also strongly induced expression of 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) and promoted triacylglycerol synthesis and cytosolic lipid droplet formation. Remarkably, complete reversal was obtained by the co-addition of either UMP or cytidine. Therefore, this study provides the first evidence that inhibition of the de novo pyrimidine synthesis by 5-AzaC disturbs cholesterol and lipid homeostasis, probably through the glycerolipid biosynthesis pathway, which may contribute mechanistically to its beneficial cytostatic properties. PMID:24855646

  18. Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading.

    PubMed

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

    2016-04-01

    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

  19. The Roles of Genetic Polymorphisms and Human Immunodeficiency Virus Infection in Lipid Metabolism

    PubMed Central

    de Almeida, Elaine Regina Delicato; Reiche, Edna Maria Vissoci; Flauzino, Tamires; Watanabe, Maria Angelica Ehara

    2013-01-01

    Dyslipidemia has been frequently observed among individuals infected with human immunodeficiency virus type 1 (HIV-1), and factors related to HIV-1, the host, and antiretroviral therapy (ART) are involved in this phenomenon. This study reviews the roles of genetic polymorphisms, HIV-1 infection, and highly active antiretroviral therapy (HAART) in lipid metabolism. Lipid abnormalities can vary according to the HAART regimen, such as those with protease inhibitors (PIs). However, genetic factors may also be involved in dyslipidemia because not all patients receiving the same HAART regimen and with comparable demographic, virological, and immunological characteristics develop variations in the lipid profile. Polymorphisms in a large number of genes are involved in the synthesis of structural proteins, and enzymes related to lipid metabolism account for variations in the lipid profile of each individual. As some genetic polymorphisms may cause dyslipidemia, these allele variants should be investigated in HIV-1-infected patients to identify individuals with an increased risk of developing dyslipidemia during treatment with HAART, particularly during therapy with PIs. This knowledge may guide individualized treatment decisions and lead to the development of new therapeutic targets for the treatment of dyslipidemia in these patients. PMID:24319689

  20. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

    PubMed

    Sallam, Tamer; Jones, Marius C; Gilliland, Thomas; Zhang, Li; Wu, Xiaohui; Eskin, Ascia; Sandhu, Jaspreet; Casero, David; Vallim, Thomas Q de Aguiar; Hong, Cynthia; Katz, Melanie; Lee, Richard; Whitelegge, Julian; Tontonoz, Peter

    2016-06-01

    Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis. PMID:27251289

  1. Identification of candidate diagnostic biomarkers for adolescent idiopathic scoliosis using UPLC/QTOF-MS analysis: a first report of lipid metabolism profiles

    PubMed Central

    Sun, Zhi-jian; Jia, Hong-mei; Qiu, Gui-xing; Zhou, Chao; Guo, Shigong; Zhang, Jian-guo; Shen, Jian-xiong; Zhao, Yu; Zou, Zhong-mei

    2016-01-01

    Adolescent idiopathic scoliosis (AIS) is a complex spine deformity, affecting approximately 1–3% adolescents. Earlier diagnosis could increase the likelihood of successful conservative treatment and hence reduce the need for surgical intervention. We conducted a serum metabonomic study to explore the potential biomarkers of AIS for early diagnosis. Serum metabolic profiles were firstly explored between 30 AIS patients and 31 healthy controls by ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, the candidate metabolites were validated in an independent cohort including 31 AIS patients and 44 controls. The results showed that metabolic profiles of AIS patients generally deviated from healthy controls in both the discovery set and replication set. Seven differential metabolites were identified as candidate diagnostic biomarkers, including PC(20:4), 2-hexenoylcarnitine, beta-D-glucopyranuronicacid, DG(38:9), MG(20:3), LysoPC(18:2) and LysoPC(16:0). These candidate metabolites indicated disrupted lipid metabolism in AIS, including glycerophospholipid, glycerolipid and fatty acid metabolism. Elevated expressions of adipose triglyceride lipase and hormone sensitive lipase in adipose tissue further corroborated our findings of increased lipid metabolism in AIS. Our findings suggest that differential metabolites discovered in AIS could be used as potential diagnostic biomarkers and that lipid metabolism plays a role in the pathogenesis of AIS. PMID:26928931

  2. Biochemical study on the protective potential of Nardostachys jatamansi extract on lipid profile and lipid metabolizing enzymes in doxorubicin intoxicated rats.

    PubMed

    Subashini, R; Ragavendran, B; Gnanapragasam, A; Yogeeta, S Kumar; Devaki, T

    2007-05-01

    Nardostachys jatamansi is a medicinally important herb of Indian origin used for centuries in Ayurvedic and Unani systems of medicine for the treatment of various ailments. The aim of the present work is to evaluate the effect of ethanolic extract of Nardostachys jatamansi rhizomes on doxorubicin induced myocardial injury with respect to lipid metabolism in serum and heart of Wistar albino rats. Altered lipid metabolism alters the cardiac function which is mainly due to changes in the property of the cardiac cell membrane. Doxorubicin exhibits cardiotoxicity by inhibition of fatty acid oxidation in the heart. The rats treated with a single dose of doxorubicin (15 mg/kg) intraperitoneally showed an increase in serum and cardiac lipids (cholesterol, triglycerides, free fatty acids and phospholipids), along with a significant rise in serum low density lipoproteins (LDL), very low density lipoproteins (VLDL) and drop in high density lipoproteins (HDL) levels, resulting in alteration of serum and cardiac lipid metabolizing enzymes. Pretreatment with a extract of Nardostachys jatamansi (500 mg/kg) orally for seven days to doxorubicin induced rats showed a significant prevention in the lipid status with the activities of the lipid metabolizing enzymes. Histopathological observations were also in correlation with the biochemical parameters. These findings suggest that the protective and hypolipidemic effect of Nardostachys jatamansi against doxorubicin induced myocardial injury in rats could possibly be mediated through its anti lipid peroxidative properties. PMID:17557749

  3. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism.

    PubMed

    Molehin, Deborah; Dekker Nitert, Marloes; Richard, Kerry

    2016-01-01

    Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. PMID:26989557

  4. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism

    PubMed Central

    Molehin, Deborah

    2016-01-01

    Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. PMID:26989557

  5. Inhibition of mitochondrial complex II affects dopamine metabolism and decreases its uptake into striatal synaptosomes.

    PubMed

    Cakała, Magdalena; Drabik, Jacek; Kaźmierczak, Anna; Kopczuk, Dorota; Adamczyk, Agata

    2006-01-01

    The mitochondrial toxin, 3-nitropropionic acid (3-NP), is a specific inhibitor of succinate dehydrogenase, complex II in the mitochondrial respiratory chain. The aim of our study was to determine the relationship between inhibition of mitochondrial complex II and dopamine (DA) metabolism and its transport into rat striatal synaptosomes after exposure to 3-NP. The study was carried out using spectrophotometric, radiochemical and HPLC methods. Our data showed that inhibition of succinate dehydrogenase by intraperitoneal (i.p.) injection of 3-NP (cumulated dose 100 mg/kg in 4 days) significantly affected DA metabolism, leading to the accumulation of its metabolites, 3,4-dihydroxylphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the rat striatum. These experimental conditions had no effect on free radical dependent lipid peroxidation in the brain. In vitro experiments revealed that DA and DOPAC significantly decrease lipid peroxidation in the brain homogenate. Moreover, 3-NP significantly inhibited [3H]DA uptake into striatal synaptosomes by specific dopamine transporter (DAT). The scavengers of superoxide radical (O2-) Tempol and Trolox had no effect on DAT function, but the nitric oxide synthase (NOS) inhibitor N w-nitro-L-arginine (100 microM) prevented 3-NP-evoked DAT down-regulation. In summary, our results indicate that inhibition of mitochondrial complex II by 3-NP enhances DA degradation and decreases its uptake into synaptosomes. It is suggested that NO and energy failure are responsible for alteration of the dopaminergic system in the striatum. PMID:17183449

  6. 'Micro-managers' of hepatic lipid metabolism and NAFLD.

    PubMed

    Liu, Wei; Cao, Hongchao; Yan, Jun; Huang, Ruimin; Ying, Hao

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is tightly associated with insulin resistance, type 2 diabetes, and obesity. As the defining feature of NAFLD, hepatic steatosis develops as a consequence of metabolic dysregulation of de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and triglycerides (TG) export. MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, play critical roles in various biological processes through regulating gene expression at post-transcriptional level. A growing body of evidence suggests that miRNAs not only maintain hepatic TG homeostasis under physiological condition, but also participate in the pathogenesis of NAFLD. In this review, we focus on the current knowledge of the hepatic miRNAs associated with the development of liver steatosis and the regulatory mechanisms involved, which might be helpful to further understand the nature of NAFLD and provide a sound scientific basis for the drug development. PMID:26198708

  7. Kruppel-like Factor 15 Is a Critical Regulator of Cardiac Lipid Metabolism*

    PubMed Central

    Prosdocimo, Domenick A.; Anand, Priti; Liao, Xudong; Zhu, Han; Shelkay, Shamanthika; Artero-Calderon, Pedro; Zhang, Lilei; Kirsh, Jacob; Moore, D'Vesharronne; Rosca, Mariana G.; Vazquez, Edwin; Kerner, Janos; Akat, Kemal M.; Williams, Zev; Zhao, Jihe; Fujioka, Hisashi; Tuschl, Thomas; Bai, Xiaodong; Schulze, P. Christian; Hoppel, Charles L.; Jain, Mukesh K.; Haldar, Saptarsi M.

    2014-01-01

    The mammalian heart, the body's largest energy consumer, has evolved robust mechanisms to tightly couple fuel supply with energy demand across a wide range of physiologic and pathophysiologic states, yet, when compared with other organs, relatively little is known about the molecular machinery that directly governs metabolic plasticity in the heart. Although previous studies have defined Kruppel-like factor 15 (KLF15) as a transcriptional repressor of pathologic cardiac hypertrophy, a direct role for the KLF family in cardiac metabolism has not been previously established. We show in human heart samples that KLF15 is induced after birth and reduced in heart failure, a myocardial expression pattern that parallels reliance on lipid oxidation. Isolated working heart studies and unbiased transcriptomic profiling in Klf15-deficient hearts demonstrate that KLF15 is an essential regulator of lipid flux and metabolic homeostasis in the adult myocardium. An important mechanism by which KLF15 regulates its direct transcriptional targets is via interaction with p300 and recruitment of this critical co-activator to promoters. This study establishes KLF15 as a key regulator of myocardial lipid utilization and is the first to implicate the KLF transcription factor family in cardiac metabolism. PMID:24407292

  8. KSRP is critical in governing hepatic lipid metabolism through controlling Per2 expression

    PubMed Central

    Chou, Chu-Fang; Zhu, Xiaolin; Lin, Yi-Yu; Gamble, Karen L.; Garvey, W. Timothy; Chen, Ching-Yi

    2015-01-01

    Hepatic lipid metabolism is controlled by integrated metabolic pathways. Excess accumulation of hepatic TG is a hallmark of nonalcoholic fatty liver disease, which is associated with obesity and insulin resistance. Here, we show that KH-type splicing regulatory protein (KSRP) ablation reduces hepatic TG levels and diet-induced hepatosteatosis. Expression of period 2 (Per2) is increased during the dark period, and circadian oscillations of several core clock genes are altered with a delayed phase in Ksrp−/− livers. Diurnal expression of some lipid metabolism genes is also disturbed with reduced expression of genes involved in de novo lipogenesis. Using primary hepatocytes, we demonstrate that KSRP promotes decay of Per2 mRNA through an RNA-protein interaction and show that increased Per2 expression is responsible for the phase delay in cycling of several clock genes in the absence of KSRP. Similar to Ksrp−/− livers, both expression of lipogenic genes and intracellular TG levels are also reduced in Ksrp−/− hepatocytes due to increased Per2 expression. Using heterologous mRNA reporters, we show that the AU-rich element-containing 3′ untranslated region of Per2 is responsible for KSRP-dependent mRNA decay. These findings implicate that KSRP is an important regulator of circadian expression of lipid metabolism genes in the liver likely through controlling Per2 mRNA stability. PMID:25514904

  9. Metabolic engineering of enhanced glycerol-3-phosphate synthesis to increase lipid production in Synechocystis sp. PCC 6803.

    PubMed

    Wang, Xi; Xiong, Xiaochao; Sa, Na; Roje, Sanja; Chen, Shulin

    2016-07-01

    With the growing attention to global warming and energy sustainability, biosynthesis of lipids by photosynthetic microorganisms has attracted more interest for the production of renewable transportation fuels. Recently, the cyanobacterium Synechocystis sp. PCC 6803 has been widely used for biofuel production through metabolic engineering because of its efficient photosynthesis and well-developed genetic tools. In lipid biosynthesis, glycerol-3-phosphate (G3P) is a key node for both CO2 fixation and lipid metabolism in cyanobacteria. However, few studies have explored the use of G3P synthesis to improve photosynthetic lipid production. In this study, metabolic engineering combined with flux balance analysis (FBA) was conducted to reveal the effect of G3P synthesis on lipid production. Heterologous genes that encoded glycerol-3-phosphate dehydrogenase (GPD) and diacylglycerol acyltransferase (DGAT) were engineered into Synechocystis sp. PCC 6803 to enhance G3P supply and lipid production. The resultant recombinant Synechocystis produced higher levels of lipids without a significant reduction in cell growth. Compared with the wild-type strain, lipid content and productivity of the engineered cyanobacteria increased by up to 36 and 31 %, respectively, under autotrophic conditions. Lipid production under mixotrophic conditions of the engineered cyanobacteria was also investigated. This work demonstrated that enhanced G3P synthesis was an important factor in photosynthetic lipid production and that introducing heterologous GPD and DGAT genes was an effective strategy to increase lipid production in Synechocystis sp. PCC 6803. PMID:27154348

  10. Brain Levels of Prostaglandins, Endocannabinoids, and Related Lipids Are Affected by Mating Strategies

    PubMed Central

    Stuart, Jordyn M.; Paris, Jason J.; Frye, Cheryl; Bradshaw, Heather B.

    2013-01-01

    Background. Endogenous cannabinoids (eCBs) are involved in the development and regulation of reproductive behaviors. Likewise, prostaglandins (PGs) drive sexual differentiation and initiation of ovulation. Here, we use lipidomics strategies to test the hypotheses that mating immediately activates the biosynthesis and/or metabolism of eCBs and PGs and that specific mating strategies differentially regulate these lipids in the brain. Methods. Lipid extractions and tandem mass spectrometric analysis were performed on brains from proestrous rats that had experienced one of two mating strategies (paced or standard mating) and two nonmated groups (chamber exposed and home cage controls). Levels of PGs (PGE2 and PGF2alpha), eCBs (AEA and 2-AG, N-arachidonoyl glycine), and 4 related lipids (4 N-acylethanolamides) were measured in olfactory bulb, hypothalamus, hippocampus, thalamus, striatum, midbrain, cerebellum, and brainstem. Results. Overall, levels of these lipids were significantly lower among paced compared to standard mated rats with the most dramatic decreases observed in brainstem, hippocampus, midbrain, and striatum. However, chamber exposed rats had significantly higher levels of these lipids compared to home cage controls and paced mated wherein the hippocampus showed the largest increases. Conclusions. These data demonstrate that mating strategies and exposure to mating arenas influence lipid signaling in the brain. PMID:24369463

  11. Perinatal Exposure to Perfluorooctane Sulfonate Affects Glucose Metabolism in Adult Offspring

    PubMed Central

    Wan, Hin T.; Zhao, Yin G.; Leung, Pik Y.; Wong, Chris K. C.

    2014-01-01

    Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders. PMID:24498028

  12. Regulation of lipid metabolism in the green microalga Chlorella protothecoides by heterotrophy-photoinduction cultivation regime.

    PubMed

    Li, Yuqin; Xu, Hua; Han, Fangxin; Mu, Jinxiu; Chen, Di; Feng, Bo; Zeng, Hongyan

    2015-09-01

    Proteomics in conjunction with biochemical strategy was employed to unravel regulation of lipid metabolism in the green microalga Chlorella protothecoides by heterotrophy-photoinduction cultivation regime (HPC). Interestingly, HPC triggered transiently synthesis of starch followed by substantial lipid accumulation. And a marked decrease in intracellular protein and chlorophyll contents was also observed after 12h of photo-induction. The highest lipid content of 50.5% was achieved upon the photo-induction stage, which represented 69.3% higher than that of the end of heterotrophic cultivation. Results suggested that turnover of carbon-nitrogen-rich compounds such as starch, protein, and chlorophyll might provide carbon or energy for lipid accumulation. The proteomics analysis indicated that several pathways including glycolysis, TCA cycle, β-oxidation of fatty acids, Calvin cycle, photosynthesis, energy and transport, protein biosynthesis, regulate and defense were involved in the lipid biosynthesis. Malate dehydrogenase and acyl-CoA dehydrogenase were suggested as key regulatory factors in enhancing lipid accumulation. PMID:25127016

  13. Metabolic phenotyping reveals a lipid mediator response to ionizing radiation.

    PubMed

    Laiakis, Evagelia C; Strassburg, Katrin; Bogumil, Ralf; Lai, Steven; Vreeken, Rob J; Hankemeier, Thomas; Langridge, James; Plumb, Robert S; Fornace, Albert J; Astarita, Giuseppe

    2014-09-01

    Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to γ radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to γ radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine. PMID:25126707

  14. The emerging role of autophagy in peroxisome dynamics and lipid metabolism of phyllosphere microorganisms.

    PubMed

    Oku, Masahide; Takano, Yoshitaka; Sakai, Yasuyoshi

    2014-01-01

    Eukaryotic microorganisms resident in the phyllosphere (above-ground, plant-surface environments) undergo dynamic changes in nutrient conditions and adapt their metabolic pathways during proliferation or in the course of infection of host plants. Some of these metabolic switches are accomplished by regulation of organelle abundance. Recent studies have shown that autophagy plays a major role in reducing the organelle quantity, thereby contributing to the metabolic switch required for survival or virulence of the microorganisms in the phyllosphere. In this mini review the metabolic pathways in several phytopathogenic fungi and the non-infectious asporogenous yeast Candida boidinii, which involve lipid droplets and peroxisomes, are summarized. The physiological functions of Atg (Autophagy-related) proteins in these organisms are discussed in relation to the dynamics of these two important organelles. PMID:24653730

  15. ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

    PubMed Central

    Vargas, Teodoro; Moreno-Rubio, Juan; Herranz, Jesús; Cejas, Paloma; Molina, Susana; González-Vallinas, Margarita; Mendiola, Marta; Burgos, Emilio; Aguayo, Cristina; Custodio, Ana B.; Machado, Isidro; Ramos, David; Gironella, Meritxell; Espinosa-Salinas, Isabel; Ramos, Ricardo; Martín-Hernández, Roberto; Risueño, Alberto; De Las Rivas, Javier; Reglero, Guillermo; Yaya, Ricardo; Fernández-Martos, Carlos; Aparicio, Jorge; Maurel, Joan; Feliu, Jaime; de Molina, Ana Ramírez

    2015-01-01

    Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group. PMID:25749516

  16. Fermentation and Hydrogen Metabolism Affect Uranium Reduction by Clostridia

    DOE PAGESBeta

    Gao, Weimin; Francis, Arokiasamy J.

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction bymore » clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H 2 ) production.« less

  17. Fermentation and hydrogen metabolism affect uranium reduction by clostridia.

    PubMed

    Gao, Weimin; Francis, Arokiasamy J

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction by clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H2) production. PMID:25937978

  18. Fermentation and Hydrogen Metabolism Affect Uranium Reduction by Clostridia

    PubMed Central

    Gao, Weimin; Francis, Arokiasamy J.

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction by clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H2) production. PMID:25937978

  19. Insulin sensitizes FGF21 in glucose and lipid metabolisms via activating common AKT pathway.

    PubMed

    Yu, Dan; Ye, Xianlong; Wu, Qiang; Li, Shujie; Yang, Yongbi; He, Jinjiao; Liu, Yunye; Zhang, Xiaoyu; Yuan, Qingyan; Liu, Mingyao; Li, Deshan; Ren, Guiping

    2016-06-01

    Previous studies reveal that fibroblast growth factor 21 (FGF21) sensitizes insulin to achieve a synergy in regulating glucose metabolism. Here, we report that insulin sensitizes FGF21 in regulating both glucose and lipid metabolisms. db/db diabetic mice were subcutaneously administrated once a day for 6 weeks. Effective dose of insulin (1 U) could control blood glucose level of the db/db mice for maximum of 2 h, increased the body weight of the db/db mice and did not improve serum lipid parameters. In contrast, effective dose of FGF21 (0.5 mg/kg) could maintain blood glucose of the db/db mice at normal level for at least 24 h, repressed the weight gain of the mice and significantly improved lipid parameters. Ineffective doses of FGF21 (0.125 mg/kg) and insulin had no effect on blood glucose level of the db/db mice after 24 h administration, body weight or lipid parameters. However, combination of the two ineffective doses could maintain blood glucose level of the db/db mice for at least 24 h, suppressed weight gain and significantly improved lipid parameters. These results suggest that insulin sensitizes FGF21 in regulating both glucose and lipid metabolism. The results aimed to study the molecular basis of FGF21 sensitization indicates that combination of the two ineffective doses increased the mRNA expression of glut1, glut4, β-Klotho, sirt1, pgc-1α, ucp-1 and AKT phosphorylation, decreased fasn. The results demonstrate that insulin sensitizes FGF21 through elevating the phosphorylation of common gene Akt and amplifying FGF21 downstream signaling, including increasing expression of glut1 sirt1, pgc-1α, ucp-1, and decreasing fasn expression. In summary, we reports herein for the first time that insulin sensitizes FGF21 to achieve a synergy in regulating glucose and lipid metabolism. Along with previous studies, we conclude that the synergistic effect between FGF21 and insulin is realized through mutual sensitization. PMID:26607153

  20. Macroautophagy and Cell Responses Related to Mitochondrial Dysfunction, Lipid Metabolism and Unconventional Secretion of Proteins

    PubMed Central

    Demine, Stéphane; Michel, Sébastien; Vannuvel, Kayleen; Wanet, Anaïs; Renard, Patricia; Arnould, Thierry

    2012-01-01

    Macroautophagy has important physiological roles and its cytoprotective or detrimental function is compromised in various diseases such as many cancers and metabolic diseases. However, the importance of autophagy for cell responses has also been demonstrated in many other physiological and pathological situations. In this review, we discuss some of the recently discovered mechanisms involved in specific and unspecific autophagy related to mitochondrial dysfunction and organelle degradation, lipid metabolism and lipophagy as well as recent findings and evidence that link autophagy to unconventional protein secretion. PMID:24710422

  1. Correlation of lipid metabolic disturbance with SOCS-3 gene variation in the Uygur nationality women in Xinjiang

    PubMed Central

    Hong, Jing; Gao, Jing; Aierken, Niluofeier; Tuerxun, Dilinigeer; Kamilijiang, Mayila; Maimaiti, Nuerguli; Chang, Gui-Juan; Li, Nan-Fang

    2015-01-01

    To study the correlation of lipid metabolic disturbance with gene variation of suppressor of cytokine signaling 3 (SOCS-3) in the Uygur nationality women in Xinjiang. We Selected 1379 Uygur nationality women as research objects and proceeded genotype assay for 3 representative loci (rs12953258, rs4969168 and rs9914220) to analyze them. There were significant difference in genotypic frequency in rs12953258 between lipid metabolic disturbance group and lipid embolism group (P=0.032) and between high density lipoprotein cholesterol (HDL-C) abnormal and normal group (P=0.029). Logistic regression analysis showed that the AA genotype of rs12953258 might be a risk factors of lipid metabolic disturbance in the Uygur nationality women in Xinjiang [CC/AA: OR=3.271, 95% CI (1.092-9.797), P=0.034]. The AA genotype might be associated with HDL-C decrease and triacylglycerol increase. The AA genotype Uygur nationality women with abnormal body mass index (BMI) were more sensitive to lipid metabolic disturbance disease. SOCS-3 gene variation may be associated with lipid metabolic disturbance in the Uygur nationality women in Xinjiang, prevalence of lipid metabolic disturbance increases significantly in crowd carrying AA genotype with abnormal BMI. PMID:26221377

  2. APOA5 polymorphisms associated with lipid metabolism in Brazilian children and adolescents.

    PubMed

    De França, E; Silva, D S B S; Silva, T F C; Dornelles, C L; Alves, J G; Alho, C S

    2016-01-01

    Single nucleotide polymorphisms in the APOA5 gene have been studied for their association with metabolic syndrome. Thus, elucidating the effect of the mechanism involved in APOA5 gene polymorphisms on lipid metabolism is of great importance. In this study we aimed to determine the allelic and genotypic frequencies of -1131T>C, Ser19Trp, and intergenic APOA4/A5 and to evaluate the association between these variants with plasma lipid levels in children and adolescents from Brazil. This study included 524 healthy children and adolescents from Mother and Child Hospital in Recife, Pernambuco, Brazil. Data were obtained on medical history, drug intake, lifestyle variables, and demography. DNA from collected samples was extracted and genotyped for the three polymorphisms. In this studied population, triglycerides and very low-density protein levels were significantly high in subjects carrying the 19WW genotype (P < 0.001), demonstrating the presence of this genetic risk factor in children and adolescents. PMID:27051036

  3. [The characteristics of changes in lipid metabolism indices of patients with severe mechanical trauma].

    PubMed

    Moroz, V V; Bessekeev, A A; Molchanova, L V; Shcherbakova, L N

    2003-01-01

    The paper contains the study results of some lipid-metabolism indices in patients with severe mechanical injury. Changing concentrations of total cholesterol, triglycerides and of different lipoprotein fractions in blood plasma are demonstrated. It was established that the investigated lipid-metabolism indices reflect a degree of liver malfunction in severely impaired homeostasis. It can be stated on the basis of comparing the study results with the clinical outcome that the dynamic concentration of total cholesterol in blood plasma is an important prognostication factor. Changing ratios of high-density lipoproteins, low-density lipoproteins and extra-low-density lipoproteins were observed in survivors yet by day 15, which is indicative of a commencing dislipidemia. PMID:14991968

  4. Proto-Organism Kinetics: Evolutionary Dynamics of Lipid Aggregates with Genes and Metabolism

    NASA Astrophysics Data System (ADS)

    Rasmussen, Steen; Chen, Liaohai; Stadler, Bärbel M. R.; Stadler, Peter F.

    2004-02-01

    A synthetic proto-organism could be self-assembled by integrating a lipid proto-container with a proto-metabolic subsystem and a proto-genetic subsystem. This three-component system can use energy and nutrients by means of either redox or photo-chemical reactions, evolve its proto-genome by means of template directed replication, and ultimately die. The evolutionary dynamics of the proto-organism depends crucially on the chemical kinetics of its sub-systems and on their interplay. In this work the template replication kinetics is investigated and it is found that the product inhibition inherent in the ligation-like replication process allows for coexistence of unrelated self-replicating proto-genes in the lipid surface layer. The combined catalytic effects from the proto-genes on the metabolic production rates determine the fate of the strain protocell.

  5. Lipase maturation factor 1: a lipase chaperone involved in lipid metabolism.

    PubMed

    Péterfy, Miklós

    2012-05-01

    Mutations in lipase maturation factor 1 (LMF1) are associated with severe hypertriglyceridemia in mice and human subjects. The underlying cause is impaired lipid clearance due to lipase deficiency. LMF1 is a chaperone of the endoplasmic reticulum (ER) and it is critically required for the post-translational activation of three vascular lipases: lipoprotein lipase (LPL), hepatic lipase (HL) and endothelial lipase (EL). As LMF1 is only required for the maturation of homodimeric, but not monomeric, lipases, it is likely involved in the assembly of inactive lipase subunits into active enzymes and/or the stabilization of active dimers. Herein, we provide an overview of current understanding of LMF1 function and propose that it may play a regulatory role in lipase activation and lipid metabolism. Further studies will be required to test this hypothesis and elucidate the full spectrum of phenotypes in combined lipase deficiency. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID:22063272

  6. Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism.

    PubMed

    Ouimet, Mireille; Koster, Stefan; Sakowski, Erik; Ramkhelawon, Bhama; van Solingen, Coen; Oldebeken, Scott; Karunakaran, Denuja; Portal-Celhay, Cynthia; Sheedy, Frederick J; Ray, Tathagat Dutta; Cecchini, Katharine; Zamore, Philip D; Rayner, Katey J; Marcel, Yves L; Philips, Jennifer A; Moore, Kathryn J

    2016-06-01

    Mycobacterium tuberculosis (Mtb) survives in macrophages by evading delivery to the lysosome and promoting the accumulation of lipid bodies, which serve as a bacterial source of nutrients. We found that by inducing the microRNA (miRNA) miR-33 and its passenger strand miR-33*, Mtb inhibited integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation to support bacterial replication. Silencing of miR-33 and miR-33* by genetic or pharmacological means promoted autophagy flux through derepression of key autophagy effectors (such as ATG5, ATG12, LC3B and LAMP1) and AMPK-dependent activation of the transcription factors FOXO3 and TFEB, which enhanced lipid catabolism and Mtb xenophagy. These data define a mammalian miRNA circuit used by Mtb to coordinately inhibit autophagy and reprogram host lipid metabolism to enable intracellular survival and persistence in the host. PMID:27089382

  7. 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway.

    PubMed

    Ma, Yongjie; Xu, Leyuan; Rodriguez-Agudo, Daniel; Li, Xiaobo; Heuman, Douglas M; Hylemon, Phillip B; Pandak, William M; Ren, Shunlin

    2008-12-01

    The oxysterol receptor LXR is a key transcriptional regulator of lipid metabolism. LXR increases expression of SREBP-1, which in turn regulates at least 32 genes involved in lipid synthesis and transport. We recently identified 25-hydroxycholesterol-3-sulfate (25HC3S) as an important regulatory molecule in the liver. We have now studied the effects of 25HC3S and its precursor, 25-hydroxycholesterol (25HC), on lipid metabolism as mediated by the LXR/SREBP-1 signaling in macrophages. Addition of 25HC3S to human THP-1-derived macrophages markedly decreased nuclear LXR protein levels. 25HC3S administration was followed by dose- and time-dependent decreases in SREBP-1 mature protein and mRNA levels. 25HC3S decreased the expression of SREBP-1-responsive genes, acetyl-CoA carboxylase-1, and fatty acid synthase (FAS) as well as HMGR and LDLR, which are key proteins involved in lipid metabolism. Subsequently, 25HC3S decreased intracellular lipids and increased cell proliferation. In contrast to 25HC3S, 25HC acted as an LXR ligand, increasing ABCA1, ABCG1, SREBP-1, and FAS mRNA levels. In the presence of 25HC3S, 25HC, and LXR agonist T0901317, stimulation of LXR targeting gene expression was repressed. We conclude that 25HC3S acts in macrophages as a cholesterol satiety signal, downregulating cholesterol and fatty acid synthetic pathways via inhibition of LXR/SREBP signaling. A possible role of oxysterol sulfation is proposed. PMID:18854425

  8. Effects of puerarin on lipid accumulation and metabolism in high-fat diet-fed mice.

    PubMed

    Zheng, Guodong; Lin, Lezhen; Zhong, Shusheng; Zhang, Qingfeng; Li, Dongming

    2015-01-01

    In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD), and HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT) weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK), carnitine acyltransferase (CAT) and hormone-sensitive lipase (HSL) were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2) was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases. PMID:25822741

  9. 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway

    PubMed Central

    Ma, Yongjie; Xu, Leyuan; Rodriguez-Agudo, Daniel; Li, Xiaobo; Heuman, Douglas M.; Hylemon, Phillip B.; Pandak, William M.; Ren, Shunlin

    2008-01-01

    The oxysterol receptor LXR is a key transcriptional regulator of lipid metabolism. LXR increases expression of SREBP-1, which in turn regulates at least 32 genes involved in lipid synthesis and transport. We recently identified 25-hydroxycholesterol-3-sulfate (25HC3S) as an important regulatory molecule in the liver. We have now studied the effects of 25HC3S and its precursor, 25-hydroxycholesterol (25HC), on lipid metabolism as mediated by the LXR/SREBP-1 signaling in macrophages. Addition of 25HC3S to human THP-1-derived macrophages markedly decreased nuclear LXR protein levels. 25HC3S administration was followed by dose- and time-dependent decreases in SREBP-1 mature protein and mRNA levels. 25HC3S decreased the expression of SREBP-1-responsive genes, acetyl-CoA carboxylase-1, and fatty acid synthase (FAS) as well as HMGR and LDLR, which are key proteins involved in lipid metabolism. Subsequently, 25HC3S decreased intracellular lipids and increased cell proliferation. In contrast to 25HC3S, 25HC acted as an LXR ligand, increasing ABCA1, ABCG1, SREBP-1, and FAS mRNA levels. In the presence of 25HC3S, 25HC, and LXR agonist T0901317, stimulation of LXR targeting gene expression was repressed. We conclude that 25HC3S acts in macrophages as a cholesterol satiety signal, downregulating cholesterol and fatty acid synthetic pathways via inhibition of LXR/SREBP signaling. A possible role of oxysterol sulfation is proposed. PMID:18854425

  10. Feeding milk replacer instead of whole milk affects blood plasma proteome and lipid profile in preruminant calves.

    PubMed

    Lepczyński, A; Herosimczyk, A; Ożgo, M; Skrzypczak, W F

    2015-01-01

    The study was undertaken to determine the effect of feeding milk or milk-replacer on the blood plasma proteome and lipid profile in calves during the second week of life. Feeding milk-replacer significantly decreased the expression of plasma apoA-I. Age of calves affected apoA-I expression, which was higher on the 8th than on the 11th and 14th day of life. A significant effect of interaction between diet and age was also observed. The expression of apoA-IV, was significantly affected by diet and was lower in calves fed milk replacer. Expression of this protein was significantly lower at the 8th day of life and was up-regulated in the calves fed milk-replacer at the second week of life. Calves fed milk-replacer had greater expression of haptoglobin, which differed significantly between days of blood sampling, being higher on the 8th than on the 11th and 14th day. The interactive effect of diet and age affected haptoglobin expression, which was successively down-regulated in calves fed milk re- placer. Diet had a significant effect on the plasma lipid profile. Animals fed milk had a greater concentration of TC, HDLC and LDLC. The composition of milk-replacer, especially fat source, is probably the main factor that affects expression of proteins involved in cholesterol metabolism and level of components of lipid profile in calves fed formula. We claim that the initially increased level of haptoglobin, followed by its decrease during the second week of life in calves fed milk-replacer may indicate the presence of short-term stress induced by changes in the feeding system. PMID:25928915

  11. Atypical Antipsychotics Rapidly and Inappropriately Switch Peripheral Fuel Utilization to Lipids, Impairing Metabolic Flexibility in Rodents

    PubMed Central

    Albaugh, Vance L.; Vary, Thomas C.; Ilkayeva, Olga; Wenner, Brett R.; Maresca, Kevin P.; Joyal, John L.; Breazeale, Steven; Elich, Tedd D.; Lang, Charles H.; Lynch, Christopher J.

    2012-01-01

    Patients taking atypical antipsychotics are frequented by serious metabolic (eg, hyperglycemia, obesity, and diabetes) and cardiac effects. Surprisingly, chronic treatment also appears to lower free fatty acids (FFAs). This finding is paradoxical because insulin resistance is typically associated with elevated not lower FFAs. How atypical antipsychotics bring about these converse changes in plasma glucose and FFAs is unknown. Chronic treatment with olanzapine, a prototypical, side effect prone atypical antipsychotic, lowered FFA in Sprague–Dawley rats. Olanzapine also lowered plasma FFA acutely, concomitantly impairing in vivo lipolysis and robustly elevating whole-body lipid oxidation. Increased lipid oxidation was evident from accelerated losses of triglycerides after food deprivation or lipid challenge, elevated FFA uptake into most peripheral tissues (∼2-fold) except heart, rises in long-chain 3-hydroxylated acyl-carnitines observed in diabetes, and rapid suppression of the respiratory exchange ratio (RER) during the dark cycle. Normal rises in RER following refeeding, a sign of metabolic flexibility, were severely blunted by olanzapine. Increased lipid oxidation in muscle could be explained by ∼50% lower concentrations of the negative cytoplasmic regulator of carnitine palmitoyltransferase I, malonyl-CoA. This was associated with loss of anapleurotic metabolites and citric acid cycle precursors of malonyl-CoA synthesis rather than adenosine monophosphate-activated kinase activation or direct ACC1/2 inhibition. The ability of antipsychotics to lower dark cycle RER in mice corresponded to their propensities to cause metabolic side effects. Our studies indicate that lipocentric mechanisms or altered intermediary metabolism could underlie the FFA lowering and hyperglycemia (Randle cycle) as well as some of the other side effects of atypical antipsychotics, thereby suggesting strategies for alleviating them. PMID:20494946

  12. 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

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

    PubMed

    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

  14. 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

  15. 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

    2016-01-01

    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

  16. Is hepatic lipid metabolism of beef cattle influenced by breed and dietary silage level?

    PubMed Central

    2014-01-01

    Background In ruminants, unsaturated dietary fatty acids are biohydrogenated in the rumen and are further metabolised in various tissues, including liver, which has an important role in lipid and lipoprotein metabolism. Therefore, manipulation of muscle fatty acid composition should take into account liver metabolism. In the present study, the influence of breed and diet on liver lipid composition and gene expression was investigated in order to clarify the role of this organ in the lipid metabolism of ruminants. Forty purebred young bulls from two phylogenetically distant autochthonous cattle breeds, Alentejana and Barrosã, were assigned to two different diets (low vs. high silage) and slaughtered at 18 months of age. Liver fatty acid composition, mRNA levels of enzymes and transcription factors involved in lipid metabolism, as well as the plasma lipid profile, were assessed. Results In spite of similar plasma non-esterified fatty acids levels, liver triacylglycerols content was higher in Barrosã than in Alentejana bulls. Moreover, the fatty acid composition of liver was clearly distinct from the remaining tissues involved in fatty acid metabolism of ruminants, as shown by Principal Components Analysis. The hepatic tissue is particularly rich in α-linolenic acid and their products of desaturation and elongation. Results indicate that DGAT1, ELOVL2, FADS1 and FADS2 genes influence the fatty acid composition of the liver the most. Moreover, genes such as DGAT1 and ELOVL2 appear to be more sensitive to genetic background than to dietary manipulation, whereas genes encoding for desaturases, such as FADS1, appear to be modulated by dietary silage level. Conclusions Our results indicate that liver plays an important role in the biosynthesis of n-3 LC-PUFA. It is also suggested that dietary silage level influences the hepatic fatty acid metabolism in a breed-dependent manner, through changes in the expression of genes encoding for enzymes associated with the

  17. Sulfation of 25-hydroxycholesterol regulates lipid metabolism, inflammatory responses, and cell proliferation

    PubMed Central

    Ning, Yanxia

    2013-01-01

    Intracellular lipid accumulation, inflammatory responses, and subsequent apoptosis are the major pathogenic events of metabolic disorders, including atherosclerosis and nonalcoholic fatty liver diseases. Recently, a novel regulatory oxysterol, 5-cholesten-3b, 25-diol 3-sulfate (25HC3S), has been identified, and hydroxysterol sulfotransferase 2B1b (SULT2B1b) has been elucidated as the key enzyme for its biosynthesis from 25-hydroxycholesterol (25HC) via oxysterol sulfation. The product 25HC3S and the substrate 25HC have been shown to coordinately regulate lipid metabolism, inflammatory responses, and cell proliferation in vitro and in vivo. 25HC3S decreases levels of the nuclear liver oxysterol receptor (LXR) and sterol regulatory element-binding proteins (SREBPs), inhibits SREBP processing, subsequently downregulates key enzymes in lipid biosynthesis, decreases intracellular lipid levels in hepatocytes and THP-1-derived macrophages, prevents apoptosis, and promotes cell proliferation in liver tissues. Furthermore, 25HC3S increases nuclear PPARγ and cytosolic IκBα and decreases nuclear NF-κB levels and proinflammatory cytokine expression and secretion when cells are challenged with LPS and TNFα. In contrast to 25HC3S, 25HC, a known LXR ligand, increases nuclear LXR and decreases nuclear PPARs and cytosol IκBα levels. In this review, we summarize our recent findings, including the discovery of the regulatory oxysterol sulfate, its biosynthetic pathway, and its functional mechanism. We also propose that oxysterol sulfation functions as a regulatory signaling pathway. PMID:24302009

  18. The Role of Food Peptides in Lipid Metabolism during Dyslipidemia and Associated Health Conditions

    PubMed Central

    Udenigwe, Chibuike C.; Rouvinen-Watt, Kirsti

    2015-01-01

    Animal and human clinical studies have demonstrated the ability of dietary food proteins to modulate endogenous lipid levels during abnormal lipid metabolism (dyslipidemia). Considering the susceptibility of proteins to gastric proteolytic activities, the hypolipidemic functions of proteins are possibly due, in part, to their peptide fragments. Food-derived peptides may directly modulate abnormal lipid metabolism in cell cultures and animal models of dyslipidemia. The peptides are thought to act by perturbing intestinal absorption of dietary cholesterol and enterohepatic bile acid circulation, and by inhibiting lipogenic enzymatic activities and gene expression in hepatocytes and adipocytes. Recent evidence indicates that the hypolipidemic activities of some peptides are due to activation of hepatic lipogenic transcription factors. However, detailed molecular mechanisms and structural requirements of peptides for these activities are yet to be elucidated. As hypolipidemic peptides can be released during enzymatic food processing, future studies can explore the prospects of combating metabolic syndrome and associated complications using peptide-rich functional food and nutraceutical products. PMID:25918936

  19. MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases

    PubMed Central

    Aranda, Juan F.; Madrigal-Matute, Julio; Rotllan, Noemi; Fernández-Hernando, Carlos

    2014-01-01

    The regulation of cholesterol metabolism is one of the most studied biological processes since its first isolation from gallstones in 1784. High levels of plasma low-density lipoprotein (LDL) cholesterol and reduced levels of plasma high-density lipoprotein (HDL) cholesterol are widely recognized as major risk factors of cardiovascular disease. An imbalance in the production of reactive oxygen species (ROS) can oxidize LDL particles increasing the levels of the highly pro-atherogenic oxidized LDLs (ox-LDLs). Furthermore, under pathological scenarios, numerous molecules can function as pro-oxidants, such as iron or high-glucose levels. In addition to the classical mechanisms regulating lipid homeostasis, recent studies have demonstrated the important role of microRNAs (miRNAs) as regulators of lipoprotein metabolism, its oxidative derivatives and redox balance. Here, we summarize the recent findings in the field, highlighting the contribution of some miRNAs in lipid and oxidative-associated pathologies. We also discuss how therapeutic intervention of miRNAs may be a promising strategy to decrease LDL, increase HDL and ameliorate lipid and oxidative related disorders, including atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome. PMID:23871755

  20. Frataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and lipid metabolism.

    PubMed

    Obis, Èlia; Irazusta, Verónica; Sanchís, Daniel; Ros, Joaquim; Tamarit, Jordi

    2014-08-01

    Friedreich ataxia (FRDA) is a hereditary disease caused by deficient frataxin expression. This mitochondrial protein has been related to iron homeostasis, energy metabolism, and oxidative stress. Patients with FRDA experience neurologic alterations and cardiomyopathy, which is the leading cause of death. The specific effects of frataxin depletion on cardiomyocytes are poorly understood because no appropriate cardiac cellular model is available to researchers. To address this research need, we present a model based on primary cultures of neonatal rat ventricular myocytes (NRVMs) and short-hairpin RNA interference. Using this approach, frataxin was reduced down to 5 to 30% of control protein levels after 7 days of transduction. At this stage the activity and amount of the iron-sulfur protein aconitase, in vitro activities of several OXPHOS components, levels of iron-regulated mRNAs, and the ATP/ADP ratio were comparable to controls. However, NRVMs exhibited markers of oxidative stress and a disorganized mitochondrial network with enlarged mitochondria. Lipids, the main energy source of heart cells, also underwent a clear metabolic change, indicated by the increased presence of lipid droplets and induction of medium-chain acyl-CoA dehydrogenase. These results indicate that mitochondria and lipid metabolism are primary targets of frataxin deficiency in NRVMs. Therefore, they contribute to the understanding of cardiac-specific mechanisms occurring in FRDA and give clues for the design of cardiac-specific treatment strategies for FRDA. PMID:24751525

  1. DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance

    PubMed Central

    Caron, Alexandre; Labbé, Sébastien M.; Mouchiroud, Mathilde; Huard, Renaud; Richard, Denis

    2016-01-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. PMID:27097662

  2. DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance.

    PubMed

    Caron, Alexandre; Labbé, Sébastien M; Mouchiroud, Mathilde; Huard, Renaud; Richard, Denis; Laplante, Mathieu

    2016-06-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. PMID:27097662

  3. Food chain transport of nanoparticles affects behaviour and fat metabolism in fish.

    PubMed

    Cedervall, Tommy; Hansson, Lars-Anders; Lard, Mercy; Frohm, Birgitta; Linse, Sara

    2012-01-01

    Nano-sized (10(-9)-10(-7) m) particles offer many technical and biomedical advances over the bulk material. The use of nanoparticles in cosmetics, detergents, food and other commercial products is rapidly increasing despite little knowledge of their effect on organism metabolism. We show here that commercially manufactured polystyrene nanoparticles, transported through an aquatic food chain from algae, through zooplankton to fish, affect lipid metabolism and behaviour of the top consumer. At least three independent metabolic parameters differed between control and test fish: the weight loss, the triglycerides∶cholesterol ratio in blood serum, and the distribution of cholesterol between muscle and liver. Moreover, we demonstrate that nanoparticles bind to apolipoprotein A-I in fish serum in-vitro, thereby restraining them from properly utilising their fat reserves if absorbed through ingestion. In addition to the metabolic effects, we show that consumption of nanoparticle-containing zooplankton affects the feeding behaviour of the fish. The time it took the fish to consume 95% of the food presented to them was more than doubled for nanoparticle-exposed compared to control fish. Since many nano-sized products will, through the sewage system, end up in freshwater and marine habitats, our study provides a potential bioassay for testing new nano-sized material before manufacturing. In conclusion, our study shows that from knowledge of the molecular composition of the protein corona around nanoparticles it is possible to make a testable molecular hypothesis and bioassay of the potential biological risks of a defined nanoparticle at the organism and ecosystem level. PMID:22384193

  4. Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands.

    PubMed

    Matczuk, Jan; Zalewska, Anna; Łukaszuk, Bartłomiej; Knaś, Małgorzata; Maciejczyk, Mateusz; Garbowska, Marta; Ziembicka, Dominika M; Waszkiel, Danuta; Chabowski, Adrian; Żendzian-Piotrowska, Małgorzata; Kurek, Krzysztof

    2016-01-01

    In today's world wrong nutritional habits together with a low level of physical activity have given rise to the development of obesity and its comorbidity, insulin resistance. More specifically, many researches indicate that lipids are vitally involved in the onset of a peripheral tissue (e.g., skeletal muscle, heart, and liver) insulin resistance. Moreover, it seems that diabetes can also induce changes in respect of lipid composition of both the salivary glands and saliva. However, judging by the number of research articles, the salivary glands lipid profile still has not been sufficiently explored. In the current study we aim to assess the changes in the main lipid fractions, namely, triacylglycerols, phospholipids, free fatty acids, and diacylglycerols, in the parotid and the submandibular salivary glands of rats exposed to a 5-week high fat diet regimen. We observed that the high caloric fat diet caused a significant change in the salivary glands lipid composition, especially with respect to PH and TG, but not DAG or FFAs, classes. The observed reduction in PH concentration is an interesting phenomenon frequently signifying the atrophy and malfunctions in the saliva secreting organs. On the other hand, the increased accumulation of TG in the glands may be an important clinical manifestation of metabolic syndrome and type 2 diabetes mellitus. PMID:27471733

  5. Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands

    PubMed Central

    Matczuk, Jan; Zalewska, Anna; Łukaszuk, Bartłomiej; Knaś, Małgorzata; Maciejczyk, Mateusz; Garbowska, Marta; Ziembicka, Dominika M.; Waszkiel, Danuta; Chabowski, Adrian; Żendzian-Piotrowska, Małgorzata

    2016-01-01

    In today's world wrong nutritional habits together with a low level of physical activity have given rise to the development of obesity and its comorbidity, insulin resistance. More specifically, many researches indicate that lipids are vitally involved in the onset of a peripheral tissue (e.g., skeletal muscle, heart, and liver) insulin resistance. Moreover, it seems that diabetes can also induce changes in respect of lipid composition of both the salivary glands and saliva. However, judging by the number of research articles, the salivary glands lipid profile still has not been sufficiently explored. In the current study we aim to assess the changes in the main lipid fractions, namely, triacylglycerols, phospholipids, free fatty acids, and diacylglycerols, in the parotid and the submandibular salivary glands of rats exposed to a 5-week high fat diet regimen. We observed that the high caloric fat diet caused a significant change in the salivary glands lipid composition, especially with respect to PH and TG, but not DAG or FFAs, classes. The observed reduction in PH concentration is an interesting phenomenon frequently signifying the atrophy and malfunctions in the saliva secreting organs. On the other hand, the increased accumulation of TG in the glands may be an important clinical manifestation of metabolic syndrome and type 2 diabetes mellitus. PMID:27471733

  6. Effect of Chromium Supplementation on Glucose Metabolism and Lipids: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective. A systematic review of the effect of chromium supplementation on glucose metabolism and lipid levels. Research Design and Methods. Literature search conducted in MEDLINE and Commonwealth Agricultural Bureau. Eligible studies were English language randomized controlled trials of chromium ...

  7. Endurance exercise training programs intestinal lipid metabolism in a rat model of obesity and type 2 diabetes

    PubMed Central

    Hung, Yu‐Han; Linden, Melissa A.; Gordon, Alicia; Scott Rector, R.; Buhman, Kimberly K.

    2015-01-01

    Abstract Endurance exercise has been shown to improve metabolic outcomes in obesity and type 2 diabetes; however, the physiological and molecular mechanisms for these benefits are not completely understood. Although endurance exercise has been shown to decrease lipogenesis, promote fatty acid oxidation (FAO), and increase mitochondrial biosynthesis in adipose tissue, muscle, and liver, its effects on intestinal lipid metabolism remain unknown. The absorptive cells of the small intestine, enterocytes, mediate the highly efficient absorption and processing of nutrients, including dietary fat for delivery throughout the body. We investigated how endurance exercise altered intestinal lipid metabolism in obesity and type 2 diabetes using Otsuka Long‐Evans Tokushima Fatty (OLETF) rats. We assessed mRNA levels of genes associated with intestinal lipid metabolism in nonhyperphagic, sedentary Long‐Evans Tokushima Otsuka (LETO) rats (L‐Sed), hyperphagic, sedentary OLETF rats (O‐Sed), and endurance exercised OLETF rats (O‐EndEx). O‐Sed rats developed hyperphagia‐induced obesity (HIO) and type 2 diabetes compared with L‐Sed rats. O‐EndEx rats gained significantly less weight and fat pad mass, and had improved serum metabolic parameters without change in food consumption compared to O‐Sed rats. Endurance exercise resulted in dramatic up‐regulation of a number of genes in intestinal lipid metabolism and mitochondrial content compared with sedentary rats. Overall, this study provides evidence that endurance exercise programs intestinal lipid metabolism, likely contributing to its role in improving metabolic outcomes in obesity and type 2 diabetes. PMID:25602012

  8. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome.

    PubMed

    Unger, Roger H

    2003-12-01

    The obesity crisis in the United States has been associated with an alarming increase in the prevalence of the metabolic syndrome (MSX) disease cluster. Here we review evidence that the MSX reflects a failure of a system of intracellular lipid homeostasis that prevents lipotoxicity in the organs of overnourished individuals by confining the lipid overload to cells specifically designed to store large quantities of surplus calories, the white adipocytes. Normally, early in obesity, adipocytes increase leptin and adiponectin secretion, hormones that enhance oxidation of surplus liquids in nonadipose tissues by activating AMP-activated protein kinase and reducing the activity and expression of lipogenic enzymes. These events combine to lower malonyl coenzyme A. Deficiency of and/or unresponsiveness to leptin prevents these protective events and results in ectopic accumulation of lipids. Increased de novo ceramide formation is probably the most damaging lipid and is a cause of lipoapoptosis, abetted by a decline in tissue Bcl-2. Pancreatic beta-cells and myocardiocytes are cellular victims of the process, leading to non-insulin-dependent diabetes and lipotoxic cardiomyopathy. The MSX is particularly prevalent in visceral obesity, probably because visceral adipocytes make less leptin than sc adipocytes. Cushing's syndrome, the lipodystrophy associated with protease inhibitor therapy of AIDS, polycystic ovarian disease, as well as diet-induced visceral obesity, all have a high waist/hip ratio, and all exhibit MSX. Increased lipid content in the heart and skeletal muscle organs of such patients is now under study. PMID:12960011

  9. Metabolomics revealed diurnal heat stress and zinc supplementation-induced changes in amino acid, lipid, and microbial metabolism.

    PubMed

    Wang, Lei; Urriola, Pedro E; Luo, Zhao-Hui; Rambo, Zachary J; Wilson, Mark E; Torrison, Jerry L; Shurson, Gerald C; Chen, Chi

    2016-01-01

    Heat stress (HS) dramatically disrupts the events in energy and nutrient metabolism, many of which requires zinc (Zn) as a cofactor. In this study, metabolic effects of HS and Zn supplementation were evaluated by examining growth performance, blood chemistry, and metabolomes of crossbred gilts fed with ZnNeg (no Zn supplementation), ZnIO (120 ppm ZnSO4), or ZnAA (60 ppm ZnSO4 + 60 ppm zinc amino acid complex) diets under diurnal HS or thermal-neutral (TN) condition. The results showed that growth performance was reduced by HS but not by Zn supplementation. Among measured serum biochemicals, HS was found to increase creatinine but decrease blood urea nitrogen (BUN) level. Metabolomic analysis indicated that HS greatly affected diverse metabolites associated with amino acid, lipid, and microbial metabolism, including urea cycle metabolites, essential amino acids, phospholipids, medium-chain dicarboxylic acids, fatty acid amides, and secondary bile acids. More importantly, many changes in these metabolite markers were correlated with both acute and adaptive responses to HS. Relative to HS-induced metabolic effects, Zn supplementation-associated effects were much more limited. A prominent observation was that ZnIO diet, potentially through its influences on microbial metabolism, yielded different responses to HS compared with two other diets, which included higher levels of short-chain fatty acids (SCFAs) in cecal fluid and higher levels of lysine in the liver and feces. Overall, comprehensive metabolomic analysis identified novel metabolite markers associated with HS and Zn supplementation, which could guide further investigation on the mechanisms of these metabolic effects. PMID:26755737

  10. Lipid Body Organelles within the Parasite Trypanosoma cruzi: A Role for Intracellular Arachidonic Acid Metabolism

    PubMed Central

    Toledo, Daniel A. M.; Roque, Natália R.; Teixeira, Lívia; Milán-Garcés, Erix A.; Carneiro, Alan B.; Almeida, Mariana R.; Andrade, Gustavo F. S.; Martins, Jefferson S.; Pinho, Roberto R.; Freire-de-Lima, Célio G.; Bozza, Patrícia T.; D’Avila, Heloisa

    2016-01-01

    Most eukaryotic cells contain varying amounts of cytosolic lipidic inclusions termed lipid bodies (LBs) or lipid droplets (LDs). In mammalian cells, such as macrophages, these lipid-rich organelles are formed in response to host-pathogen interaction during infectious diseases and are sites for biosynthesis of arachidonic acid (AA)-derived inflammatory mediators (eicosanoids). Less clear are the functions of LBs in pathogenic lower eukaryotes. In this study, we demonstrated that LBs, visualized by light microscopy with different probes and transmission electron microscopy (TEM), are produced in trypomastigote forms of the parasite Trypanosoma cruzi, the causal agent of Chagas’ disease, after both host interaction and exogenous AA stimulation. Quantitative TEM revealed that LBs from amastigotes, the intracellular forms of the parasite, growing in vivo have increased size and electron-density compared to LBs from amastigotes living in vitro. AA-stimulated trypomastigotes released high amounts of prostaglandin E2 (PGE2) and showed PGE2 synthase expression. Raman spectroscopy demonstrated increased unsaturated lipid content and AA incorporation in stimulated parasites. Moreover, both Raman and MALDI mass spectroscopy revealed increased AA content in LBs purified from AA-stimulated parasites compared to LBs from unstimulated group. By using a specific technique for eicosanoid detection, we immunolocalized PGE2 within LBs from AA-stimulated trypomastigotes. Altogether, our findings demonstrate that LBs from the parasite Trypanosoma cruzi are not just lipid storage inclusions but dynamic organelles, able to respond to host interaction and inflammatory events and involved in the AA metabolism. Acting as sources of PGE2, a potent immunomodulatory lipid mediator that inhibits many aspects of innate and adaptive immunity, newly-formed parasite LBs may be implicated with the pathogen survival in its host. PMID:27490663

  11. Lipid Body Organelles within the Parasite Trypanosoma cruzi: A Role for Intracellular Arachidonic Acid Metabolism.

    PubMed

    Toledo, Daniel A M; Roque, Natália R; Teixeira, Lívia; Milán-Garcés, Erix A; Carneiro, Alan B; Almeida, Mariana R; Andrade, Gustavo F S; Martins, Jefferson S; Pinho, Roberto R; Freire-de-Lima, Célio G; Bozza, Patrícia T; D'Avila, Heloisa; Melo, Rossana C N

    2016-01-01

    Most eukaryotic cells contain varying amounts of cytosolic lipidic inclusions termed lipid bodies (LBs) or lipid droplets (LDs). In mammalian cells, such as macrophages, these lipid-rich organelles are formed in response to host-pathogen interaction during infectious diseases and are sites for biosynthesis of arachidonic acid (AA)-derived inflammatory mediators (eicosanoids). Less clear are the functions of LBs in pathogenic lower eukaryotes. In this study, we demonstrated that LBs, visualized by light microscopy with different probes and transmission electron microscopy (TEM), are produced in trypomastigote forms of the parasite Trypanosoma cruzi, the causal agent of Chagas' disease, after both host interaction and exogenous AA stimulation. Quantitative TEM revealed that LBs from amastigotes, the intracellular forms of the parasite, growing in vivo have increased size and electron-density compared to LBs from amastigotes living in vitro. AA-stimulated trypomastigotes released high amounts of prostaglandin E2 (PGE2) and showed PGE2 synthase expression. Raman spectroscopy demonstrated increased unsaturated lipid content and AA incorporation in stimulated parasites. Moreover, both Raman and MALDI mass spectroscopy revealed increased AA content in LBs purified from AA-stimulated parasites compared to LBs from unstimulated group. By using a specific technique for eicosanoid detection, we immunolocalized PGE2 within LBs from AA-stimulated trypomastigotes. Altogether, our findings demonstrate that LBs from the parasite Trypanosoma cruzi are not just lipid storage inclusions but dynamic organelles, able to respond to host interaction and inflammatory events and involved in the AA metabolism. Acting as sources of PGE2, a potent immunomodulatory lipid mediator that inhibits many aspects of innate and adaptive immunity, newly-formed parasite LBs may be implicated with the pathogen survival in its host. PMID:27490663

  12. Impact of dietary protein on lipid metabolism-related gene expression in porcine adipose tissue

    PubMed Central

    2010-01-01

    Background High dietary protein can reduce fat deposition in animal subcutaneous adipose tissue, but little is known about the mechanism. Methods Sixty Wujin pigs of about 15 kg weight were fed either high protein (HP: 18%) or low protein (LP: 14%) diets, and slaughtered at body weights of 30, 60 or 100 kg. Bloods were collected to measure serum parameters. Subcutaneous adipose tissues were sampled for determination of adipocyte size, protein content, lipid metabolism-related gene expression, and enzyme activities. Results HP significantly reduced adipocyte size, fat meat percentage and backfat thickness, but significantly increased daily gain, lean meat percentage and loin eye area at 60 and 100 kg. Serum free fatty acid and triglyceride concentrations in the HP group were significantly higher than in the LP group. Serum glucose and insulin concentrations were not significantly affected by dietary protein at any body weight. HP significantly reduced gene expression of acetyl CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (SREBP-1c) at 60 kg and 100 kg; however, the mRNA level and enzyme activity of FAS were increased at 30 kg. HP promoted gene and protein expression and enzyme activities of lipoprotein lipase (LPL), carmitine palmtoyltransferase-1B (CPT-1B), peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte-fatty acid binding proteins (A-FABP) at 60 kg, but reduced their expression at 100 kg. Gene expression and enzyme activity of hormone sensitive lipase (HSL) was reduced markedly at 60 kg but increased at 100 kg by the high dietary protein. Levels of mRNA, enzyme activities and protein expression of ACC, FAS, SREBP-1c and PPARγ in both LP and HP groups increased with increasing body weight. However, gene and protein expression levels/enzyme activities of LPL, CPT-1B, A-FABP and HSL in both groups were higher at 60 kg than at 30 and 100 kg. Conclusion Fat deposition in Wujin pigs fed high

  13. Relevance of liver fat to the impact of dietary extrinsic sugars on lipid metabolism.

    PubMed

    Griffin, B A

    2015-08-01

    In contrast to the decline in mortality from many non-infectious, chronic diseases in the UK, death from liver disease has increased exponentially in men and women over the past 40 years. This is primarily because of the over consumption of alcohol, but also the increased prevalence of obesity, which is linked to early pathology through the accumulation of liver fat. Supra-physiological intakes of fructose-containing sugar can produce acute, adverse effects on lipid metabolism, and deliver excess energy that increases bodyweight and the deposition of fat in sites other than adipose tissue, including the liver. This review addresses the variable metabolic origins of liver fat, and the key importance of postprandial lipid metabolism in this respect. The effects of supra-physiological intakes of sugar are also considered in context of the real world and established threshold for the adverse effects of sugar on cardio-metabolic risk factors. The review concludes that while the average intake of sugar in the UK falls well below this critical threshold, intakes in subgroups of adults, and especially adolescents, may be cause for concern. There is also evidence to suggest that raised liver fat, acquired, in part, through an impaired removal of postprandial lipaemia, can increase sensitivity to the adverse effects of sugar at all ages. PMID:25992705

  14. Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism.

    PubMed

    Kwong, Eric; Li, Yunzhou; Hylemon, Phillip B; Zhou, Huiping

    2015-03-01

    The liver is the central organ involved in lipid metabolism. Dyslipidemia and its related disorders, including non-alcoholic fatty liver disease (NAFLD), obesity and other metabolic diseases, are of increasing public health concern due to their increasing prevalence in the population. Besides their well-characterized functions in cholesterol homoeostasis and nutrient absorption, bile acids are also important metabolic regulators and function as signaling hormones by activating specific nuclear receptors, G-protein coupled receptors, and multiple signaling pathways. Recent studies identified a new signaling pathway by which conjugated bile acids (CBA) activate the extracellular regulated protein kinases (ERK1/2) and protein kinase B (AKT) signaling pathway via sphingosine-1-phosphate receptor 2 (S1PR2). CBA-induced activation of S1PR2 is a key regulator of sphingosine kinase 2 (SphK2) and hepatic gene expression. This review focuses on recent findings related to the role of bile acids/S1PR2-mediated signaling pathways in regulating hepatic lipid metabolism. PMID:26579441

  15. Differentiation of strains of varicella-zoster virus by changes in neutral lipid metabolism in infected cells

    SciTech Connect

    Jerkofsky, M.; De Siervo, A.J.

    1986-03-01

    Eleven isolates of varicella-zoster virus were tested for their effects on the incorporation of (/sup 14/C)acetate into lipids in infected human embryonic lung cells. By relative percent, all virus isolates demonstrated a shift from polar lipid synthesis to neutral lipid, especially triglyceride, synthesis. By data expressed as counts per minute per microgram of protein, the VZV strains could be separated into two groups: those strains which depressed lipid synthesis and those strains which did not depress, and may even have stimulated, lipid, especially triglyceride, synthesis. These results may be useful in understanding the development of lipid changes seen in children affected with Reye's syndrome following chickenpox.

  16. Providing lipid-based nutrient supplements does not affect developmental milestones among Malawian children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to assess whether using lipid-based nutrient supplements (LNS) to complement the diets of infants and young children affected when they achieved selected developmental milestones. In rural Malawi, 840 6-month-old healthy infants were enrolled to a randomised trial. Control particip...

  17. Sexual dimorphism of lipid metabolism in very long-chain acyl-CoA dehydrogenase deficient (VLCAD-/-) mice in response to medium-chain triglycerides (MCT).

    PubMed

    Tucci, Sara; Flögel, Ulrich; Spiekerkoetter, Ute

    2015-07-01

    Medium-chain triglycerides (MCT) are widely applied in the treatment of long-chain fatty acid oxidation disorders. Previously it was shown that long-term MCT supplementation strongly affects lipid metabolism in mice. We here investigate sex-specific effects in mice with very-long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency in response to a long-term MCT modified diet. We quantified blood lipids, acylcarnitines, glucose, insulin and free fatty acids, as well as tissue triglycerides in the liver and skeletal muscle under a control and an MCT diet over 1 year. In addition, visceral and hepatic fat content and muscular intramyocellular lipids (IMCL) were assessed by in vivo(1)H magnetic resonance spectroscopy (MRS) techniques. The long-term application of an MCT diet induced a marked alteration of glucose homeostasis. However, only VLCAD-/- female mice developed a severe metabolic syndrome characterized by marked insulin resistance, dyslipidemia, severe hepatic and visceral steatosis, whereas VLCAD-/- males seemed to be protected and only presented with milder insulin resistance. Moreover, the highly saturated MCT diet is associated with a decreased hepatic stearoyl-CoA desaturase 1 (SCD1) activity in females aggravating the harmful effects of a saturated MCT diet. Long-term MCT supplementation deeply affects lipid metabolism in a sexual dimorphic manner resulting in a severe metabolic syndrome only in female mice. These findings are striking since the first signs of insulin resistance already occur in female VLCAD-/- mice during their reproductive period. How these metabolic adaptations are finally regulated needs to be determined. More important, the relevance of these findings for humans under these dietary modifications needs to be investigated. PMID:25887160

  18. DHEA Administration Activates Transcription of Muscular Lipid Metabolic Enzymes via PPARα and PPARδ in Obese Rats.

    PubMed

    Horii, N; Sato, K; Mesaki, N; Iemitsu, M

    2016-03-01

    Administration of dehydroepiandrosterone (DHEA), a precursor of sex steroid hormones, reduces total and visceral fat mass and elevates adipocytic adiponectin gene expression. The aim of this study is to investigate whether levels of peroxisome proliferator-activated receptors (PPARs) in muscle and transcription of PPAR target genes are affected by long-term DHEA administration or exercise training, and whether altered PPAR levels are associated with circulating adiponectin level in obese rats. After 14 weeks on a high-sucrose diet, obese male Wistar rats were assigned randomly to one of 3 groups: control, DHEA administration (1 mg/kg body weight), or exercise training (treadmill running for 1 h, 25 m/min, 5 days/week) for 6 weeks (n=7 for each group). Plasma DHEA and total adiponectin levels in the DHEA-treated and exercise-training groups were significantly higher than those in the obese control group. Additionally, DHEA administration and exercise training significantly increased muscular PPARα and PPARδ protein levels, with a concomitant increase in mRNA expression of 3β-hydroxyacyl-CoA dehydrogenase and cytochrome c oxidase IV, which are target genes of PPARα and PPARδ respectively. Moreover, DHEA administration increased these protein and mRNA levels to the same degree as exercise training. Circulating adiponectin level was positively correlated with plasma DHEA and with muscle levels of PPARα and PPARδ. These results suggest that in obese rats, secretion of adiponectin due to chronic DHEA administration and exercise training may contribute to an increase in the transcription of genes encoding lipid metabolic enzymes, mediated via elevated expression of PPARα and PPARδ in muscle. PMID:26406917

  19. Black leaf streak disease affects starch metabolism in banana fruit.

    PubMed

    Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

    2013-06-12

    Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots. PMID:23692371

  20. Loss of inherited genomic imprints in mice leads to severe disruption in placental lipid metabolism

    PubMed Central

    Himes, K. P.; Young, A.; Koppes, E.; Stolz, D.; Barak, Y.; Sadovsky, Y.; Chaillet, J.R.

    2015-01-01

    Introduction Monoallelic expression of imprinted genes is necessary for placental development and normal fetal growth. Differentially methylated domains (DMDs) largely determine the parental-specific monoallelic expression of imprinted genes. Maternally derived DNA (cytosine-5-) -methyltransferase 1o (DNMT1o) maintains DMDs during the eight-cell stage of development. DNMT1o-deficient mouse placentas have a generalized disruption of genomic imprints. Previous studies have demonstrated that DNMT1o deficiency alters placental morphology and broadens the embryonic weight distribution in late gestation. Lipids are critical for fetal growth. Thus, we assessed the impact of disrupted imprinting on placental lipids. Methods Lipids were quantified from DNMT1o-deficient mouse placentas and embryos at E17.5 using a modified Folch method. Expression of select genes critical for lipid metabolism was quantified with RT-qPCR. Mitochondrial morphology was assessed by TEM and mitochondrial aconitase and cytoplasmic citrate concentrations quantified. DMD methylation was determined by EpiTYPER. Results We found that DNMT1o deficiency is associated with increased placental triacylglycerol levels. Neither fetal triacylglycerol concentrations nor expression of select genes that mediate placental lipid transport were different from wild type. Placental triacylglycerol accumulation was associated with impaired beta-oxidation and abnormal citrate metabolism with decreased mitochondrial aconitase activity and increased cytoplasmic citrate concentrations. Loss of methylation at the MEST DMD was strongly associated with placental triacylglycerol accumulation. Discussion A generalized disruption of genomic imprints leads to triacylglycerol accumulation and abnormal mitochondrial function. This could stem directly from a loss of methylation at a given DMD, such as MEST, or represent a consequence of abnormal placental development. PMID:25662615

  1. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut.

    PubMed

    Joyce, Susan A; MacSharry, John; Casey, Patrick G; Kinsella, Michael; Murphy, Eileen F; Shanahan, Fergus; Hill, Colin; Gahan, Cormac G M

    2014-05-20

    Alterations in the gastrointestinal microbiota have been implicated in obesity in mice and humans, but the key microbial functions influencing host energy metabolism and adiposity remain to be determined. Despite an increased understanding of the genetic content of the gastrointestinal microbiome, functional analyses of common microbial gene sets are required. We established a controlled expression system for the parallel functional analysis of microbial alleles in the murine gut. Using this approach we show that bacterial bile salt hydrolase (BSH) mediates a microbe-host dialogue that functionally regulates host lipid metabolism and plays a profound role in cholesterol metabolism and weight gain in the host. Expression of cloned BSH enzymes in the gastrointestinal tract of gnotobiotic or conventionally raised mice significantly altered plasma bile acid signatures and regulated transcription of key genes involved in lipid metabolism (Pparγ, Angptl4), cholesterol metabolism (Abcg5/8), gastrointestinal homeostasis (RegIIIγ), and circadian rhythm (Dbp, Per1/2) in the liver or small intestine. High-level expression of BSH in conventionally raised mice resulted in a significant reduction in host weight gain, plasma cholesterol, and liver triglycerides, demonstrating the overall impact of elevated BSH activity on host physiology. In addition, BSH activity in vivo varied according to BSH allele group, indicating that subtle differences in activity can have significant effects on the host. In summary, we demonstrate that bacterial BSH activity significantly impacts the systemic metabolic processes and adiposity in the host and represents a key mechanistic target for the control of obesity and hypercholesterolemia. PMID:24799697

  2. Effects of Excess Energy Intake on Glucose and Lipid Metabolism in C57BL/6 Mice

    PubMed Central

    Huang, Xiuqing; Cui, Ju; Gong, Huan; Zhang, Tiemei

    2016-01-01

    Excess energy intake correlates with the development of metabolic disorders. However, different energy-dense foods have different effects on metabolism. To compare the effects of a high-fat diet, a high-fructose diet and a combination high-fat/high-fructose diet on glucose and lipid metabolism, male C57BL/6 mice were fed with one of four different diets for 3 months: standard chow; standard diet and access to fructose water; a high fat diet; and a high fat diet with fructose water. After 3 months of feeding, the high-fat and the combined high-fat/high-fructose groups showed significantly increased body weights, accompanied by hyperglycemia and insulin resistance; however, the high-fructose group was not different from the control group. All three energy-dense groups showed significantly higher visceral fat weights, total cholesterol concentrations, and low-density lipoprotein cholesterol concentrations compared with the control group. Assays of basal metabolism showed that the respiratory quotient of the high-fat, the high-fructose, and the high-fat/high-fructose groups decreased compared with the control group. The present study confirmed the deleterious effect of high energy diets on body weight and metabolism, but suggested that the energy efficiency of the high-fructose diet was much lower than that of the high-fat diet. In addition, fructose supplementation did not worsen the detrimental effects of high-fat feeding alone on metabolism in C57BL/6 mice. PMID:26745179

  3. To Assess the Association between Glucose Metabolism and Ectopic Lipid Content in Different Clinical Classifications of PCOS

    PubMed Central

    Göbl, Christian S.; Ott, Johannes; Bozkurt, Latife; Feichtinger, Michael; Rehmann, Victoria; Cserjan, Anna; Heinisch, Maike; Steinbrecher, Helmut; JustKukurova, Ivica; Tuskova, Radka; Leutner, Michael; Vytiska-Binstorfer, Elisabeth; Kurz, Christine; Weghofer, Andrea; Tura, Andrea; Egarter, Christian; Kautzky-Willer, Alexandra

    2016-01-01

    Aims There are emerging data indicating an association between PCOS (polycystic ovary syndrome) and metabolic derangements with potential impact on its clinical presentation. This study aims to evaluate the pathophysiological processes beyond PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their possible interaction. Differences between the two established classifications of the disease should be additionally evaluated. Methods A metabolic characterization was performed in 53 untreated PCOS patients as well as 20 controls including an extended oral glucose tolerance test (OGTT, to assess insulin sensitivity, secretion and ß-cell function) in addition to a detailed examination of ectopic lipid content in muscle and liver by nuclear magnetic resonance spectroscopy. Results Women with PCOS classified by the original NIH 1990 definition showed a more adverse metabolic risk profile compared to women characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic derangements were observed in both subgroups, including altered shapes of OGTT curves, impaired insulin action and hyperinsulinemia due to increased secretion and attenuated hepatic extraction. No differences were observed for ectopic lipids between the groups. However, particularly hepatocellular lipid content was significantly related to clinical parameters of PCOS like whole body insulin sensitivity, dyslipidemia and free androgen index. Conclusions Subtle alterations in carbohydrate metabolism are present in both PCOS classifications, but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS and controls did not differ in ectopic lipids, however, liver fat was tightly related to hyperandrogenism and an adverse metabolic risk profile. PMID:27505055

  4. Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state, and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism...

  5. Altered maternal lipid metabolism is associated with higher inflammation in obese women during late pregnancy

    PubMed Central

    Tinius, Rachel A.; Cahill, Alison G.; Strand, Eric A.; Cade, W. Todd

    2016-01-01

    Inflammation is elevated in obese pregnant women and is associated with adverse maternal and neonatal outcomes. Maternal lipid metabolism and its relationships with maternal inflammation, insulin resistance and neonatal metabolic health are poorly understood in obese pregnant women. 18 lean (age: 26.1 ± 5.0 years, pre-pregnancy BMI: 21.5 ± 1.9 kg/m2) and 16 obese (age: 25.0 ± 4.8 years, pre-pregnancy BMI: 36.3 ± 4.3 kg/m2) women participated in this case-control study during the third trimester of pregnancy. Maternal plasma markers of insulin resistance (HOMA-IR) and inflammation (C-reactive protein (CRP)) were measured at rest, and lipid concentration and kinetics (lipid oxidation rate and lipolysis) were measured at rest, during a 30-minute bout of low-intensity (40% VO2peak) exercise, and during a recovery period. Umbilical cord blood was collected for measurement of neonatal plasma insulin sensitivity, inflammation, and lipid concentration. Neonatal body composition was measured via air displacement plethysmography. Pregnant obese women had higher plasma CRP (9.1 ± 4.0 mg/L versus 2.3 ± 1.8 mg/L, p<0.001) and higher HOMA-IR (3.8 ± 1.9 versus 2.3 ± 1.5, p=0.009) compared to pregnant lean women. Obese women had higher lipid oxidation rates during recovery from low-intensity exercise (0.13 ± 0.03 g/min versus 0.11 ±0.04 g/min, p=0.02) that was associated with higher maternal CRP (r=0.55, p=0.001). Maternal CRP was positively associated with maternal HOMA-IR (r=0.40, p<0.02) and systolic blood pressure (r=0.40, p<0.02). Maternal lipid metabolism-associated inflammation may contribute to insulin resistance and higher blood pressure in obese women during pregnancy. PMID:27239331

  6. Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

    PubMed

    Mailloux, Ryan J; Florian, Maria; Chen, Qixuan; Yan, Jin; Petrov, Ivan; Coughlan, Melanie C; Laziyan, Mahemuti; Caldwell, Don; Lalande, Michelle; Patry, Dominique; Gagnon, Claude; Sarafin, Kurtis; Truong, Jocelyn; Chan, Hing Man; Ratnayake, Nimal; Li, Nanqin; Willmore, William G; Jin, Xiaolei

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with or without co

  7. Exposure to a Northern Contaminant Mixture (NCM) Alters Hepatic Energy and Lipid Metabolism Exacerbating Hepatic Steatosis in Obese JCR Rats

    PubMed Central

    Mailloux, Ryan J.; Florian, Maria; Chen, Qixuan; Yan, Jin; Petrov, Ivan; Coughlan, Melanie C.; Laziyan, Mahemuti; Caldwell, Don; Lalande, Michelle; Patry, Dominique; Gagnon, Claude; Sarafin, Kurtis; Truong, Jocelyn; Chan, Hing Man; Ratnayake, Nimal; Li, Nanqin; Willmore, William G.; Jin, Xiaolei

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with or without co

  8. Metabolism of Glycogen and Neutral Lipids by Aphelenchus avenae and Caenorhabditis sp. in Aerobic, Microaerobic and Anaerobic Environments.

    PubMed

    Cooper, A F; Van Gundy, S D

    1970-10-01

    Starving Aphelenchus avenae survived 3-4 weeks in microaerobic and anaerobic environments, but Caenorhabditis sp. survived less than 80 hr. Aerobically, both nematodes metabolize neutral lipid reserves: there was no microaerobic ( <5% O) or anaerobic neutral lipid catabolism. Early in anaerobiosis both nematodes utilized endogenous glycogen. Caenorhabditis sp. depleted the glycogen and died. A. avenae under oxygen stress longer than 120 hr entered cryptobiosis, during which there was neither measurable O uptake nor glycogen or neutral lipid utilization, Only when re-aerated, did A. avenae recover and resume "'normal" metabolism. PMID:19322317

  9. The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum

    PubMed Central

    Dulneva, Anna; Lee, Sheena; Oliver, Peter L.; Di Gleria, Katalin; Kessler, Benedikt M.; Davies, Kay E.; Becker, Esther B. E.

    2015-01-01

    The Moonwalker (Mwk) mouse is a model of dominantly inherited cerebellar ataxia caused by a gain-of-function mutation in the transient receptor potential (TRP) channel TRPC3. Here, we report impairments in dendritic growth and synapse formation early on during Purkinje cell development in the Mwk cerebellum that are accompanied by alterations in calcium signaling. To elucidate the molecular effector pathways that regulate Purkinje cell dendritic arborization downstream of mutant TRPC3, we employed transcriptomic analysis of developing Purkinje cells isolated by laser-capture microdissection. We identified significant gene and protein expression changes in molecules involved in lipid metabolism. Consistently, lipid homeostasis in the Mwk cerebellum was found to be disturbed, and treatment of organotypic cerebellar slices with ceramide significantly improved dendritic outgrowth of Mwk Purkinje cells. These findings provide the first mechanistic insights into the TRPC3-dependent mechanisms, by which activated calcium signaling is coupled to lipid metabolism and the regulation of Purkinje cell development in the Mwk cerebellum. PMID:25908616

  10. [Effect of chronic social stress on lipid metabolism in golden Syrian hamsters].

    PubMed

    Zahaĭko, A L; Voronina, L M; Kaliman, P A; Strel'chenko, K V

    2008-01-01

    The changes of total lipids, lipoproteins and their fractions, free fatty acids, triacylglyceroles, free and esterified cholesterol levels and parameters of its metabolism in the blood serum and liver, glucose-6-phosphate dehydrogenase and lysosomal lipase activity in the liver, and also post-heparin lipases activity in blood of hamsters with chronic social stress are investigated. Is has been shown, that in stressed animals the prevalence in early terms of chronic stress lipolysis above lipogenesis is observed. In later terms of chronic stress the lipogenesis activation is also observed which, alongside with active lipolysis, can cause hyperlipidemia in blood. The latter phenomenon is obviously more characteristic of males, while in females the main source of fatty acids in blood is probably lipolysis in the liver. Proatherogenic redistribution of lipoprotein fractions, which was observed at chronic stress, becomes complicated by changes of their transformations processes under blood lipases action, in particular, lipases disbalance: by increasing of hepatic lipase activity without lipoprotein lipase activity increase. The increase of CETP activity in HDL, which is observed at stress, can be accompanied by atherogenic LDLB accumulation in the blood plasma. The chronic social stress is proatherogenic owing to lipid and lipoprotein metabolism changes, which lead to the shift of balance during lipids transport and their use by tissues. PMID:19140458

  11. Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training.

    PubMed

    Friedlander, Anne L; Jacobs, Kevin A; Fattor, Jill A; Horning, Michael A; Hagobian, Todd A; Bauer, Timothy A; Wolfel, Eugene E; Brooks, George A

    2007-01-01

    To evaluate the contribution of working muscle to whole body lipid oxidation, we examined the effects of exercise intensity and endurance training (9 wk, 5 days/wk, 1 h, 75% Vo(2 peak)) on whole body and leg free fatty acid (FFA) kinetics in eight male subjects (26 +/- 1 yr, means +/- SE). Two pretraining trials [45 and 65% Vo(2 max) (45UT, 65UT)] and two posttraining trials [65% of pretraining Vo(2 peak) (ABT), and 65% of posttraining Vo(2 peak) (RLT)] were performed using [1-(13)C]palmitate infusion and femoral arteriovenous sampling. Training increased Vo(2 peak) by 15% (45.2 +/- 1.2 to 52.0 +/- 1.8 ml.kg(-1).min(-1), P < 0.05). Muscle FFA fractional extraction was lower during exercise (EX) compared with rest regardless of workload or training status ( approximately 20 vs. 48%, P < 0.05). Two-leg net FFA balance increased from net release at rest ( approximately -36 micromol/min) to net uptake during EX for 45UT (179 +/- 75), ABT (236 +/- 63), and RLT (136 +/- 110) (P < 0.05), but not 65UT (51 +/- 127). Leg FFA tracer measured uptake was higher during EX than rest for all trials and greater during posttraining in RLT (716 +/- 173 micromol/min) compared with pretraining (45UT 450 +/- 80, 65UT 461 +/- 72, P < 0.05). Leg muscle lipid oxidation increased with training in ABT (730 +/- 163 micromol/min) vs. 65UT (187 +/- 94, P < 0.05). Leg muscle lipid oxidation represented approximately 62 and 30% of whole body lipid oxidation at lower and higher relative intensities, respectively. In summary, training can increase working muscle tracer measured FFA uptake and lipid oxidation for a given power output, but both before and after training the association between whole body and leg lipid metabolism is reduced as exercise intensity increases. PMID:16896167

  12. Reprogramming Neutral Lipid Metabolism in Mouse Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes

    PubMed Central

    Lecoeur, Hervé; Giraud, Emilie; Prévost, Marie-Christine; Milon, Geneviève; Lang, Thierry

    2013-01-01

    Background After loading with live Leishmania (L) amazonensis amastigotes, mouse myeloid dendritic leucocytes/DLs are known to undergo reprogramming of their immune functions. In the study reported here, we investigated whether the presence of live L. amazonensis amastigotes in mouse bone marrow-derived DLs is able to trigger re-programming of DL lipid, and particularly neutral lipid metabolism. Methodology/Principal Findings Affymetrix-based transcriptional profiles were determined in C57BL/6 and DBA/2 mouse bone marrow-derived DLs that had been sorted from cultures exposed or not to live L. amazonensis amastigotes. This showed that live amastigote-hosting DLs exhibited a coordinated increase in: (i) long-chain fatty acids (LCFA) and cholesterol uptake/transport, (ii) LCFA and cholesterol (re)-esterification to triacyl-sn-glycerol (TAG) and cholesteryl esters (CE), respectively. As these neutral lipids are known to make up the lipid body (LB) core, oleic acid was added to DL cultures and LB accumulation was compared in live amastigote-hosting versus amastigote-free DLs by epi-fluorescence and transmission electron microscopy. This showed that LBs were both significantly larger and more numerous in live amastigote-hosting mouse dendritic leucocytes. Moreover, many of the larger LB showed intimate contact with the membrane of the parasitophorous vacuoles hosting the live L. amazonensis amastigotes. Conclusions/Significance As leucocyte LBs are known to be more than simple neutral lipid repositories, we set about addressing two related questions. Could LBs provide lipids to live amastigotes hosted within the DL parasitophorous vacuole and also deliver? Could LBs impact either directly or indirectly on the persistence of L. amazonensis amastigotes in rodent skin? PMID:23785538

  13. [Study on effect of Lactobacillus acidophilus MG2-1 on serum lipid metabolism in rats].

    PubMed

    Menghe, Bilige; Zhang, He-Ping; Chen, Yong-Fu; Guan, Hong; Zhou, Dong-Po

    2005-12-01

    Wistar rats were fed with a high lipid diet supplemented with living or thermal death bacteria of Lactobacillus acidophilus MG2-1 which was isolated from koumiss in Mongolia and was of good ability of acid tolerance and decreasing the level of cholesterol in vitro. The effect of Lb. acidophilus MG2-1 on the metabolism of serum cholesterol was discussed. It was showed that it was on the 14th day of experiment that the inhibiting effects of the increase of serum cholesterol level of rat groups fed with living bacteria and heat-killed bacteria was significantly (p > 0.05) and very significantly (p < 0.01) higher than that of the high lipid diet group respectively; at the same time, the level of serum HDL-C of the thermal death bacteria group was significantly higher than that of the high lipid diet group (p < 0.05), also arteriosclerosis index of wistar rats in experimental group is significantly lower than that of the high lipid diet group (p < 0.01). The total bile acid level of the thermal death bacteria group in fecal is significantly higher than that of the high lipid diet group (p < 0.05). It is suggested that the increase of serum cholesterol level in rats can be inhibited and arteriosclerosis can also be prevented by this strain. During the period of tests, the effect of the strain on serum lipid in rats weaken with the time going, while the dose of bacteria fed was not changed. PMID:16496693

  14. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature

    PubMed Central

    Norambuena, Fernando; Morais, Sofia; Emery, James A.; Turchini, Giovanni M.

    2015-01-01

    Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad–time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

  15. Relationship between insulin-mediated glucose disposal and lipid metabolism in man.

    PubMed Central

    Lillioja, S; Bogardus, C; Mott, D M; Kennedy, A L; Knowler, W C; Howard, B V

    1985-01-01

    To assess the possible effects of lipid metabolism on insulin-mediated glucose disposal, 18 nondiabetic Pima Indian women (age 18-35 yr) were studied using 1-14C-palmitate infusion to measure free fatty acid turnover rate followed by a euglycemic clamp (clamp) to measure in vivo insulin-mediated glucose disposal (M). Indirect calorimetry was performed in the basal state and during the clamp. This was used to assess glucose oxidation rate, lipid oxidation rate, and to calculate nonoxidative glucose disposal (storage). Basal and clamp lipid oxidation rate correlated with basal plasma free fatty acid concentration (r = 0.81, P less than or equal to 0.0001, r = 0.67, P less than 0.003, respectively). The fall in lipid oxidation was highly correlated with the increase in glucose oxidation during the insulin infusion (r = 0.96, P less than or equal to 0.0001). The clamp lipid oxidation rate negatively correlated with the glucose oxidation rate (r = -0.85, P less than 0.0001) and with the M value (r = -0.60, P less than 0.01) but was not correlated with the clamp glucose storage (r = -0.2, P = 0.4). On the other hand, glucose storage appeared to make a greater contribution to the difference in M value between the upper and lower extremes of M than did glucose oxidation, as evidenced by an increase in glucose storage of 0.59 mg/kg fat-free mass times minute per 1 mg/kg fat-free mass times minute increase in glucose disposal. The M value was negatively correlated with obesity as measured by percent body fat (r = -0.64, P less than 0.004), but neither basal free fatty acid concentration, basal free fatty acid turnover, basal lipid oxidation, nor clamp lipid oxidation correlated with percent body fat. We conclude that an interaction of lipid and glucose metabolism in a glucose fatty acid cycle, as proposed by Randle et al. (1), may be operative in the regulation of glucose oxidation in man. The disposal of glucose however has two components. The storage component does not

  16. Disorders of Carbohydrate Metabolism

    MedlinePlus

    ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Carbohydrates are sugars. ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism NOTE: This is ...

  17. Αcute Exercise Alters the Levels of Human Saliva miRNAs Involved in Lipid Metabolism.

    PubMed

    Konstantinidou, A; Mougios, V; Sidossis, L S

    2016-06-01

    The response of micro-ribonucleic acid (miRNA) expression to exercise has not been studied in saliva, although saliva combines non-invasive collection with the largest number of miRNA species among biological fluids and tissues. Thus, the purpose of this study was to investigate the effect of acute exercise on the expression of 8 human saliva miRNAs involved in lipid metabolism. 19 healthy, physically active men (VO2max, 40.9±1.6 mL·kg(-1)·min(-1), mean±se) performed a 50-min interval exercise program on stationary bicycle (spinning). Saliva samples were collected before and after exercise for miRNA expression analysis by real-time polymerase chain reaction. Statistically significant (p<0.05) changes after exercise were found in 2 of the 8 miRNAs, namely, hsa-miR-33a (fold change, 7.66±2.94; p=0.012), which regulates cholesterol homeostasis and fatty acid metabolism in the liver, and hsa-miR-378a (fold change 0.79±0.11, p=0.048), which regulates energy homeostasis and affects lipogenesis and adipogenesis. These alterations may contribute to our understanding of physiological responses to exercise and the therapeutic potential of exercise against cardiovascular disease, obesity, and the metabolic syndrome. Moreover, our findings open the possibility of noninvasively studying miRNAs that regulate the function of specific organs. PMID:27116339

  18. Chromium and vanadium effects on glucose and lipid metabolism of guinea pigs and obese and diabetic mice

    SciTech Connect

    Li, Y.C.

    1987-01-01

    Severe chromium deficiency in experimental animals may contribute to insulin resistance, impaired glucose tolerance and elevated serum cholesterol concentration. Vanadium also has been reported to be a nutritionally important element for both chicks and rats, but its function and even its essentiality are still in question. Chromium absorption even from supplemented diets is poor, thus efforts were made to study the site of absorption of /sup 51/Cr from CrCl/sub 3/. /sup 51/Cr was found to move very rapidly through the GI tract and appears to flow with dietary and secreted water. It was not absorbed from the stomach. In a study with guinea pigs, vanadate supplementation appeared to affect cholesterol fraction. Chromium supplementation lowered serum triacylglycerol concentrations at the end of an 18-week study. Since the previous study and others have indicated a role for chromium and vanadium in lipid carbohydrate metabolism, experiments were designed to compare effects of chromium and vanadium supplements on related parameters.

  19. Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulate carotenoid and lipid metabolism in mice.

    PubMed

    Ford, Nikki A; Elsen, Amy C; Erdman, John W

    2013-09-01

    Carotene-15,15'-monooxygenase (CMO-I) cleaves β-carotene to form vitamin A, whereas carotene-9',10'-monooxygenase (CMO-II) preferentially cleaves non-provitamin A carotenoids. Recent reports indicate that β-carotene metabolites regulate dietary lipid uptake, whereas lycopene regulates peroxisome proliferator-activated receptor expression. To determine the physiologic consequences of carotenoids and their interactions with CMO-I and CMO-II, we characterized mammalian carotenoid metabolism, metabolic perturbations, and lipid metabolism in female CMO-I(-/-) and CMO-II(-/-) mice fed lycopene or tomato-containing diets for 30 days. We hypothesized that there would be significant interactions between diet and genotype on carotenoid accumulation and lipid parameters. CMO-I(-/-) mice had higher levels of leptin, insulin, and hepatic lipidosis but lower levels of serum cholesterol. CMO-II(-/-) mice had increased tissue lycopene and phytofluene accumulation, reduced insulin-like growth factor 1 levels and cholesterol levels, but elevated liver lipids and cholesterol compared with wild-type mice. The diets did not modulate these genotypic perturbations, but lycopene and tomato powder significantly decreased serum insulin-like growth factor 1. Tomato powder also increased hepatic peroxisome proliferator-activated receptor expression, independent of genotype. These data point to the pleiotropic actions of CMO-I and CMO-II supporting a strong role of these proteins in regulating tissue carotenoid accumulation and the lipid metabolic phenotype as well as tomato carotenoid-independent regulation of lipid metabolism. PMID:24034573

  20. Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulates carotenoid and lipid metabolism in mice

    PubMed Central

    Ford, Nikki A.; Elsen, Amy C.; Erdman, John W.

    2013-01-01

    Carotene-15,15'-monooxygenase (CMO-I) cleaves β-carotene to form vitamin A while carotene-9’,10’-monooxygenase (CMO-II) preferentially cleaves non-provitamin A carotenoids. Recent reports indicate that beta-carotene metabolites regulate dietary lipid uptake while lycopene regulates peroxisome-proliferated activator receptor (PPAR) expression. To determine the physiologic consequences of carotenoids and their interactions with CMO-I and CMO-II, we characterized mammalian carotenoid metabolism, metabolic perturbations and lipid metabolism in female CMO-I−/− and CMO-II−/− mice fed lycopene or tomato-containing diets for 30 days. We hypothesized that there would be significant interactions between diet and genotype on carotenoid accumulation and lipid parameters. CMO-I−/− mice had higher levels of leptin, insulin and hepatic lipidosis, but lower levels of serum cholesterol. CMO-II−/− mice had increased tissue lycopene and phytofluene accumulation, reduced IGF-1 levels and cholesterol levels, but elevated liver lipids and cholesterol compared with WT mice. The diets did not modulate these genotypic perturbations, but lycopene and tomato powder did significantly decrease serum insulin-like growth factor-I. Tomato powder also reduced hepatic PPAR expression, independent of genotype. These data point to the pleiotropic actions of CMO-I and CMO-II supporting a strong role of these proteins in regulating tissue carotenoid accumulation and the lipid metabolic phenotype, as well as tomato carotenoid-independent regulation of lipid metabolism. PMID:24034573

  1. Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis.

    PubMed

    Shih, Diana M; Wang, Zeneng; Lee, Richard; Meng, Yonghong; Che, Nam; Charugundla, Sarada; Qi, Hannah; Wu, Judy; Pan, Calvin; Brown, J Mark; Vallim, Thomas; Bennett, Brian J; Graham, Mark; Hazen, Stanley L; Lusis, Aldons J

    2015-01-01

    We performed silencing and overexpression studies of flavin containing monooxygenase (FMO) 3 in hyperlipidemic mouse models to examine its effects on trimethylamine N-oxide (TMAO) levels and atherosclerosis. Knockdown of hepatic FMO3 in LDL receptor knockout mice using an antisense oligonucleotide resulted in decreased circulating TMAO levels and atherosclerosis. Surprisingly, we also observed significant decreases in hepatic lipids and in levels of plasma lipids, ketone bodies, glucose, and insulin. FMO3 overexpression in transgenic mice, on the other hand, increased hepatic and plasma lipids. Global gene expression analyses suggested that these effects of FMO3 on lipogenesis and gluconeogenesis may be mediated through the PPARα and Kruppel-like factor 15 pathways. In vivo and in vitro results were consistent with the concept that the effects were mediated directly by FMO3 rather than trimethylamine/TMAO; in particular, overexpression of FMO3 in the human hepatoma cell line, Hep3B, resulted in significantly increased glucose secretion and lipogenesis. Our results indicate a major role for FMO3 in modulating glucose and lipid homeostasis in vivo, and they suggest that pharmacologic inhibition of FMO3 to reduce TMAO levels would be confounded by metabolic interactions. PMID:25378658

  2. Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis[S

    PubMed Central

    Shih, Diana M.; Wang, Zeneng; Lee, Richard; Meng, Yonghong; Che, Nam; Charugundla, Sarada; Qi, Hannah; Wu, Judy; Pan, Calvin; Brown, J. Mark; Vallim, Thomas; Bennett, Brian J.; Graham, Mark; Hazen, Stanley L.; Lusis, Aldons J.

    2015-01-01

    We performed silencing and overexpression studies of flavin containing monooxygenase (FMO) 3 in hyperlipidemic mouse models to examine its effects on trimethylamine N-oxide (TMAO) levels and atherosclerosis. Knockdown of hepatic FMO3 in LDL receptor knockout mice using an antisense oligonucleotide resulted in decreased circulating TMAO levels and atherosclerosis. Surprisingly, we also observed significant decreases in hepatic lipids and in levels of plasma lipids, ketone bodies, glucose, and insulin. FMO3 overexpression in transgenic mice, on the other hand, increased hepatic and plasma lipids. Global gene expression analyses suggested that these effects of FMO3 on lipogenesis and gluconeogenesis may be mediated through the PPARα and Kruppel-like factor 15 pathways. In vivo and in vitro results were consistent with the concept that the effects were mediated directly by FMO3 rather than trimethylamine/TMAO; in particular, overexpression of FMO3 in the human hepatoma cell line, Hep3B, resulted in significantly increased glucose secretion and lipogenesis. Our results indicate a major role for FMO3 in modulating glucose and lipid homeostasis in vivo, and they suggest that pharmacologic inhibition of FMO3 to reduce TMAO levels would be confounded by metabolic interactions. PMID:25378658

  3. Hdac3 Deficiency Increases Marrow Adiposity and Induces Lipid Storage and Glucocorticoid Metabolism in Osteochondroprogenitor Cells.

    PubMed

    McGee-Lawrence, Meghan E; Carpio, Lomeli R; Schulze, Ryan J; Pierce, Jessica L; McNiven, Mark A; Farr, Joshua N; Khosla, Sundeep; Oursler, Merry Jo; Westendorf, Jennifer J

    2016-01-01

    Bone loss and increased marrow adiposity are hallmarks of aging skeletons. Conditional deletion of histone deacetylase 3 (Hdac3) in murine osteochondroprogenitor cells causes osteopenia and increases marrow adiposity, even in young animals, but the origins of the increased adiposity are unclear. To explore this, bone marrow stromal cells (BMSCs) from Hdac3-depleted and control mice were cultured in osteogenic medium. Hdac3-deficient cultures accumulated lipid droplets in greater abundance than control cultures and expressed high levels of genes related to lipid storage (Fsp27/Cidec, Plin1) and glucocorticoid metabolism (Hsd11b1) despite normal levels of Pparγ2. Approximately 5% of the lipid containing cells in the wild-type cultures expressed the master osteoblast transcription factor Runx2, but this population was threefold greater in the Hdac3-depleted cultures. Adenoviral expression of Hdac3 restored normal gene expression, indicating that Hdac3 controls glucocorticoid activation and lipid storage within osteoblast lineage cells. HDAC3 expression was reduced in bone cells from postmenopausal as compared to young women, and in osteoblasts from aged as compared to younger mice. Moreover, phosphorylation of S424 in Hdac3, a posttranslational mark necessary for deacetylase activity, was suppressed in osseous cells from old mice. Thus, concurrent declines in transcription and phosphorylation combine to suppress Hdac3 activity in aging bone, and reduced Hdac3 activity in osteochondroprogenitor cells contributes to increased marrow adiposity associated with aging. © 2015 American Society for Bone and Mineral Research. PMID:26211746

  4. Hdac3 Deficiency Increases Marrow Adiposity and Induces Lipid Storage and Glucocorticoid Metabolism in Osteochondroprogenitor Cells

    PubMed Central

    McGee-Lawrence, Meghan E; Carpio, Lomeli R; Schulze, Ryan J; Pierce, Jessica L; McNiven, Mark A; Farr, Joshua N; Khosla, Sundeep; Oursler, Merry Jo; Westendorf, Jennifer J

    2016-01-01

    Bone loss and increased marrow adiposity are hallmarks of aging skeletons. Conditional deletion of histone deacetylase 3 (Hdac3) in murine osteochondroprogenitor cells causes osteopenia and increases marrow adiposity, even in young animals, but the origins of the increased adiposity are unclear. To explore this, bone marrow stromal cells (BMSCs) from Hdac3-depleted and control mice were cultured in osteogenic medium. Hdac3-deficient cultures accumulated lipid droplets in greater abundance than control cultures and expressed high levels of genes related to lipid storage (Fsp27/Cidec, Plin1) and glucocorticoid metabolism (Hsd11b1) despite normal levels of Pparγ2. Approximately 5% of the lipid containing cells in the wild-type cultures expressed the master osteoblast transcription factor Runx2, but this population was threefold greater in the Hdac3-depleted cultures. Adenoviral expression of Hdac3 restored normal gene expression, indicating that Hdac3 controls glucocorticoid activation and lipid storage within osteoblast lineage cells. HDAC3 expression was reduced in bone cells from postmenopausal as compared to young women, and in osteoblasts from aged as compared to younger mice. Moreover, phosphorylation of S424 in Hdac3, a posttranslational mark necessary for deacetylase activity, was suppressed in osseous cells from old mice. Thus, concurrent declines in transcription and phosphorylation combine to suppress Hdac3 activity in aging bone, and reduced Hdac3 activity in osteochondroprogenitor cells contributes to increased marrow adiposity associated with aging. PMID:26211746

  5. High-Throughput Genetics Strategies for Identifying New Components of Lipid Metabolism in the Green Alga Chlamydomonas reinhardtii.

    PubMed

    Li, Xiaobo; Jonikas, Martin C

    2016-01-01

    Microalgal lipid metabolism is of broad interest because microalgae accumulate large amounts of triacylglycerols (TAGs) that can be used for biodiesel production (Durrett et al Plant J 54(4):593-607, 2008; Hu et al Plant J 54(4):621-639, 2008). Additionally, green algae are close relatives of land plants and serve as models to understand conserved lipid metabolism pathways in the green lineage. The green alga Chlamydomonas reinhardtii (Chlamydomonas hereafter) is a powerful model organism for understanding algal lipid metabolism. Various methods have been used to screen Chlamydomonas mutants for lipid amount or composition, and for identification of the mutated loci in mutants of interest. In this chapter, we summarize the advantages and caveats for each of these methods with a focus on screens for mutants with perturbed TAG content. We also discuss technical opportunities and new tools that are becoming available for screens of mutants altered in TAG content or perturbed in other processes in Chlamydomonas. PMID:27023238

  6. HIF prolyl 4-hydroxylase-2 inhibition improves glucose and lipid metabolism and protects against obesity and metabolic dysfunction.

    PubMed

    Rahtu-Korpela, Lea; Karsikas, Sara; Hörkkö, Sohvi; Blanco Sequeiros, Roberto; Lammentausta, Eveliina; Mäkelä, Kari A; Herzig, Karl-Heinz; Walkinshaw, Gail; Kivirikko, Kari I; Myllyharju, Johanna; Serpi, Raisa; Koivunen, Peppi

    2014-10-01

    Obesity is a major public health problem, predisposing subjects to metabolic syndrome, type 2 diabetes, and cardiovascular diseases. Specific prolyl 4-hydroxylases (P4Hs) regulate the stability of the hypoxia-inducible factor (HIF), a potent governor of metabolism, with isoenzyme 2 being the main regulator. We investigated whether HIF-P4H-2 inhibition could be used to treat obesity and its consequences. Hif-p4h-2-deficient mice, whether fed normal chow or a high-fat diet, had less adipose tissue, smaller adipocytes, and less adipose tissue inflammation than their littermates. They also had improved glucose tolerance and insulin sensitivity. Furthermore, the mRNA levels of the HIF-1 targets glucose transporters, glycolytic enzymes, and pyruvate dehydrogenase kinase-1 were increased in their tissues, whereas acetyl-CoA concentration was decreased. The hepatic mRNA level of the HIF-2 target insulin receptor substrate-2 was higher, whereas that of two key enzymes of fatty acid synthesis was lower. Serum cholesterol levels and de novo lipid synthesis were decreased, and the mice were protected against hepatic steatosis. Oral administration of an HIF-P4H inhibitor, FG-4497, to wild-type mice with metabolic dysfunction phenocopied these beneficial effects. HIF-P4H-2 inhibition may be a novel therapy that not only protects against the development of obesity and its consequences but also reverses these conditions. PMID:24789921

  7. Genes regulating lipid and protein metabolism are highly expressed in mammary gland of lactating dairy goats.

    PubMed

    Shi, Hengbo; Zhu, Jiangjiang; Luo, Jun; Cao, Wenting; Shi, Huaiping; Yao, Dawei; Li, Jun; Sun, Yuting; Xu, Huifen; Yu, Kang; Loor, Juan J

    2015-05-01

    Dairy goats serve as an important source of milk and also fulfill agricultural and economic roles in developing countries. Understanding the genetic background of goat mammary gland is important for research on the regulatory mechanisms controlling tissue function and the synthesis of milk components. We collected tissue at four different stages of goat mammary gland development and generated approximately 25 GB of data from Illumina de novo RNA sequencing. The combined reads were assembled into 51,361 unigenes, and approximately 60.07 % of the unigenes had homology to other proteins in the NCBI non-redundant protein database (NR). Functional classification through eukaryotic Ortholog Groups of Protein (KOG), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the unigenes from goat mammary glands are involved in a wide range of biological processes and metabolic pathways, including lipid metabolism and lactose metabolism. The results of qPCR revealed that genes encoding FABP3, FASN, SCD, PLIN2, whey proteins (LALBA and BLG), and caseins (CSN1S1, CSN1S2, CSN2 and CSN3) at 100 and 310 days postpartum increased significantly compared with the non-lactating period. In addition to their role in lipid and protein synthesis, the higher expression at 310 days postpartum could contribute to mammary cell turnover during pregnancy. In conclusion, this is the first study to characterize the complete transcriptome of goat mammary glands and constitutes a comprehensive genomic resource available for further studies of ruminant lactation. PMID:25433708

  8. DHEA-Mediated Inhibition of the Pentose Phosphate Pathway Alters Oocyte Lipid Metabolism in Mice

    PubMed Central

    Jimenez, Patricia T.; Frolova, Antonina I.; Chi, Maggie M.; Grindler, Natalia M.; Willcockson, Alexandra R.; Reynolds, Kasey A.; Zhao, Quihong

    2013-01-01

    Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered hormone levels and suffer from ovarian dysfunction leading to subfertility. We have attempted to generate a model of hyperandrogenism by feeding mice chow supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is often elevated in women with PCOS. Treated mice had polycystic ovaries, low ovulation rates, disrupted estrous cycles, and altered hormone levels. Because DHEA is an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the pentose phosphate pathway, we tested the hypothesis that oocytes from DHEA-exposed mice would have metabolic disruptions. Citrate levels, glucose-6-phosphate dehydrogenase activity, and lipid content in denuded oocytes from these mice were significantly lower than controls, suggesting abnormal tricarboxylic acid and pentose phosphate pathway metabolism. The lipid and citrate effects were reversible by supplementation with nicotinic acid, a precursor for reduced nicotinamide adenine dinucleotide phosphate. These findings suggest that elevations in systemic DHEA can have a negative impact on oocyte metabolism and may contribute to poor pregnancy outcomes in women with hyperandrogenism and PCOS. PMID:24036000

  9. Similar and Additive Effects of Ovariectomy and Diabetes on Insulin Resistance and Lipid Metabolism

    PubMed Central

    Tawfik, Shady H.; Mahmoud, Bothaina F.; Saad, Mohamed I.; Shehata, Mona; Kamel, Maher A.; Helmy, Madiha H.

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is among the leading causes of death in postmenopausal women. The disruption of ovarian function may contribute to the incidence of T2DM. The purpose of this study was to investigate the effects of ovariectomy and T2DM on glucose and lipid homeostasis, perilipin levels in adipose tissues, as a lipolytic regulator, and levels of certain adipokines. Ovariectomized (OVX) rats were used as a model for postmenopausal women. The study was performed on sham, OVX, sham diabetic, and OVX diabetic female rats. The results indicated that ovariectomy alters adipose tissue metabolism through reducing perilipin content in white adipose tissue (WAT); however it has no effect on perilipin level in brown adipose tissue (BAT). OVX diabetic females suffer from serious metabolic disturbances, suggested by exacerbation of insulin resistance in terms of disrupted lipid profile, higher HOMA-IR, hyperinsulinemia, higher leptin, and lower adiponectin concentrations. These metabolic derangements may underlie the predisposition for cardiovascular disease in women after menopause. Therefore, for efficient treatment, the menopausal status of diabetic female should be addressed, and the order of events is of great importance because ovariectomy following development of diabetes has more serious complications compared to development of diabetes as result of menopause. PMID:25834745

  10. Similar and additive effects of ovariectomy and diabetes on insulin resistance and lipid metabolism.

    PubMed

    Tawfik, Shady H; Mahmoud, Bothaina F; Saad, Mohamed I; Shehata, Mona; Kamel, Maher A; Helmy, Madiha H

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is among the leading causes of death in postmenopausal women. The disruption of ovarian function may contribute to the incidence of T2DM. The purpose of this study was to investigate the effects of ovariectomy and T2DM on glucose and lipid homeostasis, perilipin levels in adipose tissues, as a lipolytic regulator, and levels of certain adipokines. Ovariectomized (OVX) rats were used as a model for postmenopausal women. The study was performed on sham, OVX, sham diabetic, and OVX diabetic female rats. The results indicated that ovariectomy alters adipose tissue metabolism through reducing perilipin content in white adipose tissue (WAT); however it has no effect on perilipin level in brown adipose tissue (BAT). OVX diabetic females suffer from serious metabolic disturbances, suggested by exacerbation of insulin resistance in terms of disrupted lipid profile, higher HOMA-IR, hyperinsulinemia, higher leptin, and lower adiponectin concentrations. These metabolic derangements may underlie the predisposition for cardiovascular disease in women after menopause. Therefore, for efficient treatment, the menopausal status of diabetic female should be addressed, and the order of events is of great importance because ovariectomy following development of diabetes has more serious complications compared to development of diabetes as result of menopause. PMID:25834745

  11. Argininosuccinate synthetase regulates hepatic AMPK linking protein catabolism and ureagenesis to hepatic lipid metabolism.

    PubMed

    Madiraju, Anila K; Alves, Tiago; Zhao, Xiaojian; Cline, Gary W; Zhang, Dongyan; Bhanot, Sanjay; Samuel, Varman T; Kibbey, Richard G; Shulman, Gerald I

    2016-06-14

    A key sensor of cellular energy status, AMP-activated protein kinase (AMPK), interacts allosterically with AMP to maintain an active state. When active, AMPK triggers a metabolic switch, decreasing the activity of anabolic pathways and enhancing catabolic processes such as lipid oxidation to restore the energy balance. Unlike oxidative tissues, in which AMP is generated from adenylate kinase during states of high energy demand, the ornithine cycle enzyme argininosuccinate synthetase (ASS) is a principle site of AMP generation in the liver. Here we show that ASS regulates hepatic AMPK, revealing a central role for ureagenesis flux in the regulation of metabolism via AMPK. Treatment of primary rat hepatocytes with amino acids increased gluconeogenesis and ureagenesis and, despite nutrient excess, induced both AMPK and acetyl-CoA carboxylase (ACC) phosphorylation. Antisense oligonucleotide knockdown of hepatic ASS1 expression in vivo decreased liver AMPK activation, phosphorylation of ACC, and plasma β-hydroxybutyrate concentrations. Taken together these studies demonstrate that increased amino acid flux can activate AMPK through increased AMP generated by ASS, thus providing a novel link between protein catabolism, ureagenesis, and hepatic lipid metabolism. PMID:27247419

  12. Argininosuccinate synthetase regulates hepatic AMPK linking protein catabolism and ureagenesis to hepatic lipid metabolism

    PubMed Central

    Madiraju, Anila K.; Alves, Tiago; Zhao, Xiaojian; Cline, Gary W.; Zhang, Dongyan; Bhanot, Sanjay; Samuel, Varman T.; Kibbey, Richard G.; Shulman, Gerald I.

    2016-01-01

    A key sensor of cellular energy status, AMP-activated protein kinase (AMPK), interacts allosterically with AMP to maintain an active state. When active, AMPK triggers a metabolic switch, decreasing the activity of anabolic pathways and enhancing catabolic processes such as lipid oxidation to restore the energy balance. Unlike oxidative tissues, in which AMP is generated from adenylate kinase during states of high energy demand, the ornithine cycle enzyme argininosuccinate synthetase (ASS) is a principle site of AMP generation in the liver. Here we show that ASS regulates hepatic AMPK, revealing a central role for ureagenesis flux in the regulation of metabolism via AMPK. Treatment of primary rat hepatocytes with amino acids increased gluconeogenesis and ureagenesis and, despite nutrient excess, induced both AMPK and acetyl-CoA carboxylase (ACC) phosphorylation. Antisense oligonucleotide knockdown of hepatic ASS1 expression in vivo decreased liver AMPK activation, phosphorylation of ACC, and plasma β-hydroxybutyrate concentrations. Taken together these studies demonstrate that increased amino acid flux can activate AMPK through increased AMP generated by ASS, thus providing a novel link between protein catabolism, ureagenesis, and hepatic lipid metabolism. PMID:27247419

  13. Monoolein-based cubosomes affect lipid profile in HeLa cells.

    PubMed

    Rosa, Antonella; Murgia, Sergio; Putzu, Danilo; Meli, Valeria; Falchi, Angela Maria

    2015-10-01

    Monoolein-based cubosomes are promising drug delivery nanocarriers for theranostic purposes. Nevertheless, a small amount of research has been undertaken to investigate the impact of these biocompatible nanoparticles on cell lipid profile. The purpose of the present investigation was to explore changes in lipid components occurring in human carcinoma HeLa cells when exposed to short-term treatments (2 and 4h) with monoolein-based cubosomes stabilized by Pluronic F108 (MO/PF108). A combination of TLC and reversed-phase HPLC with DAD and ELSD detection was performed to analyze cell total fatty acid profile and levels of phospholipids, free cholesterol, triacylglycerols, and cholesteryl esters. The treatments with MO/PF108 cubosomes, at non-cytotoxic concentration (83μg/mL of MO), affected HeLa fatty acid profile, and a significant increase in the level of oleic acid 18:1 n-9 was observed in treated cells after lipid component saponification. Nanoparticle uptake modulated HeLa cell lipid composition, inducing a remarkable incorporation of oleic acid in the phospholipid and triacylglycerol fractions, whereas no changes were observed in the cellular levels of free cholesterol and cholesteryl oleate. Moreover, cell-based fluorescent measurements of intracellular membranes and lipid droplet content were assessed on cubosome-treated cells with an alternative technique using Nile red staining. A significant increase in the amount of the intracellular membranes and mostly in the cytoplasmic lipid droplets was detected, confirming that monoolein-based cubosome treatment influences the synthesis of intracellular membranes and accumulation of lipid droplets. PMID:26341749

  14. A sterol binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing

    PubMed Central

    Mousley, Carl J.; Yuan, Peihua; Gaur, Naseem A.; Trettin, Kyle D.; Nile, Aaron H.; Deminoff, Stephen J.; Dewar, Brian J.; Wolpert, Max; Macdonald, Jeffrey M.; Herman, Paul K.; Hinnebusch, Alan G.; Bankaitis, Vytas A.

    2012-01-01

    SUMMARY Kes1, and other oxysterol binding protein (OSBP) superfamily members, are involved in membrane and lipid trafficking through trans-Golgi network (TGN) and endosomal systems. We demonstrate that Kes1 represents a sterol-regulated antagonist of TGN/endosomal phosphatidylinositol-4-phosphate signaling. This regulation modulates TOR activation by amino acids, and dampens gene expression driven by Gcn4; the primary transcriptional activator of the general amino acid control regulon. Kes1-mediated repression of Gcn4 transcription factor activity is characterized by nonproductive Gcn4 binding to its target sequences, involves TGN/endosome-derived sphingolipid signaling, and requires activity of the cyclin-dependent kinase 8 (CDK8) module of the enigmatic ‘large Mediator’ complex. These data describe a pathway by which Kes1 integrates lipid metabolism with TORC1 signaling and nitrogen sensing. PMID:22341443

  15. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids

    PubMed Central

    Fu, Xianghui; Dong, Bingning; Tian, Yan; Lefebvre, Philippe; Meng, Zhipeng; Wang, Xichun; Pattou, François; Han, Weidong; Wang, Xiaoqiong; Lou, Fang; Jove, Richard; Staels, Bart; Moore, David D.; Huang, Wendong

    2015-01-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet–fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D. PMID:25961460

  16. Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells

    SciTech Connect

    Jones, Meredith B.; Tomiya, Noboru; Betenbaugh, Michael J.; Krag, Sharon S.

    2010-04-23

    Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man{sub 5}GlcNAc{sub 2}-P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man{sub 9}GlcNAc{sub 2}-P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man{sub 5}GlcNAc{sub 2}-PP-Dol through Glc{sub 1}Man{sub 9}GlcNAc{sub 2}-PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.

  17. Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis.

    PubMed

    Tan, Terrence C H; Crawford, Darrell H G; Jaskowski, Lesley A; Murphy, Therese M; Heritage, Mandy L; Subramaniam, V Nathan; Clouston, Andrew D; Anderson, Gregory J; Fletcher, Linda M

    2011-11-01

    The HFE protein plays a crucial role in the control of cellular iron homeostasis. Steatosis is commonly observed in HFE-related iron-overload disorders, and current evidence suggests a causal link between iron and steatosis. Here, we investigated the potential contribution of HFE mutations to hepatic lipid metabolism and its role in the pathogenesis of nonalcoholic fatty liver disease. Wild-type (WT) and Hfe knockout mice (Hfe(-/-)) were fed either standard chow, a monounsaturated low fat, or a high-fat, high-carbohydrate diet (HFD) and assessed for liver injury, body iron status, and markers of lipid metabolism. Despite hepatic iron concentrations and body weights similar to WT controls, Hfe(-/-) mice fed the HFD developed severe hypoxia-related steatohepatitis, Tnf-α activation, and mitochondrial respiratory complex and antioxidant dysfunction with early fibrogenesis. These features were associated with an upregulation in the expression of genes involved in intracellular lipid synthesis and trafficking, while transcripts for mitochondrial fatty acid β-oxidation and adiponectin signaling-related genes were significantly attenuated. In contrast, HFD-fed WT mice developed bland steatosis only, with no inflammation or fibrosis and no upregulation of lipogenesis-related genes. A HFD led to reduced hepatic iron in Hfe(-/-) mice compared with chow-fed mice, despite higher serum iron, decreased hepcidin expression, and increased duodenal ferroportin mRNA. In conclusion, our results demonstrate that Hfe(-/-) mice show defective hepatic-intestinal iron and lipid signaling, which predispose them toward diet-induced hepatic lipotoxicity, accompanied by an accelerated progression of injury to fibrosis. PMID:21817060

  18. [Impact of lipid metabolism parameters on the development and progression of coronary artery disease : An update].

    PubMed

    Sinning, D; Leistner, D M; Landmesser, U

    2016-06-01

    Disorders of lipid metabolism play a major role in the development and progression of coronary artery disease. Dyslipidemia therefore plays a central role in therapeutic approaches for prevention and treatment of cardiovascular events associated with coronary artery disease. Epidemiological studies have shown an association between various lipid metabolism parameters, the risk of developing coronary artery disease and progression of a pre-existing disease. In particular, increased levels of low-density lipoprotein cholesterol (LDL-C), reduced levels of HDL cholesterol (HDL-C), as well as high levels of triglycerides and increased lipoprotein(a) [Lp(a)] levels can be taken into account when assessing the risk stratification of patients for primary prevention of coronary artery disease. Lifestyle and dietary changes, intensified statin therapy and possibly the addition of ezetimibe remain the major interventions in both primary and secondary prevention of coronary artery disease, as they improve the prognosis particularly by lowering levels of LDL-C. Recently, genetic studies have contributed to extending our understanding of the relationship between lipid metabolism and coronary artery disease. A causal role for progression of coronary artery disease could be demonstrated for LDL-C, Lpa and triglyceride-rich lipoproteins (TRL), which could not be demonstrated for HDL-C in various studies. Furthermore, the effect of reduction of LDL-C by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and by the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib on cardiovascular events is currently being investigated in large clinical outcome study programs. PMID:27215419

  19. Food odors trigger an endocrine response that affects food ingestion and metabolism.

    PubMed

    Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

    2015-08-01

    Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling. PMID:25782410

  20. Effects of coumestrol on lipid and glucose metabolism as a farnesoid X receptor ligand

    SciTech Connect

    Takahashi, Miki; Kanayama, Tomohiko; Yashiro, Takuya; Kondo, Hidehiko; Murase, Takatoshi; Hase, Tadashi; Tokimitsu, Ichiro; Nishikawa, Jun-ichi; Sato, Ryuichiro

    2008-08-01

    In the course of an effort to identify novel agonists of the farnesoid X receptor (FXR), coumestrol was determined to be one such ligand. Reporter and in vitro coactivator interaction assays revealed that coumestrol bound and activated FXR. Treatment of Hep G2 cells with coumestrol stimulated the expression of FXR target genes, thereby regulating the expression of target genes of the liver X receptor and hepatocyte nuclear factor-4{alpha}. Through these actions, coumestrol is expected to exert beneficial effects on lipid and glucose metabolism.

  1. [Basic characteristics of lipid metabolism in patients with sepsis during kidney replacement therapy].

    PubMed

    Shcherbakova, L N; Iakovleva, I I; Molchanova, L V

    2003-01-01

    The changing indices of lipid metabolism were studied in patients with sepsis who were undergoing the substitution renal therapy. A sharp reduction of high-density lipoproteins (HDLP) and a higher concentration of triglyceride (TG) and of an extremely low-density lipoproteins (ELDLP) were shown in the blood plasma of such patients irrespective of a clinical outcome. The positive dynamics of TG and ELDLP concentrations as observed in the process of treatment was considered to be a good prognostication sign in sepsis and septic shock. PMID:14991975

  2. Adipose triglyceride lipase regulates lipid metabolism in dairy goat mammary epithelial cells.

    PubMed

    Li, Jun; Luo, Jun; Wang, Hui; Shi, Hengbo; Zhu, Jiangjiang; Sun, Yuting; Yu, Kang; Yao, Dawei

    2015-01-01

    Adipose triglyceride lipase (ATGL) catalyzes the initial step in the lipid lipolysis process, hydrolyzing triglyceride (TG) to produce diacylglycerol (DG) and free fatty acids (FFA). In addition, ATGL regulates lipid storage and release in adipocyte cells. However, its role in mammary gland tissue remains unclear. To assess the role of the ATGL gene in the goat mammary gland, this study analyzed the tissue distribution and expression of key genes together with lipid accumulation after knockdown of the ATGL gene. The mRNA of ATGL was highly expressed in subcutaneous adipose tissue, the lung and the mammary gland with a significant increase in expression during the lactation period compared with the dry period of the mammary gland. Knockdown of the ATGL gene in goat mammary epithelial cells (GMECs) using siRNA resulted in a significant decrease in both ATGL mRNA and protein levels. Silencing of the ATGL gene markedly increased lipid droplet accumulation and intracellular TG concentration (P<0.05), while it reduced FFA levels in GMECs (P<0.05). Additionally, the expression of HSL for lipolysis, FABP3 for fatty acid transport, PPARα for fatty acid oxidation, ADFP, BTN1A1, and XDH for milk fat formation and secretion was down-regulated (P<0.05) after knockdown of the ATGL gene, with increased expression of CD36 for fatty acid uptake (P<0.05). In conclusion, these data suggest that the ATGL gene plays an important role in triglyceride lipolysis in GMECs and provides the first experimental evidence that ATGL may be involved in lipid metabolism during lactation. PMID:25307872

  3. Developmental Ethanol Exposure Leads to Dysregulation of Lipid Metabolism and Oxidative Stress in Drosophila

    PubMed Central

    Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L.

    2014-01-01

    Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. PMID:25387828

  4. Developmental ethanol exposure leads to dysregulation of lipid metabolism and oxidative stress in Drosophila.

    PubMed

    Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L

    2014-01-01

    Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. PMID:25387828

  5. Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations.

    PubMed

    Seiva, Fábio R F; Chuffa, Luiz Gustavo A; Braga, Camila Pereira; Amorim, João Paulo A; Fernandes, Ana Angélica H

    2012-10-01

    We reported the effects of quercetin on metabolic and hormonal profile as well as serum antioxidant activities in a model of MSG (monosodium glutamate)-induced obesity. Rats were divided into 4 groups: MSG group, submitted to neonatal treatment with high doses of MSG, administrated subcutaneously during 10 days, from 2 day-old; control groups, which received the same volume of saline. After completing 30 day-old, these groups were subdivided into 4 groups: control and MSG groups treated and non-treated with quercetin at doses of 75 mg/kg body weight (i.p.) over 42 days. BW gain and food consumption were higher in MSG treated rats and quercetin significantly reduced BW by 25%. While MSG increased triacylglycerol, total cholesterol and fractions, and reduced HDL concentrations, administration of quercetin normalized HDL-cholesterol and reduced others lipids. Insulin, leptin, glucose and creatinine levels were raised in MSG-treated rats and reduced after quercetin treatment. Alanine transaminase, aspartate transaminase, lactate dehydrogenase and alkaline phosphatase activities were lower after MSG-quercetin combination compared to rats given only MSG. MSG-quercetin combination augmented total protein and urea levels as well as glutathione peroxidase and superoxide dismutase activities in contrast to MSG-treated animals. Quercetin normalized serum lipid and glucose profile and minimized the MSG-related toxic effects, which was associated to its antioxidant properties. PMID:22809473

  6. Construction of Global Acyl Lipid Metabolic Map by Comparative Genomics and Subcellular Localization Analysis in the Red Alga Cyanidioschyzon merolae

    PubMed Central

    Mori, Natsumi; Moriyama, Takashi; Toyoshima, Masakazu; Sato, Naoki

    2016-01-01

    Pathways of lipid metabolism have been established in land plants, such as Arabidopsis thaliana, but the information on exact pathways is still under study in microalgae. In contrast with Chlamydomonas reinhardtii, which is currently studied extensively, the pathway information in red algae is still in the state in which enzymes and pathways are estimated by analogy with the knowledge in plants. Here we attempt to construct the entire acyl lipid metabolic pathways in a model red alga, Cyanidioschyzon merolae, as an initial basis for future genetic and biochemical studies, by exploiting comparative genomics and localization analysis. First, the data of whole genome clustering by Gclust were used to identify 121 acyl lipid-related enzymes. Then, the localization of 113 of these enzymes was analyzed by GFP-based techniques. We found that most of the predictions on the subcellular localization by existing tools gave erroneous results, probably because these tools had been tuned for plants or green algae. The experimental data in the present study as well as the data reported before in our laboratory will constitute a good training set for tuning these tools. The lipid metabolic map thus constructed show that the lipid metabolic pathways in the red alga are essentially similar to those in A. thaliana, except that the number of enzymes catalyzing individual reactions is quite limited. The absence of fatty acid desaturation to produce oleic and linoleic acids within the plastid, however, highlights the central importance of desaturation and acyl editing in the endoplasmic reticulum, for the synthesis of plastid lipids as well as other cellular lipids. Additionally, some notable characteristics of lipid metabolism in C. merolae were found. For example, phosphatidylcholine is synthesized by the methylation of phosphatidylethanolamine as in yeasts. It is possible that a single 3-ketoacyl-acyl carrier protein synthase is involved in the condensation reactions of fatty acid

  7. Construction of Global Acyl Lipid Metabolic Map by Comparative Genomics and Subcellular Localization Analysis in the Red Alga Cyanidioschyzon merolae.

    PubMed

    Mori, Natsumi; Moriyama, Takashi; Toyoshima, Masakazu; Sato, Naoki

    2016-01-01

    Pathways of lipid metabolism have been established in land plants, such as Arabidopsis thaliana, but the information on exact pathways is still under study in microalgae. In contrast with Chlamydomonas reinhardtii, which is currently studied extensively, the pathway information in red algae is still in the state in which enzymes and pathways are estimated by analogy with the knowledge in plants. Here we attempt to construct the entire acyl lipid metabolic pathways in a model red alga, Cyanidioschyzon merolae, as an initial basis for future genetic and biochemical studies, by exploiting comparative genomics and localization analysis. First, the data of whole genome clustering by Gclust were used to identify 121 acyl lipid-related enzymes. Then, the localization of 113 of these enzymes was analyzed by GFP-based techniques. We found that most of the predictions on the subcellular localization by existing tools gave erroneous results, probably because these tools had been tuned for plants or green algae. The experimental data in the present study as well as the data reported before in our laboratory will constitute a good training set for tuning these tools. The lipid metabolic map thus constructed show that the lipid metabolic pathways in the red alga are essentially similar to those in A. thaliana, except that the number of enzymes catalyzing individual reactions is quite limited. The absence of fatty acid desaturation to produce oleic and linoleic acids within the plastid, however, highlights the central importance of desaturation and acyl editing in the endoplasmic reticulum, for the synthesis of plastid lipids as well as other cellular lipids. Additionally, some notable characteristics of lipid metabolism in C. merolae were found. For example, phosphatidylcholine is synthesized by the methylation of phosphatidylethanolamine as in yeasts. It is possible that a single 3-ketoacyl-acyl carrier protein synthase is involved in the condensation reactions of fatty acid

  8. Dietary lipid and gross energy affect protein utilization in the rare minnow Gobiocypris rarus

    NASA Astrophysics Data System (ADS)

    Wu, Benli; Xiong, Xiaoqin; Xie, Shouqi; Wang, Jianwei

    2016-07-01

    An 8-week feeding trial was conducted to detect the optimal dietary protein and energy, as well as the effects of protein to energy ratio on growth, for the rare minnow ( Gobiocypris rarus), which are critical to nutrition standardization for model fish. Twenty-four diets were formulated to contain three gross energy (10, 12.5, 15 kJ/g), four protein (20%, 25%, 30%, 35%), and two lipid levels (3%, 6%). The results showed that optimal dietary E/P was 41.7-50 kJ/g for maximum growth in juvenile rare minnows at 6% dietary crude lipid. At 3% dietary lipid, specific growth rate (SGR) increased markedly when E/P decreased from 62.5 kJ/g to 35.7 kJ/g and gross energy was 12.5 kJ/g, and from 75 kJ/g to 42.9 kJ/g when gross energy was 15.0 kJ/g. The optimal gross energy was estimated at 12.5 kJ/g and excess energy decreased food intake and growth. Dietary lipid exhibited an apparent protein-sparing effect. Optimal protein decreased from 35% to 25%-30% with an increase in dietary lipid from 3% to 6% without adversely effecting growth. Dietary lipid level affects the optimal dietary E/P ratio. In conclusion, recommended dietary protein and energy for rare minnow are 20%-35% and 10-12.5 kJ/g, respectively.

  9. Dietary lipid and gross energy affect protein utilization in the rare minnow Gobiocypris rarus

    NASA Astrophysics Data System (ADS)

    Wu, Benli; Xiong, Xiaoqin; Xie, Shouqi; Wang, Jianwei

    2015-10-01

    An 8-week feeding trial was conducted to detect the optimal dietary protein and energy, as well as the effects of protein to energy ratio on growth, for the rare minnow (Gobiocypris rarus), which are critical to nutrition standardization for model fish. Twenty-four diets were formulated to contain three gross energy (10, 12.5, 15 kJ/g), four protein (20%, 25%, 30%, 35%), and two lipid levels (3%, 6%). The results showed that optimal dietary E/P was 41.7-50 kJ/g for maximum growth in juvenile rare minnows at 6% dietary crude lipid. At 3% dietary lipid, specific growth rate (SGR) increased markedly when E/P decreased from 62.5 kJ/g to 35.7 kJ/g and gross energy was 12.5 kJ/g, and from 75 kJ/g to 42.9 kJ/g when gross energy was 15.0 kJ/g. The optimal gross energy was estimated at 12.5 kJ/g and excess energy decreased food intake and growth. Dietary lipid exhibited an apparent protein-sparing effect. Optimal protein decreased from 35% to 25%-30% with an increase in dietary lipid from 3% to 6% without adversely effecting growth. Dietary lipid level affects the optimal dietary E/P ratio. In conclusion, recommended dietary protein and energy for rare minnow are 20%-35% and 10-12.5 kJ/g, respectively.

  10. Free fatty acids chain length distribution affects the permeability of skin lipid model membranes.

    PubMed

    Uchiyama, Masayuki; Oguri, Masashi; Mojumdar, Enamul H; Gooris, Gert S; Bouwstra, Joke A

    2016-09-01

    The lipid matrix in the stratum corneum (SC) plays an important role in the barrier function of the skin. The main lipid classes in this lipid matrix are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The aim of this study was to determine whether a variation in CER subclass composition and chain length distribution of FFAs affect the permeability of this matrix. To examine this, we make use of lipid model membranes, referred to as stratum corneum substitute (SCS). We prepared SCS containing i) single CER subclass with either a single FFA or a mixture of FFAs and CHOL, or ii) a mixture of various CER subclasses with either a single FFA or a mixture of FFAs and CHOL. In vitro permeation studies were performed using ethyl-p-aminobenzoic acid (E-PABA) as a model drug. The flux of E-PABA across the SCS containing the mixture of FFAs was higher than that across the SCS containing a single FA with a chain length of 24 C atoms (FA C24), while the E-PABA flux was not effected by the CER composition. To select the underlying factors for the changes in permeability, the SCSs were examined by Fourier transform infrared spectroscopy (FTIR) and Small angle X-ray scattering (SAXS). All lipid models demonstrated a similar phase behavior. However, when focusing on the conformational ordering of the individual FFA chains, the shorter chain FFA (with a chain length of 16, 18 or 20 C atoms forming only 11m/m% of the total FFA level) had a higher conformational disordering, while the conformational ordering of the chains of the CER and FA C24 and FA C22 hardly did not change irrespective of the composition of the SCS. In conclusion, the conformational mobility of the short chain FFAs present only at low levels in the model SC lipid membranes has a great impact on the permeability of E-PABA. PMID:27287726

  11. Effect of in utero exposure of Toddy (coconut palm wine) on liver function and lipid metabolism in rat fetuses.

    PubMed

    Lal, J J; Sreeranjit Kumar, C V; Suresh, M V; Indira, M; Vijayammal, P L

    1998-01-01

    The objective of this study was to determine the effects of a country liquor Toddy (Coconut palm wine) and an equivalent quantity of ethanol on liver function and lipid metabolism in utero. Female albino rats with an average weight of 125 +/- 5 g were exposed to Toddy from coconut palm (24.5 ml/kg body weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before conception and during pregnancy. On day 13 and day 19 of gestation, altered liver function and hyperlipidemia were seen in the fetuses of both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase, aldehyde dehydrogenase, glutamic oxaloacetic transaminase (aspartate amino transferase (GOT)), glutamic pyruvic transaminase (alanine amino transferase (GPT)). Hyperlipidemia was caused by increased biosynthesis since the incorporation of 14C acetate into lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated. Toddy treated fetuses were more severely affected than those exposed to an equivalent quantity of ethanol. Toddy seemed to potentiate the toxicity induced by alcohol suggesting the role of non alcoholic components. Hepatic functions of the day 13 fetuses were effected to a lesser degree than those in the day 19 hepatic liver. PMID:9950082

  12. Association of genes of lipid metabolism with measures of subclinical cardiovascular disease in the Diabetes Heart Study

    PubMed Central

    Burdon, K; Langefeld, C; Beck, S; Wagenknecht, L; Carr, J; Freedman, B; Herrington, D; Bowden, D

    2005-01-01

    Background: Dyslipidaemia is a well known risk factor for cardiovascular disease (CVD). Lipid metabolism is affected by a range of genes and proteins. This study investigated whether some of these genes are associated with measures of subclinical CVD. Methods: Polymorphisms of paraoxonase 1 and 2, cholesteryl ester transfer protein, hepatic lipase, and lipoprotein lipase were tested for associations with measures of subclinical CVD including carotid intima-media thickness measured by B-mode ultrasound and carotid and coronary arterial calcification measured by computed tomography. Analysis was performed in 620 European American participants in the Diabetes Heart Study, 83% of whom had type 2 diabetes mellitus. Associations of genotypes with subclinical CVD were tested by computing a series of generalised estimating equations. Results: The Q192R variant of paraoxonase 1 and rs285 of lipoprotein lipase were associated with carotid artery calcium (p values = 0.002 and 0.005, respectively). Paraoxonase 2 S311C was associated with coronary artery calcium (p value = 0.037). Conclusions: There is evidence for modest, but significant, association of multiple single nucleotide polymorphisms in lipid genes with measures of subclinical CVD. PMID:16141008

  13. Retinoid acid-related orphan receptor γ, RORγ, participates in diurnal transcriptional regulation of lipid metabolic genes

    PubMed Central

    Takeda, Yukimasa; Kang, Hong Soon; Lih, Fred B.; Jiang, Hongfeng; Blaner, William S.; Jetten, Anton M.

    2014-01-01

    The hepatic circadian clock plays a pivotal role in regulating major aspects of energy homeostasis and lipid metabolism. In this study, we show that RORγ robustly regulates the rhythmic expression of several lipid metabolic genes, including the insulin-induced gene 2a, Insig2a, elongation of very long chain fatty acids-like 3, Elovl3 and sterol 12α-hydroxylase, Cyp8b1, by enhancing their expression at ZT20-4. The time-dependent increase in their expression correlates with the rhythmic expression pattern of RORγ. The enhanced recruitment of RORγ to ROREs in their promoter region, increased histone acetylation, and reporter and mutation analysis support the concept that RORγ regulates the transcription of several lipid metabolic genes directly by binding ROREs in their promoter regulatory region. Consistent with the disrupted expression of a number of lipid metabolic genes, loss of RORγ reduced the level of several lipids in liver and blood in a ZT-preferred manner. Particularly the whole-body bile acid pool size was considerably reduced in RORγ−/− mice in part through its regulation of several Cyp genes. Similar observations were made in liver-specific RORγ-deficient mice. Altogether, our study indicates that RORγ functions as an important link between the circadian clock and the transcriptional regulation of several metabolic genes. PMID:25143535

  14. Tissue lipid metabolism and hepatic metabolomic profiling in response to supplementation of fermented cottonseedmeal in the diets of broiler chickens*

    PubMed Central

    Nie, Cun-xi; Zhang, Wen-ju; Wang, Yong-qiang; Liu, Yan-feng; Ge, Wen-xia; Liu, Jian-cheng

    2015-01-01