WorldWideScience

Sample records for brain lipid metabolism

  1. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    OpenAIRE

    Lam, Tony K.T.

    2007-01-01

    Brain glucose-sensing mechanisms are implicated in the regulation of feeding behavior and hypoglycemic-induced hormonal counter-regulation. This commentary discusses recent findings indicating that the brain senses glucose to regulate both hepatic glucose and lipid production.

  2. Effect of cadmium on lipid metabolism of brain

    International Nuclear Information System (INIS)

    Gulati, S.; Gill, K.D.; Nath, R.

    1987-01-01

    The effect of early postnatal cadmium exposure on the in vivo incorporation of (1- 14 C) sodium acetate into various lipid classes of the weanling rat brain was studied. A stimulated incorporation of the label was observed in total lipids, phospholipids, cholesterol, cerebrosides and sulphatides of the brain of Cd-exposed animals compared to controls. (author)

  3. Effect of cadmium on lipid metabolism of brain. In vivo incorporation of labelled acetate into lipids

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, S; Gill, K D; Nath, R

    1987-01-01

    The effect of early postnatal cadmium exposure on the in vivo incorporation of (1-/sup 14/C) sodium acetate into various lipid classes of the weanling rat brain was studied. A stimulated incorporation of the label was observed in total lipids, phospholipids, cholesterol, cerebrosides and sulphatides of the brain of Cd-exposed animals compared to controls.

  4. Impact of Estrogens and Estrogen Receptor Alpha (ESR1) in Brain Lipid Metabolism.

    Science.gov (United States)

    Morselli, Eugenia; de Souza Santos, Roberta; Gao, Su; Ávalos, Yenniffer; Criollo, Alfredo; Palmer, Biff F; Clegg, Deborah J

    2018-03-06

    Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system.

  5. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    Science.gov (United States)

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. Published by Oxford University Press on behalf of the

  6. Effect of ethanol in utero on higher nervous activity and protein and lipid metabolism in the rat brain

    International Nuclear Information System (INIS)

    Zabbudovskii, A.L.; Zhulin, V.V.

    1985-01-01

    The authors study parameters of protein phosphorylation and glycoprotein and phospholipid synthesis in the neocortex and hippocampus of adult rats and compare the findings with the results of an investigation of formation and preservation of defensive conditioned reflexes. The pattern of changes in these metabolic parameters are studied in response to stress. For the biochemical tests, the animals were lightly anesthetized with ether and injected with a mixture of (P 32)-orthophosphate and (H 3)-fucose. Phospholipids were identified with molybdate reagent and radioactivity of the protein digest and lipids was measured in Bray's scintillator. The study shows that the use of stress brought metabolic differences between the brain of the experimental and control rats more clearly to light

  7. Acyl-Lipid Metabolism

    Science.gov (United States)

    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

  8. Metabolic Profiles of Brain Metastases

    Directory of Open Access Journals (Sweden)

    Tone F. Bathen

    2013-01-01

    Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

  9. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Directory of Open Access Journals (Sweden)

    Angeliki Lyssimachou

    Full Text Available Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT, which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR and peroxisome proliferator-activated receptor gamma (PPARγ. In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  10. The Mammalian “Obesogen” Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G.; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C. Marisa R.; Teixeira, Catarina; Castro, L. Filipe C.; Santos, Miguel M.

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an “obesogenic” phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound. PMID:26633012

  11. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C Marisa R; Teixeira, Catarina; Castro, L Filipe C; Santos, Miguel M

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  12. Lipid metabolism in cancer cachexia.

    OpenAIRE

    Mulligan, H. D.; Beck, S. A.; Tisdale, M. J.

    1992-01-01

    The effect of cancer cachexia on the oxidative metabolism of lipids has been studied in mice transplanted either with the MAC16 adenocarcinoma, which induces profound loss of body weight and depletion of lipid stores, or the MAC13 adenocarcinoma, which is the same histological type, but which grows without an effect on host body weight or lipid stores. While oxidation of D-[U-14C]glucose did not differ between animals bearing tumours of either type and non-tumour bearing controls, oxidation o...

  13. 18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of rats; the influence of time after injection, depressed lipid metabolism and glucose-insulin

    International Nuclear Information System (INIS)

    Kasalicky, J.; Konopkova, M.; Melichar, F.

    2001-01-01

    To study the effect of lipid depressing drugs on 18 FDG myocardial concentration. The changes of 18 FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. 5.55 MBq of 18 FDG were administered to Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following intravenous injection and the radioactivity concentration (cpm/g of tissue) in relation to injected cpm was determined in a well crystal adjusted to 511 KeV in order to check the time of maximal 18 FDG tissue uptake. The radioactivity in myocardium, skeletal muscle and brain in intact animals was compared with that of rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately before 18 FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before 18 FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before 18 FDG). The animals were killed 45 minutes following 18 FDG injection. Tyloxapol and acipimox significantly elevated myocardial 18 FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in 18 FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in 18 FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of 18 FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. The highest 18 FDG uptake in myocardium could be achieved by depressing the lipid metabolism and not by administration of glucose with insulin only. A marked increase in glucose accumulation in myocardium is not possible without previous shift from the utilisation of fatty acids. This finding is fully in agreement with present knowledge about energetic metabolism of myocardium. (author)

  14. Targeting Lipid Metabolic Reprogramming as Anticancer Therapeutics

    OpenAIRE

    Cha, Ji-Young; Lee, Ho-Jae

    2016-01-01

    Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells c...

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

    Science.gov (United States)

    Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

    2016-02-01

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

  16. Lipid transport and human brain development.

    Science.gov (United States)

    Betsholtz, Christer

    2015-07-01

    How the human brain rapidly builds up its lipid content during brain growth and maintains its lipids in adulthood has remained elusive. Two new studies show that inactivating mutations in MFSD2A, known to be expressed specifically at the blood-brain barrier, lead to microcephaly, thereby offering a simple and surprising solution to an old enigma.

  17. Unraveling lipid metabolism in lipid-dependent pathogenic Malassezia yeasts

    OpenAIRE

    Celis Ramirez, A.M.

    2017-01-01

    Malassezia yeasts are lipid-dependent fungal species that are common members of the human and animal skin microbiota. The lipid-dependency is a crucial trait in the adaptation process to grow on the skin but also plays a role in their pathogenic life style. Malassezia species can cause several skin infections like dandruff or seborrheic dermatitis but also bloodstream infections. Understanding the lipid metabolism in Malassezia is essential to understand its life style as skin commensal and p...

  18. Computational Modeling of Lipid Metabolism in Yeast

    Directory of Open Access Journals (Sweden)

    Vera Schützhold

    2016-09-01

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

  19. Metabolism of lipids in Epidermophyton floccosum

    Energy Technology Data Exchange (ETDEWEB)

    Chopra, A; Khuller, G K [Post-Graduate Inst. of Medical Education and Research, Chandigarh (India)

    1981-03-01

    Metabolism of major lipids in E. floccosum was studied with /sup 14/C-acetate as a precursor. Among the phosphatides, phosphatidylcholine exhibited the maximum rate of synthesis and degradation, followed by phosphatidylethanolamine and phosphatidylserine. These phospholipids appear to exist in two pools, one metabolically more active than the other. In neutral lipids, maximum uptake was observed in triglycerides, followed by free fatty acids, diglycerides and monoglycerides. However, on chase of the labelled lipids, a continuous synthesis of all neutral lipid fractions was observed suggesting a recycling of the labelled carbon.

  20. [Changes of neurotransmitter, lipid peroxide and their metabolic related enzyme activities in the brain of rats exposed to noise and vitamin E].

    Science.gov (United States)

    Sakuma, N

    1984-09-01

    Effects of noise on locomotor activities were analysed in rat. In addition, changes in lipid peroxide (LPX), their metabolic related enzyme activities, and neurotransmitter in the rat brain due to noise exposure and the effects of vitamin E on the rats were studied. The results obtained were as follows: After white noise exposure of 95 dB (A), the locomotor activities of rat increased. But 3 weeks after noise exposure, the activities began to decrease. LPX and glutathione peroxidase (GSH-Px) activities in hypothalamus and cortex increased at the 14th day after noise exposure or at the 21st day after noise exposure. Superoxide dismutase (SOD) activities increased in hippocampus at the 4th day after noise exposure, and decreased in midbrain and thalamus at the 14th day and the 21th day after noise exposure. Norepinephrine (NE) increased in hypothalamus at the 1st day, the 2nd day and the 7th day after noise exposure, and increased in striatum at the 7th day after noise exposure, in cortex at the 4th day and the 7th day after exposure. At the 14th day after noise exposure, NE decreased in cerebellum, in medulla and pons, in midbrain and thalamus, and in cortex. In cortex NE also decreased at the 21st day after noise exposure. Serotonin increased in hypothalamus and in midbrain and thalamus at the 1st and 4th day after noise exposure, and increased in striatum at the 7th day after noise exposure. Decrease in serotonin was observed in cerebellum at the 14th day after noise exposure. Vitamin E decreased LPX in rat brain and the liver.

  1. Lipid Metabolism, Apoptosis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Chunfa Huang

    2015-01-01

    Full Text Available 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.

  2. ER Stress and Lipid Metabolism in Adipocytes

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    Beth S. Zha

    2012-01-01

    Full Text Available The role of endoplasmic reticulum (ER stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

  3. Normal and abnormal lipid and lipoprotein metabolism

    African Journals Online (AJOL)

    2009-03-20

    Mar 20, 2009 ... This article focuses on lipid and lipoprotein metabolism and introduces a range of genetic ... spherical structures that are suspended in the plasma and whose ..... atherosclerosis. Table II suggests a simple classification of.

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

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    Pablo Esteban Morales

    2017-01-01

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

  5. Impact of Hypoglycemia on Brain Metabolism During Diabetes.

    Science.gov (United States)

    Rehni, Ashish K; Dave, Kunjan R

    2018-04-10

    Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy, because it induces metabolic alterations in the brain. Metabolic alterations are one of the central mechanisms mediating hypoglycemia-related functional changes in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple metabolic pathways, and exposure to hypoglycemia increases consumption of alternate respiratory substrates such as ketone bodies, glycogen, and monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia-induced metabolic alterations in the brain in glucose counterregulation, uptake, utilization and metabolism, cellular respiration, amino acid and lipid metabolism, and the significance of other sources of energy. The present review summarizes information on hypoglycemia-induced metabolic changes in the brain of diabetic and non-diabetic subjects and the manner in which they may affect brain function.

  6. Peroxisomes, lipid metabolism, and human disease

    NARCIS (Netherlands)

    Wanders, R. J.

    2000-01-01

    In the past few years, much has been learned about the metabolic functions of peroxisomes. These studies have shown that peroxisomes play a major role in lipid metabolism, including fatty acid beta-oxidation, etherphospholipid biosynthesis, and phytanic acid alpha-oxidation. This article describes

  7. Serotonin metabolism in rat brain

    International Nuclear Information System (INIS)

    Schutte, H.H.

    1976-01-01

    The metabolism of serotonin in rat brain was studied by measuring specific activities of tryptophan in plasma and of serotonin, 5-hydroxyindole acetic acid and tryptophan in the brain after intravenous injection of tritiated tryptophan. For a detailed analysis of the specific activities, a computer simulation technique was used. It was found that only a minor part of serotonin in rat brain is synthesized from tryptophan rapidly transported from the blood. It is suggested that the brain tryptophan originates from brain proteins. It was also found that the serotonin in rat brain is divided into more than one metabolic compartment

  8. microRNAs and lipid metabolism

    Science.gov (United States)

    Aryal, Binod; Singh, Abhishek K.; Rotllan, Noemi; Price, Nathan; Fernández-Hernando, Carlos

    2017-01-01

    Purpose of review Work over the last decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism. Recent findings A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the last two years has identified additional functions of miR-33 including the regulation of macrophage activation and mitochondrial metabolism. Moreover, it has recently been shown that miR-33 regulates vascular homeostasis and cardiac adaptation in response to pressure overload. In addition to miR-33 and miR-122, recent GWAS have identified single nucleotide polymorphisms (SNP) in the proximity of miRNAs genes associated with abnormal levels of circulating lipids in humans. Several of these miRNA, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the low-density lipoprotein receptor (LDLR) and the ATP-binding cassette A1 (ABCA1). Summary microRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field highlighting the novel mechanisms by which miR-33 controls lipid metabolism and atherogenesis and the identification of novel miRNAs that regulate LDL metabolism. Finally, we summarize the recent findings that identified miR-33 as an important non-coding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism. PMID:28333713

  9. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  10. Brain docosahexaenoic acid uptake and metabolism.

    Science.gov (United States)

    Lacombe, R J Scott; Chouinard-Watkins, Raphaël; Bazinet, Richard P

    2018-02-08

    Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the brain where it serves to regulate several important processes and, in addition, serves as a precursor to bioactive mediators. Given that the capacity of the brain to synthesize DHA locally is appreciably low, the uptake of DHA from circulating lipid pools is essential to maintaining homeostatic levels. Although, several plasma pools have been proposed to supply the brain with DHA, recent evidence suggests non-esterified-DHA and lysophosphatidylcholine-DHA are the primary sources. The uptake of DHA into the brain appears to be regulated by a number of complementary pathways associated with the activation and metabolism of DHA, and may provide mechanisms for enrichment of DHA within the brain. Following entry into the brain, DHA is esterified into and recycled amongst membrane phospholipids contributing the distribution of DHA in brain phospholipids. During neurotransmission and following brain injury, DHA is released from membrane phospholipids and converted to bioactive mediators which regulate signaling pathways important to synaptogenesis, cell survival, and neuroinflammation, and may be relevant to treating neurological diseases. In the present review, we provide a comprehensive overview of brain DHA metabolism, encompassing many of the pathways and key enzymatic regulators governing brain DHA uptake and metabolism. In addition, we focus on the release of non-esterified DHA and subsequent production of bioactive mediators and the evidence of their proposed activity within the brain. We also provide a brief review of the evidence from post-mortem brain analyses investigating DHA levels in the context of neurological disease and mood disorder, highlighting the current disparities within the field. Copyright © 2017. Published by Elsevier Ltd.

  11. Exercise Intensity Modulation of Hepatic Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Fábio S. Lira

    2012-01-01

    Full Text Available Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL, ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge.

  12. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. The Mediator Complex and Lipid Metabolism.

    Science.gov (United States)

    Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

    2013-03-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

  14. Insights into Brain Glycogen Metabolism

    Science.gov (United States)

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-01-01

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  15. CREBH Regulates Systemic Glucose and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Yoshimi Nakagawa

    2018-05-01

    Full Text Available The cyclic adenosine monophosphate (cAMP-responsive element-binding protein H (CREBH, encoded by CREB3L3 is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet. A deficiency of CREBH in mice leads to severe hypertriglyceridemia, fatty liver, and atherosclerosis. CREBH, in synergy with peroxisome proliferator-activated receptor α (PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis including glucose and lipid metabolism. CREBH binds to and functions as a co-activator for both PPARα and liver X receptor alpha (LXRα in regulating gene expression of lipid metabolism. Therefore, CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine.

  16. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    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.

  17. Relation between plasma and brain lipids

    DEFF Research Database (Denmark)

    Wellington, Cheryl L; Frikke-Schmidt, Ruth

    2016-01-01

    : Plasma levels of traditional lipids and lipoproteins are not consistently associated with risk of dementia even though low plasma levels of apolipoprotein E, through unknown mechanisms, robustly predict future dementia. Experimental evidence suggests neuroprotective roles of several brain...... and cerebrospinal fluid apolipoproteins. Whether plasma levels of apolipoprotein E, or any other apolipoprotein with possible central nervous system and/or blood-brain barrier functions (apolipoproteins J, A-I, A-II, A-IV, D, C-I, and C-III) may become accessible biomarker components that improve risk prediction...

  18. The role of the kidney in lipid metabolism

    DEFF Research Database (Denmark)

    Moestrup, Søren K; Nielsen, Lars Bo

    2005-01-01

    PURPOSE OF REVIEW: Cellular uptake of plasma lipids is to a large extent mediated by specific membrane-associated proteins that recognize lipid-protein complexes. In the kidney, the apical surface of proximal tubules has a high capacity for receptor-mediated uptake of filtered lipid-binding plasma...... proteins. We describe the renal receptor system and its role in lipid metabolism in health and disease, and discuss the general effect of the diseased kidney on lipid metabolism. RECENT FINDINGS: Megalin and cubilin are receptors in the proximal tubules. An accumulating number of lipid......-binding and regulating proteins (e.g. albumin, apolipoprotein A-I and leptin) have been identified as ligands, suggesting that their receptors may directly take up lipids in the proximal tubules and indirectly affect plasma and tissue lipid metabolism. Recently, the amnionless protein was shown to be essential...

  19. Spastin binds to lipid droplets and affects lipid metabolism.

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    Chrisovalantis Papadopoulos

    2015-04-01

    Full Text Available 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.

  20. Unraveling lipid metabolism in lipid-dependent pathogenic Malassezia yeasts

    NARCIS (Netherlands)

    Celis Ramirez, A.M.

    2017-01-01

    Malassezia yeasts are lipid-dependent fungal species that are common members of the human and animal skin microbiota. The lipid-dependency is a crucial trait in the adaptation process to grow on the skin but also plays a role in their pathogenic life style. Malassezia species can cause several skin

  1. Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

    Science.gov (United States)

    Martín, Virginia; Fabelo, Noemí; Santpere, Gabriel; Puig, Berta; Marín, Raquel; Ferrer, Isidre; Díaz, Mario

    2010-01-01

    Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

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

    Science.gov (United States)

    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.

  3. Assessment of lipid metabolism in thyroid dysfunction

    Directory of Open Access Journals (Sweden)

    V. G. Kadzharyan

    2014-02-01

    Full Text Available 1. Actuality According to WHO Thyroid dysfunction is one of the most prevalent in humans and is one of the risk factors of cardiovascular diseases. Hypothyroidism affects the mechanisms of potentiation of cardiovascular risk factors, suggesting the need to study the level of the blood lipids in all patients with thyroid dysfunction. 2. The purpose of this study. To define features of lipid metabolism, depending on the functional state of the thyroid gland. 3. Material and methods. The study included 95 patients, mean age was 49,8 ± 12,9 years. 74 of them were women (78% and 21 - men (22%. In accordance with the purpose of the work 3 groups of subjects were formed. I-st group - 35 patients with hypothyroidism, mean age 52,5 ± 10,3 years, II-nd group - 37 patients with hyperthyroidism, the average age was 45,1 ± 13 years, III (control group - 23 patients with euthyroid, mean age 53,9 ± 14,8 years. Levels of TSH, triiodothyronine, thyroxine, microsomal antibodies to thyroglobulin and thyroid peroxidase were evaluated for total and biochemical analysis. To determine the type of hyperlipoproteinemia Fredrickson, 1967 recommendations were used. 4. Results of the study Lipid profile parameters in the I-st group compared with the control were even higher. Cholesterol increased up to 6,9% (p <0,005, Tg - 8,6% (p <0,005, β -DP - 6,8% (p <0,5, in comparison with the II-nd: cholesterol - 56% (p <0,005, TG - 55% (p <0,005 and β-PL 44% (p <0.5. In group II rates were lower than in the III- cholesterol - 8% (p <0,005, Tg 8,3% (p <0,005 and β-PL 6,5% (p <0,5. Patients from the I-st group had the following distribution of hyperlipidemia (Fredrickson, 1967.: I type - 10 patients (29%; IIb type - 15 subjects (43%; IIa type - 9 subjects (26%; IV type - 1 patient (2%. The correlation dependence of TSH and cholesterol (r = +0,37, p <0,05, TG (r = +0,25, p <0,05, β-PL (r = +0,74, p <0.05, TG AT (r = +0,55, p <0,05, the level of bilirubin (r = +0,29, p <0

  4. Carboxylesterases in lipid metabolism: from mouse to human

    Directory of Open Access Journals (Sweden)

    Jihong Lian

    2017-07-01

    Full Text Available ABSTRACT Mammalian carboxylesterases hydrolyze a wide range of xenobiotic and endogenous compounds, including lipid esters. Physiological functions of carboxylesterases in lipid metabolism and energy homeostasis in vivo have been demonstrated by genetic manipulations and chemical inhibition in mice, and in vitro through (overexpression, knockdown of expression, and chemical inhibition in a variety of cells. Recent research advances have revealed the relevance of carboxylesterases to metabolic diseases such as obesity and fatty liver disease, suggesting these enzymes might be potential targets for treatment of metabolic disorders. In order to translate pre-clinical studies in cellular and mouse models to humans, differences and similarities of carboxylesterases between mice and human need to be elucidated. This review presents and discusses the research progress in structure and function of mouse and human carboxylesterases, and the role of these enzymes in lipid metabolism and metabolic disorders.

  5. Metabolic control by S6 kinases depends on dietary lipids.

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    Tamara R Castañeda

    Full Text Available Targeted deletion of S6 kinase (S6K 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and this effect is not dependent upon amino acids. Comparison of male mice lacking S6K1 and 2 (S6K-dko with wt controls showed that S6K-dko mice are protected against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice fed a high-fat diet had increased energy expenditure, improved glucose tolerance, lower fat mass gain, and changes in markers of lipid metabolism. Importantly, however, these metabolic phenotypes were dependent upon dietary lipids, with no such effects observed in S6K-dko mice fed a fat-free diet. These changes appear to be mediated via modulation of cellular metabolism in skeletal muscle, as shown by the expression of genes involved in energy metabolism. Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism.

  6. Brain Ceramide Metabolism in the Control of Energy Balance

    Directory of Open Access Journals (Sweden)

    Céline Cruciani-Guglielmacci

    2017-10-01

    Full Text Available The regulation of energy balance by the central nervous system (CNS is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D. Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate, the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance.

  7. Hepatitis C Virus Life Cycle and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Costin-Ioan Popescu

    2014-12-01

    Full Text Available Hepatitis C Virus (HCV infects over 150 million people worldwide. In most cases HCV infection becomes chronic, causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. HCV affects the cholesterol homeostasis and at the molecular level, every step of the virus life cycle is intimately connected to lipid metabolism. In this review, we present an update on the lipids and apolipoproteins that are involved in the HCV infectious cycle steps: entry, replication and assembly. Moreover, the result of the assembly process is a lipoviroparticle, which represents a peculiarity of hepatitis C virion. This review illustrates an example of an intricate virus-host interaction governed by lipid metabolism.

  8. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost Munk; Tvede, Michael

    2013-01-01

    and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

  9. Gut microbiome and lipid metabolism : from associations to mechanisms

    NARCIS (Netherlands)

    Wang, Zheng; Koonen, Debby; Hofker, Marten; Fu, Jingyuan

    Purpose of review The gut microbiome has now been convincingly linked to human metabolic health but the underlying causality and mechanisms remain poorly understood. This review focuses on the recent progress in establishing the associations between gut microbiome species and lipid metabolism in

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

    Energy Technology Data Exchange (ETDEWEB)

    Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

    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

  11. Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.

    Science.gov (United States)

    Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

    2015-04-07

    Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

  12. Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis

    Science.gov (United States)

    Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

    2015-01-01

    Metabolic homeostasis is regulated by the brain, whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipids levels. Importantly, this function of metabolic learning requires not only the mushroom body but the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis. PMID:25848677

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

    Directory of Open Access Journals (Sweden)

    Rosa L. Miyares

    2014-07-01

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

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

    Science.gov (United States)

    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. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Effects of environmental stressors on lipid metabolism in aquatic invertebrates.

    Science.gov (United States)

    Lee, Min-Chul; Park, Jun Chul; Lee, Jae-Seong

    2018-07-01

    Lipid metabolism is crucial for the survival and propagation of the species, since lipids are an essential cellular component across animal taxa for maintaining homeostasis in the presence of environmental stressors. This review aims to summarize information on the lipid metabolism under environmental stressors in aquatic invertebrates. Fatty acid synthesis from glucose via de novo lipogenesis (DNL) pathway is mostly well-conserved across animal taxa. The structure of free fatty acid (FFA) from both dietary and DNL pathway could be transformed by elongase and desaturase. In addition, FFA can be stored in lipid droplet as triacylglycerol, upon attachment to glycerol. However, due to the limited information on both gene and lipid composition, in-depth studies on the structural modification of FFA and their storage conformation are required. Despite previously validated evidences on the disturbance of the normal life cycle and lipid homeostasis by the environmental stressors (e.g., obesogens, salinity, temperature, pCO 2 , and nutrients) in the aquatic invertebrates, the mechanism behind these effects are still poorly understood. To overcome this limitation, omics approaches such as transcriptomic and proteomic analyses have been used, but there are still gaps in our knowledge on aquatic invertebrates as well as the lipidome. This paper provides a deeper understanding of lipid metabolism in aquatic invertebrates. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Intermittent metabolic switching, neuroplasticity and brain health

    Science.gov (United States)

    Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

    2018-01-01

    During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. LIPID RATIOS: AS A PREDICTOR OF METABOLIC SYNDROME

    OpenAIRE

    Pushpa; Mahadeva; Raghunath; Hamsa

    2015-01-01

    Metabolic Syndrome (MetS) is a group of disorders characterized by obesity, hypertension, glucose intolerance and dyslipidemia. This study was undertaken to determine whether lipid ratios calculated by routinely measured lipid profile can be used as predictor of MetS and which among them could be used as better predictor. MATERIALS AND METHODS Data consisting of anthropometric measurements, blood pressure, laboratory parameters like fasting blood sugar, Total Cholesterol (TC), Triglycer...

  19. THE ROLE OF GROWTH HORMONE IN LIPID METABOLISM

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Dewi Ratnayanti

    2013-04-01

    Full Text Available Growth hormone (GH is one of the hormones that regulate metabolism, including lipid metabolism. GH can regulate the amount of fat in the tissue and also the level of lipid profile. Growth hormone affects the lipid in the tissue and blood by modulating the lipid metabolism, especially through the regulation of synthesis, excretion and breakdown of internal lipids. Research showed that GH could consistently lower the level of total cholesterol and LDL, whereas its effect on triglyceride and HDL level showed varying results. Growth hormone induces lypolisis by stimulating the activity of HSL and LPL and thereby influenced the triglyceride level and tissue fat storage. Cholesterol and lipoprotein levels are controlled by regulating the synthesis of cholesterol by lowering the activity of HMGCoA reductase. The excretion of cholesterol through the bile is also enhanced by stimulating the activity of enzymes C7?OH. The breakdown of VLDL and LDL are enhanced by increasing the expression of LDL receptor and ApoE as well as affecting the editing of mRNA ApoB100. Increase activity of LPL is also known to be the important factor in the HDL metabolism

  20. Insulin-resistance and lipids metabolism in women at menopause

    Directory of Open Access Journals (Sweden)

    Marina Dmitrуina Gresko

    2018-01-01

    Full Text Available The article describes lipid metabolism in women during premenopausal and considered their relationship with the level of insulin sensitivity and abdominal obesity. Examined 20 women aged 46-48 years, with fixed transition to pre-menopause on the bases of menstrual cycle dysfunction or amenorrhea during a year as well as a decrease of visualized follicular reserve according to the results of ultrasonic examination of the organs of the small pelvis, were involved into investigation. Body mass increase with abdominal obese formation and disorders of the lipid metabolism against a background of insulin resistance is observed in women during pre-menopause against a background of sexual hormones deficiency.

  1. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    OpenAIRE

    Kleinridders, Andr?; Ferris, Heather A.; Cai, Weikang; Kahn, C. Ronald

    2014-01-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in t...

  2. Lipidomics: Novel insight into the biochemical mechanism of lipid metabolism and dysregulation-associated disease.

    Science.gov (United States)

    Zhao, Ying-Yong; Miao, Hua; Cheng, Xian-Long; Wei, Feng

    2015-10-05

    The application of lipidomics, after genomics, proteomics and metabolomics, offered largely opportunities to illuminate the entire spectrum of lipidome based on a quantitative or semi-quantitative level in a biological system. When combined with advances in proteomics and metabolomics high-throughput platforms, lipidomics provided the opportunity for analyzing the unique roles of specific lipids in complex cellular processes. Abnormal lipid metabolism was demonstrated to be greatly implicated in many human lifestyle-related diseases. In this review, we focused on lipidomic applications in brain injury disease, cancer, metabolic disease, cardiovascular disease, respiratory disease and infectious disease to discover disease biomarkers and illustrate biochemical metabolic pathways. We also discussed the analytical techniques, future perspectives and potential problems of lipidomic applications. The application of lipidomics in disease biomarker discovery provides the opportunity for gaining novel insights into biochemical mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Analysis of lipid raft molecules in the living brain slices.

    Science.gov (United States)

    Kotani, Norihiro; Nakano, Takanari; Ida, Yui; Ito, Rina; Hashizume, Miki; Yamaguchi, Arisa; Seo, Makoto; Araki, Tomoyuki; Hojo, Yasushi; Honke, Koichi; Murakoshi, Takayuki

    2017-08-24

    Neuronal plasma membrane has been thought to retain a lot of lipid raft components which play important roles in the neural function. Although the biochemical analyses of lipid raft using brain tissues have been extensively carried out in the past 20 years, many of their experimental conditions do not coincide with those of standard neuroscience researches such as neurophysiology and neuropharmacology. Hence, the physiological methods for lipid raft analysis that can be compatible with general neuroscience have been required. Herein, we developed a system to physiologically analyze ganglioside GM1-enriched lipid rafts in brain tissues using the "Enzyme-Mediated Activation of Radical Sources (EMARS)" method that we reported (Kotani N. et al. Proc. Natl. Acad. Sci. U S A 105, 7405-7409 (2008)). The EMARS method was applied to acute brain slices prepared from mouse brains in aCSF solution using the EMARS probe, HRP-conjugated cholera toxin subunit B, which recognizes ganglioside GM1. The membrane molecules present in the GM1-enriched lipid rafts were then labeled with fluorescein under the physiological condition. The fluorescein-tagged lipid raft molecules called "EMARS products" distributed differentially among various parts of the brain. On the other hand, appreciable differences were not detected among segments along the longitudinal axis of the hippocampus. We further developed a device to label the lipid raft molecules in acute hippocampal slices under two different physiological conditions to detect dynamics of the lipid raft molecules during neural excitation. Using this device, several cell membrane molecules including Thy1, known as a lipid raft resident molecule in neurons, were confirmed by the EMARS method in living hippocampal slices. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Bioactivities of Milk Polar Lipids in Influencing Intestinal Barrier Integrity, Systemic Inflammation, and Lipid Metabolism

    OpenAIRE

    Zhou, Albert Lihong

    2013-01-01

    The purpose of lactation is for nutrient provision and also importantly for protection from various environmental stressors. Milk polar lipids reduce cholesterol, protect against bacterial infection, reduce inflammation and help maintain gut integrity. Dynamic interactions within dietary fat, lipid metabolism, gut permeability and inflammatory cytokines remain unclear in the context of obesity and systemic inflammation. A rat model and three mouse models were developed to test the hypotheses ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Guang-feng [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Xiao, Di; Gong, Wei-jing [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Liu, Hui-xia; Liu, Jun [Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Zhou, Hong-hao [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China)

    2014-03-14

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

  7. Heritability and genetics of lipid metabolism

    DEFF Research Database (Denmark)

    Fenger, Mogens

    2007-01-01

    In this article, the concept of heritability and genetic effect will be reviewed and our current knowledge of the genetics of lipid metabolism summarized. The concepts of polygenic conditions and epistasis are discussed at length, and an effort is made to put the biological processes in context...... in the search for genetic factors influencing the metabolic pathways. Particular physiological heterogeneity is addressed and procedures to handle this complex issue are suggested....

  8. Metabolic Syndrome in Children: Clinical Picture, Features of Lipid and Carbohydrate Metabolism

    Directory of Open Access Journals (Sweden)

    O.S. Bobrykovych

    2013-09-01

    Full Text Available The study included 225 children aged from 14 to 18 years with various manifestations of the metabolic syndrome in neighborhoods, different by iodine provision. The physical development (height, weight, body mass index, waist and hip circumferences has been examined. Biochemical investigations are focused on the study of lipid and carbohydrate metabolism in children. It is found that children who live in mountains have more severe obesity. In parallel with the increase of the degree of obesity, disorders of lipid and carbohydrate metabolism aggravate in children with sings of metabolic syndrome.

  9. Astrocyte lipid metabolism is critical for synapse development and function in vivo.

    Science.gov (United States)

    van Deijk, Anne-Lieke F; Camargo, Nutabi; Timmerman, Jaap; Heistek, Tim; Brouwers, Jos F; Mogavero, Floriana; Mansvelder, Huibert D; Smit, August B; Verheijen, Mark H G

    2017-04-01

    The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo. Hippocampal protein expression for the sterol regulatory element-binding protein (SREBP) and its target gene fatty acid synthase (Fasn) was found in astrocytes but not in neurons. Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage-activating protein (SCAP) was deleted from GFAP-expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes. Interestingly, SCAP mutant mice showed more immature synapses, lower presynaptic protein SNAP-25 levels as well as reduced numbers of synaptic vesicles, indicating impaired development of the presynaptic terminal. Accordingly, hippocampal short-term and long-term synaptic plasticity were defective in mutant mice. These findings establish a critical role for astrocyte lipid metabolism in presynaptic terminal development and function in vivo. GLIA 2017;65:670-682. © 2017 Wiley Periodicals, Inc.

  10. Lipid metabolism during embryonic development of the common snapping turtle, Chelydra serpentina.

    Science.gov (United States)

    Lawniczak, Cynthia J; Teece, Mark A

    2009-05-01

    The metabolism of lipids and fatty acids during embryonic development of Chelydra serpentina (common snapping turtle) was investigated. Substantial changes in lipid class and fatty acid composition occurred as lipids were transferred from the yolk to the yolk sac membrane (YSM) and then to the brain, eyes, heart, and lungs of the hatchling. Lipids were hydrolyzed in the yolk prior to transport to the YSM, shown by a large increase in free fatty acids (FFAs) during the second half of development. Triglyceride-derived docosahexaenoic acid (DHA) was utilized preferentially to phospholipid-derived DHA. In the YSM, arachidonic acid (ARA) was selectively incorporated into phospholipids while DHA was preferentially incorporated into triglycerides. Selective incorporation of DHA and ARA into the brain and eyes, and ARA into the heart was observed, indicating the importance of these PUFAs for organ development and function. The amount of DHA and ARA in each organ was less than 1% of that measured in the yolk of the freshly laid egg, indicating that only a small portion of yolk PUFAs were incorporated into the hatchling organs studied. We discuss the differences in the mechanisms and utilization of yolk lipids in turtles compared with lipid uptake during embryonic development in birds.

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

    Directory of Open Access Journals (Sweden)

    Jordyn M. Stuart

    2013-01-01

    Full Text Available 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.

  12. Lipid Metabolism during Infection and Endotoxemia

    Science.gov (United States)

    1981-01-01

    metabolic response of theV guinea - pig to diphtheria toxin; Border et al. (1970) reported that sepsis without starvation caused a decrease in skeletal muscle...fat emulsions utilized in intravenous alimentation consist of a mixture of neutral triglycerides of predominantly unsaturated fatty acids, it is

  13. Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?

    Directory of Open Access Journals (Sweden)

    José Pedro Castro

    2018-04-01

    Full Text Available The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis, cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function has been observed during aging, metabolic diseases such as type 2 diabetes and in neurodegenerative diseases such as Alzheimer’s (AD, Parkinson’s (PD or even Huntington’s (HD diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.

  14. Effect of chloroquine on intestinal lipid metabolism

    International Nuclear Information System (INIS)

    Mansbach, C.M. II; Arnold, A.; Garrett, M.

    1987-01-01

    Most studies that have quantitated recovery of infused lipid in the intestinal mucosa and mesenteric lymph have only been able to recapture 50-75%. One possibility is that the missing lipid enters a triacylglycerol (TG) storage pool in the enterocyte and is hydrolyzed by lysosomal lipase, and the free fatty acid released is transported by the portal vein. This postulate was tested by comparing glyceryl trioleate (TO)-infused rats pretreated with the lysosomotropic drug, chloroquine (6.3 mg.kg-1.h-1) with saline controls. Chloroquine increased mucosal TG from 94 +/- 6 to 128 +/- 8 mumol. Additionally, the specific activity of the mucosal TG relative to the infused [ 3 H]TO was reduced in the treated rats. The mucosal TG increase was not due to impaired TG output, which remained the same as controls. We conclude that the TG in the acid lipase-sensitive pool derives most of its glyceride-glycerol from endogenous sources. Furthermore, the increment in mucosal TG caused by chloroquine is not enough to explain the majority of the acyl groups unaccounted for in the mucosa and lymph after a TG infusion. For these a direct passage of acyl groups through the enterocyte is postulated

  15. Heritability and genetics of lipid metabolism

    DEFF Research Database (Denmark)

    Fenger, Mogens

    2007-01-01

    In this article, the concept of heritability and genetic effect will be reviewed and our current knowledge of the genetics of lipid metabolism summarized. The concepts of polygenic conditions and epistasis are discussed at length, and an effort is made to put the biological processes in context...

  16. Apolipoprotein M in lipid metabolism and cardiometabolic diseases

    DEFF Research Database (Denmark)

    Borup, Anna; Christensen, Pernille Meyer; Nielsen, Lars B.

    2015-01-01

    : The apoM/S1P axis and its implications in atherosclerosis and lipid metabolism have been thoroughly studied. Owing to the discovery of the apoM/S1P axis, the scope of apoM research has broadened. ApoM and S1P have been implicated in lipid metabolism, that is by modulating HDL particles. Also......PURPOSE: This review will address recent findings on apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) in lipid metabolism and inflammatory diseases. RECENT FINDINGS: ApoM's likely role(s) in health and disease has become more diverse after the discovery that apoM functions...... as a chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P. SUMMARY...

  17. Timing of potential and metabolic brain energy

    DEFF Research Database (Denmark)

    Korf, Jakob; Gramsbergen, Jan Bert

    2007-01-01

    functions. We introduce the concepts of potential and metabolic brain energy to distinguish trans-membrane gradients of ions or neurotransmitters and the capacity to generate energy from intra- or extra-cerebral substrates, respectively. Higher brain functions, such as memory retrieval, speaking......The temporal relationship between cerebral electro-physiological activities, higher brain functions and brain energy metabolism is reviewed. The duration of action potentials and transmission through glutamate and GABA are most often less than 5 ms. Subjects may perform complex psycho......-physiological tasks within 50 to 200 ms, and perception of conscious experience requires 0.5 to 2 s. Activation of cerebral oxygen consumption starts after at least 100 ms and increases of local blood flow become maximal after about 1 s. Current imaging technologies are unable to detect rapid physiological brain...

  18. Homocysteine regulates fatty acid and lipid metabolism in yeast.

    Science.gov (United States)

    Visram, Myriam; Radulovic, Maja; Steiner, Sabine; Malanovic, Nermina; Eichmann, Thomas O; Wolinski, Heimo; Rechberger, Gerald N; Tehlivets, Oksana

    2018-04-13

    S -Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S -adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Gene expression in plant lipid metabolism in Arabidopsis seedlings.

    Directory of Open Access Journals (Sweden)

    An-Shan Hsiao

    Full Text Available 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.

  20. Effect of leptin level upon lipid metabolism in climacteric women

    International Nuclear Information System (INIS)

    Peng Lijing; Yan Ruming; Sun Enhua

    2005-01-01

    To observe the relationship between leptin and obesity of climacteric women with their lipid metabolism, 110 cases of climacteric women were chosen as observation group, consisting of 69 cases obese subgroup and 45 cases non-obese group, and 60 cases of normal reproduction- age women were arranged as control group. Blood levels of leptin, INS, LDL-C, TG, HDL-C, apoA1, apoB, LH, FSH, E-2, T, and P were detected and BMI was calculated. The results showed that blood levels of leptin and INS of obese subgroup were significantly higher than those of non-obese sub-group and control group(P<0.01), and that LDL-C(5.01 mmol/L), TG(2.21mmal/L) and apoB(0.89g/L) levels in obese subgroup were significantly higher than those of control group. Furthermore, an important observation was that in climacteric women group, blood leptin level was positively and significantly correlated with insulin, BMI and several atherogenic blood lipid parameters, including LDL-C, TG and apoB. Thus, a preliminary conclusion might be reached as that the high climacteric level of leptin is associated with abnormal lipid metabolism related to atherogenity, and so leptin and lipid metabolism as a whole should be paid more attention in climateric women, especially those with obesity. (authors)

  1. Lipid Uptake, Metabolism, and Transport in the Larval Zebrafish

    Directory of Open Access Journals (Sweden)

    Vanessa H. Quinlivan

    2017-11-01

    Full Text Available The developing zebrafish is a well-established model system for studies of energy metabolism, and is amenable to genetic, physiological, and biochemical approaches. For the first 5 days of life, nutrients are absorbed from its endogenous maternally deposited yolk. At 5 days post-fertilization, the yolk is exhausted and the larva has a functional digestive system including intestine, liver, gallbladder, pancreas, and intestinal microbiota. The transparency of the larval zebrafish, and the genetic and physiological similarity of its digestive system to that of mammals make it a promising system in which to address questions of energy homeostasis relevant to human health. For example, apolipoprotein expression and function is similar in zebrafish and mammals, and transgenic animals may be used to examine both the transport of lipid from yolk to body in the embryo, and the trafficking of dietary lipids in the larva. Additionally, despite the identification of many fatty acid and lipid transport proteins expressed by vertebrates, the cell biological processes that mediate the transport of dietary lipids from the intestinal lumen to the interior of enterocytes remain to be elucidated. Genetic tractability and amenability to live imaging and a range of biochemical methods make the larval zebrafish an ideal model in which to address open questions in the field of lipid transport, energy homeostasis, and nutrient metabolism.

  2. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    DEFF Research Database (Denmark)

    Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco

    2014-01-01

    Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary...... phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic...... and explain how cells switch neutral lipid metabolism from storage to consumption....

  3. Insulin action in brain regulates systemic metabolism and brain function.

    Science.gov (United States)

    Kleinridders, André; Ferris, Heather A; Cai, Weikang; Kahn, C Ronald

    2014-07-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. © 2014 by the American Diabetes Association.

  4. Metabolic drift in the aging brain.

    Science.gov (United States)

    Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

    2016-05-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication.

  5. Effect of cadmium exposure on lipids, lipid peroxidation and metal distribution in rat brain regions

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, T; Ali, M M; Chandra, S V

    1985-01-01

    Effect of cadmium treatment on brain lipids, lipid peroxidation and distribution of Zn, Cu and Fe in rat brain regions was investigated. Adult male rats were exposed to Cd (100 ppm Cd as cadmium acetate) in drinking water for 30 days. The Cd exposure resulted in a significant decrease in the phospholipid content and an increase in the lipid peroxidation in the cerebral cortex and cerebellum. The total lipid content was not affected in any of the regions but a significant decrease in cholesterol and cerebroside contents were observed only in the cerebral cortex. A positive correlation between the increase in lipid peroxidation and decrease in the phospholipid content in the cerebral cortex and cerebellum was observed. A maximum accumulation of Cd occurred in the cerebral cortex. The Cu and Fe contents were significantly increased but the Zn levels decreased in the Cd-treated rats in all but the midbrain region. Results suggest that the increased peroxidation decomposition of structural lipids and the altered distribution of the essential trace metals in brain may play a significant role in Cd-induced neurotoxicity. 27 references, 2 tables.

  6. Metabolic changes in the brain

    International Nuclear Information System (INIS)

    Meermann, H.

    1982-01-01

    A positron emission tomograph (PET) is described for displaying the flow pattern of radioactive isotope-labelled substances injected into the human brain. This is claimed to assist in diagnosis of circulation disturbances and to show sugar and oxygen uptake. Emitted gamma rays are detected by rings of 96 detectors whose outputs are used to produce a computer-generated reproduction of the brain, with different colours or densities on a cathode ray tube representing concentration of the labelled substance. Epileptic spasms, Huntington's chorea and drug uptake, as well as albumen content variations due to tumours, are stated to be capable of display. Future uses of the ''PET'' tomograph are discussed. (G.M.E.)

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

    Science.gov (United States)

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

    2010-01-01

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

  8. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael

    2013-01-01

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

  9. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael

    2013-01-01

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

  10. Effect of Cyolane on carbohydrate and lipid metabolism in rat

    Energy Technology Data Exchange (ETDEWEB)

    Bahig, M E; Hassanin, M M [Radioisotope Dept., Atomic energy Establishment, Cairo (Egypt)

    1995-10-01

    Cyolane was orally administrated daily for 1-5 weeks (1 mg/kg body weight), induced a marked increase in liver glycogen content reaching its highest values after 1,2,3 and 15 weeks. In kidney and brain the glycogen contents showed a significant increase after 10, 12 and 15 weeks of intoxication. Serum glucose content was increased after 2, 3 and 8 weeks. It has been found that Cyolane caused a fluctuation in liver, kidney and brain total lipid through the first 8 weeks, thereafter it exhibited a significant increase after 10, 12 and 15 weeks. Serum total lipid exhibited a highly significant increase after 2-12 weeks, reaching its maximum value (288.66%) after 15 weeks. 3 figs., 4 tabs.

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

    Science.gov (United States)

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

    2007-04-01

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

  12. Current trends to comprehend lipid metabolism in diatoms.

    Science.gov (United States)

    Zulu, Nodumo Nokulunga; Zienkiewicz, Krzysztof; Vollheyde, Katharina; Feussner, Ivo

    2018-04-01

    Diatoms are the most dominant phytoplankton species in oceans and they continue to receive a great deal of attention because of their significant contributions in ecosystems and the environment. Due to triacylglycerol (TAG) profiles that are abundant in medium-chain fatty acids, diatoms have emerged to be better feed stocks for biofuel production, in comparison to the commonly studied green microalgal species (chlorophytes). Importantly, diatoms are also known for their high levels of the essential ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are considered to be a promising alternative source of these components. The two most commonly exploited diatoms include Thalassiosira pseudonana and Phaeodactylum tricornutum. Although obvious similarities between diatoms and chlorophytes exist, there are some substantial differences in their lipid metabolism. This review provides an overview on lipid metabolism in diatoms, with P. tricornutum as the most explored model. Special emphasis is placed on the synthesis and incorporation of very long chain ω3 fatty acids into lipids. Furthermore, current approaches including genetic engineering and biotechnological methods aimed at improving and maximizing lipid production in P. tricornutum are also discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. The effect of Cu2+ on osmoregulation in rainbow trout (Oncorhynchus mykiss) assayed by changes in plasma salinity and gill lipid metabolism

    DEFF Research Database (Denmark)

    Hansen, Heinz J.M.; Olsen, Allan Gylling; Rosenkilde, Per

    1993-01-01

    Zoofysiologi, Osmoregulation, Lipid metabolism, Ecotoxicology, Rainbow trout, Oncorhynchus mykiss.......Zoofysiologi, Osmoregulation, Lipid metabolism, Ecotoxicology, Rainbow trout, Oncorhynchus mykiss....

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

    Science.gov (United States)

    Shimano, Hitoshi; Sato, Ryuichiro

    2017-12-01

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

  15. Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Liver Lipidomics

    Directory of Open Access Journals (Sweden)

    Zhao Li

    2017-11-01

    Full Text Available Background: The aim of this study was to characterize the disorder of lipid metabolism in hepatocellular carcinoma (HCC. HCC is a worldwide disease. The research into the disorder of lipid metabolism in HCC is very limited. Study of lipid metabolism in liver cancer tissue may have the potential to provide new insight into HCC mechanisms. Methods: A lipidomics study of HCC based on Ultra high performance liquid chromatography-electronic spray ionization-QTOF mass spectrometer (UPLC-ESI-QTOF MS and Matrix assisted laser desorption ionization-fourier transform ion cyclotron resonance mass spectrometer (MALDI-FTICR MS was performed. Results: Triacylglycerols (TAGs with the number of double bond (DB > 2 (except 56:5 and 56:4 TAG were significantly down-regulated; conversely, others (except 52:2 TAG were greatly up-regulated in HCC tissues. Moreover, the more serious the disease was, the higher the saturated TAG concentration and the lower the polyunsaturated TAG concentration were in HCC tissues. The phosphatidylcholine (PC, phosphatidylethanolamine (PE and phosphatidylinositol (PI were altered in a certain way. Sphingomyelin (SM was up-regulated and ceramide (Cer were down-regulated in HCC tissues. Conclusions: To our knowledge, this is the first such report showing a unique trend of TAG, PC, PE and PI. The use of polyunsaturated fatty acids, like eicosapentanoic and docosahexanoic acid, as supplementation, proposed for the treatment of Non-alcoholic steatohepatitis (NASH, may also be effective for the treatment of HCC.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Laforêt, Pascal; Vianey-Saban, Christine

    2010-11-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Samuel Rommelaere

    Full Text Available 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.

  20. Precision Nutrition for Targeting Lipid Metabolism in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Cristina Aguirre-Portolés

    2017-09-01

    Full Text Available Cancer is a multistage and multifactorial condition with genetic and environmental factors modulating tumorogenesis and disease progression. Nevertheless, cancer is preventable, as one third of cancer deaths could be avoided by modifying key risk factors. Nutrients can directly affect fundamental cellular processes and are considered among the most important risk factors in colorectal cancer (CRC. Red and processed meat, poultry consumption, fiber, and folate are the best-known diet components that interact with colorectal cancer susceptibility. In addition, the direct association of an unhealthy diet with obesity and dysbiosis opens new routes in the understanding of how daily diet nutrients could influence cancer prognosis. In the “omics” era, traditional nutrition has been naturally evolved to precision nutrition where technical developments have contributed to a more accurate discipline. In this sense, genomic and transcriptomic studies have been extensively used in precision nutrition approaches. However, the relation between CRC carcinogenesis and nutrition factors is more complex than originally expected. Together with classical diet-nutrition-related genes, nowadays, lipid-metabolism-related genes have acquired relevant interest in precision nutrition studies. Lipids regulate very diverse cellular processes from ATP synthesis and the activation of essential cell-signaling pathways to membrane organization and plasticity. Therefore, a wide range of tumorogenic steps can be influenced by lipid metabolism, both in primary tumours and distal metastasis. The extent to which genetic variants, together with the intake of specific dietary components, affect the risk of CRC is currently under investigation, and new therapeutic or preventive applications must be explored in CRC models. In this review, we will go in depth into the study of co-occurring events, which orchestrate CRC tumorogenesis and are essential for the evolution of precision

  1. Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2011-01-01

    Full Text Available Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine and control group. Fasting blood glucose (FBG, weight, total cholesterol (TC, triglyceride (TG, high-density lipoprotein-cholesterol (HDL-c, low-density lipoprotein-cholesterol (LDL-c, and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT was performed. RT2 PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC, fasting serum insulin (FINS, homeostasis model assessment insulin resistance (HOMA-IR index, TC, and TG, compared with those of control group. RT2 profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4, mitogen-activated protein kinase 14 (MAPK14, MAPK8(c-jun N-terminal kinase, JNK, peroxisome proliferator-activated receptor α (PPARα, uncoupling protein 2 (UCP2, and hepatic nuclear factor 4α(HNF4α, whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP, PPARγ coactivator 1α(PGC 1α, and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK- p38 MAPK-GLUT4, JNK pathway, and PPARα pathway.

  2. The WWOX Gene Modulates HDL and Lipid Metabolism

    Science.gov (United States)

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

    2014-01-01

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

  3. Alterations in lipid metabolism and antioxidant status in lichen planus

    Directory of Open Access Journals (Sweden)

    Falguni H Panchal

    2015-01-01

    Full Text Available 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

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

    Science.gov (United States)

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

    2012-01-01

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

  5. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    International Nuclear Information System (INIS)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-01-01

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage

  6. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Richardson, Jason R. [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States); Heck, Diane E. [Environmental Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  7. Acyl-CoA synthetase activity links wild-type but not mutant a-Synuclein to brain arachidonate metabolism

    DEFF Research Database (Denmark)

    Golovko, Mikhail; Rosenberger, Thad; Færgeman, Nils J.

    2006-01-01

    Because alpha-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that the loss of alpha-synuclein had on brain arachidonic acid (20:4n-6) metabolism in vivo using Snca-/- mice. We measured [1-(14)C]20:4n-6 incorporation and turnover kinetics in brain phospholipids using......, our data demonstrate that alpha-synuclein has a major role in brain 20:4n-6 metabolism through its modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity, although mutant forms of alpha-synuclein fail to restore this activity....

  8. Hyperthyroidism affects lipid metabolism in lactating and suckling rats.

    Science.gov (United States)

    Varas, S M; Jahn, G A; Giménez, M S

    2001-08-01

    Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.

  9. The effects of vitamine C on lipid metabolism.

    Science.gov (United States)

    Kotzé, J P

    1975-09-20

    Evidence is presented showing that vitamin C had definite effects on lipid metabolism. The stress of captivity on free-living baboons causes a decrease in serum vitamin C levels and an increase in serum cholesterol levels. Increased dietary intake of vitamin C during the initial stages of captivity significantly decreases the serum cholesterol values. Dietary vitamin C stimulates the synthesis of cholesterol from 14C-labelled acetate and mevalonate in baboon liver homogenates and increases the turnover rate of the cholesterol body pool. Vitamin C inhibits baboon cardiac lipoprotein lipase activity.

  10. Kisspeptin and Metabolism: The Brain and Beyond

    Directory of Open Access Journals (Sweden)

    Monika Dudek

    2018-04-01

    Full Text Available Apart from the well-established role of kisspeptin (Kp in the regulation of reproductive functions, recent data described its action in the control of metabolism. Of particular interest for the review is the population of Kp neurons localized in the arcuate nucleus (ARC of the hypothalamus, the site of the brain where reproductive and metabolic cross talk occurs. However, within the hypothalamus Kp does not work alone, but rather interacts with other neuropeptides, e.g., neurokinin B, dynorphin A, proopiomelanocortin, the cocaine- and amphetamine-regulated transcript, agouti-related peptide, and neuropeptide Y. Beyond the brain, Kp is expressed in peripheral tissues involved in metabolic functions. In this review, we will mainly focus on the local action of this peptide in peripheral organs such as the pancreas, liver, and the adipose tissue. We will concentrate on dysregulation of the Kp system in cases of metabolic imbalance, e.g., obesity and diabetes. Importantly, these patients besides metabolic health problems often suffer from disruptions of the reproductive system, manifested by abnormalities in menstrual cycles, premature child birth, miscarriages in women, decreased testosterone levels and spermatogenesis in men, hypogonadism, and infertility. We will review the evidence from animal models and clinical data indicating that Kp could serve as a promising agent with clinical applications in regulation of reproductive problems in individuals with obesity and diabetes. Finally, emerging data indicate a role of Kp in regulation of insulin secretion, potentially leading to development of further therapeutic uses of this peptide to treat metabolic problems in patients with these lifestyle diseases.

  11. Kisspeptin and Metabolism: The Brain and Beyond.

    Science.gov (United States)

    Dudek, Monika; Ziarniak, Kamil; Sliwowska, Joanna H

    2018-01-01

    Apart from the well-established role of kisspeptin (Kp) in the regulation of reproductive functions, recent data described its action in the control of metabolism. Of particular interest for the review is the population of Kp neurons localized in the arcuate nucleus (ARC) of the hypothalamus, the site of the brain where reproductive and metabolic cross talk occurs. However, within the hypothalamus Kp does not work alone, but rather interacts with other neuropeptides, e.g., neurokinin B, dynorphin A, proopiomelanocortin, the cocaine- and amphetamine-regulated transcript, agouti-related peptide, and neuropeptide Y. Beyond the brain, Kp is expressed in peripheral tissues involved in metabolic functions. In this review, we will mainly focus on the local action of this peptide in peripheral organs such as the pancreas, liver, and the adipose tissue. We will concentrate on dysregulation of the Kp system in cases of metabolic imbalance, e.g., obesity and diabetes. Importantly, these patients besides metabolic health problems often suffer from disruptions of the reproductive system, manifested by abnormalities in menstrual cycles, premature child birth, miscarriages in women, decreased testosterone levels and spermatogenesis in men, hypogonadism, and infertility. We will review the evidence from animal models and clinical data indicating that Kp could serve as a promising agent with clinical applications in regulation of reproductive problems in individuals with obesity and diabetes. Finally, emerging data indicate a role of Kp in regulation of insulin secretion, potentially leading to development of further therapeutic uses of this peptide to treat metabolic problems in patients with these lifestyle diseases.

  12. Effects of Castration on Expression of Lipid Metabolism Genes in the Liver of Korean Cattle

    OpenAIRE

    Baik, Myunggi; Nguyen, Trang Hoa; Jeong, Jin Young; Piao, Min Yu; Kang, Hyeok Joong

    2015-01-01

    Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-01-16

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

  15. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    Directory of Open Access Journals (Sweden)

    Daniel F. Markgraf

    2014-01-01

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

  16. Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Johan W.E. Jocken

    2014-10-01

    Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

  17. Impaired insulin action in the human brain: causes and metabolic consequences.

    Science.gov (United States)

    Heni, Martin; Kullmann, Stephanie; Preissl, Hubert; Fritsche, Andreas; Häring, Hans-Ulrich

    2015-12-01

    Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism. However, brain imaging studies have revealed that not everybody responds equally to insulin and that a substantial number of people are brain insulin resistant. In this Review, we provide an overview of the effects of insulin in the brain in humans and the relevance of the effects for physiology. We present emerging evidence for insulin resistance of the human brain. Factors associated with brain insulin resistance such as obesity and increasing age, as well as possible pathogenic factors such as visceral fat, saturated fatty acids, alterations at the blood-brain barrier and certain genetic polymorphisms, are reviewed. In particular, the metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.

  18. Oxidative status and lipid profile in metabolic syndrome: gender differences.

    Science.gov (United States)

    Kaya, Aysem; Uzunhasan, Isil; Baskurt, Murat; Ozkan, Alev; Ataoglu, Esra; Okcun, Baris; Yigit, Zerrin

    2010-02-01

    Metabolic syndrome is associated with cardiovascular disease and oxidative stress. The aim of this study was to investigate the differences of novel oxidative stress parameters and lipid profiles in men and women with metabolic syndrome. The study population included 88 patients with metabolic syndrome, consisting of 48 postmenauposal women (group I) and 40 men (group II). Premenauposal women were excluded. Plasma levels of total antioxidant status (TAS) and total oxidative status (TOS) were determined by using the Erel automated measurement method, and oxidative stress index (OSI) was calculated. To perform the calculation, the resulting unit of TAS, mmol Trolox equivalent/L, was converted to micromol equivalent/L and the OSI value was calculated as: OSI = [(TOS, micromol/L)/(TAS, mmol Trolox equivalent/L) x 100]. The Student t-test, Mann-Whitney-U test, and chi-squared test were used for statistical analysis; the Pearson correlation coefficient and Spearman rank test were used for correlation analysis. P women and men had similar properties regarding demographic characteristics and biochemical work up. Group II had significantly lower levels of antioxidant levels of TAS and lower levels of TOS and OSI compared with group I (P = 0.0001, P = 0.0035, and P = 0,0001). Apolipoprotein A (ApoA) levels were significantly higher in group I compared with group II. Our findings indicate that women with metabolic syndrome have a better antioxidant status and higher ApoA levels compared with men. Our findings suggest the existence of a higher oxidative stress index in men with metabolic syndrome. Considering the higher risk of atherosclerosis associated with men, these novel oxidative stress parameters may be valuable in the evaluation of patients with metabolic sydrome.

  19. Overexpression of SIRT1 in mouse forebrain impairs lipid/glucose metabolism and motor function.

    Directory of Open Access Journals (Sweden)

    Dongmei Wu

    Full Text Available SIRT1 plays crucial roles in glucose and lipid metabolism, and has various functions in different tissues including brain. The brain-specific SIRT1 knockout mice display defects in somatotropic signaling, memory and synaptic plasticity. And the female mice without SIRT1 in POMC neuron are more sensitive to diet-induced obesity. Here we created transgenic mice overexpressing SIRT1 in striatum and hippocampus under the control of CaMKIIα promoter. These mice, especially females, exhibited increased fat accumulation accompanied by significant upregulation of adipogenic genes in white adipose tissue. Glucose tolerance of the mice was also impaired with decreased Glut4 mRNA levels in muscle. Moreover, the SIRT1 overexpressing mice showed decreased energy expenditure, and concomitantly mitochondria-related genes were decreased in muscle. In addition, these mice showed unusual spontaneous physical activity pattern, decreased activity in open field and rotarod performance. Further studies demonstrated that SIRT1 deacetylated IRS-2, and upregulated phosphorylation level of IRS-2 and ERK1/2 in striatum. Meanwhile, the neurotransmitter signaling in striatum and the expression of endocrine hormones in hypothalamus and serum T3, T4 levels were altered. Taken together, our findings demonstrate that SIRT1 in forebrain regulates lipid/glucose metabolism and motor function.

  20. Lipid metabolism in rats fed diets containing different types of lipids

    Directory of Open Access Journals (Sweden)

    Águila Márcia Barbosa

    2002-01-01

    Full Text Available OBJECTIVE: To assess the effect of different types of lipid diets on the lipid metabolism of aging rats. METHODS: Fifty male Wistar rats were studied from the time of weaning to 12 and 18 months of age. Their diets were supplemented as follows: with soybean oil (S, canola oil (CA, lard and egg yolk (LE, and canola oil + lard and egg yolk (CA + LE. Blood pressure (BP was measured every month, and the heart/body ratio (H/BR was determined. The rats were euthanized at the age of 12 and 18 months, and blood samples were collected for lipid analysis as follows: total cholesterol (TC, LDL-C, VLDL-C, HDL-C, triglycerides (TG, and glucose. RESULTS: The type of oil ingested by the animals significantly altered BP, H/BR, and serum lipid levels in rats at 12 and 18 months. No difference was observed in the survival curve of the animals in the different groups. The LE group had the highest BP, and the CA group was the only one in which BP did not change with aging. A reduction in the H/BR was observed in the LE and CA+LE animals. At the age of 12 months, differences in TC, HDL-C, LDL-C, VLDL-C, TG, and glucose were observed. At the age of 18 months, a significant difference in TC, HDL-C, and glucose was observed. The highest TC value was found in the CA group and the lowest in the S group. CONCLUSION: No increase in BP occurred, and an improvement was evident in the lipid profile of rats fed a diet supplemented with CA, in which an elevation in HDL-C levels was observed, as compared with levels with the other types of diet.

  1. Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function

    Directory of Open Access Journals (Sweden)

    George A. Robinson

    2017-11-01

    Full Text Available It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β, and sterol regulatory element-binding proteins in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid, and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed.

  2. HPLC-MS-Based Metabonomics Reveals Disordered Lipid Metabolism in Patients with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Xinjie Zhao

    2011-12-01

    Full Text Available Ultra-high performance liquid chromatography/ quadrupole time of flight mass spectrometry-based metabonomics platform was employed to profile the plasma metabolites of patients with metabolic syndrome and the healthy controls. Data analysis revealed lots of differential metabolites between the two groups, and most of them were identified as lipids. Several fatty acids and lysophosphatidylcholines were of higher plasma levels in the patient group, indicating the occurrence of insulin resistance and inflammation. The identified ether phospholipids were decreased in the patient group, reflecting the oxidative stress and some metabolic disorders. These identified metabolites can also be used to aid diagnosis of patients with metabolic syndrome. These results showed that metabonomics was a promising and powerful method to study metabolic syndrome.

  3. Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders.

    Science.gov (United States)

    Hebbar, Sarita; Khandelwal, Avinash; Jayashree, R; Hindle, Samantha J; Chiang, Yin Ning; Yew, Joanne Y; Sweeney, Sean T; Schwudke, Dominik

    2017-12-15

    Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD. © 2017 Hebbar et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. Linking neuronal brain activity to the glucose metabolism

    OpenAIRE

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regul...

  5. Features of lipid metabolism disturbances in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    A E Sizikov

    2009-01-01

    Full Text Available Objective. To characterize specters of common and modified lipoproteins (LP in serum of pts with rheumatoid arthritis (RA according to age and sex and compare with healthy donors (with normal lipid level. Material and methods. 103 pts with RA (88 female and 15 male aged 21 to 69 years were included. Specters of common and modified LP in serum and plasma were evaluated with small-angle x-ray scattering. Results. Low level of intermediate density lipoproteins (IDLP subfractions and very low density lipoproteins (VLDLP as well as high level of low density lipoproteins (LDLP30 was revealed in pts with RA. Mean level of LP modification was about 60%. High density lipoproteins (HDLP subfraction was least and IDLP subfraction – most susceptible to modification. LP modification level increased due to LDLP and VLDLP fractions. This level had a tendency to increase with age because of elevation of atherogenic LP part. Mean values of common LP did not differ between sex and age groups of pts with RA. Unexpectedly low (in comparison with normal lipid content level of LP modification of the whole fraction of HDLP was the feature of modified LP specter in pts with RA. Conclusion. Level of common and modified LP in blood plasma and serum of RA pts is connected with general state of lipid metabolism and immune defense factors balance. Low level of VLDLP cholesterol and high level of LDLP cholesterol as well as high degree of LP of these fractions modification may be probably considered as markers of RA activity.

  6. Effect of fatty Amazon fish consumption on lipid metabolism

    Directory of Open Access Journals (Sweden)

    Francisca das Chagas do Amaral Souza

    2014-01-01

    Full Text Available OBJECTIVE: The present study aimed to evaluate the effect of feeding diets enriched with fatty fish from the Amazon basin on lipid metabolism. METHODS: Male Wistar rats were divided into four groups: control group treated with commercial chow; Mapará group was fed diet enriched with Hypophthalmus edentatus; Matrinxã group was fed diet enriched with Brycon spp.; and, Tambaqui group was fed diet enriched with Colossoma macropomum. Rats with approximately 240g±0.60 of body weight were fed ad libitum for 30 days, and then were sacrificed for collection of whole blood and tissues. RESULTS: The groups treated with enriched diets showed a significant reduction in body mass and lipogenesis in the epididymal and retroperitoneal adipose tissues and carcass when compared with the control group. However, lipogenesis in the liver showed an increase in Matrinxã group compared with the others groups. The levels of serum triglycerides in the treated groups with Amazonian fish were significantly lower than those of the control group. Moreover, total cholesterol concentration only decreased in the group Matrinxã. High Density Lipoprotein cholesterol levels increased significantly in the Mapará and Tambaqui compared with control group and Matrinxã group. The insulin and leptin levels increased significantly in all treatment groups. CONCLUSION: This study demonstrated that diets enriched with fatty fish from the Amazon basin changed the lipid metabolism by reducing serum triglycerides and increasing high density lipoprotein-cholesterol in rats fed with diets enriched with Mapará, Matrinxã, and Tambaqui.

  7. Nanocellulose size regulates microalgal flocculation and lipid metabolism

    Science.gov (United States)

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

    2016-01-01

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

  8. 2009 Plant Lipids: Structure, Metabolism & Function Gordon Research Conference - February 1- 6 ,2009

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    NARCIS (Netherlands)

    Chrast, R.; Saher, G.; Nave, K.A.; Verheijen, M.H.G.

    2011-01-01

    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid

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

    DEFF Research Database (Denmark)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

    2015-01-01

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...

  11. Altered brain arginine metabolism in schizophrenia.

    Science.gov (United States)

    Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

    2016-08-16

    Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

  12. [Characteristics of lipid metabolism and the cardiovascular system in glycogenosis types I and III].

    Science.gov (United States)

    Polenova, N V; Strokova, T V; Starodubova, A V

    Glycogen storage disease (GSD) is an inherited metabolic disorder characterized by early childhood lipid metabolic disturbances with potentially proatherogenic effects. The review outlines the characteristics of impaired lipid composition and other changes in the cardiovascular system in GSD types I and III. It analyzes the factors enabling and inhibiting the development of atherosclerosis in patients with GSD. The review describes the paradox of vascular resistance to the development of early atherosclerosis despite the proatherogenic composition of lipids in the patients of this group.

  13. [The lipid metabolism abnormality in patients administered with olanzapine].

    Science.gov (United States)

    Amano, Taku; Hosaka, Shigetoshi; Takami, Hiroshi; Sugiyama, Chie; Oda, Kazue; Morikawa, Ryuichi

    2012-11-01

    The atypical antipsychotic medication olanzapine is a useful agent in acute and maintenance treatment of schizophrenia and related disorders. It has beneficial effects on both positive and negative symptoms, an early onset of antipsychotic action and a favourable side effect profile. On the other hand, olanzapine has many reports of causing weight gain, glucose metabolism disturbances and lipidosis. We carried out blood tests (leptin, adiponectin, remnant-like lipoprotein cholesterol (RLP-C), total cholesterol, HbA1C, 75-OGTT and etc.) on patients with schizophrenia who had taken olanzapine. As a result, leptin, neutral lipid and RLP-C were significantly correlated by BMI. (The average blood test data and BMI revealed a normal range). Most analysis results of the lipoprotein fraction by a polyacrylamide-gel-electrophoresis method were normal patterns. Furthermore, the serum insulin concentrations from 75 g glucose tolerance (75 g-OGTT) 30 minutes later, in one third of patients receiving olanzapine, registered more than 100 microU/ml. The mechanism of the insulin secretion rise by olannzapine is unknown. Olanzapine may impair glucose tolerance due in part to increased insulin resistance. These findings do not necessarily imply that olanzapine is directly associated with a risk of impairment of weight gain, glucose metabolism disturbances and lipidosis. These results suggest that it is useful to promote diet cure and exercise therapy with patients with high BMI levels.

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

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    Sang Hoon Lee

    2015-01-01

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

  15. Effect of hypoxia on the incorporation of [2-3H] glycerol and [1-14C[-palmitate into lipids of various brain regions

    International Nuclear Information System (INIS)

    Alberghina, M.; Giuffrida, A.M.

    1981-01-01

    The lipid metabolism in guinea pig brain after intermittent hypoxia, prolonged for 80 hrs, was markedly impaired. The in vivo incorporation of [2-3H] glycerol and [1-14C] palmitate into lipids of microsomes, mitochondria, myelin, and synaptosomes, purified form cerebral hemispheres, was significantly lower in the hypoxic animals than in the controls. The same effect was observed on the incorporation of labeled precursors into lipids of mitochondria purified from cerebellum and brainstem. In particular, the labeling of th major phospholipids present - ie, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) - in the mitochondria of the three brain regions examined decreased after hypoxic treatment

  16. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    Energy Technology Data Exchange (ETDEWEB)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-11-15

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

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

    Science.gov (United States)

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

    2011-03-01

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

  18. Flight metabolism in Panstrongylus megistus (Hemiptera: Reduviidae): the role of carbohydrates and lipids

    OpenAIRE

    Canavoso, Lilián E; Stariolo, Raúl; Rubiolo, Edilberto R

    2003-01-01

    The metabolism of lipids and carbohydrates related to flight activity in Panstrongylus megistus was investigated. Insects were subjected to different times of flight under laboratory conditions and changes in total lipids, lipophorin density and carbohydrates were followed in the hemolymph. Lipids and glycogen were also assayed in fat body and flight muscle. In resting insects, hemolymph lipids averaged 3.4 mg/ml and significantly increased after 45 min of flight (8.8 mg/ml, P < 0.001). High-...

  19. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  20. Prion protein accumulation in lipid rafts of mouse aging brain.

    Directory of Open Access Journals (Sweden)

    Federica Agostini

    Full Text Available The cellular form of the prion protein (PrP(C is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C. In old mice, this change favors PrP(C accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C translocation into detergent-resistant membranes (DRMs, we looked at PrP(C compartmentalization in hippocampi from acid sphingomyelinase (ASM knockout (KO mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases.

  1. Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism[S

    Science.gov (United States)

    Palczewski, Grzegorz; Widjaja-Adhi, M. Airanthi K.; Amengual, Jaume; Golczak, Marcin; von Lintig, Johannes

    2016-01-01

    Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals. PMID:27389691

  2. Astrocyte glycogen and brain energy metabolism.

    Science.gov (United States)

    Brown, Angus M; Ransom, Bruce R

    2007-09-01

    The brain contains glycogen but at low concentration compared with liver and muscle. In the adult brain, glycogen is found predominantly in astrocytes. Astrocyte glycogen content is modulated by a number of factors including some neurotransmitters and ambient glucose concentration. Compelling evidence indicates that astrocyte glycogen breaks down during hypoglycemia to lactate that is transferred to adjacent neurons or axons where it is used aerobically as fuel. In the case of CNS white matter, this source of energy can extend axon function for 20 min or longer. Likewise, during periods of intense neural activity when energy demand exceeds glucose supply, astrocyte glycogen is degraded to lactate, a portion of which is transferred to axons for fuel. Astrocyte glycogen, therefore, offers some protection against hypoglycemic neural injury and ensures that neurons and axons can maintain their function during very intense periods of activation. These emerging principles about the roles of astrocyte glycogen contradict the long held belief that this metabolic pool has little or no functional significance.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Dove; Finlay, Liam; Butler, Judy [Linus Pauling Institute, Oregon State University (United States); Gómez, Luis; Smith, Eric [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States); Moreau, Régis [Linus Pauling Institute, Oregon State University (United States); Hagen, Tory [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States)

    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.

  5. Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

    Directory of Open Access Journals (Sweden)

    Wen Liang

    Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

  6. PM2.5-bound metal metabolic distribution and coupled lipid abnormality at different developmental windows.

    Science.gov (United States)

    Ku, Tingting; Zhang, Yingying; Ji, Xiaotong; Li, Guangke; Sang, Nan

    2017-09-01

    Atmospheric fine particulate matter (PM 2.5 ) is a serious threat to human health. As a toxicant constituent, metal leads to significant health risks in a population, but exposure to PM 2.5 -bound metals and their biological impacts are not fully understood. In this study, we determined the metal contents of PM 2.5 samples collected from a typical coal-burning city and then investigated the metabolic distributions of six metals (Zn, Pb, Mn, As, Cu, and Cd) following PM 2.5 inhalation in mice in different developmental windows. The results indicate that fine particles were mainly deposited in the lung, but PM 2.5 -bound metals could reach and gather in secondary off-target tissues (the lung, liver, heart and brain) with a developmental window-dependent property. Furthermore, elevations in triglycerides and cholesterol levels in sensitive developmental windows (the young and elderly stages) occurred, and significant associations between metals (Pb, Mn, As and Cd) and cholesterol in the heart, brain, liver and lung were observed. These findings suggest that PM 2.5 inhalation caused selective metal metabolic distribution in tissues with a developmental window-dependent property and that the effects were associated with lipid alterations. This provides a foundation for the underlying systemic toxicity following PM 2.5 exposure based on metal components. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Brain Lactate Metabolism in Humans With Subarachnoid Hemorrhage

    OpenAIRE

    Oddo M; Levine JM; Frangos S; Maloney-Wilensky E; Carrera E; Daniel RT; Levivier M; Magistretti PJ; LeRoux PD

    2012-01-01

    Abstract BACKGROUND AND PURPOSE: Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. METHODS: Thirty one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxi...

  8. Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

    OpenAIRE

    Yao, Junjie; Xia, Jun; Maslov, Konstantin I.; Nasiriavanaki, Mohammadreza; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

    2012-01-01

    We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood–brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for ...

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

    Science.gov (United States)

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

    2014-12-05

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

  10. APOA2 Polymorphism in Relation to Obesity and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Moushira Erfan Zaki

    2013-01-01

    Full Text Available Objectives. This study aims to analysis the relationship between c.-492T>C polymorphism in APOA2 gene and the risk for obesity in a sample of Egyptian adolescents and investigates its effect on body fat distribution and lipid metabolism. Material and Methods. A descriptive, cross-sectional study was conducted on 303 adolescents. They were 196 obese and 107 nonobese, aged 16–19 years old. Variables examined included body mass index (BMI, waist circumference (WC, waist to hip ratio (WHR, systolic and diastolic blood pressure (BP, body fat percentage (BF%, abdominal visceral fat layer, and dietary intake. Abdominal visceral fat thickness was determined by ultrasonography. The polymorphism in the APOA2 c.-492T>C was analyzed by PCR amplification. Results. Genotype frequencies were in Hardy-Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases compared to nonobese. After multivariate adjustment, waist, BF% and visceral adipose layer, food consumption, and HDL-C were significantly higher in homozygous allele CC carriers than TT+TC carriers. Conclusions. Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue and serum HDL-C. Moreover, the study shows association between the APOA2 c.-492T>C polymorphism and food consumption.

  11. [Effects of progestogens on the metabolism of lipids and carbohydrates. Practical consequences (author's transl)].

    Science.gov (United States)

    Ghéron, G

    Estrogens which are one of the components of contraceptive less than pills greater than are incriminated in many cardiovascular accidents. These occur as a result of metabolic disorders (involving lipids and carbohydrates), of modifications in coagulation factors, etc. The possible influence of progestogens was ignored for a long time. The widespread use of these compounds, prescribed for contraception as well as during hormonal replacement therapy for absolute or relative luteinic insufficiency, makes careful monitoring of lipid and carbohydrate metabolism imperative. This position is strengthened by a preliminary review of the literature which leads to several conclusions concerning lipid and carbohydrate metabolism.

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

    Directory of Open Access Journals (Sweden)

    Zhu Zhu

    2016-01-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2017-08-10

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

  14. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    Science.gov (United States)

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  15. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Lauren P. Klosinski

    2015-12-01

    Full Text Available White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  16. Zebrafish Embryonic Lipidomic Analysis Reveals that the Yolk Cell Is Metabolically Active in Processing Lipid

    Directory of Open Access Journals (Sweden)

    Daniel Fraher

    2016-02-01

    Full Text Available The role of lipids in providing energy and structural cellular components during vertebrate development is poorly understood. To elucidate these roles further, we visualized lipid deposition and examined expression of key lipid-regulating genes during zebrafish embryogenesis. We also conducted a semiquantitative analysis of lipidomic composition using liquid chromatography (LC-mass spectrometry. Finally, we analyzed processing of boron-dipyrromethene (BODIPY lipid analogs injected into the yolk using thin layer chromatography. Our data reveal that the most abundant lipids in the embryo are cholesterol, phosphatidylcholine, and triglyceride. Moreover, we demonstrate that lipids are processed within the yolk prior to mobilization to the embryonic body. Our data identify a metabolically active yolk and body resulting in a dynamic lipid composition. This provides a foundation for studying lipid biology during normal or pharmacologically compromised embryogenesis.

  17. A Role of Lipid Metabolism during Cumulus-Oocyte Complex Maturation: Impact of Lipid Modulators to Improve Embryo Production

    Directory of Open Access Journals (Sweden)

    E. G. Prates

    2014-01-01

    Full Text Available Oocyte intracellular lipids are mainly stored in lipid droplets (LD providing energy for proper growth and development. Lipids are also important signalling molecules involved in the regulatory mechanisms of maturation and hence in oocyte competence acquisition. Recent studies show that LD are highly dynamic organelles. They change their shape, volume, and location within the ooplasm as well as their interaction with other organelles during the maturation process. The droplets high lipid content has been correlated with impaired oocyte developmental competence and low cryosurvival. Yet the underlying mechanisms are not fully understood. In particular, the lipid-rich pig oocyte might be an excellent model to understand the role of lipids and fatty acid metabolism during the mammalian oocyte maturation and their implications on subsequent monospermic fertilization and preimplantation embryo development. The possibility of using chemical molecules to modulate the lipid content of oocytes and embryos to improve cryopreservation as well as its biological effects during development is here described. Furthermore, these principles of lipid content modulation may be applied not only to germ cells and embryo cryopreservation in livestock production but also to biomedical fundamental research.

  18. PPAR-α, a lipid-sensing transcription factor, regulates blood-brain barrier efflux transporter expression.

    Science.gov (United States)

    More, Vijay R; Campos, Christopher R; Evans, Rebecca A; Oliver, Keith D; Chan, Gary Ny; Miller, David S; Cannon, Ronald E

    2017-04-01

    Lipid sensor peroxisome proliferator-activated receptor alpha (PPAR- α) is the master regulator of lipid metabolism. Dietary release of endogenous free fatty acids, fibrates, and certain persistent environmental pollutants, e.g. perfluoroalkyl fire-fighting foam components, are peroxisome proliferator-activated receptor alpha ligands. Here, we define a role for peroxisome proliferator-activated receptor alpha in regulating the expression of three ATP-driven drug efflux transporters at the rat and mouse blood-brain barriers: P-glycoprotein (Abcb1), breast cancer resistance protein (Bcrp/Abcg2), and multidrug resistance-associated protein 2 (Mrp2/Abcc2). Exposing isolated rat brain capillaries to linoleic acid, clofibrate, or PKAs increased the transport activity and protein expression of the three ABC transporters. These effects were blocked by the PPAR- α antagonist, GW6471. Dosing rats with 20 mg/kg or 200 mg/kg of clofibrate decreased the brain accumulation of the P-glycoprotein substrate, verapamil, by 50% (in situ brain perfusion; effects blocked by GW6471) and increased P-glycoprotein expression and activity in capillaries ex vivo. Fasting C57Bl/6 wild-type mice for 24 h increased both serum lipids and brain capillary P-glycoprotein transport activity. Fasting did not alter P-glycoprotein activity in PPAR- α knockout mice. These results indicate that hyperlipidemia, lipid-lowering fibrates and exposure to certain fire-fighting foam components activate blood-brain barrier peroxisome proliferator-activated receptor alpha, increase drug efflux transporter expression and reduce drug delivery to the brain.

  19. Life-stage-associated remodelling of lipid metabolism regulation in Atlantic salmon.

    Science.gov (United States)

    Gillard, Gareth; Harvey, Thomas N; Gjuvsland, Arne; Jin, Yang; Thomassen, Magny; Lien, Sigbjørn; Leaver, Michael; Torgersen, Jacob S; Hvidsten, Torgeir R; Vik, Jon Olav; Sandve, Simen R

    2018-03-01

    Atlantic salmon migrates from rivers to sea to feed, grow and develop gonads before returning to spawn in freshwater. The transition to marine habitats is associated with dramatic changes in the environment, including water salinity, exposure to pathogens and shift in dietary lipid availability. Many changes in physiology and metabolism occur across this life-stage transition, but little is known about the molecular nature of these changes. Here, we use a long-term feeding experiment to study transcriptional regulation of lipid metabolism in Atlantic salmon gut and liver in both fresh- and saltwater. We find that lipid metabolism becomes significantly less plastic to differences in dietary lipid composition when salmon transitions to saltwater and experiences increased dietary lipid availability. Expression of genes in liver relating to lipogenesis and lipid transport decreases overall and becomes less responsive to diet, while genes for lipid uptake in gut become more highly expressed. Finally, analyses of evolutionary consequences of the salmonid-specific whole-genome duplication on lipid metabolism reveal several pathways with significantly different (p < .05) duplicate retention or duplicate regulatory conservation. We also find a limited number of cases where the whole-genome duplication has resulted in an increased gene dosage. In conclusion, we find variable and pathway-specific effects of the salmonid genome duplication on lipid metabolism genes. A clear life-stage-associated shift in lipid metabolism regulation is evident, and we hypothesize this to be, at least partly, driven by nondietary factors such as the preparatory remodelling of gene regulation and physiology prior to sea migration. © 2018 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Shengxi Meng

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

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

  2. Fatty acid composition of total lipids and phospholipids of muscular tissue and brain of rats under the impact of vibration

    Directory of Open Access Journals (Sweden)

    N. M. Kostyshyn

    2016-06-01

    Full Text Available Fatty acids are important structural components of biological membranes, energy substrate of cells involved in fixing phospholipid bilayer proteins, and acting as regulators and modulators of enzymatic activity. Under the impact of vibration oscillations there can occur shifts in the ratio of different groups of fatty acids, and degrees of their saturation may change. The imbalance between saturated, monounsaturated and polyunsaturated fatty acids, which occurs later in the cell wall, disrupts fluidity and viscosity of lipid phase and causes abnormal cellular metabolism. Aim. In order to study the impact of vibration on the level of fatty acids of total lipids in muscular tissue and fatty acid composition of phospholipids in muscles and brain, experimental animals have been exposed to vertical vibration oscillations with different frequency for 28 days. Methods and results. Tissues fragments of hip quadriceps and brain of rats were used for obtaining methyl esters of fatty acids studied by the method of gas-liquid chromatography. It was found that the lipid content, ratio of its separate factions and fatty acid composition in muscular tissue and brain of animals with the action of vibration considerably varies. With the increase of vibration acceleration tendency to increase in absolute quantity of total lipids fatty acids can be observed at the account of increased level of saturated and monounsaturated ones. These processes are caused by activation of self-defense mechanisms of the body under the conditions of deviations from stabilized physiological norm, since adaptation requires certain structural and energy costs. Increase in the relative quantity of saturated and monounsaturated fatty acids in phospholipids of muscles and brain and simultaneous reduction in concentration of polyunsaturated fatty acids are observed. Conclusion. These changes indicate worsening of structural and functional organization of muscles and brain cell membranes of

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1975-01-01

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

  4. Dietary L-Carnitine and energy and lipid metabolism in African catfish (Clarias gariepinus) juveniles

    NARCIS (Netherlands)

    A. Ozório, de R.O.

    2001-01-01

    As the lipid content of the diet increases so does the requirement for certain components involved in lipid metabolism. Carnitine is a normal constituent of animal tissues and plasma, which is required for the transport of long-chain fatty acids (LCFAs) to the site of

  5. Metabolomic profiles of lipid metabolism, arterial stiffness and hemodynamics in male coronary artery disease patients

    Directory of Open Access Journals (Sweden)

    Kaido Paapstel

    2016-06-01

    Conclusions: We demonstrated an independent association between the serum medium- and long-chain acylcarnitine profile and aortic stiffness for the CAD patients. In addition to the lipid-related classical CVD risk markers, the intermediates of lipid metabolism may serve as novel indicators for altered vascular function.

  6. Characterization and mechanisms of lipid metabolism in high-fat diet ...

    African Journals Online (AJOL)

    Osumah

    Hepatic lipid vacuolization and even fibrosis in gerbils were greatly formed in ... to generate data on metabolic diseases, they have limita- tions as models of lipid ... cholesterol, 7% lard, 10% yolk powder and 0.5% bile salts as previously ..... Tzallas Ch, Kakafika A, Kiortsis D, Goudevenos I, Elisaf M (2000). Liver function ...

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

    International Nuclear Information System (INIS)

    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 β-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

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

    Science.gov (United States)

    Tian, Lei; Li, Yuanjing; Tian, Chunjie

    2016-01-04

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

  9. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

    KAUST Repository

    Magistretti, Pierre J.

    2015-05-01

    The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

  10. Linking neuronal brain activity to the glucose metabolism.

    Science.gov (United States)

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-08-29

    Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

  11. A calorimetric study of the thermotropic behaviour of mixtures of brain cerebrosides with other brain lipids.

    Science.gov (United States)

    Johnston, D S; Chapman, D

    1988-04-22

    We have used a computer-controlled differential scanning calorimeter to determine the phases present in mixtures of the brain galactocerebrosides with other representative brain lipids. There are two types of brain galactocerebroside, those which possess an alpha-hydroxy substituent on the acyl chain (HFA) and those that do not (NFA). In the liquid crystalline state both cerebrosides were miscible with all the lipids studied, but in the gel state they were immiscible with cholesterol and the brain phosphatidylcholines. However, cholesterol mixtures in which the cholesterol mole fraction exceeded one third formed homogeneous metastable gel states on cooling from above the melting point of the cerebroside. Relaxation to the stable two phase state took place slowly over several hours. The solubilities of the galactocerebrosides in the other main brain sphingolipid, sphingomyelin, were much higher. Only in the case of the NFA galactocerebroside and at low mole fractions of sphingomyelin was immiscibility detected. Ternary mixtures of the two cerebrosides with sphingomyelin/cholesterol and phosphatidylcholine/cholesterol (PC/Chol) showed different miscibility characteristics. On cooling from 80 degrees C all mixtures formed homogeneous gel states. However, on standing the cerebrosides separated into discrete gel phases in all mixtures but one, that in which HFA galactocerebrosides were mixed with sphingomyelin and cholesterol. The cerebroside in the mixture with the composition closest to that of myelin, HFA/PC/Chol, melted at 38 degrees C. On scanning guinea pig CNS myelin which had been equilibrated at 5 degrees C a transition was detected with Tmax 33 degrees C. On the basis of comparison with the HFA/PC/Chol mixture we propose that the transition in myelin at this temperature is due to the melting of a galactocerebroside gel phase.

  12. Lipid metabolism in the heart. Contribution of BMIPP to the diseased heart

    Energy Technology Data Exchange (ETDEWEB)

    Nohara, Ryuji [Tazuke Kofukai Medical Research Inst., Osaka (Japan). Kitano Hospital

    2001-10-01

    Lipid contributes greatly in cardiac metabolism to produce high energy ATPs, and is suggested to be related to the progression and deterioration of heart disease. It is fortunate that the I-123-betamethyliodophenylpentadecanoic acid (BMIPP) imaging technique is now available in determining heart condition, but we must be cautious about the interpretation of images obtained with new tracer. From the uptake of BMIPP into the cell to breakdown and catabolism of it, there exist so many critical enzymatical pathways relating to the modification of BMIPP imaging. In clinical evaluation, the image will be translated as the integral effects of these pathways. In order words, we must be aware of these critical pathways regulating lipid metabolism and modifying factors in order to correctly understand BMIPP imaging. Lipid transport is affected by the albumin/FFA ratio in the blood, and extraction with membrane transporter proteins. Fatty acid binding protein (FABP) in the cytosole will play an important role in regulating lipid flux and following metabolism. Lipid will be utilized either for oxidation, triglyceride or phospholipid formation. For oxidation, carnitine palmitoil transferase is the key enzyme for the entrance of lipid into mitochondria, and oxidative enzymes such as acyl CoA dehydrogenase (MCAD, LCAD, HAD) will determine lipid use for the TCA cycle. ATPs produced in the mitochondria again limit the TG store. It is well known that BMIPP imaging completely changes in the ischemic condition, and is also shown that lipid metabolical regulation completely differs from normal in the very early phase of cardiac hypertrophy. In the process of deteriorating heart failure, metabolical switching of lipid with glucose will take place. In such a different heart disease conditions, it is clear that lipid metabolical regulation, including many lipid enzymes, works differently from in the healthy condition. These lipid enzymes are regulated by nuclear factor peroxisome

  13. The disturbances of lipid metabolism regulation after the prenatal low-level irradiation

    International Nuclear Information System (INIS)

    Rogov, Yu.I.; Danil'chik, V.S.; Spivak, L.V.; Rubchenya, I.N.

    2000-01-01

    The objective of this study was to assess the influence of low-level irradiation on lipid metabolism in rats after prenatal exposure. Pregnant rats were irradiated during the period of gestation with the whole final dose 0,5 Gy/rat. The blood lipid fractions were investigated in newborn rats and in 6-month age rats. In irradiated offspring the lipo synthesis processes exceeded lipolysis in comparison with that of the control. The negative consequences of embryo low-level irradiation in the lipid metabolism regulation are discussed in this report. (authors)

  14. In vitro lipid metabolism, growth and metabolic hormone concentrations in hyperthyroid chickens.

    Science.gov (United States)

    Rosebrough, R W; McMurtry, J P; Vasilatos-Younken, R

    1992-11-01

    Indian River male broiler chickens growing from 7 to 28 d of age were fed on diets containing energy:protein values varying from 43 to 106 MJ/kg protein and containing 0 or 1 mg triiodothyronine (T3)/kg diet to study effects on growth, metabolic hormone concentrations and in vitro lipogenesis. In vitro lipid synthesis was determined in liver explants in the presence and absence of ouabain (Na+, K(+)-transporting ATPase (EC 3.6.1.37) inhibitor) to estimate the role of enzyme activity in explants synthesizing lipid. Growth and feed consumption increased (P 53 MJ/kg protein) and dietary T3 lowered (P 53 MJ/kg protein) increased (P < 0.01) lipogenesis, plasma growth hormone (GH) and decreased plasma insulin-like growth factor 1 (IGF-1). Also, T3 decreased plasma GH, IGF-1 in vitro lipogenesis. Ouabain inhibited a greater proportion of in vitro lipogenesis in those explants synthesizing fat at a high rate. Both dietary T3 and in vitro ouabain decrease lipogenesis, but, when combined, the effects are not cumulative.

  15. 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.

    Science.gov (United States)

    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. Copyright © 2016 National Lipid Association. All rights reserved.

  16. 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.

    Science.gov (United States)

    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. Copyright © 2016 National Lipid Association. All rights reserved.

  17. Introduction to the Thematic Minireview Series: Brain glycogen metabolism.

    Science.gov (United States)

    Carlson, Gerald M; Dienel, Gerald A; Colbran, Roger J

    2018-05-11

    The synthesis of glycogen allows for efficient intracellular storage of glucose molecules in a soluble form that can be rapidly released to enter glycolysis in response to energy demand. Intensive studies of glucose and glycogen metabolism, predominantly in skeletal muscle and liver, have produced innumerable insights into the mechanisms of hormone action, resulting in the award of several Nobel Prizes over the last one hundred years. Glycogen is actually present in all cells and tissues, albeit at much lower levels than found in muscle or liver. However, metabolic and physiological roles of glycogen in other tissues are poorly understood. This series of Minireviews summarizes what is known about the enzymes involved in brain glycogen metabolism and studies that have linked glycogen metabolism to multiple brain functions involving metabolic communication between astrocytes and neurons. Recent studies unexpectedly linking some forms of epilepsy to mutations in two poorly understood proteins involved in glycogen metabolism are also reviewed. © 2018 Carlson et al.

  18. Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts.

    Directory of Open Access Journals (Sweden)

    Lindsay Van den Bossche

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a poorly understood multifactorial pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common feature in canine congenital portosystemic shunts. The aim of this study was to gain detailed insight into the pathogenesis of steatosis in this large animal model. Hepatic lipid accumulation, gene-expression analysis and HPLC-MS of neutral lipids and phospholipids in extrahepatic (EHPSS and intrahepatic portosystemic shunts (IHPSS was compared to healthy control dogs. Liver organoids of diseased dogs and healthy control dogs were incubated with palmitic- and oleic-acid, and lipid accumulation was quantified using LD540. In histological slides of shunt livers, a 12-fold increase of lipid content was detected compared to the control dogs (EHPSS P<0.01; IHPSS P = 0.042. Involvement of lipid-related genes to steatosis in portosystemic shunting was corroborated using gene-expression profiling. Lipid analysis demonstrated different triglyceride composition and a shift towards short chain and omega-3 fatty acids in shunt versus healthy dogs, with no difference in lipid species composition between shunt types. All organoids showed a similar increase in triacylglycerols after free fatty acids enrichment. This study demonstrates that steatosis is probably secondary to canine portosystemic shunts. Unravelling the pathogenesis of this hepatic steatosis might contribute to a better understanding of steatosis in NAFLD.

  19. Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders.

    Science.gov (United States)

    Pistorio, Elisabetta; Luca, Maria; Luca, Antonina; Messina, Vincenzo; Calandra, Carmela

    2011-10-28

    To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated. Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

  20. Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders

    Directory of Open Access Journals (Sweden)

    Messina Vincenzo

    2011-10-01

    Full Text Available Abstract Objective To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI as a new possible biomarker. Methods 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs. The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV and lipid metabolism has been investigated. Results Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Conclusions Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

  1. Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 5

    NARCIS (Netherlands)

    Rakhshandehroo, Maryam; Sanderson-Kjellberg, L.M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; Groot, de Philip; Muller, Michael; Kersten, Sander

    2007-01-01

    PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an

  2. Comprehensive analysis of PPARa-dependent regulation of hepatic lipid metabolism by expression profiling

    NARCIS (Netherlands)

    Rakhshandehroo, Maryam; Sanderson-Kjellberg, L.M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; Groot, de Philip; Muller, Michael; Kersten, Sander

    2007-01-01

    PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to

  3. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    Science.gov (United States)

    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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival

    Directory of Open Access Journals (Sweden)

    Duncan Howie

    2018-01-01

    Full Text Available The differentiation and effector functions of both the innate and adaptive immune system are inextricably linked to cellular metabolism. The features of metabolism which affect both arms of the immune system include metabolic substrate availability, expression of enzymes, transport proteins, and transcription factors which control catabolism of these substrates, and the ability to perform anabolic metabolism. The control of lipid metabolism is central to the appropriate differentiation and functions of T lymphocytes, and ultimately to the maintenance of immune tolerance. This review will focus on the role of fatty acid (FA metabolism in T cell differentiation, effector function, and survival. FAs are important sources of cellular energy, stored as triglycerides. They are also used as precursors to produce complex lipids such as cholesterol and membrane phospholipids. FA residues also become incorporated into hormones and signaling moieties. FAs signal via nuclear receptors and their channeling, between storage as triacyl glycerides or oxidation as fuel, may play a role in survival or death of the cell. In recent years, progress in the field of immunometabolism has highlighted diverse roles for FA metabolism in CD4 and CD8 T cell differentiation and function. This review will firstly describe the sensing and modulation of the environmental FAs and lipid intracellular signaling and will then explore the key role of lipid metabolism in regulating the balance between potentially damaging pro-inflammatory and anti-inflammatory regulatory responses. Finally the complex role of extracellular FAs in determining cell survival will be discussed.

  5. Effects of Quercetin Supplementation on Lipid and Protein Metabolism after Classic Boxing Training

    Science.gov (United States)

    Demirci, Nevzat

    2017-01-01

    The metabolic fitness (MF) is a component of athletes' physical conditioning. This study aims to investigate the effects of quercetin supplementation on Turkish Junior athletes' lipid and protein metabolism relating to MF after one month classic boxing training. Totally 20 voluntary junior male athletes were separated into two equal groups as the…

  6. Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies.

    Science.gov (United States)

    Rooijackers, Hanne M M; Wiegers, Evita C; Tack, Cees J; van der Graaf, Marinette; de Galan, Bastiaan E

    2016-02-01

    Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain's handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.

  7. Superovulation Induced Changes of Lipid Metabolism in Ovaries and Embryos and Its Probable Mechanism.

    Directory of Open Access Journals (Sweden)

    Li-Ya Wang

    Full Text Available 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.

  8. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    Directory of Open Access Journals (Sweden)

    Motoyama Caio SM

    2011-09-01

    Full Text Available Abstract Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H or the alternation of chow (C and an H diet (CH regimen induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

  9. Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts.

    Science.gov (United States)

    Van den Bossche, Lindsay; Schoonenberg, Vivien A C; Burgener, Iwan A; Penning, Louis C; Schrall, Ingrid M; Kruitwagen, Hedwig S; van Wolferen, Monique E; Grinwis, Guy C M; Kummeling, Anne; Rothuizen, Jan; van Velzen, Jeroen F; Stathonikos, Nikolas; Molenaar, Martijn R; Helms, Bernd J; Brouwers, Jos F H M; Spee, Bart; van Steenbeek, Frank G

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a poorly understood multifactorial pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common feature in canine congenital portosystemic shunts. The aim of this study was to gain detailed insight into the pathogenesis of steatosis in this large animal model. Hepatic lipid accumulation, gene-expression analysis and HPLC-MS of neutral lipids and phospholipids in extrahepatic (EHPSS) and intrahepatic portosystemic shunts (IHPSS) was compared to healthy control dogs. Liver organoids of diseased dogs and healthy control dogs were incubated with palmitic- and oleic-acid, and lipid accumulation was quantified using LD540. In histological slides of shunt livers, a 12-fold increase of lipid content was detected compared to the control dogs (EHPSS Plipid-related genes to steatosis in portosystemic shunting was corroborated using gene-expression profiling. Lipid analysis demonstrated different triglyceride composition and a shift towards short chain and omega-3 fatty acids in shunt versus healthy dogs, with no difference in lipid species composition between shunt types. All organoids showed a similar increase in triacylglycerols after free fatty acids enrichment. This study demonstrates that steatosis is probably secondary to canine portosystemic shunts. Unravelling the pathogenesis of this hepatic steatosis might contribute to a better understanding of steatosis in NAFLD.

  10. Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency

    NARCIS (Netherlands)

    A.M. Boot (Annemieke); M.A. Engels (Melanie); G.J.M. Boerma (Geert); E.P. Krenning (Eric); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    1997-01-01

    textabstractAdults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in

  11. Air pollutant sulfur dioxide-induced alterations on the levels of lipids, lipid peroxidation and lipase activity in various regions of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Haider, S S; Hasan, M; Khan, N H

    1982-07-01

    The exposure of rats to SO/sub 2/ (10 p.p.m.) for one hour daily for 30 days caused depletion of total lipids in all brain areas. The contents of phospholipid were elevated in cerebellum and brain stem, but were depleted in cerebral hemisphere. Cholesterol levels showed an increase in various brain regions. On the other hand, gangliosides were increased in cerebellum and brain stem, but were decreased in cerebral hemisphere. Interestingly, cholesterol/phospholipid ratio was increased in different regions of the brain. Lipase activity was elevated in cerebral hemisphere. Lipid peroxidation showed marked increment in whole brain and in all the brain areas studied. The results suggest that SO/sub 2/-exposure induces degradation of lipids. Interestingly, the lipid contents are affected differentially in the various parts of the brain.

  12. TORCing up metabolic control in the brain.

    Science.gov (United States)

    Hietakangas, Ville; Cohen, Stephen M

    2008-05-01

    Transducer of regulated CREB activity 2 (TORC2) is a coactivator of CREB and an important regulator of energy balance in mammals through control of gluconeogenesis in the liver. In this issue of Cell Metabolism, Wang and coworkers (2008) report an intriguing role for Drosophila TORC in the neuronal regulation of metabolism.

  13. Association of Polymorphisms of Genes Involved in Lipid Metabolism with Blood Pressure and Lipid Values in Mexican Hypertensive Individuals

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    Blanca Estela Ríos-González

    2014-01-01

    Full Text Available 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.

  14. Siofor influence on the process of lipid peroxidation and antioxidant status at patients with metabolic syndrome

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    Elena N. Chernysheva

    2014-10-01

    Full Text Available The purpose of the work is to research siofor influence (metformin on the activity of the process of lipid peroxidation and antioxidant activity of blood serum at patients with metabolic syndrome. Material and Methods — 62 patients with metabolic syndrome at the age from 30 till 60 were examined and treated by siofor (1700 mg per day during a year. The process of lipid peroxidation was studied due to the level of lipid hydroperoxide of blood serum. Antioxidant capacity was based on the antioxidant reaction in the blood serum with definite number of exogenic hydrogen dioxide (mkmole/l with the method of enzyme-linked immunosorbent assay (ELISA. Results — Intensification of process of lipid peroxidation has been observed at patients with metabolic syndrome — the level of lipid hydroperoxide of blood serum has been 2.9 (1.9, 3.9 mkM (presented as median and interquartile range, antioxidant activity of blood serum has been decreased — 276.4 (239.0, 379.9 mkmole/l. In 12 months of siofor intake hydroperoxide level has been decreased till 1.1 (0.8, 1.9 mkМ, but antioxidant activity has been increased and amounted 320.0 (278.9, 334.3 mkmole/l. Conclusion — Siofor has been proved to be a highly effective medicine for correction of process of lipid peroxidation and for improvement of antioxidant activity of blood serum at patients with metabolic syndrome.

  15. Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes.

    Science.gov (United States)

    Chen, Hui; Zhang, Liang; Li, Xinwei; Li, Xiaobing; Sun, Guoquan; Yuan, Xue; Lei, Liancheng; Liu, Juxiong; Yin, Liheng; Deng, Qinghua; Wang, Jianguo; Liu, Zhaoxi; Yang, Wentao; Wang, Zhe; Zhang, Hui; Liu, Guowen

    2013-11-01

    Adiponectin (Ad) plays a crucial role in hepatic lipid metabolism. However, the regulating mechanism of hepatic lipid metabolism by Ad in dairy cows is unclear. Hepatocytes from a newborn female calf were cultured in vitro and treated with different concentrations of Ad and BML-275 (an AMPKα inhibitor). The results showed that Ad significantly increased the expression of two Ad receptors. Furthermore, the phosphorylation and activity of AMPKα, as well as the expression levels and transcriptional activity of peroxisome proliferator activated receptor-α (PPARα) and its target genes involved in lipid oxidation, showed a corresponding trend of upregulation. However, the expression levels and transcriptional activity of sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) decreased in a similar manner. When BML-275 was added, the p-AMPKα level as well as the expression and activity of PPARα and its target genes were significantly decreased. However, the expression levels of SREBP-1c, ChREBP and their target genes showed a trend of upregulation. Furthermore, the triglyceride (TG) content was significantly decreased in the Ad-treated groups. These results indicate that Ad activates the AMPK signaling pathway and mediates lipid metabolism in bovine hepatocytes cultured in vitro by promoting lipid oxidation, suppressing lipid synthesis and reducing hepatic lipid accumulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Acquisition of lipid metabolic capability in hepatocyte-like cells directly induced from mouse fibroblasts

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    Shizuka eMiura

    2014-08-01

    Full Text Available Recently, the numbers of patients with non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH have increased worldwide. NAFLD and NASH are known as risk factors for liver cirrhosis and hepatocellular carcinoma. Because many factors can promote the progression of NAFLD and NASH, the treatment of these patients involves various strategies. Thus, it is desired that drugs for patients with NAFLD and NASH should be developed more easily and rapidly using cultures of primary hepatocytes. However, it is difficult to use hepatocytes as a tool for drug screening, because these cells cannot be functionally maintained in culture. Thus, in this study, we sought to examine whether induced hepatocyte-like (iHep cells, which were directly induced from mouse dermal fibroblasts by infection with a retrovirus expressing Hnf4α and Foxa3, possess the potential for lipid metabolism, similar to hepatocytes. Our data showed that iHep cells were capable of synthesizing lipids from a cis-unsaturated fatty acid, a trans-unsaturated fatty acid, and a saturated fatty acid, accumulating the synthesized lipids in cellular vesicles, and secreting the lipids into the culture medium. Moreover, the lipid synthesis in iHep cells was significantly inhibited in cultures with lipid metabolism improvers. These results demonstrate that iHep cells could be useful not only for screening of drugs for patients with NAFLD and NASH, but also for elucidation of the mechanisms underlying hereditary lipid metabolism disorders, as an alternative to hepatocytes.

  17. Danqi Pill regulates lipid metabolism disorder induced by myocardial ischemia through FATP-CPTI pathway.

    Science.gov (United States)

    Wang, Yong; Li, Chun; Wang, Qiyan; Shi, Tianjiao; Wang, Jing; Chen, Hui; Wu, Yan; Han, Jing; Guo, Shuzhen; Wang, Yuanyuan; Wang, Wei

    2015-02-21

    Danqi Pill (DQP), which contains Chinese herbs Salvia miltiorrhiza Bunge and Panax notoginseng, is widely used in the treatment of myocardial ischemia (MI) in China. Its regulatory effects on MI-associated lipid metabolism disorders haven't been comprehensively studied so far. We aimed to systematically investigate the regulatory mechanism of DQP on myocardial ischemia-induced lipid metabolism disorders. Myocardial ischemia rat model was induced by left anterior descending coronary artery ligation. The rat models were divided into three groups: model group with administration of normal saline, study group with administration of DanQi aqueous solution (1.5 mg/kg) and positive-control group with administration of pravastatin aqueous solution (1.2 mg/kg). In addition, another sham-operated group was set as negative control. At 28 days after treatment, cardiac function and degree of lipid metabolism disorders in rats of different groups were measured. Plasma lipid disorders were induced by myocardial ischemia, with manifestation of up-regulation of triglyceride (TG), low density lipoprotein (LDL), Apolipoprotein B (Apo-B) and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR). DQP could down-regulate the levels of TG, LDL, Apo-B and HMGCR. The Lipid transport pathway, fatty acids transport protein (FATP) and Carnitine palmitoyltransferase I (CPTI) were down-regulated in model group. DQP could improve plasma lipid metabolism by up-regulating this lipid transport pathway. The transcription factors peroxisome proliferator-activated receptor α (PPARα) and retinoid X receptors (RXRs), which regulate lipid metabolism, were also up-regulated by DQP. Furthermore, DQP was able to improve heart function and up-regulate ejection fraction (EF) by increasing the cardiac diastolic volume. Our study reveals that DQP would be an ideal alternative drug for the treatment of dyslipidemia which is induced by myocardial ischemia.

  18. Resistin Regulates Pituitary Lipid Metabolism and Inflammation In Vivo and In Vitro

    Directory of Open Access Journals (Sweden)

    F. Rodriguez-Pacheco

    2013-01-01

    Full Text Available The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way and in vitro (adenopituitary cell cultures treated with the adipokine. Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism.

  19. Resistin Regulates Pituitary Lipid Metabolism and Inflammation In Vivo and In Vitro

    Science.gov (United States)

    Rodriguez-Pacheco, F.; Novelle, M. G.; Vazquez, M. J.; Garcia-Escobar, E.; Soriguer, F.; Rojo-Martinez, G.; García-Fuentes, E.; Malagon, M. M.; Dieguez, C.

    2013-01-01

    The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH) secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way) and in vitro (adenopituitary cell cultures treated with the adipokine). Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism. PMID:23710116

  20. Effects of castration on expression of lipid metabolism genes in the liver of korean cattle.

    Science.gov (United States)

    Baik, Myunggi; Nguyen, Trang Hoa; Jeong, Jin Young; Piao, Min Yu; Kang, Hyeok Joong

    2015-01-01

    Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (pcastration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration.

  1. Endothelial progenitor cells physiology and metabolic plasticity in brain angiogenesis and blood-brain barrier modeling

    Directory of Open Access Journals (Sweden)

    Natalia Malinovskaya

    2016-12-01

    Full Text Available Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons. Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies.

  2. Devastating metabolic brain disorders of newborns and young infants.

    Science.gov (United States)

    Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

    2014-01-01

    Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis. ©RSNA, 2014.

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

    Directory of Open Access Journals (Sweden)

    Yusuke Murata

    2011-01-01

    Full Text Available 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.

  4. Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

    Science.gov (United States)

    Yao, Junjie; Xia, Jun; Maslov, Konstantin; Avanaki, Mohammadreza R. N.; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

    2013-03-01

    To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

  5. In vivo metabolic fingerprinting of neutral lipids with hyperspectral stimulated Raman scattering microscopy.

    Science.gov (United States)

    Fu, Dan; Yu, Yong; Folick, Andrew; Currie, Erin; Farese, Robert V; Tsai, Tsung-Huang; Xie, Xiaoliang Sunney; Wang, Meng C

    2014-06-18

    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.

  6. The metabolism of malate by cultured rat brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, M.C.; Tildon, J.T.; Couto, R.; Stevenson, J.H.; Caprio, F.J. (Department of Pediatrics, University of Maryland School of Medicine, Baltimore (USA))

    1990-12-01

    Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-(U-14C)malate in rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain.

  7. Interactions of Lipid Genetic Risk Scores with Estimates of Metabolic Health in a Danish Population

    DEFF Research Database (Denmark)

    Justesen, Johanne M; Allin, Kristine H; Sandholt, Camilla H

    2015-01-01

    Background—There are several well-established lifestyle factors influencing dyslipidemia and currently; 157 genetic susceptibility loci have been reported to be associated with serum lipid levels at genome-wide statistical significance. However, the interplay between lifestyle risk factors...... and these susceptibility loci has not been fully elucidated. We tested whether genetic risk scores (GRS) of lipid-associated single nucleotide polymorphisms associate with fasting serum lipid traits and whether the effects are modulated by lifestyle factors or estimates of metabolic health. Methods and Results—The single......-cholesterol, high-density lipoprotein-cholesterol, or triglyceride, 4 weighted GRS were constructed. In a cross-sectional design, we investigated whether the effect of these weighted GRSs on lipid levels were modulated by diet, alcohol consumption, physical activity, and smoking or the individual metabolic health...

  8. Skeletal muscle lipid metabolism in exercise and insulin resistance

    DEFF Research Database (Denmark)

    Kiens, Bente

    2006-01-01

    Lipids as fuel for energy provision originate from different sources: albumin-bound long-chain fatty acids (LCFA) in the blood plasma, circulating very-low-density lipoproteins-triacylglycerols (VLDL-TG), fatty acids from triacylglycerol located in the muscle cell (IMTG), and possibly fatty acids...... of insulin resistance in skeletal muscle, including possible molecular mechanisms involved, is discussed....

  9. Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes

    Directory of Open Access Journals (Sweden)

    Shiqi Zhang

    2018-03-01

    Full Text Available Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1, an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c and its target genes, diacylglycerol acyltransferase (DGAT 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL and CGI-58 for adipose triglyceride lipase (ATGL, thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α, interleukin 1 beta (IL-1β, and interleukin 6 (IL-6 induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

  10. Effects of Castration on Expression of Lipid Metabolism Genes in the Liver of Korean Cattle

    Directory of Open Access Journals (Sweden)

    Myunggi Baik

    2015-01-01

    Full Text Available Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001 hepatic lipids contents and higher (p<0.01 mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2 and fatty acid (FA oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration.

  11. Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes.

    Science.gov (United States)

    Zhang, Shiqi; Liu, Guowen; Xu, Chuang; Liu, Lei; Zhang, Qiang; Xu, Qiushi; Jia, Hongdou; Li, Xiaobing; Li, Xinwei

    2018-01-01

    Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

  12. Mass Spectrometry Imaging Shows Cocaine and Methylphenidate Have Opposite Effects on Major Lipids in Drosophila Brain.

    Science.gov (United States)

    Philipsen, Mai H; Phan, Nhu T N; Fletcher, John S; Malmberg, Per; Ewing, Andrew G

    2018-03-20

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to study the effects of cocaine versus methylphenidate administration on both the localization and abundance of lipids in Drosophila melanogaster brain. A J105 ToF-SIMS with a 40 keV gas cluster primary ion source enabled us to probe molecular ions of biomolecules on the fly with a spatial resolution of ∼3 μm, giving us unique insights into the effect of these drugs on molecular lipids in the nervous system. Significant changes in phospholipid composition were observed in the central brain for both. Principal components image analysis revealed that changes occurred mainly for phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols. When the lipid changes caused by cocaine were compared with those induced by methylphenidate, it was shown that these drugs exert opposite effects on the brain lipid structure. We speculate that this might relate to the molecular mechanism of cognition and memory.

  13. MR spectroscopy detection of lactate and lipid signals in the brains of healthy elderly people

    Energy Technology Data Exchange (ETDEWEB)

    Sijens, P.E.; Heijboer, R.J.J.; Oudkerk, M. [Dept. of Radiology, Univ. Hospital Groningen (Netherlands); Heijer, T. den; Leeuw, F.E. de; Groot, J.C. de; Hofman, A.; Breteler, M.M.B. [Dept. of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam (Netherlands); Achten, E. [Dept. of Magnetic Resonance, Gent University Hospital (Belgium)

    2001-08-01

    Magnetic resonance spectroscopy was used to assess the presence of brain lactate and lipid signals, frequently associated with the presence of pathology, in healthy persons of 60-90 years old (n=540). Lactate and lipid signals were observed in, respectively, 25 and 6% of women, and 18 and 2% of men. Upon adjustment for age, and for MRI-detected cerebral atrophy and white matter lesions, the gender differences in lactate and lipid remained the same (p=0.05 and p=0.03, respectively). Brain lactate and lipid signals appear to be intrinsic to aging. However, the presence of these metabolites in very focal areas only, rather than in any distributed fashion within the brain (the latter generally the case with cerebral atrophy and white matter lesions), strongly suggests the existence of asymptomatic focal pathology not shown on MRI. (orig.)

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

    DEFF Research Database (Denmark)

    Caesar, Robert; Nygren, Heli; Orešič, Matej

    2016-01-01

    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...... 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...

  15. Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

    Science.gov (United States)

    Yao, Junjie; Xia, Jun; Maslov, Konstantin I.; Nasiriavanaki, Mohammadreza; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

    2012-01-01

    We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively decoupled by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area had a clear vascular pattern and spread wider than the somatosensory region. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism. PMID:22940116

  16. Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.

    Science.gov (United States)

    Singh, Indu; Swami, Rajan; Pooja, Deep; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

    2016-01-01

    Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively. Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation. It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than

  17. Membrane lipid alterations in the metabolic syndrome and the role of dietary oils.

    Science.gov (United States)

    Perona, Javier S

    2017-09-01

    The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue. Diet intervention has been proposed as a powerful tool to prevent the development of the metabolic syndrome, since healthy diets have been shown to have a protective role against the components of the metabolic syndrome. Particularly, dietary fatty acids are capable of modulating the deleterious effects of these conditions, among other mechanisms, by modifications of the lipid composition of the membranes in insulin-sensitive tissues. However, there is still scarce data based of high-level evidence on the effects of dietary oils on the effects of the metabolic syndrome and its components. This review summarizes the current knowledge on the effects of dietary oils on improving alterations of the components of the metabolic syndrome. It also examines their influence in the modulation of plasma membrane lipid composition and in the functionality of membrane proteins involved in insulin activity, like the insulin receptor, GLUT-4, CD36/FAT and ABCA-1, and their effect in the metabolism of glucose, fatty acids and cholesterol, and, in turn, the key features of the metabolic syndrome. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review.

    Science.gov (United States)

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2011-09-01

    Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.

  19. Alteration in lipid metabolism induced by a diet rich in soya-oil and ...

    African Journals Online (AJOL)

    PGD

    2013-09-11

    Sep 11, 2013 ... metabolism in brain, liver and plasma of albino rat model. ... decrease in the levels of the steroidal sex hormones in the starved and other dietary groups compared ..... enriched diet rat group with significant differences only in.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    Highlights: • Use of cross-omics technologies to evaluate toxic effects of microcystin-LR. • Disturbance of hepatic lipid metabolism by oral exposure to microcystin-LR. • Crucial roles of gut microbial community shift in the metabolic disturbance induced by microcystin-LR. - Abstract: 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 0.2 mg/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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zongyao [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Center for Environmental Health Research, South China Institute of Environmental Sciences, The Ministry of Environmental Protection of PRC, Guangzhou 510655 (China); Zhang, Xu-Xiang, E-mail: zhangxx@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Wu, Bing; Yin, Jinbao [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China); Yu, Yunjiang [Center for Environmental Health Research, South China Institute of Environmental Sciences, The Ministry of Environmental Protection of PRC, Guangzhou 510655 (China); Yang, Liuyan, E-mail: yangly@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023 (China)

    2016-09-05

    Highlights: • Use of cross-omics technologies to evaluate toxic effects of microcystin-LR. • Disturbance of hepatic lipid metabolism by oral exposure to microcystin-LR. • Crucial roles of gut microbial community shift in the metabolic disturbance induced by microcystin-LR. - Abstract: 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 0.2 mg/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.

  2. MR spectroscopy in metabolic disorders of the brain

    International Nuclear Information System (INIS)

    Yilmaz, U.

    2017-01-01

    Metabolic disorders of the brain often present a particular challenge for the neuroradiologist, since the disorders are rare, changes on conventional MR are often non-specific and there are numerous differential diagnoses for the white substance lesions. As a complementary method to conventional brain MRI, MR spectroscopy may help to reduce the scope of the differential diagnosis. Entities with specific MR spectroscopy patterns are Canavan disease, maple syrup urine disease, nonketotic hyperglycinemia and creatine deficiency. (orig.) [de

  3. The effect of hypokinesia on lipid metabolism in adipose tissue

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting; Kiens, Bente

    2014-01-01

    Exercise increases the utilization of lipids in muscle. The sources of lipids are long-chain fatty acids taken up from the plasma and fatty acids released from stores of intramuscular triacylglycerol by the action of intramuscular lipases. In the present review, we focus on the role of fatty acid...... binding proteins, particularly fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in the exercise- and contraction-induced increase in uptake of long-chain fatty acids in muscle. The FAT/CD36 translocates from intracellular depots to the surface membrane upon initiation of exercise/muscle...... triglyceride lipase in regulation of muscle lipolysis. Although the molecular regulation of the lipases in muscle is not understood, it is speculated that intramuscular lipolysis may be regulated in part by the availability of the plasma concentration of long-chain fatty acids....

  5. [Influence of diets with qualitatively different carbohydrates on lipid metabolism].

    Science.gov (United States)

    Markelova, V F; Zalesskaia, Iu M

    1977-01-01

    Tests conducted with rats demonstrated that rations carrying saccharose cause a rise in the pre-beta-lipoproteids, blood triglycerides, total lipids and triglycerides in the aorta, as well as an accelerated biosynthesis of the latter in the liver and the fatty tissue. The effect of the saccharose making part of an isocaloric ration depends upon the quality of the diet as a whole. In rats receiving saccharose in a ration with a reduced amount of fat (11% bythe calorific value) there takes place an accelerated biosynthesis of phospholipids with no evidence of fatty degeneration of the liver. Animals receiving saccharose in a ration with a physiological level of fat (26% by caloricity) demonstrated a higher content of beta-lipoproteids in the blood, of total lipids and tryglycerides in the liver with lacking acceleration of the phospholipids biosynthesis in the latter.

  6. A new fluorescence-based method identifies protein phosphatases regulating lipid droplet metabolism.

    Directory of Open Access Journals (Sweden)

    Bruno L Bozaquel-Morais

    Full Text Available 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.

  7. Glucose metabolism, diet composition, and the brain

    NARCIS (Netherlands)

    Diepenbroek, C.

    2017-01-01

    Excessive intake of saturated fat and sugar contributes to both obesity and diabetes development. Since intake of fat and sugar-sweetened beverages exceeds recommended levels worldwide, it is essential to: 1) Understand how fat and sugar intake affect glucose metabolism, and 2) Expand the knowledge

  8. Effects of diabetes on brain metabolism - is brain glycogen a significant player?

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Waagepetersen, Helle S.

    2015-01-01

    Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the br......Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose...... to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may...... understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes....

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

    Science.gov (United States)

    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 (pglucose 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

  10. Study of brain metabolism using positron emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Heiss, W D

    1983-03-21

    Positron emission tomography permits the three-dimensional regional measurement of metabolism and blood flow in the brain. For the determination of cerebral metabolic rates of glucose by PET /sup 18/fluordeoxyglucose is usually applied: cerebral metabolic rate of glucose was found to be 36 to 47 ..mu..mol/100 g/min in the grey matter and 23 to 29 ..mu..mol/100 g/min in the white matter of normal volunteers. During physiologic activation metabolic rate of glucose is increased in the respective brain areas in relation to the strength and complexity of the stimulation. In patients suffering from ischaemic stroke glucose metabolism is markedly decreased within the infarction. Additonally, glucose metabolism is reduced by 20% in morphologically intact areas of the homolateral cortex, in the basal ganglia, in the cortical area contralateral to the infarction and in the contralateral cerebellum. This remote reduction of glucose utilization is probably caused by functional inactivation of these brain structures; it could be responsible for the diffuse organic syndrome in stroke victims not caused by the focal lesion. In patients suffering from dementia of the multi-infarct type and of the Alzheimer type glucose metabolism is reduced; the lesions in Alzheimer cases are most prominent in partietal and frontal cortical areas. In Chorea Huntington cases glucose metabolism is primarily disturbed in the striate, especially in the caudate nucleus; in these cases the metabolic disturbance can be detected earlier than the atrophy in computed tomograms. Disturbances of glucose and oxygen utilization are not necessary causes, but may also be sequelae od functional impairment. Additional information on pathogentic mechanisms may be obtained by the investigation of the protein synthesis.

  11. Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals.

    Science.gov (United States)

    Carmona-Antoñanzas, Greta; Tocher, Douglas R; Martinez-Rubio, Laura; Leaver, Michael J

    2014-01-15

    Lipid content and composition in aquafeeds have changed rapidly as a result of the recent drive to replace ecologically limited marine ingredients, fishmeal and fish oil (FO). Terrestrial plant products are the most economic and sustainable alternative; however, plant meals and oils are devoid of physiologically important cholesterol and long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acids. Although replacement of dietary FO with vegetable oil (VO) has little effect on growth in Atlantic salmon (Salmo salar), several studies have shown major effects on the activity and expression of genes involved in lipid homeostasis. In vertebrates, sterols and LC-PUFA play crucial roles in lipid metabolism by direct interaction with lipid-sensing transcription factors (TFs) and consequent regulation of target genes. The primary aim of the present study was to elucidate the role of key TFs in the transcriptional regulation of lipid metabolism in fish by transfection and overexpression of TFs. The results show that the expression of genes of LC-PUFA biosynthesis (elovl and fads2) and cholesterol metabolism (abca1) are regulated by Lxr and Srebp TFs in salmon, indicating highly conserved regulatory mechanism across vertebrates. In addition, srebp1 and srebp2 mRNA respond to replacement of dietary FO with VO. Thus, Atlantic salmon adjust lipid metabolism in response to dietary lipid composition through the transcriptional regulation of gene expression. It may be possible to further increase efficient and effective use of sustainable alternatives to marine products in aquaculture by considering these important molecular interactions when formulating diets. © 2013.

  12. The sweet path to metabolic demise: fructose and lipid synthesis

    Science.gov (United States)

    Herman, Mark A.; Samuel, Varman T.

    2016-01-01

    Epidemiological studies link fructose consumption with metabolic disease, an association attributable in part to fructose mediated lipogenesis. The mechanisms governing fructose-induced lipogenesis and disease remain debated. Acutely, fructose increases de novo lipogenesis through the efficient and uninhibited action of Ketohexokinase and Aldolase B, which yields substrates for fatty-acid synthesis. Chronic fructose consumption further enhances the capacity for hepatic fructose metabolism via activation of several key transcription factors (i.e. SREBP1c and ChREBP), which augment expression of lipogenic enzymes, increasing lipogenesis, further compounding hypertriglyceridemia, and hepatic steatosis. Hepatic insulin resistance develops from diacylglycerol-PKCε mediated impairment of insulin signaling and possibly additional mechanisms. Initiatives that decrease fructose consumption and therapies that block fructose mediated lipogenesis are needed to avert future metabolic pandemics. PMID:27387598

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

    Science.gov (United States)

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

    2012-01-01

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

  14. Diacylglycerol-enriched structured lipids containing CLA and capric acid alter body fat mass and lipid metabolism in rats.

    Science.gov (United States)

    Kim, Hye-Jin; Lee, Ki-Teak; Lee, Mi-Kyung; Jeon, Seon-Min; Choi, Myung-Sook

    2006-01-01

    The present study compared the effect of corn oil, diacylglycerol (DG) oil, and DG-enriched structured lipids (SL-DG) produced from corn oil, capric and conjugated linoleic acid on adiposity in rats fed an AIN-76 diet (5% fat) for 6 weeks. The plasma and hepatic lipids, adipose tissue weight, and enzyme activities related to fatty acid metabolism were determined. The weights of the epididymal white adipose tissue (WAT), perirenal WAT, and interscapular WAT were significantly lower in the SL-DG group than in the DG group. Reduction of fat mass in the SL-DG group was related to suppressing fatty acid synthase activities and enhancing beta-oxidation activity in perirenal WAT. The plasma leptin was lower in the SL-DG group than in the DG group, plus a lower plasma TG level was accompanied by an increase in adipocyte LPL activity. Meanwhile the SL-DG supplement lowered the plasma and hepatic cholesterol level. In addition, the hepatic HMG-CoA reductase and ACAT activities were significantly lower in the SL-DG group than in the other groups. The DG-enriched SL used in this study was effective in enhancing triglyceride metabolism in adipose tissue, especially as regards reducing the abdominal fat mass and cholesterol metabolism in the liver. Copyright 2006 S. Karger AG, Basel.

  15. Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury

    OpenAIRE

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

    2017-01-01

    Abstract Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET). We consecutively enrolled 11 patients with FOG after HIBI. The patients’ overall brain metabolism was measured by F-18 FDG PET, and we co...

  16. Effects of dietary phospholipid level in cobia (Rachycentron canadum) larvae: growth, survival, plasma lipids and enzymes of lipid metabolism.

    Science.gov (United States)

    Niu, J; Liu, Y J; Tian, L X; Mai, K S; Yang, H J; Ye, C X; Zhu, Y

    2008-03-01

    A study was conducted to determine the effects of dietary phospholipid (PL) levels in cobia (Rachycentron canadum) larvae with regard to growth, survival, plasma lipids and enzymes of lipid metabolism. Fish with an average weight of 0.4 g were fed diets containing four levels of PL (0, 20, 40 and 80 g kg(-1)dry matter: purity 97%) for 42 days. Final body weight (FBW), weight gain (WG) and survival ratio were highest in the 8% PL diet group and mortality was highest in PL-free diet group. We examined the activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in liver, lecithin-cholesterolacyltransferase (LCAT) in plasma as well as plasma lipids and lipoprotein. LCAT activity showed a decrease of more than two-fold in PL-supplemented diet groups compared with the PL-free diet group. HL activity was highest in the 8% PL diet group and the other three groups showed no difference. LPL activity was significantly higher in the PL-supplemented diet groups than in the PL-free diet group. The dietary intervention significantly increased plasma phospholipids and total cholesterol (TC) levels, and the higher free cholesterol (FC) level contributed to the TC level. However, the fish fed PL exhibited a significantly decreased plasma triglyceride (TG) level. The lipoprotein fractions were also affected significantly by the PL. The PL-supplemented diet groups had significantly higher high-density lipoprotein (HDL) compared with the PL-free diet group, but showed a marked decrease in very low-density lipoprotein (VLDL). The results suggested that PL could modify plasma lipoprotein metabolism and lipid profile, and that the optimal dietary PL level may well exceed 80 g kg(-1) for cobia larvae according to growth and survival.

  17. Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

    Science.gov (United States)

    Volonté, M A; Garibotto, V; Spagnolo, F; Panzacchi, A; Picozzi, P; Franzin, A; Giovannini, E; Leocani, L; Cursi, M; Comi, G; Perani, D

    2012-07-01

    Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Insulin resistance, metabolic syndrome, and lipids in African women

    African Journals Online (AJOL)

    2016-01-27

    Jan 27, 2016 ... high‑density lipoprotein (TG/HDL), total cholesterol (TC)/HDL, and atherogenic index of ... Key words: Insulin resistance, metabolic syndrome, triglycerides, women ... been reported that a TG/HDL ratio of >3.0 is predictive of.

  19. Lipid metabolism in peroxisomes in relation to human disease

    NARCIS (Netherlands)

    Wanders, R. J.; Tager, J. M.

    1998-01-01

    Peroxisomes were long believed to play only a minor role in cellular metabolism but it is now clear that they catalyze a number of important functions. The importance of peroxisomes in humans is stressed by the existence of a group of genetic diseases in man in which one or more peroxisomal

  20. Insulin resistance, metabolic syndrome, and lipids in African women ...

    African Journals Online (AJOL)

    HDL, and atherogenic index of plasma; log (TG/HDL) were calculated and compared with IR. Metabolic syndrome was sought for using both the WHO and the harmonized joint criteria. Results: The mean age was 44.4 (13.1) years. Hypertension ...

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

    Science.gov (United States)

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

    2015-10-01

    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. © 2015 Authors; published by Portland Press Limited.

  2. Icariin Is A PPARα Activator Inducing Lipid Metabolic Gene Expression in Mice

    Directory of Open Access Journals (Sweden)

    Yuan-Fu Lu

    2014-11-01

    Full Text Available Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg, or clofibrate (500 mg/kg for five days. Liver total RNA was isolated and the expressions of PPARα and lipid metabolism genes were examined. PPARα and its marker genes Cyp4a10 and Cyp4a14 were induced 2-4 fold by icariin, and 4-8 fold by clofibrate. The fatty acid (FA binding and co-activator proteins Fabp1, Fabp4 and Acsl1 were increased 2-fold. The mRNAs of mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2 were increased 2-3 fold. The mRNAs of proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh were also increased by icariin and clofibrate. The expression of mRNAs for sterol regulatory element-binding factor-1 (Srebf1 and FA synthetase (Fasn were unaltered by icariin. The lipid lysis genes Lipe and Pnpla2 were increased by icariin and clofibrate. These results indicate that icariin is a novel PPARα agonist, activates lipid metabolism gene expressions in liver, which could be a basis for its lipid-lowering effects and its beneficial effects against diabetes.

  3. Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

    Science.gov (United States)

    Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

    2017-08-01

    Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Lactate storm marks cerebral metabolism following brain trauma.

    Science.gov (United States)

    Lama, Sanju; Auer, Roland N; Tyson, Randy; Gallagher, Clare N; Tomanek, Boguslaw; Sutherland, Garnette R

    2014-07-18

    Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Reduced brain/serum glucose ratios predict cerebral metabolic distress and mortality after severe brain injury.

    Science.gov (United States)

    Kurtz, Pedro; Claassen, Jan; Schmidt, J Michael; Helbok, Raimund; Hanafy, Khalid A; Presciutti, Mary; Lantigua, Hector; Connolly, E Sander; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A

    2013-12-01

    The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury. We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality. A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

  6. Lipid metabolism and body composition in Gclm(−/−) mice

    International Nuclear Information System (INIS)

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

    2011-01-01

    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: ► A high fat diet does not produce body weight and fat gain in Gclm(−/−) mice. ► A high fat diet does not induce steatosis or insulin resistance in Gclm(−/−) mice. ► Gclm(−/−) mice have high basal metabolism and mitochondrial oxygen consumption.

  7. Metabolic regulation in meagre, Argyrosomus regius (Asso, 1801: Study of gene-diet interactions on lipid metabolism

    Directory of Open Access Journals (Sweden)

    Francisca Silva-Brito

    2014-06-01

    profile on fads2 (fatty acyl desaturase gene and elovl5 (fatty acyl elongase gene expression in liver and brain of meagre (Argyrosomus regius. The four isoproteic and isolipidic diets (50% protein and 12% lipid, dry matter basis were formulated with fish oil (FO or a blend of vegetable oils (VO, rapeseed, linseed and soybean, each with selenium (S, 1mg/kg diet or without selenium (NS. Fish were fed ad libitum for 60 days under a controlled rearing conditions (temperature = 20,7 ± 0,7 ºC; pH = 8; O2 = > 6 ppm. Ribonucleic acid (RNA was extracted from two tissues: liver and brain using RNAspin Mini RNAIsolation Kit (GE Healthcare, with includes a step with DNase I to remove the presence of DNA. The integrity of the extracted RNA was verified by agarose electrophoresis. The RNA concentrations were obtained by nanodrop. From the total RNA, 0.5µg were transcribed to complementary DNA (cDNA using iScript Reverse Transcription Supermix for RT-PCR (BioRad following the manufacturer protocol. Gene expression from fads2 and elovl5 were quantified by analysis of RT-PCR. The β-actine was used as a reference gene. On VO diet hepatic fads2 expression was significantly higher, but not elovl5 expression. In brain of VO fed fish, fads2 and elovl5 expression was not significantly different when compared with FO fed fish (Table 1. With selenium supplementation hepatic fads2 expression was lower in FO (P 0.05. The same trend was evident for hepatic elovl5 expression (P> 0.05 (Table1. Recently, Monroig et al. (2013 described the first functional characterization of meagre Fads2 and Elovl5. This work concluded that, unlike most teleosts, the Fads2 pocesses ∆6 and ∆8 activity. However, conversion rates of meagre Fads2 were low when compared to Salmo salar ∆6 Fads_c (Monroig et al., 2011. On the other hand, meagre Elovl5 showed high activity towards C18 and C20. Thus, ∆6/∆8 activity might be ineffective in converting C18 PUFA and therefore an increase of dietary C18 PUFA may

  8. Brain metabolism in health, aging, and neurodegeneration.

    Science.gov (United States)

    Camandola, Simonetta; Mattson, Mark P

    2017-06-01

    Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

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

    International Nuclear Information System (INIS)

    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

    2014-01-01

    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

  10. Lipid Metabolism in Vascular Smooth Muscle Cells Infuenced by HCMV Infection

    Directory of Open Access Journals (Sweden)

    Lingfang Li

    2016-10-01

    Full Text Available Background: The present study was designed to observe the infection of human cytomegalovirus (HCMV to human vascular smooth muscle cells (VSMCs, and the effect of viral infection on lipid metabolism in VSMCs. Methods: The cytopathic effects were observed by inverted microscopy and viral infection were examined by electron microscopy and RT-PCR. The lipid metabolism related gene profiling of VSMCs after HCMV infection was assayed by cDNA assay and the abnormal expression of genes were validated by quantitative RT-PCR. The content of cholesterol in VSMCs after HCMV infection was assayed by cholesterol detection kit. Results: VSMCs showed obvious cytopathic effects after HCMV infection. Intact viral particles could be detected in VSMCs using electron microscope. By use of RT-PCR technology, IE gene of HCMV could be amplified from VSMCs. The expression of cell lipid metabolism related gene profiling showed obvious disorders. The expression levels of HMG-CoA synthase and HMG-CoA reductase after infection increased significantly. The cellular cholesterol content (µmol/106 cells was significantly higher than that of mock infected group at 72h post infection. Conclusion: HCMV can infect VSMCs and the infection can affect cellular lipid metabolism related gene expression, which get involved in the occurrence and development of atherosclerosis (AS.

  11. PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism

    NARCIS (Netherlands)

    Diepen, van J.A.; Jansen, P.A.; Ballak, D.B.; Hijmans, A.; Hooiveld, G.J.E.J.; Rommelaere, S.; Kersten, A.H.; Stienstra, R.

    2014-01-01

    Background & Aims Peroxisome proliferator-activated receptor alpha (PPARa) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARa target gene in liver, but its function in hepatic lipid metabolism is unknown.

  12. Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes

    NARCIS (Netherlands)

    Sadeghian, Saeed; Boroumand, Mohammad Ali; Sotoudeh-Anvari, Maryam; Rahbani, Shahram; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    Background: This experimental study was performed to determine the impact of opium use on serum lipid profile and glucose metabolism in rats with streptozotocin-induced diabetes. Material and methods: To determine the effect of opium, 20 male rats were divided into control (n = 10) and opium-treated

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

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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...

  15. Disorders of lipid metabolism in 3 patients with diabetes mellitus type 2

    NARCIS (Netherlands)

    Wolffenbuttel, B.H.R.; Huijberts, M.S.P.

    2001-01-01

    Disorders of lipid metabolism in 3 patients with diabetes mellitus type 2] [Article in Dutch] Wolffenbuttel BH, Huijberts MS. Academisch Ziekenhuis, afd. Endocrinologie, Postbus 5800, 6202 AZ Maastrict. bwo@sint.azm.nl Three patients with diabetes mellitus (type 2) and cardiovascular disease had

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

    Energy Technology Data Exchange (ETDEWEB)

    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 [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Sang Gyu [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Inkyu [School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842 (Korea, Republic of); Kim, Myoung Ok [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Yoon, Duhak, E-mail: dhyoon@knu.ac.kr [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Ryoo, Zae Young, E-mail: jaewoong64@hanmail.net [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of)

    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.

  17. Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose

    DEFF Research Database (Denmark)

    Bülow, J; Simonsen, L; Wiggins, D

    1999-01-01

    The integration of lipid metabolism in the splanchnic bed and in subcutaneous adipose tissue before and after ingestion of a 75 g glucose load was studied by Fick's principle in seven healthy subjects. Six additional subjects were studied during a hyperinsulinemic euglycemic clamp. Release of non...

  18. Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight

    DEFF Research Database (Denmark)

    Meidtner, Karina; Fisher, Eva; Angquist, Lars

    2014-01-01

    We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI...

  19. A study on the effect of resveratrol on lipid metabolism in ...

    African Journals Online (AJOL)

    The objective of this paper was to study the effect of resveratrol on lipid metabolism in hyperlipidemia mice. Materials andMethods: Through the establishment of an experimental mouse model of hyperlipidemia, the effect of resveratrol on change in total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol ...

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

    Science.gov (United States)

    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

  1. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    Science.gov (United States)

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

  2. Estrogen Interactions With Lipid Rafts Related to Neuroprotection. Impact of Brain Ageing and Menopause

    Directory of Open Access Journals (Sweden)

    Raquel Marin

    2018-03-01

    Full Text Available Estrogens (E2 exert a plethora of neuroprotective actions against aged-associated brain diseases, including Alzheimer's disease (AD. Part of these actions takes place through binding to estrogen receptors (ER embedded in signalosomes, where numerous signaling proteins are clustered. Signalosomes are preferentially located in lipid rafts which are dynamic membrane microstructures characterized by a peculiar lipid composition enriched in gangliosides, saturated fatty acids, cholesterol, and sphingolipids. Rapid E2 interactions with ER-related signalosomes appear to trigger intracellular signaling ultimately leading to the activation of molecular mechanisms against AD. We have previously observed that the reduction of E2 blood levels occurring during menopause induced disruption of ER-signalosomes at frontal cortical brain areas. These molecular changes may reduce neuronal protection activities, as similar ER signalosome derangements were observed in AD brains. The molecular impairments may be associated with changes in the lipid composition of lipid rafts observed in neurons during menopause and AD. These evidences indicate that the changes in lipid raft structure during aging may be at the basis of alterations in the activity of ER and other neuroprotective proteins integrated in these membrane microstructures. Moreover, E2 is a homeostatic modulator of lipid rafts. Recent work has pointed to this relevant aspect of E2 activity to preserve brain integrity, through mechanisms affecting lipid uptake and local biosynthesis in the brain. Some evidences have demonstrated that estrogens and the docosahexaenoic acid (DHA exert synergistic effects to stabilize brain lipid matrix. DHA is essential to enhance molecular fluidity at the plasma membrane, promoting functional macromolecular interactions in signaling platforms. In support of this, DHA detriment in neuronal lipid rafts has been associated with the most common age-associated neuropathologies

  3. Metabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3-iodothyronamine.

    Science.gov (United States)

    Selen Alpergin, Ebru S; Bolandnazar, Zeinab; Sabatini, Martina; Rogowski, Michael; Chiellini, Grazia; Zucchi, Riccardo; Assadi-Porter, Fariba M

    2017-01-01

    Complex diseases such as polycystic ovary syndrome (PCOS) are associated with intricate pathophysiological, hormonal, and metabolic feedbacks that make their early diagnosis challenging, thus increasing the prevalence risks for obesity, cardiovascular, and fatty liver diseases. To explore the crosstalk between endocrine and lipid metabolic pathways, we administered 3-iodothyronamine (T1AM), a natural analog of thyroid hormone, in a mouse model of PCOS and analyzed plasma and tissue extracts using multidisciplinary omics and biochemical approaches. T1AM administration induces a profound tissue-specific antilipogenic effect in liver and muscle by lowering gene expression of key regulators of lipid metabolism, PTP1B and PLIN2, significantly increasing metabolites (glucogenic, amino acids, carnitine, and citrate) levels, while enhancing protection against oxidative stress. In contrast, T1AM has an opposing effect on the regulation of estrogenic pathways in the ovary by upregulating STAR, CYP11A1, and CYP17A1. Biochemical measurements provide further evidence of significant reduction in liver cholesterol and triglycerides in post-T1AM treatment. Our results shed light onto tissue-specific metabolic vs. hormonal pathway interactions, thus illuminating the intricacies within the pathophysiology of PCOS This study opens up new avenues to design drugs for targeted therapeutics to improve quality of life in complex metabolic diseases. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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

    Czech Academy of Sciences Publication Activity Database

    Masoodi, M.; Kuda, Ondřej; Rossmeisl, Martin; Flachs, Pavel; Kopecký, Jan

    2015-01-01

    Roč. 1851, č. 4 (2015), s. 503-518 ISSN 1388-1981 R&D Projects: GA ČR(CZ) GA13-00871S; GA MŠk(CZ) 7E12073; GA MŠk(CZ) LH14040 Institutional support: RVO:67985823 Keywords : adipocyte * futile substrate cycle * macrophage Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.779, year: 2015

  5. Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice.

    Science.gov (United States)

    Uebanso, Takashi; Kano, Saki; Yoshimoto, Ayumi; Naito, Chisato; Shimohata, Takaaki; Mawatari, Kazuaki; Takahashi, Akira

    2017-07-14

    The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans . It is used as a food additive to prevent caries. We previously showed that 1.5-4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella , whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism.

  6. Features of lipid metabolism in chronic heart failure of different genesis with concomitant overweight and obesity

    Directory of Open Access Journals (Sweden)

    Р. P. Bidzilya

    2016-08-01

    Full Text Available Recently clinical studies demonstrated reciprocal association between traditional cardiovascular risk factors, in particular, hyperlipidemia and obesity, with worse clinical outcomes in CHF. Unlike ischemic heart disease (IHD, where high levels of atherogenic and low of antiatherogenic lipids fraction traditionally associated with worsening of prognosis and course of disease, in conditions of the CHF proven negative impact of the reduction of lipid levels and body mass index. Demonstrated the phenomena called "cholesterol paradox" and "obesity paradox". Aim. To study the features of lipid metabolism in CHF of different genesis with concomitant overweight and obesity. Materials and methods. 240 patients with I–III functional class (FC of the disease with concomitant overweight and abdominal obesity I–III degree were examined. FC of the disease was established according to the classification of New York Heart Association (NYHA.Normal, overweight and the degree of abdominal obesity was identified by calculating the body mass index. Etiologic factors of CHF were chronic forms of IHD, arterial hypertension, and/or a combination of both. With the help of biochemical blood tests lipid metabolism were assessed. Results. The maximum values as atherogenic and antiatherogenic lipid indicators are investigated in non-ischemic (hypertensive CHF. Patients with CHF of ischemic genesis are characterized by minimal values of atherogenic fractions of lipids. Patients with combined etiology of CHF occupy the intermediate position of atherogenic fractions content, while they demonstrate the minimum value in the antiatherogenic HDL-cholesterol. Conclusion. Changes of lipid metabolism are varied depending on the etiology of CHF in patients with concomitant overweight and obesity and the most unfavorable in ischemic form of the disease.

  7. Energy and lipid metabolism during direct and diapause development in a pierid butterfly.

    Science.gov (United States)

    Lehmann, Philipp; Pruisscher, Peter; Posledovich, Diana; Carlsson, Mikael; Käkelä, Reijo; Tang, Patrik; Nylin, Sören; Wheat, Christopher W; Wiklund, Christer; Gotthard, Karl

    2016-10-01

    Diapause is a fundamental component of the life cycle in the majority of insects living in environments characterized by strong seasonality. The present study addresses poorly understood associations and trade-offs between endogenous diapause duration, thermal sensitivity of development, energetic cost of development and cold tolerance. Diapause intensity, metabolic rate trajectories and lipid profiles of directly developing and diapausing animals were studied using pupae and adults of Pieris napi butterflies from a population in which endogenous diapause has been well studied. Endogenous diapause was terminated after 3 months and termination required chilling. Metabolic and post-diapause development rates increased with diapause duration, while the metabolic cost of post-diapause development decreased, indicating that once diapause is terminated, development proceeds at a low rate even at low temperature. Diapausing pupae had larger lipid stores than the directly developing pupae, and lipids constituted the primary energy source during diapause. However, during diapause, lipid stores did not decrease. Thus, despite lipid catabolism meeting the low energy costs of the diapausing pupae, primary lipid store utilization did not occur until the onset of growth and metamorphosis in spring. In line with this finding, diapausing pupae contained low amounts of mitochondria-derived cardiolipins, which suggests a low capacity for fatty acid β-oxidation. While ontogenic development had a large effect on lipid and fatty acid profiles, only small changes in these were seen during diapause. The data therefore indicate that the diapause lipidomic phenotype is developed early, when pupae are still at high temperature, and retained until post-diapause development. © 2016. Published by The Company of Biologists Ltd.

  8. Metabolic incorporation of unsaturated fatty acids into boar spermatozoa lipids and de novo formation of diacylglycerols

    DEFF Research Database (Denmark)

    Svetlichnyy, V.; Müller, P.; Günther-Pomorski, Thomas

    2014-01-01

    Lipids play an important role in the maturation, viability and function of sperm cells. In this study, we examined the neutral and polar lipid composition of boar spermatozoa by thin-layer chromatography/mass spectrometry. Main representatives of the neutral lipid classes were diacylglycerols...... containing saturated (myristoyl, palmitoyl and stearoyl) fatty acyl residues. Glycerophosphatidylcholine and glycerophosphatidylethanolamine with alk(en)yl ether residues in the sn-1 position and unsaturated long chained fatty acyl residues in sn-2 position were identified as the most prominent polar lipids....... The only glycoglycerolipid was sulfogalactosylglycerolipid carrying 16:0-alkyl- and 16:0-acyl chains. Using stable isotope-labelling, the metabolic incorporation of exogenously supplied fatty acids was analysed. Boar spermatozoa incorporated hexadecenoic (16:1), octadecenoic (18:1), octadecadienoic (18...

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

    Science.gov (United States)

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

    2016-05-01

    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.

  10. Intracerebroventricular ghrelin treatment affects lipid metabolism in liver of rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Velasco, Cristina; Librán-Pérez, Marta; Otero-Rodiño, Cristina; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2016-03-01

    We aimed to elucidate in rainbow trout (Oncorhynchus mykiss) the effects of central ghrelin (GHRL) treatment on the regulation of liver lipid metabolism, and the possible modulatory effect of central GHRL treatment on the simultaneous effects of raised levels of oleate. Thus, we injected intracerebroventricularly (ICV) rainbow trout GHRL in the presence or absence of oleate and evaluated in liver variables related to lipid metabolism. Oleate treatment elicited in liver of rainbow trout decreased lipogenesis and increased oxidative capacity in agreement with previous studies. Moreover, as demonstrated for the first time in fish in the present study, GHRL also acts centrally modulating lipid metabolism in liver, resulting in increased potential for lipogenesis and decreased potential for fatty acid oxidation, i.e. the converse effects to those elicited by central oleate treatment. The simultaneous treatment of GHRL and oleate confirmed these counteractive effects. Thus, the nutrient sensing mechanisms present in hypothalamus, particularly those involved in sensing of fatty acid, are involved in the control of liver energy metabolism in fish, and this control is modulated by the central action of GHRL. These results give support to the notion of hypothalamus as an integrative place for the regulation of peripheral energy metabolism in fish. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

    DEFF Research Database (Denmark)

    Mulla, N A; Simonsen, L; Bülow, J

    2000-01-01

    , a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease......One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid...... metabolism during a 3 h post-exercise period. Six subjects were studied twice. In one experiment, they exercised for 90 min at 40% of maximal O2 consumption (VO2,max) and in the other experiment they exercised at 60% VO2,max for 60 min. For both experiments, catheters were inserted in an artery...

  12. Evaluation of the application of chemical shift for the detection of lipid in brain lesion

    Energy Technology Data Exchange (ETDEWEB)

    Lim, C.J. [Department of Biomedical Imaging, Faculty of Medicine, University of Malaya Medical Centre, Kuala Lumpur (Malaysia); Ng, K.H., E-mail: ngkh@um.edu.m [Department of Biomedical Imaging, Faculty of Medicine, University of Malaya Medical Centre, Kuala Lumpur (Malaysia); Ramli, N.; Azman, R.R. [Department of Biomedical Imaging, Faculty of Medicine, University of Malaya Medical Centre, Kuala Lumpur (Malaysia)

    2011-02-15

    Non-invasive detection of the presence of lipids is particularly important in staging of intracranial tumours. Presence of lipid peak in aggressive intracranial tumours has been reported widely using MR spectroscopy. However this method has limitation due to long imaging time and artefacts formed by adjacent bones. Chemical shift MR imaging (with has shorter imaging time) is an alternative method that had been used to detect presence of lipid in vivo by means of signal intensity loss. The purpose of this study was to evaluate gradient echo in- and opposed-phase chemical shift pulse sequences for detection of lipid elements in brain lesion. Ten cylindered phantoms measuring 3 x 3 cm were filled with various mixtures of lipid and water: 0-90% lipid, in 10% step by weight. The gradient echo in- and opposed-phase chemical shift sequences were performed using a 1.5 T MRI (Magnetom Vision, Siemens) with a head coil. In addition, we performed MRI and chemical shift studies on 32 patients with brain lesion. We then analysed the association between out of phase intensity value and classification of the lesions. For phantom containing 50% lipid, maximum signal loss on opposed-phase images was observed. There were significant differences between in- and opposed-phase lipid-water phantom images (P = 0.0054). Most of the benign lesions fall into the positive out of phase intensity value, and malignant lesions fall into negative out of phase intensity value. We conclude that chemical shift artefact can be applied in detecting and characterising lipid elements in brain lesion.

  13. Evaluation of the application of chemical shift for the detection of lipid in brain lesion

    International Nuclear Information System (INIS)

    Lim, C.J.; Ng, K.H.; Ramli, N.; Azman, R.R.

    2011-01-01

    Non-invasive detection of the presence of lipids is particularly important in staging of intracranial tumours. Presence of lipid peak in aggressive intracranial tumours has been reported widely using MR spectroscopy. However this method has limitation due to long imaging time and artefacts formed by adjacent bones. Chemical shift MR imaging (with has shorter imaging time) is an alternative method that had been used to detect presence of lipid in vivo by means of signal intensity loss. The purpose of this study was to evaluate gradient echo in- and opposed-phase chemical shift pulse sequences for detection of lipid elements in brain lesion. Ten cylindered phantoms measuring 3 x 3 cm were filled with various mixtures of lipid and water: 0-90% lipid, in 10% step by weight. The gradient echo in- and opposed-phase chemical shift sequences were performed using a 1.5 T MRI (Magnetom Vision, Siemens) with a head coil. In addition, we performed MRI and chemical shift studies on 32 patients with brain lesion. We then analysed the association between out of phase intensity value and classification of the lesions. For phantom containing 50% lipid, maximum signal loss on opposed-phase images was observed. There were significant differences between in- and opposed-phase lipid-water phantom images (P = 0.0054). Most of the benign lesions fall into the positive out of phase intensity value, and malignant lesions fall into negative out of phase intensity value. We conclude that chemical shift artefact can be applied in detecting and characterising lipid elements in brain lesion.

  14. Hydrogen isotopic messages in sulfate reducer lipids: a recorder of metabolic state?

    Science.gov (United States)

    Bradley, A. S.; Leavitt, W.; Zhou, A.; Cobban, A.; Suess, M.

    2017-12-01

    A significant range in microbial lipid 2H/1H ratios is observed in modern marine sediments. The magnitude of hydrogen isotope fractionation between microbial lipids and growth water (2ɛlipid-H2O) is hypothesized to relate to the central carbon and energy metabolism. These observations raise the possibility for culture independent identification of the dominant metabolic pathways operating in a given environment [Zhang et al. 2009]. One such metabolism we aim to track is microbial sulfate reduction. To-date, sulfate reducing bacteria have been observed to produce lipids that are depleted in fatty acid H-isotope composition, relative to growth water (2ɛlipid-H2O -50 to -175 ‰) [Campbell et al. 2009; Dawson et al. 2015; Osburn et al.], with recent work demonstrating a systematic relationship between lipid/water fractionation and growth rate when the electron-bifurcating NAD(P)(H) transhydrogenase (ebTH) activity was disrupted and the available electron requires the ebTH [Leavitt et al. 2016. Front Microbio]. Recent work in aerobic methylotrophs [Bradley et al. 2014. AGU] implicates non-bifurcating NAD(P)(H) transhydrogenase activity is a critical control on 2ɛlipid-H2O. This suggests a specific mechanism to control the range in fractionation is the ratio of intracellular NADPH/NADH/NADP/NAD in aerobes and perhaps the same in anaerobes with some consideration for FADH/FAD. Fundamentally this implies 2ɛlipid-H2O records intracellular redox state. In our sulfate reducer model system Desulfovibrio alaskensis strain G20 a key component of energy metabolism is the activity of ebTH. Nonetheless, this strain contains two independent copies of the genes, only one of which generates a distinctive isotopic phenotype [Leavitt et al. 2016. Front Microbio]. In this study we extend the recent work in G20 to continuous culture experiments comparing WT to nfnAB-2 transposon interruptions, where both organisms are cultivated continuously, at the rate of the slower growing mutant

  15. Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

    Science.gov (United States)

    Mathieu, Cécile; Li de la Sierra-Gallay, Ines; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-08-26

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Brain-targeted solid lipid nanoparticles containing riluzole: preparation, characterization and biodistribution.

    Science.gov (United States)

    Bondì, Maria Luisa; Craparo, Emanuela Fabiola; Giammona, Gaetano; Drago, Filippo

    2010-01-01

    Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for amyotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodistribution of riluzole blended into solid lipid nanoparticles was carried out after administration to rats and the results were compared with those obtained by riluzole aqueous dispersion administration. Rats were sacrificed at time intervals of 8, 16 and 30 h, and the riluzole concentration in the blood and organs such as the brain, liver, spleen, heart and kidney was determined. It was demonstrated that these solid lipid nanoparticles were able to successfully carry riluzole into the CNS. Moreover, a low drug biodistribution in organs such as the liver, spleen, heart, kidneys and lung was found when riluzole was administered as drug-loaded solid lipid nanoparticles. Riluzole-loaded solid lipid nanoparticles showed colloidal size and high drug loading, a greater efficacy than free riluzole in rats, a higher capability to carry the drug into the brain and a lower indiscriminate biodistribution.

  17. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    NARCIS (Netherlands)

    Cutts, DA; Maguire, RP; Leenders, KL; Spyrou, NM

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. This study determines whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was

  18. Terminalia pallida fruit ethanolic extract ameliorates lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

    Directory of Open Access Journals (Sweden)

    Althaf Hussain Shaik

    2018-03-01

    Full Text Available The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON in isoproterenol (ISO-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500 mg/kg body weight (bw and gallic acid (15 mg/kg bw for 30 days challenged with concurrent injection of ISO (85 mg/kg bw on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats. Keywords: Terminalia pallida fruit, Gallic acid, Isoproterenol, Lipid metabolism marker enzymes, Paraoxonase, Myocardial infarction

  19. Brain lactate metabolism in humans with subarachnoid hemorrhage.

    Science.gov (United States)

    Oddo, Mauro; Levine, Joshua M; Frangos, Suzanne; Maloney-Wilensky, Eileen; Carrera, Emmanuel; Daniel, Roy T; Levivier, Marc; Magistretti, Pierre J; LeRoux, Peter D

    2012-05-01

    Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxic (PbtO(2) 119 μmol/L) versus nonhyperglycolytic. Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%-95%] in nonsurvivors versus 9% [interquartile range 3%-17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%-87%] versus 88% [interquartile range, 27%-99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0-3 1.49; CI, 1.08-2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59-1.03; P=0.08). Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

  20. Selective upregulation of lipid metabolism in skeletal muscle of foraging juvenile king penguins: an integrative study.

    Science.gov (United States)

    Teulier, Loic; Dégletagne, Cyril; Rey, Benjamin; Tornos, Jérémy; Keime, Céline; de Dinechin, Marc; Raccurt, Mireille; Rouanet, Jean-Louis; Roussel, Damien; Duchamp, Claude

    2012-06-22

    The passage from shore to marine life of juvenile penguins represents a major energetic challenge to fuel intense and prolonged demands for thermoregulation and locomotion. Some functional changes developed at this crucial step were investigated by comparing pre-fledging king penguins with sea-acclimatized (SA) juveniles (Aptenodytes patagonicus). Transcriptomic analysis of pectoralis muscle biopsies revealed that most genes encoding proteins involved in lipid transport or catabolism were upregulated, while genes involved in carbohydrate metabolism were mostly downregulated in SA birds. Determination of muscle enzymatic activities showed no changes in enzymes involved in the glycolytic pathway, but increased 3-hydroxyacyl-CoA dehydrogenase, an enzyme of the β-oxidation pathway. The respiratory rates of isolated muscle mitochondria were much higher with a substrate arising from lipid metabolism (palmitoyl-L-carnitine) in SA juveniles than in terrestrial controls, while no difference emerged with a substrate arising from carbohydrate metabolism (pyruvate). In vivo, perfusion of a lipid emulsion induced a fourfold larger thermogenic effect in SA than in control juveniles. The present integrative study shows that fuel selection towards lipid oxidation characterizes penguin acclimatization to marine life. Such acclimatization may involve thyroid hormones through their nuclear beta receptor and nuclear coactivators.

  1. Gender Differences in Musculoskeletal Lipid Metabolism as Assessed by Localized Two-Dimensional Correlation Spectroscopy

    Directory of Open Access Journals (Sweden)

    S. Sendhil Velan; Department of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, U.S.A.

    2008-01-01

    Full Text Available Gender differences in lipid metabolism are poorly understood and difficult to study using conventional approaches. Magnetic resonance spectroscopy (MRS permits non-invasive investigation of lipid metabolism. We employed novel two- dimensional MRS techniques to quantify intramyocellular (IMCL and extramyocellular (EMCL lipid compartments and their degree of unsaturation in normal weight adult male and female subjects. Using muscle creatine (Cr for normalization, a statistically significant (p 0.05 increase in IMCL/Cr (7.8 ± 1.6 and EMCL/Cr (22.5 ± 3.6 for female subjects was observed (n = 8, as compared to IMCL/Cr (5.9 ± 1.7 and EMCL/Cr (18.4 ± 2.64 for male subjects. The degree of unsaturation within IMCL and EMCL was lower in female subjects, 1.3 ± 0.075 and 1.04 ± 0.06, respectively, as compared to that observed in males (n = 8, 1.5 ± 0.08 and 1.12 ± 0.03, respectively (p 0.05 male vs female for both comparisons. We conclude that certain salient gender differences in lipid metabolism can be assessed noninvasively by advanced MRS approaches.

  2. Gender Differences in Musculoskeletal Lipid Metabolism as Assessed by Localized Two-Dimensional Correlation Spectroscopy

    Directory of Open Access Journals (Sweden)

    S. Sendhil Velan

    2008-01-01

    Full Text Available Gender differences in lipid metabolism are poorly understood and difficult to study using conventional approaches. Magnetic resonance spectroscopy (MRS permits non-invasive investigation of lipid metabolism. We employed novel two-dimensional MRS techniques to quantify intramyocellular (IMCL and extramyocellular (EMCL lipid compartments and their degree of unsaturation in normal weight adult male and female subjects. Using muscle creatine (Cr for normalization a statistically significant (p < 0.05 increase in IMCL/Cr (7.8 ± 1.6 and EMCL/Cr (22.5 ± 3.6 for female subjects was observed (n = 8, as compared to IMCL/Cr (5.9 ± 1.7 and EMCL/Cr (18.4 ± 2.64 for male subjects. The degree of unsaturation within IMCL and EMCL was lower in female subjects, 1.3 ± 0.075 and 1.04 ± 0.06, respectively, as compared to that observed in males (n = 8, 1.5 ± 0.08 and 1.12 ± 0.03, respectively (p < 0.05 male vs female for both comparisons. We conclude that certain salient gender differences in lipid metabolism can be assessed noninvasively by advanced MRS approaches.

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

    International Nuclear Information System (INIS)

    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

    2008-01-01

    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

  4. Detrimental effects of fluvastatin on plasma lipid metabolism in rat breast carcinoma model

    Directory of Open Access Journals (Sweden)

    Kapinová Andrea

    2013-01-01

    Full Text Available From clinical practice, obvious positive effects of statins on plasma lipid metabolism are well known. On the other hand, there are several experimental rodent studies, where these beneficial effects were not confirmed. The effects of fluvastatin on selected serum lipid parameters in a rat model of experimental breast cancer were determined. The drug was dietary administered at two concentrations of 20 and 200 mg/kg. At the end of the study (experiment duration - 18 weeks the blood from each animal was collected and serum lipid parameters were evaluated. Fluvastatin in both treated groups significantly increased parameters of serum lipids (mostly in a dose dependent manner. Fluvastatin in both treated groups of animals significantly increased serum levels of triacylglycerols, total cholesterol, and LDL-, HDL-, VLDL-cholesterol when compared to the control group. Our results pointed out to the apparent harmful effects of fluvastatin on plasma lipid metabolism in rat mammary carcinogenesis. Based on our previous results, it seems that rats commonly used in cancer model studies are generally unresponsive to the hypocholesterolemic effects of statins.

  5. Metabolic response to lipid infusion in fasting winter-acclimatized king penguin chicks (Aptenodytes patagonicus).

    Science.gov (United States)

    Teulier, Loïc; Tornos, Jérémy; Rouanet, Jean-Louis; Rey, Benjamin; Roussel, Damien

    2013-05-01

    During the cold austral winter, king penguin chicks are infrequently fed by their parents and thus experience severe nutritional deprivation under harsh environmental conditions. These energetic constraints lead to a range of energy sparing mechanisms balanced by the maintenance of efficient thermogenic processes. The present work investigated whether the high thermogenic capacities exhibited by winter-acclimatized king penguin chicks could be related to an increase in lipid substrate supply and oxidation in skeletal muscle, the main site of thermogenesis in birds. To test this hypothesis, we examined i) the effect of an experimental rise in plasma triglyceride on the whole metabolic rate in winter-acclimatized (WA) and de-acclimatized king penguin chicks kept at thermoneutrality (TN), and ii) investigated the fuel preference of muscle mitochondria. In vivo, a perfusion of a lipid emulsion induced a small 10% increase of metabolic rate in WA chicks but not in TN group. In vitro, the oxidation rate of muscle mitochondria respiring on lipid-derived substrate was +40% higher in WA chicks than in TN, while no differences were found between groups when mitochondria oxidized carbohydrate-derived substrate or succinate. Despite an enhanced fuel selection towards lipid oxidation in skeletal muscle, a rise of circulating lipids per se was not sufficient to fully unravel the thermogenic capacity of winter-acclimatized king penguin chicks. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Effect of dietary docosahexaenoic acid connecting phospholipids on the lipid peroxidation of the brain in mice.

    Science.gov (United States)

    Hiratsuka, Seiichi; Ishihara, Kenji; Kitagawa, Tomoko; Wada, Shun; Yokogoshi, Hidehiko

    2008-12-01

    The effect of dietary docosahexaenoic acid (DHA, C22:6n-3) with two lipid types on lipid peroxidation of the brain was investigated in streptozotocin (STZ)-induced diabetic mice. Each group of female Balb/c mice was fed a diet containing DHA-connecting phospholipids (DHA-PL) or DHA-connecting triacylglycerols (DHA-TG) for 5 wk. Safflower oil was fed as the control. The lipid peroxide level of the brain was significantly lower in the mice fed the DHA-PL diet when compared to those fed the DHA-TG and safflower oil diets, while the alpha-tocopherol level was significantly higher in the mice fed the DHA-PL diet than in those fed the DHA-TG and safflower oil diets. The DHA level of phosphatidylethanolamine in the brain was significantly higher in the mice fed the DHA-PL diet than in those fed the safflower oil diet. The dimethylacetal levels were significantly higher in the mice fed the DHA-PL diet than in those fed the safflower oil and DHA-TG diets. These results suggest that the dietary DHA-connecting phospholipids have an antioxidant activity on the brain lipids in mice, and the effect may be related to the brain plasmalogen.

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

    NARCIS (Netherlands)

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

    2017-01-01

    Malassezia species are lipophilic and lipid-dependent yeasts belonging to the human and animal microbiota. Typically, they are isolated from regions rich in sebaceous glands. They have been associated with dermatological diseases such as seborrheic dermatitis, pityriasis versicolor, atopic

  8. Effects of lithium on brain glucose metabolism in healthy men.

    Science.gov (United States)

    Kohno, Tomoya; Shiga, Tohru; Toyomaki, Atsuhito; Kusumi, Ichiro; Matsuyama, Tetsuaki; Inoue, Tetsuya; Katoh, Chietsugu; Koyama, Tsukasa; Tamaki, Nagara

    2007-12-01

    Lithium is clinically available for the treatment of mood disorders. However, it has remained unclear how lithium acts on the brain to produce its effects. The aim of this study was to evaluate the effects of chronic lithium on human brain activity using positron emission tomography and clarify the correlation between brain activity changes and cognitive functional changes as induced by chronic lithium administration. A total of 20 healthy male subjects (mean age, 32 +/- 6 years) underwent positron emission tomographic scans with F-fluorodeoxyglucose and a battery of neuropsychological tests at baseline condition and after 4 weeks of lithium administration. Brain metabolic data were analyzed using statistical parametric mapping. Lithium increased relative regional cerebral glucose metabolism (rCMRglc) in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased rCMRglc in the right cerebellum and left lingual gyrus/cuneus. There was no difference in any of the variables of cognitive functions between the baseline condition and after chronic lithium administration. There was no correlation between rCMRglc changes in any of the brain regions and individual variable changes in any of the neuropsychological tests. The results suggest that the effects of chronic lithium are associated with increased activity in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased activity in the right cerebellum and left lingual gyrus/cuneus.

  9. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The ketogenic diet: metabolic influences on brain excitability and epilepsy

    Science.gov (United States)

    Lutas, Andrew; Yellen, Gary

    2012-01-01

    A dietary therapy for pediatric epilepsy known as the ketogenic diet has seen a revival in its clinical use in the past decade. Though the diet’s underlying mechanism remains unknown, modern scientific approaches like genetic disruption of glucose metabolism are allowing for more detailed questions to be addressed. Recent work indicates that several mechanisms may exist for the ketogenic diet including disruption of glutamatergic synaptic transmission, inhibition of glycolysis, and activation of ATP-sensitive potassium channels. Here we describe on-going work in these areas that is providing a better understanding of metabolic influences on brain excitability and epilepsy. PMID:23228828

  11. Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

    Directory of Open Access Journals (Sweden)

    Wanchun Yang

    2014-01-01

    Full Text Available Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR, a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1 activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1 as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals.

  12. The effect of ionizing radiation on lipid metabolism in lymphoid cells

    International Nuclear Information System (INIS)

    Kolomiytseva, I.K.; Novoselova, E.G.; Kulagina, T.P.; Kuzin, A.M.

    1987-01-01

    Lipid metabolism was studied in lymphoid tissues of rats after whole body irradiation with doses producing damage of different degrees to lymphoid cells (4-10 Gy). The content of free cholesterol, cholesterol esters, and total phospholipids was determined in peripheral blood lymphocytes and thymocytes 1-2 h after exposure. Simultaneously, the rate of in vitro incorporation of 2 14 C-acetate into total lipids, phospholipids, and cholesterol of lymphoid cells was estimated. It was shown that exposure of rats to ionizing radiation caused activation of lipogenesis. Cholesterol synthesis was activated after a dose of 4 Gy and decreased with increasing dose. (author)

  13. Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle

    DEFF Research Database (Denmark)

    Langfort, Jozef; Jagsz, Slawomir; Dobrzyn, Pawel

    2010-01-01

    Fatty acids, which are the major cardiac fuel, are derived from lipid droplets stored in cardiomyocytes, among other sources. The heart expresses hormone-sensitive lipase (HSL), which regulates triglycerides (TG) breakdown, and the enzyme is under hormonal control. Evidence obtained from adipose...... levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid...

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

    Science.gov (United States)

    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. © 2016 Poultry Science Association Inc.

  15. Brain energy metabolism and blood flow differences in healthy aging

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar

    2012-01-01

    Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

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

    Science.gov (United States)

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

    2016-12-01

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

  17. Regulation of lipid metabolism by energy availability: a role for the central nervous system.

    Science.gov (United States)

    Nogueiras, R; López, M; Diéguez, C

    2010-03-01

    The central nervous system (CNS) is crucial in the regulation of energy homeostasis. Many neuroanatomical studies have shown that the white adipose tissue (WAT) is innervated by the sympathetic nervous system, which plays a critical role in adipocyte lipid metabolism. Therefore, there are currently numerous reports indicating that signals from the CNS control the amount of fat by modulating the storage or oxidation of fatty acids. Importantly, some CNS pathways regulate adipocyte metabolism independently of food intake, suggesting that some signals possess alternative mechanisms to regulate energy homeostasis. In this review, we mainly focus on how neuronal circuits within the hypothalamus, such as leptin- ghrelin-and resistin-responsive neurons, as well as melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting the complicated interactions between peripheral signals and neuronal circuits regulating lipid metabolism might open new avenues for the development of new therapies preventing and treating obesity and its associated cardiometabolic sequelae.

  18. [Lipid and metabolic profiles in adolescents are affected more by physical fitness than physical activity (AVENA study)].

    Science.gov (United States)

    García-Artero, Enrique; Ortega, Francisco B; Ruiz, Jonatan R; Mesa, José L; Delgado, Manuel; González-Gross, Marcela; García-Fuentes, Miguel; Vicente-Rodríguez, Germán; Gutiérrez, Angel; Castillo, Manuel J

    2007-06-01

    To determine whether the level of physical activity or physical fitness (i.e., aerobic capacity and muscle strength) in Spanish adolescents influences lipid and metabolic profiles. From a total of 2859 Spanish adolescents (age 13.0-18.5 years) taking part in the AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes) study, 460 (248 male, 212 female) were randomly selected for blood analysis. Their level of physical activity was determined by questionnaire. Aerobic capacity was assessed using the Course-Navette test. Muscle strength was evaluated using manual dynamometry, the long jump test, and the flexed arm hang test. A lipid-metabolic cardiovascular risk index was derived from the levels of triglycerides, low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and glucose. No relationship was found between the level of physical activity and lipid-metabolic index in either sex. In contrast, there was an inverse relationship between the lipid-metabolic index and aerobic capacity in males (P=.003) after adjustment for physical activity level and muscle strength. In females, a favorable lipid-metabolic index was associated with greater muscle strength (P=.048) after adjustment for aerobic capacity. These results indicate that, in adolescents, physical fitness, and not physical activity, is related to lipid and metabolic cardiovascular risk. Higher aerobic capacity in males and greater muscle strength in females were associated with lower lipid and metabolic risk factors for cardiovascular disease.

  19. Dietary fatty acids early in life affect lipid metabolism and adiposity in young rats.

    Science.gov (United States)

    Silva, Ana Paula S; Guimarães, Daniella E D; Mizurini, Daniella M; Maia, Ingrid C; Ortiz-Costa, Susana; Sardinha, Fátima L; do Carmo, Maria G Tavares

    2006-06-01

    The purpose of this study was to evaluate the effects of four isoenergetic diets of differing fat composition on blood lipid profile and adiposity in young rats. Diets containing different lipid sources--partially hydrogenated vegetable oil (PHVO), palm oil (PO), canola oil (CO), and soy oil (SO)--were fed to lactating rats during the 21 days of lactation, and then fed to young males following weaning until the 45th day of life. In vivo lipogenesis rate (LR), lipid content (LC), relative level of FA, and the activity of lipoprotein lipase (LPL) enzyme were measured in epididymal adipose tissue (EPI). Fasting blood lipoproteins and LC in the carcass were also appraised. Body weight of PO and PHVO groups was significantly higher than CO and SO groups from day 14 of lactation to day 45, despite the lower food intake in the PHVO group. PO and PHVO groups presented higher LR and LC in EPI than SO and CO groups. Carcass fat content was significantly higher in PHVO and PO groups than in CO and SO groups. The LPL activity in EPI was unaffected by dietary lipids. PHVO group had increased total cholesterol and TAG concentrations in comparison with the PO group, and significantly lower HDL level compared with the other groups. These results show that the kind of FA in the dietary lipid offered early in life can affect lipid metabolism and adiposity.

  20. Flight metabolism in Panstrongylus megistus (Hemiptera: Reduviidae): the role of carbohydrates and lipids.

    Science.gov (United States)

    Canavoso, Lilián E; Stariolo, Raúl; Rubiolo, Edilberto R

    2003-10-01

    The metabolism of lipids and carbohydrates related to flight activity in Panstrongylus megistus was investigated. Insects were subjected to different times of flight under laboratory conditions and changes in total lipids, lipophorin density and carbohydrates were followed in the hemolymph. Lipids and glycogen were also assayed in fat body and flight muscle. In resting insects, hemolymph lipids averaged 3.4 mg/ml and significantly increased after 45 min of flight (8.8 mg/ml, P < 0.001). High-density lipophorin was the sole lipoprotein observed in resting animals. A second fraction with lower density corresponding to low-density lipophorin appeared in insects subjected to flight. Particles from both fractions showed significant differences in diacylglycerol content and size. In resting insects, carbohydrate levels averaged 0.52 mg/ml. They sharply declined more than twofold after 15 min of flight, being undetectable in hemolymph of insects flown for 45 min. Lipid and glycogen from fat body and flight muscle decreased significantly after 45 min of flight. Taken together, the results indicate that P. megistus uses carbohydrates during the initiation of the flight after which, switching fuel for flight from carbohydrates to lipids.

  1. Flight metabolism in Panstrongylus megistus (Hemiptera: Reduviidae: the role of carbohydrates and lipids

    Directory of Open Access Journals (Sweden)

    Lilián E Canavoso

    2003-10-01

    Full Text Available The metabolism of lipids and carbohydrates related to flight activity in Panstrongylus megistus was investigated. Insects were subjected to different times of flight under laboratory conditions and changes in total lipids, lipophorin density and carbohydrates were followed in the hemolymph. Lipids and glycogen were also assayed in fat body and flight muscle. In resting insects, hemolymph lipids averaged 3.4 mg/ml and significantly increased after 45 min of flight (8.8 mg/ml, P < 0.001. High-density lipophorin was the sole lipoprotein observed in resting animals. A second fraction with lower density corresponding to low-density lipophorin appeared in insects subjected to flight. Particles from both fractions showed significant differences in diacylglycerol content and size. In resting insects, carbohydrate levels averaged 0.52 mg/ml. They sharply declined more than twofold after 15 min of flight, being undetectable in hemolymph of insects flown for 45 min. Lipid and glycogen from fat body and flight muscle decreased significantly after 45 min of flight. Taken together, the results indicate that P. megistus uses carbohydrates during the initiation of the flight after which, switching fuel for flight from carbohydrates to lipids.

  2. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  3. Adiposity, insulin and lipid metabolism in post-menopausal women.

    Science.gov (United States)

    Lovegrove, J A; Silva, K D R R; Wright, J W; Williams, C M

    2002-04-01

    To investigate relationships between body fat and its distribution and carbohydrate and lipid tolerance using statistical comparisons in post-menopausal women. Sequential meal, postprandial study (600 min) which included a mixed standard breakfast (30 g fat) and lunch (44 g fat) given at 0 and 270 min, respectively, after an overnight fast. Twenty-eight post-menopausal women with a diverse range of body weight (body mass index (BMI), mean 27.2, range 20.5-38.8 kg/m2) and abdominal fat deposition (waist, mean 86.4, range 63.5-124.0 cm). Women with BMI 37 kg/m2, age > 80 y and taking hormone replacement therapy (HRT) were excluded. Anthropometric measurements were performed to assess total and regional fat deposits. The concentrations of plasma total cholesterol, high density lipoprotein (HDL) cholesterol, triacylglycerol (TAG), glucose, insulin (ins), non-esterified fatty acids (NEFA) and apolipoprotein (apo) B-48 were analysed in plasma collected at baseline (fasted state) and at 13 postprandial time points for a 600 min period. Insulin concentrations in the fasted and fed state were significantly correlated with all measures of adiposity (BMI, waist, waist-hip ratio (W/H), waist-height ratio (W/Ht) and sum of skinfold thickness (SSk)). After controlling for BMI, waist remained significantly and positively associated with fasted insulin (r=0.559) with waist contributing 53% to the variability after multiple regression analysis. After controlling for waist, BMI remained significantly correlated with postprandial (IAUC) insulin (r=0.535) contributing 66% of the variability of this measurement. No association was found between any measures of adiposity and glucose concentrations, although insulin concentration in relation to glucose concentration (glucose-insulin ratio) was significantly negatively correlated with all measures of adiposity. A significant positive correlation was found between fasted TAG and BMI (r=0.416), waist (r=0.393) and Ssk (r=0.457) and

  4. Stearoyl-CoA desaturase – the lipid metabolism regulator

    Directory of Open Access Journals (Sweden)

    Mirosław Kucharski

    2014-03-01

    Full Text Available Stearoyl-CoA desaturase is an enzyme from the class of oxidoreductase, which catalyzes the formation of a fatty acid double bond between C9 and C10. It plays a key role in composition of the fatty acid profile in adipose tissue and animal products such as meat and milk. Additionally, it is an important regulator of metabolic processes in the body, and it determines the maintenance of energy homeostasis. This enzyme is encoded by an SCD gene, which, depending on the species, may exist as different isoforms. mRNA expression of stearoyl-CoA desaturase is dependent on many factors, including diet, hormones, and the activity of other genes. In previous studies, several mutations were characterized within the sequence of Δ9-desaturase, which may affect the activity of the protein in the tissues, as well as the value of breeding animals. Effects of particular mutations of the gene encoding the enzyme appears to be particularly important for diseases associated with obesity, diabetes, hypertension, heart diseases or cancer in humans. Also, it seems that using sheep as a potential animal model could be helpful in uncovering and understanding the mechanisms regulated by stearoyl-CoA desaturase.

  5. Expensive Brains: “Brainy” Rodents have Higher Metabolic Rate

    Science.gov (United States)

    Sobrero, Raúl; May-Collado, Laura J.; Agnarsson, Ingi; Hernández, Cristián E.

    2011-01-01

    Brains are the centers of the nervous system of animals, controlling the organ systems of the body and coordinating responses to changes in the ecological and social environment. The evolution of traits that correlate with cognitive ability, such as relative brain size is thus of broad interest. Brain mass relative to body mass (BM) varies among mammals, and diverse factors have been proposed to explain this variation. A recent study provided evidence that energetics play an important role in brain evolution (Isler and van Schaik, 2006). Using composite phylogenies and data drawn from multiple sources, these authors showed that basal metabolic rate (BMR) correlates with brain mass across mammals. However, no such relationship was found within rodents. Here we re-examined the relationship between BMR and brain mass within Rodentia using a novel species-level phylogeny. Our results are sensitive to parameter evaluation; in particular how species mass is estimated. We detect no pattern when applying an approach used by previous studies, where each species BM is represented by two different numbers, one being the individual that happened to be used for BMR estimates of that species. However, this approach may compromise the analysis. When using a single value of BM for each species, whether representing a single individual, or available species mean, our findings provide evidence that brain mass (independent of BM) and BMR are correlated. These findings are thus consistent with the hypothesis that large brains evolve when the payoff for increased brain mass is greater than the energetic cost they incur. PMID:21811456

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

    Science.gov (United States)

    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

  7. Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig

    NARCIS (Netherlands)

    van Hulst, Robert A.; Drenthen, Judith; Haitsma, Jack J.; Lameris, Thomas W.; Visser, Gerhard H.; Klein, Jan; Lachmann, Burkhard

    2005-01-01

    OBJECTIVE: To evaluate the effects of hyperbaric oxygen treatment after cerebral air embolism on intracranial pressure, brain oxygenation, brain glucose/lactate metabolism, and electroencephalograph. DESIGN: Prospective animal study. SETTING: Hyperbaric chamber. SUBJECTS: Eleven Landrace/Yorkshire

  8. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Aviral, E-mail: draviraljain@gmail.com; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi [Adina Institute of Pharmaceutical Sciences, Pharmaceutics Research Laboratory, Department of Pharmaceutics (India)

    2013-03-15

    Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 {+-} 3.22 nm with entrapment efficiency of 69.83 {+-} 2.52 and 249 {+-} 2.61 nm with entrapment efficiency decreased to 64.21 {+-} 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

  9. Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

    Science.gov (United States)

    Jain, Aviral; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi

    2013-03-01

    Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 ± 3.22 nm with entrapment efficiency of 69.83 ± 2.52 and 249 ± 2.61 nm with entrapment efficiency decreased to 64.21 ± 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

  10. The effect of cytidine-diphosphate choline (CDP-choline) on brain lipid changes during aging

    International Nuclear Information System (INIS)

    De Medio, G.E.; Trovarelli, G.; Piccinin, G.L.; Porcellati, G.

    1984-01-01

    Lipid synthesis has been tested in vivo in different brain areas of 12-month-old male rats. Cortex, striatum, brainstem, and subcortex of brain have been examined. The cerebellum was discarded. Mixtures of (2- 3 H)glycerol and (Me- 14 C)choline were injected into the lateral ventricle of the brain as lipid precursors, and their incorporation into total lipid, water-soluble intermediates and choline-containing phospholipids was examined 1 hr after isotope injection. In another series of experiments cytidine-5'-diphosphate choline (CDP-choline) was injected intraventricularly to the aged rats 10 min before sacrifice with a simultaneous injection, and radioactivity assays were performed as above. Distribution of radioactivity content of CDP-choline among brain areas 10 min after its administration showed a noticeable enrichment of the nucleotide and water-soluble-related compounds in the examined areas, but to a lesser degree in the cerebral cortex. The incorporation of labelled glycerol, which is severely depressed in aged rats in all four areas [Gaiti et al, 1982, 1983], was increased only in the cortex, and apparently decreased in the other areas. This last result is probably due to a dilution effect brought about by the administered cold CDP-choline upon the ( 14 C)-containing water-soluble metabolites. As a consequence, the ( 3 H)/( 14 C) ratio in total lipid and in isolated phosphatidylcholine and choline plasmalogen increased after CDP-choline treatment

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

    Science.gov (United States)

    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.

  12. Genetic disorders of thyroid metabolism and brain development

    Science.gov (United States)

    Kurian, Manju A; Jungbluth, Heinz

    2014-01-01

    Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

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

    Directory of Open Access Journals (Sweden)

    Guodong Zheng

    Full Text Available 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.

  14. Urea application promotes amino acid metabolism and membrane lipid peroxidation in Azolla.

    Directory of Open Access Journals (Sweden)

    Jiana Chen

    Full Text Available A pot experiment was conducted to evaluate the effect of urea on nitrogen metabolism and membrane lipid peroxidation in Azolla pinnata. Compared to controls, the application of urea to A. pinnata resulted in a 44% decrease in nitrogenase activity, no significant change in glutamine synthetase activity, 660% higher glutamic-pyruvic transaminase, 39% increase in free amino acid levels, 22% increase in malondialdehyde levels, 21% increase in Na+/K+- levels, 16% increase in Ca2+/Mg2+-ATPase levels, and 11% decrease in superoxide dismutase activity. In terms of H2O2 detoxifying enzymes, peroxidase activity did not change and catalase activity increased by 64% in urea-treated A. pinnata. These findings suggest that urea application promotes amino acid metabolism and membrane lipid peroxidation in A. pinnata.

  15. Urea application promotes amino acid metabolism and membrane lipid peroxidation in Azolla.

    Science.gov (United States)

    Chen, Jiana; Huang, Min; Cao, Fangbo; Pardha-Saradhi, P; Zou, Yingbin

    2017-01-01

    A pot experiment was conducted to evaluate the effect of urea on nitrogen metabolism and membrane lipid peroxidation in Azolla pinnata. Compared to controls, the application of urea to A. pinnata resulted in a 44% decrease in nitrogenase activity, no significant change in glutamine synthetase activity, 660% higher glutamic-pyruvic transaminase, 39% increase in free amino acid levels, 22% increase in malondialdehyde levels, 21% increase in Na+/K+- levels, 16% increase in Ca2+/Mg2+-ATPase levels, and 11% decrease in superoxide dismutase activity. In terms of H2O2 detoxifying enzymes, peroxidase activity did not change and catalase activity increased by 64% in urea-treated A. pinnata. These findings suggest that urea application promotes amino acid metabolism and membrane lipid peroxidation in A. pinnata.

  16. Lipids Reprogram Metabolism to Become a Major Carbon Source for Histone Acetylation

    DEFF Research Database (Denmark)

    McDonnell, Eoin; Crown, Scott B; Fox, Douglas B

    2016-01-01

    Cells integrate nutrient sensing and metabolism to coordinate proper cellular responses to a particular nutrient source. For example, glucose drives a gene expression program characterized by activating genes involved in its metabolism, in part by increasing glucose-derived histone acetylation....... Here, we find that lipid-derived acetyl-CoA is a major source of carbon for histone acetylation. Using (13)C-carbon tracing combined with acetyl-proteomics, we show that up to 90% of acetylation on certain histone lysines can be derived from fatty acid carbon, even in the presence of excess glucose...

  17. The Significance of Epidermal Lipid Metabolism in Whole-Body Physiology

    DEFF Research Database (Denmark)

    Kruse, Vibeke; Neess, Ditte; Færgeman, Nils J

    2017-01-01

    The skin is the largest sensory organ of the human body. The skin not only prevents loss of water and other components of the body, but also is involved in regulation of body temperature and serves as an essential barrier, protecting mammals from both routine and extreme environments. Given...... the importance of the skin in temperature regulation, it is surprising that adaptive alterations in skin functions and morphology only vaguely have been associated with systemic physiological responses. Despite that impaired lipid metabolism in the skin often impairs the epidermal permeability barrier...... and insulation properties of the skin, its role in regulating systemic physiology and metabolism is yet to be recognized....

  18. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between...

  19. Effects of achilline on lipid metabolism gene expression in cell culture

    Directory of Open Access Journals (Sweden)

    A. V. Ratkin

    2016-01-01

    Full Text Available Objective. Evaluation in vitro of the mechanisms of the hypolipidemic effect of sesquiterpene γ-lactone achilline in the hepatoma tissue culture (HTC.Materials and methods.The influence of sesquiterpene γ-lactone achilline and gemfibrozil (comparison drug on the viability, lipid content and expression of key genes of lipid metabolism in the hepatoma tissue culture. The lipid content was assessed by fluorescent method with the vital dye Nile Red, the cell viability was assessed using MTT assay.Results. Cultivation of of cell cultures of rat’s hepatoma cell line HTC for 48 h with achilline in a concentration of from 0.25 to 1.0 mm and gemfibrozil from 0,25 to 0,5 mm did not change cell viability compared to control. In these same concentrations of the test substance reduced the lipid content in the cells, assessed by fluorescent method with the vital dye Nile Red. To study the mechanism of hypolipidemicaction of achillinedetermined the expression of key genes of lipid metabolism in cell culture lines HTC. The possible mechanism of hypolipidemic action of achilline can be attributed to the increased transport and oxidation of long-chain fatty acids in mitochondria, as evidenced by the increase in the gene expression of carnitine-palmitoyltransferase 2 (Cpt2. The decrease in cholesterol level may be due to increased synthesis of bile acids from cholesterol, due to increased gene expression of 7-alphahydroxylase (Cyp7a1. Conclusion. In cell cultures of rat’s hepatoma cell line HTC sesquiterpene γ-lactone achilline reduces the accumulation of lipids in cells, as evidenced by the decrease in the fluorescence of Nile Red, increased gene expression of the carnitine-palmitoyltransferase 2 (Cpt2 gene and 7-alpha-hydroxylase (Cyp7a1.

  20. Effects of lipid-lowering pharmaceuticals bezafibrate and clofibric acid on lipid metabolism in fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Weston, Anna; Caminada, Daniel; Galicia, Hector; Fent, Karl

    2009-12-01

    The lipid-lowering agents bezafibrate and clofibric acid, which occur at concentrations up to 3.1 and 1.6 microg/L, respectively, are among the most frequently found human pharmaceuticals in the aquatic environment. In contrast to knowledge about their environmental occurrence, little is known about their effects in the environment. The aim of the present study was to analyze effects of these lipid-lowering agents in fish by focusing on their modes of action, lipid metabolism. Fathead minnows were exposed in aquaria to measured concentrations of 0.1, 1.27, 10.18, 101.56, and 106.7 mg/L bezafibrate and to 1.07, 10.75, and 108.91 mg/L clofibric acid for 14 and 21 d, respectively. After exposure, fish liver was analyzed for expression of peroxisome proliferator-activated receptor alpha (PPARalpha) by quantitative polymerase chain reaction (PCR), and the PPAR-regulated enzyme fatty acyl-coenzyme-A oxidase (FAO) involved in fatty acid oxidation. Bezafibrate had no effect, either on PPARalpha expression or on FAO activity, at all concentrations. In contrast, clofibric acid induced FAO activity in male fathead minnows at 108.91 mg/L. No increase in expression of PPARalpha messenger ribonucleic acid was observed. Egg production was apparently decreased after 21 d of exposure to 108.91 mg/L clofibric acid. The present study demonstrates that bezafibrate has very little or no effect on PPARalpha expression and FAO activity, but clofibric acid affects FAO activity.

  1. Betatrophin provides a new insight into diabetes treatment and lipid metabolism (Review)

    OpenAIRE

    ZHU, JIN-ZHOU; YU, CHAO-HUI; LI, YOU-MING

    2014-01-01

    Replenishing the insulin-producing β-cell mass is considered to be a potential cure for diabetes. A recent study identified a secreted protein, known as betatrophin, which potently induces pancreatic β-cell proliferation. Notably, a number of studies reportedly identified betatrophin, which is also known as lipasin, atypical angiopoietin-like 8 and refeeding-induced fat and liver protein, and considered to be a novel regulator in lipid metabolism according to the studies. The identification o...

  2. Impact of grape pomace consumption on the blood lipid profile and liver genes associated with lipid metabolism of young rats.

    Science.gov (United States)

    Yu, Jianmei; Bansode, Rishipal R; Smith, Ivy N; Hurley, Steven L

    2017-08-01

    Herein, we investigated the effects of grape pomace (GP) in diet on body weight, blood lipid profile, and expression of liver genes associated with lipid metabolism using a young rat model. In this study, twenty female Sprague-Dawley rats at 7 weeks of age were randomly divided into 4 groups, which were fed modified AIN-93G diets containing 0% (control), 6.9%, 13.8%, and 20.7% of GP for 10 weeks. Feed consumption and body weight were weekly determined. Blood samples were obtained at the beginning and end of the feeding period for cholesterol, alanine aminotransferase (ALT), and glucose analysis. At the end of the feeding period, all rats were fasted overnight and euthanized. Heart, kidney, and liver samples were obtained and weighed. Liver tissues were used for gene expression analysis. GP-containing diet did not influence the body weight of the rats. As GP content increased, blood triglyceride and very low density lipoprotein (VLDL) decreased (P consumption of a diet containing appropriate amount of GP may help in the reduction of body fat accumulation and prevention of obesity. This is the first study revealing the change in gene expression caused by long-term consumption of GP-containing diet.

  3. Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles

    Energy Technology Data Exchange (ETDEWEB)

    Maradonna, F.; Nozzi, V. [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); Santangeli, S. [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Traversi, I. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita, Università di Genova, 16132 Genova (Italy); Gallo, P. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Dipartimento di Chimica, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Napoli (Italy); Fattore, E. [Dipartimento Ambiente e Salute, IRCCS–Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 Milano (Italy); Mita, D.G. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Mandich, A. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Dipartimento di Scienze della Terra, dell’Ambiente e della Vita, Università di Genova, 16132 Genova (Italy); Carnevali, O., E-mail: o.carnevali@univpm.it [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy)

    2015-10-15

    Highlights: • Diets contaminated with NP, BPA, or t-OP affect lipid metabolism. • Xenobiotic-contaminated diets induce metabolic disorders. • Hepatic metabolic disorders may be related to environmental pollution. - Abstract: The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparβ mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes

  4. Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles

    International Nuclear Information System (INIS)

    Maradonna, F.; Nozzi, V.; Santangeli, S.; Traversi, I.; Gallo, P.; Fattore, E.; Mita, D.G.; Mandich, A.; Carnevali, O.

    2015-01-01

    Highlights: • Diets contaminated with NP, BPA, or t-OP affect lipid metabolism. • Xenobiotic-contaminated diets induce metabolic disorders. • Hepatic metabolic disorders may be related to environmental pollution. - Abstract: The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparβ mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes

  5. Correlation of lipid metabolism characteristics with bile acid metabolism and placental hypoxia injury in patients with intrahepatic cholestasis of pregnancy

    Directory of Open Access Journals (Sweden)

    Liang Tang

    2017-05-01

    Full Text Available Objective: To study the correlation of lipid metabolism characteristics with bile acid metabolism and placental hypoxia injury in patients with intrahepatic cholestasis of pregnancy (ICP. Methods: ICP pregnant women and healthy pregnant women who received antenatal care and delivered in Obstetrics Department of Panzhihua Maternal and Child Health Care Hospital between May 2013 and October 2016 were collected and included in ICP group and control group respectively. Serum lipid metabolism and bile acid metabolism indexes were measured at 20 weeks, 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation; mitochondria damage molecule expression levels in placenta were determined after childbirth. Results: Serum TC, LDL-C and HDL-C levels were not different between two groups of pregnant women at 20 weeks of gestation, and serum TC and LDL-C levels of ICP group at 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation were significantly higher than those of control group while HDL-C levels were significantly lower than those of control group; serum TBA, ALT and AST levels were not different between two groups of pregnant women at 20 weeks, 24 weeks and 28 weeks of gestation, and serum TBA, ALT and AST levels of ICP group at 32 weeks and 36 weeks of gestation were significantly higher than those of control group; CCO, ATPase, SDH and Bcl-2 protein expression in placenta tissue of ICP group were significantly lower than those of control group while Bax and Caspase-3 protein expression were significantly higher than those of control group. Serum LDL-C levels at 24 weeks, 28 weeks, 32 weeks and 36 weeks of gestation were positively correlated with TBA, ALT and AST levels in serum as well as Bax and Caspase-3 protein expression in placental tissue, and negatively correlated with CCO, ATPase, SDH and Bcl-2 protein expression in placental tissue. Conclusion: Midtrimester lipid metabolism characteristics can early predict the risk of ICP and evaluate the

  6. Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

    Science.gov (United States)

    Gupta, Shweta; Kesarla, Rajesh; Chotai, Narendra; Misra, Ambikanandan

    2017-01-01

    The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients. PMID:28243600

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

  9. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma.

    Science.gov (United States)

    Cha, Yoon Jin; Kim, Hye Min; Koo, Ja Seung

    2017-01-23

    We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN). HSL, perilipin A, and FABP4 expression (all p invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC ( p cancers, HSL and FABP4 were more highly expressed in ILC ( p < 0.001). Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity ( p = 0.004) and acyl-CoA oxidase 1 positivity ( p = 0.032) and of shorter overall survival with acyl-CoA oxidase 1 positivity ( p = 0.027). In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.

  10. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma

    Directory of Open Access Journals (Sweden)

    Yoon Jin Cha

    2017-01-01

    Full Text Available We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC and invasive ductal carcinoma (IDC of the breast. A total of 584 breast cancers (108 ILC and 476 IDC were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL, perilipin A, fatty acid binding protein (FABP4, carnitine palmitoyltransferase (CPT-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN. HSL, perilipin A, and FABP4 expression (all p < 0.001 differed significantly: HSL and FABP4 were more frequently present in ILC, whereas perilipin A was more frequently detected in IDC. Among all invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC (p < 0.001 and perilipin A in luminal A-type IDC (p = 0.007. Among luminal B-type cancers, HSL and FABP4 were more highly expressed in ILC (p < 0.001. Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity (p = 0.004 and acyl-CoA oxidase 1 positivity (p = 0.032 and of shorter overall survival with acyl-CoA oxidase 1 positivity (p = 0.027. In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.

  11. The Effect of Hippocampal Cognitive Impairment and XIAP on Glucose and Lipids Metabolism in Rats

    Directory of Open Access Journals (Sweden)

    Chunbo Xia

    2016-02-01

    Full Text Available Background/Aims: To investigate the effect of cognitive impairment and X-linked inhibitor of apoptosis protein (XIAP on glucolipid metabolism. Materials and Methods: β-amyloid (Aβ 1-42 was injected into the hippocampus of rats to establish a cognitive impairment model. Trans-activator of transcription (TAT-XIAP fusion protein (the TAT-XIAP group, PBS (the model group, or XIAP antisense oligonucleotides (the ASODN group was injected into the lateral ventricles of the rats to increase and decrease the activity of XIAP in the hippocampus. To determine the level of blood glucose and lipids, adenosine monophosphate-activated protein kinase (AMPK expression of liver and hipppocamual neuronal apoptosis. Results: The levels of FPG, TG, TC and LDL were significantly higher in the TAT-XIAP group, the model group and the ASODN group than in the blank group (P Conclusion: Cognitive impairment and hippocampal neuron apoptosis can cause glucose and lipids metabolic abnormalities, possibly by regulating gastrointestinal motility and AMPK expression in the liver. The changes in the function of XIAP, which is an anti-apoptotic protein in the hippocampus, may affect the metabolism of glucose and lipids.

  12. Neuroimaging of Lipid Storage Disorders

    Science.gov (United States)

    Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

    2013-01-01

    Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

  13. Radiolabelling studies on the lipid metabolism in the marine brown alga Dictyopteris membranacea

    International Nuclear Information System (INIS)

    Hofmann, M.; Eichenberger, W.

    1998-01-01

    The lipid metabolism of the marine brown alga D. membranacea was investigated using [2- 14 C]acetate, [1- 14 C]myristate, [1- 14 C]oleate and [1- 14 C]arachidonate as precursors. On incubation with [2- 14 C]acetate, 18:1 and 16:0 were the main products formed by de novo synthesis and incorporated into polar lipids. With all the exogenous substrates used, DGTA was strongly labelled and the subsequent rapid turnover of radioactivity suggested a key role for this lipid in the redistribution of acyl chains and most likely also in the biosynthesis of the eukaryotic galactolipids produced in the absence of PC. In the glycolipids a continuous accumulation of radioactivity was observed with all the substrates used. The labelling kinetics of molecular species of MGDG suggested the desaturation of 18:1 to 18:4 and of 20:4 (n-6) to 20:5 (n-3) acids on this lipid. Both PG and PE were primary acceptors of de novo synthesized fatty acids and exogenous [1- 14 C]oleate, but no evidence exists for a further processing of acyl chains on these lipids. TAG, although strongly labelled with all exogenous [1- 14 C]acids, was not labelled when [2- 14 C]acetate was used as a precursor indicating the flux of endogenous fatty acids to be different of that of exogenously supplied fatty acids. (author)

  14. Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides

    Science.gov (United States)

    Geiselman, Gina M; Ito, Masakazu; Mondo, Stephen J; Reilly, Morgann C; Cheng, Ya-Fang; Bauer, Stefan; Grigoriev, Igor V; Gladden, John M; Simmons, Blake A; Brem, Rachel B

    2018-01-01

    The basidiomycete yeast Rhodosporidium toruloides (also known as Rhodotorula toruloides) accumulates high concentrations of lipids and carotenoids from diverse carbon sources. It has great potential as a model for the cellular biology of lipid droplets and for sustainable chemical production. We developed a method for high-throughput genetics (RB-TDNAseq), using sequence-barcoded Agrobacterium tumefaciens T-DNA insertions. We identified 1,337 putative essential genes with low T-DNA insertion rates. We functionally profiled genes required for fatty acid catabolism and lipid accumulation, validating results with 35 targeted deletion strains. We identified a high-confidence set of 150 genes affecting lipid accumulation, including genes with predicted function in signaling cascades, gene expression, protein modification and vesicular trafficking, autophagy, amino acid synthesis and tRNA modification, and genes of unknown function. These results greatly advance our understanding of lipid metabolism in this oleaginous species and demonstrate a general approach for barcoded mutagenesis that should enable functional genomics in diverse fungi. PMID:29521624

  15. Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats

    Directory of Open Access Journals (Sweden)

    RN Jadeja

    Full Text Available The present study was undertaken to evaluate the efficacy of freeze dried extract of Clerodendron glandulosum Coleb., Verbenaceae, leaves (FECG on alteration in lipid and cholesterol metabolism in high fat diet fed hyperlipidemic rats. Plasma and hepatic lipid profiles, lipid and cholesterol metabolizing enzymes in target tissues and fecal total lipids and bile acid contents were evaluated in FECG treated normolipidemic and hyperlipidemic rats. These results were compared with synthetic hypolipidemic drug Lovastatin (LVS. Results indicate that FECG was able to positively regulate induced experimental hyperlipidemia by significant alteration in plasma and tissue lipid profiles. These results can be attributed to reduced absorption, effective elimination and augmented catabolism of lipids and cholesterol possibly due to high content of saponin and phytosterols in C. glandulosum. Use of C. glandulosum extract as a potential therapeutic agent against hypercholesterolemia and hypertriglyceridemia is indicated.

  16. Investigation of protein and lipid metabolism in thyroid pathology using whole-body radiometry

    International Nuclear Information System (INIS)

    Gorobets, V.F.; Matveenko, E.G.

    1987-01-01

    Radiometry of the whole body and its organs was employed to study certain aspects of protein-aminoacid and lipid metabolism in patients with thyroid diseases. Metabolism of human serum 131 I-albumin was studied in 12 patients with neurocirculatory dystonia, in 13 patients with diffuse toxic goiter (in 10 before and after drug therapy) and in 9 controls. 75 Se-methionine aminoacid metabolism was investigated in 9 patients with toxic thyroid adenoma and in 13 controls. The body cell mass was determined in 82 patients with thyrotoxicosis by a measurable amount of 40 K. These data were compared with those of 249 healthy persons. An increase in catabolism of labeled albumin, intensification of labeled methionine metabolism at the tissue level, signs of a decrease in the total amount of metabolic albumin in the body were revealed. Intensification of protein metabolism resulted in a decrease in the body cell mass of these patients. After adequate therapy the above indices of protein metabolism in patients with thyrotoxicosis returned to normal. The assimilation of fatty acids and neutral fat was disturbed both in thyrotoxicosis and hypothyroidism

  17. Neurovascular coupling and energy metabolism in the developing brain

    Science.gov (United States)

    Kozberg, M.; Hillman, E.

    2016-01-01

    In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418

  18. Influence of cigarette smoking on hormone and lipid metabolism in women in late reproductive stage

    Directory of Open Access Journals (Sweden)

    Szkup M

    2018-01-01

    Full Text Available Małgorzata Szkup,1 Anna Jurczak,2 Beata Karakiewicz,3 Artur Kotwas,3 Jacek Kopeć,4 Elżbieta Grochans1 1Department of Nursing, 2Department of Clinical Nursing, 3Department of Public Health, Pomeranian Medical University in Szczecin, Szczecin, Poland; 4School of Population and Public Health, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada Background: The aim of the study was to analyze lipid and hormone metabolism, body mass index (BMI, and age parameters in late reproductive stage women in relation to cigarette smoking.Methods: The study enrolled 345 healthy late reproductive stage women living in Poland; 13.33% were smokers. The first part of the study assessed lipid metabolism (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides and hormone metabolism (estradiol [E2], follicle-stimulating hormone [FSH], and anti-Müllerian hormone [AMH] levels in women in the early phase of the follicular menstrual cycle. The second part of study was carried out using the diagnostic survey method, with a standardized questionnaire (Primary Care Evaluation of Mental Disorders [PRIME-MD] and the authors’ own research tools.Results: The women were aged 42.3±4.5 years (mean ± SD. The BMI (24.8±4.04 kg/m2 did not differ significantly between the groups. The women who smoked cigarettes had a statistically significantly (p<0.05 lower level of HDL as well as higher LDL and triglyceride levels (p<0.05. Differences were also shown in hormone levels: non-smoking participants had statistically significantly higher levels of E2 and FSH (p<0.05. In the group of non-smoking women, age was a predictor exerting a significant positive impact on the levels of total cholesterol, LDL, triglycerides, and AMH (p<0.05. BMI contributed to a decline in HDL and triglyceride levels. In the group of smoking women, age significantly positively influenced the level of E2, and negatively influenced AMH

  19. Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling.

    Science.gov (United States)

    Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

    2017-05-06

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. Copyright © 2017. Published by Elsevier Inc.

  20. Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men

    OpenAIRE

    Urho M Kujala; Markku Peltonen; Merja K. Laine; Merja K. Laine; Jaakko Kaprio; Jaakko Kaprio; Jaakko Kaprio; Olli. J. Heinonen; Jouko Sundvall; Johan G. Eriksson; Johan G. Eriksson; Johan G. Eriksson; Antti Jula; Seppo Sarna; Heikki Kainulainen

    2016-01-01

    Aims/hypothesis Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid (TCA) cycle, intramyocellular lipid storage and oxidation thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed wheth...

  1. Consumption of Alcopops During Brain Maturation Period: Higher Impact of Fructose Than Ethanol on Brain Metabolism

    Directory of Open Access Journals (Sweden)

    Dounia El Hamrani

    2018-05-01

    Full Text Available Alcopops are flavored alcoholic beverages sweetened by sodas, known to contain fructose. These drinks have the goal of democratizing alcohol among young consumers (12–17 years old and in the past few years have been considered as fashionable amongst teenagers. Adolescence, however, is a key period for brain maturation, occurring in the prefrontal cortex and limbic system until 21 years old. Therefore, this drinking behavior has become a public health concern. Despite the extensive literature concerning the respective impacts of either fructose or ethanol on brain, the effects following joint consumption of these substrates remains unknown. Our objective was to study the early brain modifications induced by a combined diet of high fructose (20% and moderate amount of alcohol in young rats by 13C Nuclear Magnetic Resonance (NMR spectroscopy. Wistar rats had isocaloric pair-fed diets containing fructose (HF, 20%, ethanol (Et, 0.5 g/day/kg or both substrates at the same time (HFEt. After 6 weeks of diet, the rats were infused with 13C-glucose and brain perchloric acid extracts were analyzed by NMR spectroscopy (1H and 13C. Surprisingly, the most important modifications of brain metabolism were observed under fructose diet. Alterations, observed after only 6 weeks of diet, show that the brain is vulnerable at the metabolic level to fructose consumption during late-adolescence throughout adulthood in rats. The main result was an increase in oxidative metabolism compared to glycolysis, which may impact lactate levels in the brain and may, at least partially, explain memory impairment in teenagers consuming alcopops.

  2. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

    Science.gov (United States)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J; Beebe, Kirk; Gall, Walt; Venditti, Charles P; Patti, Mary-Elizabeth

    2016-10-01

    Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  3. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Full Text Available Objective: Plasma levels of branched-chain amino acids (BCAA are consistently elevated in obesity and type 2 diabetes (T2D and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. Methods: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28. We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Results: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D. Keywords: Insulin sensitivity, BCAA, Fatty acid oxidation, TCA cycle

  4. Human myotubes from myoblast cultures undergoing senescence exhibit defects in glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Nehlin, Jan O; Just, Marlene; Rustan, Arild C

    2011-01-01

    Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways. As the prolif......Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways...... number and could be explained by reduced incorporation into diacyl- and triacylglycerols. The levels of long-chain acyl-CoA esters decreased with increased passage number. Late-passage, non-proliferating, myoblast cultures showed strong senescence-associated β-galactosidase activity indicating...... that the observed metabolic defects accompany the induction of a senescent state. The main function of SCs is regeneration and skeletal muscle-build up. Thus, the metabolic defects observed during aging of SC-derived myotubes could have a role in sarcopenia, the gradual age-related loss of muscle mass and strength....

  5. Diet-gene interactions between dietary fat intake and common polymorphisms in determining lipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Corella, D.

    2009-07-01

    Current dietary guidelines for fat intake have not taken into consideration the possible genetic differences underlying the individual variability in responsiveness to dietary components. Genetic variability has been identified in humans for all the known lipid metabolism-related genes resulting in a plethora of candidate genes and genetic variants to examine in diet-gene interaction studies focused on fat consumption. Some examples of fat-gene interaction are reviewed. These include: the interaction between total intake and the 14C/T in the hepatic lipase gene promoter in determining high-density lipoprotein cholesterol (HDL-C) metabolism; the interaction between polyunsaturated fatty acids (PUFA) and the 5G/A polymorphism in the APOA1 gene plasma HDL-C concentrations; the interaction between PUFA and the L162V polymorphism in the PPARA gene in determining triglycerides and APOC3 concentrations; and the interaction between PUFA intake and the -1131T>C in the APOA5 gene in determining triglyceride metabolism. Although hundreds of diet-gene interaction studies in lipid metabolism have been published, the level of evidence to make specific nutritional recommendations to the population is still low and more research in nutrigenetics has to be undertaken. (Author) 31 refs.

  6. Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.

    Science.gov (United States)

    Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

    2016-05-01

    The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential -18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

  7. Measurement of tritiated norepinephrine metabolism in intact rat brain

    International Nuclear Information System (INIS)

    Levitt, M.; Kowalik, S.; Barkai, A.I.

    1983-01-01

    A procedure for the study of NE metabolism in the intact rat brain is described. The method involves ventriculocisternal perfusion of the adult male rat with artificial CSF containing [ 3 H]NE. Radioactivity in the perfusate associated with NE and its metabolites 3,4-dihydroxymandelic acid (DOMA), 3,4-dihydroxphenylethyleneglycol (DHPG), 3-methoxy-4-hydroxymandelic acid (VMA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), and normetanephrine (NMN) is separated using high-performance liquid chromatography (HPLC). After 80 min the radioactivity in the perfusate reaches an apparent steady-state. Analysis of the steady-state samples shows higher activity in the fractions corresponding to DHPG and MHPG than in those corresponding to DOMA and VMA, confirming glycol formation as the major pathway of NE metabolism in rat brain. Pretreatment with an MAO inhibitor (tranylcypromine) results in a marked decrease in the deaminated metabolites DHPG and MHPG and a concurrent increase in NMN. The results indicate this to be a sensitive procedure for the in vivo determination of changes in NE metabolism. (Auth.)

  8. Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

    International Nuclear Information System (INIS)

    Chen, Qi-Liang; Gong, Yuan; Luo, Zhi; Zheng, Jia-Lang; Zhu, Qing-Ling

    2013-01-01

    Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

  9. Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Gong, Yuan [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Luo, Zhi, E-mail: luozhi99@mail.hzau.edu.cn [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Zheng, Jia-Lang; Zhu, Qing-Ling [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China)

    2013-10-15

    Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

  10. Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature.

    Science.gov (United States)

    López-Malo, María; García-Ríos, Estéfani; Chiva, Rosana; Guillamon, José M

    2014-10-29

    Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 - 15°C). The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1 , LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must.

  11. Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature

    Directory of Open Access Journals (Sweden)

    María López-Malo

    2014-10-01

    Full Text Available Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 – 15°C. The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1, LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must.

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

    Science.gov (United States)

    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

  13. Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Weiqin Chen

    Full Text Available Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that Bscl2 (-/- mice develop lipodystrophy of white adipose tissue (WAT due to unbridled lipolysis. The residual epididymal WAT (EWAT displays a browning phenotype with much smaller lipid droplets (LD and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/- mice. Analysis of total saponified fatty acids revealed that the residual EWAT of Bscl2(-/- mice contained a much higher proportion of oleic 18:1n9 acid concomitant with a lower proportion of palmitic 16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA remodeling. The acyl chains in major species of triacylglyceride (TG and diacylglyceride (DG in the residual EWAT of Bscl2(-/- mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, Bscl2(-/- adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal β-oxidation genes were also markedly increased in Bscl2(-/- adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, Bscl2 is also important in fatty acid remodeling and energy homeostasis.

  14. [Intensity of pentose phosphate metabolism of carbohydrates in various brain areas in normal and starved animals].

    Science.gov (United States)

    Kerimov, B F

    2002-01-01

    The activities of key enzymes of pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G-6 PD) and 6-phosphogluconate dehydrogenase (6-PGD), were studied in cytoplasmatic fractions of brain cortical (limbic, orbital, sensorimotor cortex) and subcortical (myelencefalon, mesencefalon, hypothalamus) structures of rats subjected to starvation for 1, 2, 3, 5 and 7 days. Short-term starvation (1-3 days) caused activation of 6-GPD and 6-PGD both in cortical and subcortical structures. Long-term starvation for 5-7 days caused a decrease of activities of the pentose phosphate pathway enzymes in all studied structures. It is suggested that enzymes of pentose phosphate pathway in nervous tissues are functionally and metabolically related to glutathione system and during starvation they indirectly participate in the regulation lipid peroxidation processes.

  15. Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury: A pilot study.

    Science.gov (United States)

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

    2017-11-01

    Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET).We consecutively enrolled 11 patients with FOG after HIBI. The patients' overall brain metabolism was measured by F-18 FDG PET, and we compared their regional brain metabolic activity with that from 15 healthy controls using a voxel-by-voxel-based statistical mapping analysis. Additionally, we correlated each patient's FOG severity with the brain metabolism using a covariance analysis.Patients with FOG had significantly decreased brain glucose metabolism in the midbrain, bilateral thalamus, bilateral cingulate gyri, right supramarginal gyrus, right angular gyrus, right paracentral lobule, and left precentral gyrus (PFDR-corrected brain metabolism were noted in patients with FOG. The covariance analysis identified significant correlations between the FOG severity and the brain metabolism in the right lingual gyrus, left fusiform gyrus, and bilateral cerebellar crus I (Puncorrected brain regions in the gait-related neural network, including the cerebral cortex, subcortical structures, brainstem, and cerebellum, may significantly contribute to the development of FOG in HIBI. Moreover, the FOG severity may be associated with the visual cortex and cerebellar regions.

  16. Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans.

    Science.gov (United States)

    Hussey, Rosalind; Stieglitz, Jon; Mesgarzadeh, Jaleh; Locke, Tiffany T; Zhang, Ying K; Schroeder, Frank C; Srinivasan, Supriya

    2017-05-01

    It is now established that the central nervous system plays an important role in regulating whole body metabolism and energy balance. However, the extent to which sensory systems relay environmental information to modulate metabolic events in peripheral tissues has remained poorly understood. In addition, it has been challenging to map the molecular mechanisms underlying discrete sensory modalities with respect to their role in lipid metabolism. In previous work our lab has identified instructive roles for serotonin signaling as a surrogate for food availability, as well as oxygen sensing, in the control of whole body metabolism. In this study, we now identify a role for a pair of pheromone-sensing neurons in regulating fat metabolism in C. elegans, which has emerged as a tractable and highly informative model to study the neurobiology of metabolism. A genetic screen revealed that GPA-3, a member of the Gα family of G proteins, regulates body fat content in the intestine, the major metabolic organ for C. elegans. Genetic and reconstitution studies revealed that the potent body fat phenotype of gpa-3 null mutants is controlled from a pair of neurons called ADL(L/R). We show that cAMP functions as the second messenger in the ADL neurons, and regulates body fat stores via the neurotransmitter acetylcholine, from downstream neurons. We find that the pheromone ascr#3, which is detected by the ADL neurons, regulates body fat stores in a GPA-3-dependent manner. We define here a third sensory modality, pheromone sensing, as a major regulator of body fat metabolism. The pheromone ascr#3 is an indicator of population density, thus we hypothesize that pheromone sensing provides a salient 'denominator' to evaluate the amount of food available within a population and to accordingly adjust metabolic rate and body fat levels.

  17. Multifunctional roles of enolase in Alzheimer's disease brain: beyond altered glucose metabolism.

    Science.gov (United States)

    Butterfield, D Allan; Lange, Miranda L Bader

    2009-11-01

    Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer's disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, as there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified alpha-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD, and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, alpha-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, early-onset AD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder.

  18. The action of D-dopachrome tautomerase as an adipokine in adipocyte lipid metabolism.

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    Takeo Iwata

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

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

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    Mariateresa Maldini

    2015-06-01

    Full Text Available 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

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

    Science.gov (United States)

    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

  1. Effects of NS lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet

    Science.gov (United States)

    2013-01-01

    Background Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression

  2. Reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live Leishmania amazonensis amastigotes.

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    Hervé Lecoeur

    Full Text Available 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?

  3. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

    Science.gov (United States)

    Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

    2016-05-01

    Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Sadeghian, Saeed; Boroumand, Mohammad Ali; Sotoudeh-Anvari, Maryam; Rabbani, Shahram; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    This experimental study was performed to determine the impact of opium use on serum lipid profile and glucose metabolism in rats with streptozotocin-induced diabetes. To determine the effect of opium, 20 male rats were divided into control (n = 10) and opium-treated (n = 10) groups. After diabetes induction, the animals were investigated for daily glucose measurements for 35 days. Serum lipid profile and haemoglobin A1c (HbA(1c)) were assayed at the baseline (before induction of diabetes) and at 35-day follow-up. The glycaemia levels in the rats treated with opium were similar to the levels measured in the control rats (544.8 +/- 62.2 mg/dl v. 524.6 +/- 50.0 mg/dl, P = 0.434). In addition, there was no difference between the opium-treated rats and control rats in HbA(1c) (6.5 +/- 0.5% v. 6.6 +/- 0.2%, P = 0.714). Compared to the control rats, the serum total cholesterol, high density lipoprotein (HDL), triglyceride and lipoprotein (a) in the test animals were similar. Opium use has no significant effect on glucose metabolism and serum lipid profile in rats with induced diabetes.

  5. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

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    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-03-11

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

  6. 13C NMR for the assessment of human brain glucose metabolism in vivo

    International Nuclear Information System (INIS)

    Beckman, N.; Seelig, J.; Turkalj, I.; Keller, U.

    1991-01-01

    Proton-decoupled 13 C NMR spectra of the human head were obtained during hyperglycemic glucose clamping using intravenous infusions of [1- 13 C]glucose in normal volunteers. In addition to 13 C signals of mobile lipids, a variety of new metabolite resonances could be resolved for the first time in the human brain. At an enrichment level of 20% [1- 13 C]glucose, the signals of α- and β-glucose at 92.7 and 96.6 ppm, respectively, could be detected in the human brain after only an infusion period of 15 minutes. The spatial localization of the different regions of interest was confirmed by 13 C NMR spectroscopic imaging with a time resolution of 9 minutes. Increasing the enrichment level to 99% [1- 13 C]glucose not only improved the time resolution but allowed the detection of metabolic breakdown products of [1- 13 C]glucose. The time course of 13 C label incorporation into the C 2 , C 3 , and C 4 resonances of glutamate/glutamine and into lactate could be recorded in the human brain. These results suggest the possibility of obtaining time-resolved, spatially selective, and chemically specific information on the human body

  7. Cerebral Glucose Metabolism and Sedation in Brain-injured Patients: A Microdialysis Study.

    Science.gov (United States)

    Hertle, Daniel N; Santos, Edgar; Hagenston, Anna M; Jungk, Christine; Haux, Daniel; Unterberg, Andreas W; Sakowitz, Oliver W

    2015-07-01

    Disturbed brain metabolism is a signature of primary damage and/or precipitates secondary injury processes after severe brain injury. Sedatives and analgesics target electrophysiological functioning and are as such well-known modulators of brain energy metabolism. Still unclear, however, is how sedatives impact glucose metabolism and whether they differentially influence brain metabolism in normally active, healthy brain and critically impaired, injured brain. We therefore examined and compared the effects of anesthetic drugs under both critical (1 mmol/L) extracellular brain glucose levels. We performed an explorative, retrospective analysis of anesthetic drug administration and brain glucose concentrations, obtained by bedside microdialysis, in 19 brain-injured patients. Our investigations revealed an inverse linear correlation between brain glucose and both the concentration of extracellular glutamate (Pearson r=-0.58, P=0.01) and the lactate/glucose ratio (Pearson r=-0.55, P=0.01). For noncritical brain glucose levels, we observed a positive linear correlation between midazolam dose and brain glucose (Pbrain glucose levels, extracellular brain glucose was unaffected by any type of sedative. These findings suggest that the use of anesthetic drugs may be of limited value in attempts to influence brain glucose metabolism in injured brain tissue.

  8. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.

    Directory of Open Access Journals (Sweden)

    Xinwei Li

    Full Text Available The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid and BML-275 (an AMPKα inhibitor. Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.

  9. Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulates carotenoid and lipid metabolism in mice

    Science.gov (United States)

    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

  10. Safety profile of the intravenous administration of brain-targeted stable nucleic acid lipid particles

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    Mariana Conceição

    2016-03-01

    Full Text Available In a clinical setting, where multiple administrations of the therapeutic agent are usually required to improve the therapeutic outcome, it is crucial to assess the immunogenicity of the administered nanoparticles. In this data work, we investigated the safety profile of the repeated intravenous administration of brain-targeted stable nucleic acid lipid particles (RVG-9r-targeted SNALPs. To evaluate local activation of the immune system, we performed analysis of mouse tissue homogenates and sections from cerebellum. To investigate peripheral activation of the immune system, we used serum of mice that were intravenously injected with RVG-9r-targeted SNALPs. These data are related and were discussed in the accompanying research article entitled “Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado–Joseph disease neurological phenotype” (Conceição et al., in press [1].

  11. Effects of intermittent fasting and chronic swimming exercise on body composition and lipid metabolism.

    Science.gov (United States)

    Moraes, Ruan Carlos Macedo de; Portari, Guilherme Vannucchi; Ferraz, Alex Soares Marreiros; da Silva, Tiago Eugênio Oliveira; Marocolo, Moacir

    2017-12-01

    Intermittent fasting protocol (IFP) has been suggested as a strategy to change body metabolism and improve health. The effects of IFP seem to be similar to aerobic exercise, having a hormetic adaptation according to intensity and frequency. However, the effects of combining both interventions are still unknown. Therefore, the aim of the present study was to evaluate the effects of IFP with and without endurance-exercise training on body composition, food behavior, and lipid metabolism. Twenty-week-old Wistar rats were kept under an inverted circadian cycle of 12 h with water ad libitum and assigned to 4 different groups: control group (ad libitum feeding and sedentary), exercise group (ad libitum feeding and endurance training), intermittent fasting group (IF; intermittent fasting and sedentary), and intermittent fasting and exercise group (IFEX; intermittent fasting and endurance training). After 6 weeks, the body weight of IF and IFEX animals decreased without changes in food consumption. Yet, the body composition between the 2 groups was different, with the IFEX animals containing higher total protein and lower total fat content than the IF animals. The IFEX group also showed increases in total high-density lipoprotein cholesterol and increased intramuscular lipid content. The amount of brown adipose tissue was higher in IF and IFEX groups; however, the IFEX group showed higher expression levels of uncoupling protein 1 in this tissue, indicating a greater thermogenesis. The IFP combined with endurance training is an efficient method for decreasing body mass and altering fat metabolism, without inflicting losses in protein content.

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

    Science.gov (United States)

    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.

  13. Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism.

    Science.gov (United States)

    Palczewski, Grzegorz; Widjaja-Adhi, M Airanthi K; Amengual, Jaume; Golczak, Marcin; von Lintig, Johannes

    2016-09-01

    Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  14. Comparative evaluation of the influence of diabetic retinopathy progression factors on indices of lipid metabolism in metabolic syndrome

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    L.Yu. Pуlуpenko

    2017-11-01

    Full Text Available Background. The search and study of new risk factors for the development and progression of diabetic retinopathy (DRP and their modifying influence on the components of metabolic syndrome in type 2 diabetes mellitus (T2DM remain relevant. The purpose was to conduct a comparative evaluation of the impact of certain DRP development factors on indices of lipid metabolism in metabolic syndrome. Materials and methods. The research was carried out in 64 patients (95 eyes with T2DM, metabolic syndrome and DRP (males and females, average age 61.55 ± 2.37 years, average duration of diabetes 11.23 ± 2.11 years, average level of HbA1c 9.89 ± 0.78 %, average body mass index 34.55 ± 3.75 kg/m2, who were divided into 3 groups depending on the stage of DRP. Results. Results had showed that the following factors have modifying influence on the level of total cholesterol in the blood of patients with T2DM and DRP: age of patients (under 60 years, duration of diabetes (less than 10 years, decompensation of carbohydrates metabolism — for the 3rd stage of DRP, features of therapy for T2DM (oral hypoglycemic drugs — for the 2nd stage of DRP; on the level of low-density lipoprotein cholesterol: younger age of patients, decompensation of diabetes — for the 3rd stage of DRP, features of hypoglycemic therapy (insulin therapy, shorter duration of diabetes — for the 2nd stage of DRP; on the level of triglycerides: age of patients (under 60 years, duration of diabetes (less than 10 years and insulin therapy — for the 1st and 3rd stages of DRP. Conclusions. It is concluded that features of hypoglycemic therapy can be a new modifying factor for the risk of DRP progression.

  15. Betatrophin provides a new insight into diabetes treatment and lipid metabolism (Review).

    Science.gov (United States)

    Zhu, Jin-Zhou; Yu, Chao-Hui; Li, You-Ming

    2014-07-01

    Replenishing the insulin-producing β-cell mass is considered to be a potential cure for diabetes. A recent study identified a secreted protein, known as betatrophin, which potently induces pancreatic β-cell proliferation. Notably, a number of studies reportedly identified betatrophin, which is also known as lipasin, atypical angiopoietin-like 8 and refeeding-induced fat and liver protein, and considered to be a novel regulator in lipid metabolism according to the studies. The identification of betatrophin was considered to create novel opportunities for potential diabetes therapy. In the present study, the current knowledge of betatrophin is reviewed, with regards to its character and function in lipid homeostasis and pancreatic β-cell proliferation.

  16. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, J.; Poulsen, P.; Vaag, A.

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03

  17. Comparison of 1H-MRS-detected metabolic characteristics in single metastatic brain tumors of different origin

    International Nuclear Information System (INIS)

    Chernov, M.F.; Ono, Yuko; Kubo, Osami; Hori, Tomokatsu

    2006-01-01

    Various types of intracranial metastases exhibit different growth patterns, which can be reflected in their metabolic characteristics and investigated noninvasively by proton magnetic resonance spectroscopy ( 1 H-MRS). The objective of the present study was comparison of the 1 H-MRS-detected metabolic parameters in brain metastases of different origin. Twenty-five patients (15 men and 10 women; mean age, 62.0 years) with single, previously nontreated metastatic brain tumors were investigated by long-echo single-voxel volume-selected 1 H-MRS. The primary cancer was located in the lungs (10 cases), colon and rectum (8 cases), breast (3 cases), kidney (2 cases), prostate (1 case), and cardiac muscle (1 case). Comparison of clinical and radiological variables, including type of tumor contrast enhancement and extension of peritumoral edema, did not disclose statistically significant differences in metastatic brain tumors of different origin. At the same time, comparison of 1 H-MRS-detected metabolic characteristics revealed that metastases of colorectal carcinoma have greater content of mobile lipids (Lip) compared to other neoplasms. In conclusion, high Lip content in the viable brain metastases of colorectal carcinoma can be used as an additional diagnostic clue for noninvasive identification of these tumors and should be taken into consideration in cases of 1 H-MRS-based differentiation of their recurrence and radiation-induced necrosis after radiosurgical or radiotherapeutic treatment. (author)

  18. Effects of Kisspeptin-10 on Lipid Metabolism in Cultured Chicken Hepatocytes

    Directory of Open Access Journals (Sweden)

    J. Wu

    2012-09-01

    Full Text Available Our previous studies showed that kisspeptin-10 (Kp-10 injected in vivo can markedly increase lipid anabolism in liver of quails. In order to investigate the direct effect of Kp-10 on lipid metabolism of hepatocytes in birds, cells were separated from embryos livers and cultured in vitro with 0, 100 and 1,000 nM Kp-10, respectively. The results showed that after 24 h treatment, cells viability was not affected by 100 nM Kp-10, but showed a mild decrease with 1,000 nM Kp-10 compared to the control cells. Based on the results of the cell viability, 100 nM dosage of Kp-10 was selected for the further study and analysis. Compared with control cells, total cholesterol (Tch contents in 100 nM treated cells were increased by 51.23%, but did not reach statistical significance, while the level of triglyceride (TG, high density of lipoprotein-cholesterol (HDL-C and low density of lipoprotein-cholesterol (LDL-C were significantly increased. Real-time PCR results showed that ApoVLDL-II mRNA expression had a tendency to increase, genes including sterol regulatory element-binding protein-1 (SREBP-1, acetyl coenzyme A carboxylase α (ACCα, carnitine palmitoyltransferase 1 (CPT1, 3-hydroxyl-3-methylglutaryl-coenzyme A reductases (HMGCR and stearyl coenzyme A dehydrogenase-1 (SCD1 mRNA in hepatocytes were significantly down-regulated by 100 nM Kp-10. However, contrary to its gene expression, SREBP-1 protein expression was significantly up-regulated by 100 nM Kp-10. Some of the significant correlations in mRNA expression were found between genes encoding hepatic factors or enzymes involved in lipid metabolism in liver of birds. These results indicate that Kp-10 stimulates lipid synthesis directly in primary cultured hepatocytes of chickens.

  19. Investigating the effects of statins on cellular lipid metabolism using a yeast expression system.

    Directory of Open Access Journals (Sweden)

    Agata Leszczynska

    Full Text Available In humans, defects in lipid metabolism are associated with a number of severe diseases such as atherosclerosis, obesity and type II diabetes. Hypercholesterolemia is a primary risk factor for coronary artery disease, the major cause of premature deaths in developed countries. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR, the key enzyme of the sterol synthesis pathway. Since yeast Saccharomyces cerevisiae harbours many counterparts of mammalian enzymes involved in lipid-synthesizing pathways, conclusions drawn from research with this single cell eukaryotic organism can be readily applied to higher eukaryotes. Using a yeast strain with deletions of both HMG1 and HMG2 genes (i.e. completely devoid of HMGR activity with introduced wild-type or mutant form of human HMGR (hHMGR gene we investigated the effects of statins on the lipid metabolism of the cell. The relative quantification of mRNA demonstrated a different effect of simvastatin on the expression of the wild-type and mutated hHMGR gene. GC/MS analyses showed a significant decrease of sterols and enhanced conversion of squalene and sterol precursors into ergosterol. This was accompanied by the mobilization of ergosterol precursors localized in lipid particles in the form of steryl esters visualized by confocal microscopy. Changes in the level of ergosterol and its precursors in cells treated with simvastatin depend on the mutation in the hHMGR gene. HPLC/MS analyses indicated a reduced level of phospholipids not connected with the mevalonic acid pathway. We detected two significant phenomena. First, cells treated with simvastatin develop an adaptive response compensating the lower activity of HMGR. This includes enhanced conversion of sterol precursors into ergosterol, mobilization of steryl esters and increased expression of the hHMGR gene. Second, statins cause a substantial drop in the level of glycerophospholipids.

  20. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    KAUST Repository

    Baud, Maxime O.; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J.; Petit, Jean-Marie

    2016-01-01

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs

  1. The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2014-05-01

    Full Text Available Currently, two-thirds of American adults are overweight or obese. This high prevalence of overweight/obesity negatively affects the health of the population, as obese individuals tend to develop several chronic diseases, such as type 2 diabetes and cardiovascular diseases. Due to obesity’s impact on health, medical costs, and longevity, the rise in the number of obese people has become a public health concern. Both genetic and environmental/dietary factors play a role in the development of metabolic diseases. Intuitively, it seems to be obvious to link over-nutrition to the development of obesity and other metabolic diseases. However, the underlying mechanisms are still unclear. Dietary nutrients not only provide energy derived from macronutrients, but also factors such as micronutrients with regulatory roles. How micronutrients, such as vitamin A (VA; retinol, regulate macronutrient homeostasis is still an ongoing research topic. As an essential micronutrient, VA plays a key role in the general health of an individual. This review summarizes recent research progress regarding VA’s role in carbohydrate, lipid, and protein metabolism. Due to the large amount of information regarding VA functions, this review focusses on metabolism in metabolic active organs and tissues. Additionally, some perspectives for future studies will be provided.

  2. Molecular effect of fenofibrate on PBMC gene transcription related to lipid metabolism in patients with metabolic syndrome.

    Science.gov (United States)

    Moreno-Indias, I; Tinahones, F J; Clemente-Postigo, M; Castellano-Castillo, D; Fernández-García, J C; Macias-Gonzalez, M; Queipo-Ortuño, M I; Cardona, F

    2017-06-01

    Both fasting and postprandial hypertriglyceridaemia are considered independent risk factors for atherosclerosis. Treatment of hypertriglyceridaemia is based on fibrates, which activate the peroxisome proliferator-activated receptor alpha (PPARα). However, the metabolic pathways that activate or inhibit fibrates, and how the postprandial triglyceride levels are modified, have not yet been fully described. Accordingly, the aim of this study was to determine the feasibility of peripheral blood mononuclear cells (PBMC) to study the effects of fenofibrate in patients with the metabolic syndrome. A fat overload was given to 50 patients before and after treatment with fenofibrate for 3 months. Anthropometric and biochemical variables as well as gene expression in PBMC were analysed. After treatment with fenofibrate, we observed a decrease in both baseline and postprandial (3 h after the fat overload) levels of serum triglycerides, cholesterol and uric acid and an increase in HDL cholesterol and apolipoprotein AI levels. After treatment, there was also a rise in PPARα and RXRα expression and changes in genes regulated by PPARα, both baseline and postprandial. Furthermore, in vitro experiments showed that a PPARα agonist changed the expression of genes related with lipid metabolism. Treatment with fenofibrate reduced fasting and postprandial serum triglyceride levels, possibly through a mechanism related with an increase in the expression of RXRα and PPARα, by activating the pathways involved in the uptake and degradation of triglycerides and increasing the synthesis of apolipoprotein. These results suggest that PBMC may be useful for the easy study of fenofibrate actions. © 2017 John Wiley & Sons Ltd.

  3. Metabolic distress in lipid & one carbon metabolic pathway through low vitamin B-12: a population based study from North India.

    Science.gov (United States)

    Saraswathy, Kallur Nava; Joshi, Shipra; Yadav, Suniti; Garg, Priyanka Rani

    2018-04-25

    population is vulnerable to severe under-nutrition due to the association of vitamin B-12 with HDL, leading to metabolic disturbance in both the pathways; lipid and one carbon metabolic pathway. Co-factors such as ethnicity, cultural practices, and lifestyle & dietary habits must be considered while making public health policies to control diseases.

  4. Disruption of behavior and brain metabolism in artificially reared rats.

    Science.gov (United States)

    Aguirre-Benítez, Elsa L; Porras, Mercedes G; Parra, Leticia; González-Ríos, Jacquelina; Garduño-Torres, Dafne F; Albores-García, Damaris; Avendaño, Arturo; Ávila-Rodríguez, Miguel A; Melo, Angel I; Jiménez-Estrada, Ismael; Mendoza-Garrido, Ma Eugenia; Toriz, César; Diaz, Daniel; Ibarra-Coronado, Elizabeth; Mendoza-Ángeles, Karina; Hernández-Falcón, Jesús

    2017-12-01

    Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[ 18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017. © 2017 Wiley Periodicals, Inc.

  5. Molecular modifications of cholesterol metabolism in the liver and the brain after chronic contamination with cesium 137.

    Science.gov (United States)

    Racine, R; Grandcolas, L; Grison, S; Gourmelon, P; Guéguen, Y; Veyssière, G; Souidi, M

    2009-07-01

    Twenty years after Chernobyl accident, the daily ingestion of foodstuff grown on contaminated grounds remains the main source for internal exposure to ionizing radiations, and primarily to cesium 137 ((137)Cs). Though the effects of a long-term internal contamination with radionuclides are poorly documented, several non-cancerous pathologies have been described in this population. However, lipid metabolism was never investigated after chronic internal contamination although disturbances were observed in externally-exposed people. In this regard, we assessed the effects of a chronic ingestion of (137)Cs on hepatic and cerebral cholesterol metabolism. To mimic a chronically-exposed population, rats were given (137)Cs-supplemented water at a post-accidental dose (150 Bq/rat/day) during 9 months. The plasma profile, and brain and liver cholesterol concentrations were unchanged. A decrease of ACAT 2, Apo E, and LXRmRNA levels was recorded in the liver. In the brain, a decrease of CYP27A1 and ACAT 1 gene expression was observed. These results clearly show that cholesterol metabolism is not disrupted by a chronic ingestion of (137)Cs, although several molecular alterations are observed. This work would be interestingly completed by studying the influence of (137)Cs in models likely more sensitive to contaminants, such as the fetus or individuals susceptible to a lipidic disease.

  6. Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain.

    Science.gov (United States)

    Scherer, Thomas; Lindtner, Claudia; O'Hare, James; Hackl, Martina; Zielinski, Elizabeth; Freudenthaler, Angelika; Baumgartner-Parzer, Sabina; Tödter, Klaus; Heeren, Joerg; Krššák, Martin; Scheja, Ludger; Fürnsinn, Clemens; Buettner, Christoph

    2016-06-01

    Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. Common variants in SOCS7 gene predict obesity, disturbances in lipid metabolism and insulin resistance.

    Science.gov (United States)

    Tellechea, M L; Steinhardt, A Penas; Rodriguez, G; Taverna, M J; Poskus, E; Frechtel, G

    2013-05-01

    Specific Suppressor of Cytokine Signaling (SOCS) members, such as SOCS7, may play a role in the development of insulin resistance (IR) owing to their ability to inhibit insulin signaling pathways. The objective was to explore the association between common variants and related haplotypes in SOCS7 gene and metabolic traits related to obesity, lipid metabolism and IR. 780 unrelated men were included in a cross-sectional study. We selected three tagged SNPs that capture 100% of SNPs with minor allele frequency ≥ 0.10. Analyses were done separately for each SNP and followed up by haplotype analysis. rs8074124C was associated with both obesity (p = 0.005) and abdominal obesity (p = 0.002) and allele C carriers showed, in comparison with TT carriers, lower BMI (p = 0.001) and waist circumference (p = 0.001). rs8074124CC- carriers showed lower fasting insulin (p = 0.017) and HOMA-IR (p = 0.018) than allele T carriers. rs12051836C was associated with hypertriglyceridemia (p = 0.009) and hypertriglyceridemic waist (p = 0.006). rs12051836CC- carriers showed lower fasting insulin (p = 0.043) and HOMA-IR (p = 0.042). Haplotype-based association analysis (rs8074124 and rs12051836 in that order) showed associations with lipid and obesity -related phenotypes, consistent with single locus analysis. Haplotype analysis also revealed association between haplotype CT and both decreased HDL-C (p = 0.026) and HDL-C (p = 0.014) as a continuous variable. We found, for the first time, significant associations between SOCS7 common variants and related haplotypes and obesity, IR and lipid metabolism disorders. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  8. Dynapenic obesity as an associated factor to lipid and glucose metabolism disorders and metabolic syndrome in older adults - Findings from SABE Study.

    Science.gov (United States)

    Alexandre, Tiago da Silva; Aubertin-Leheudre, Mylène; Carvalho, Lívia Pinheiro; Máximo, Roberta de Oliveira; Corona, Ligiana Pires; Brito, Tábatta Renata Pereira de; Nunes, Daniella Pires; Santos, Jair Licio Ferreira; Duarte, Yeda Aparecida de Oliveira; Lebrão, Maria Lúcia

    2018-08-01

    There is little evidence showing that dynapenic obesity is associated with lipid and glucose metabolism disorders, high blood pressure, chronic disease and metabolic syndrome. Our aim was to analyze whether dynapenic abdominal obesity can be associated with lipid and glucose metabolism disorders, high blood pressure, metabolic syndrome and cardiovascular diseases in older adults living in São Paulo. This cross-sectional study included 833 older adults who took part of the third wave of the Health, Well-being and Aging Study in 2010. Based on waist circumference (>88 cm women and >102 cm men) and handgrip strength (metabolic syndrome and cardiovascular diseases. Logistic regression was used to analyze the associations between dynapenia and abdominal obesity status and lipid and glucose metabolic profiles, blood pressure, cardiovascular diseases and metabolic syndrome. The fully adjusted models showed that D/AO individuals had higher prevalence of low HDL plasma concentrations (OR = 2.51, 95%CI: 1.40-4.48), hypertriglyceridemia (OR = 2.53, 95%CI: 1.43-4.47), hyperglycemia (OR = 2.05, 95%CI: 1.14-3.69), high glycated-haemoglobin concentrations (OR = 1.84, 95%CI: 1.03-3.30) and metabolic syndrome (OR = 12.39, 95%CI: 7.38-20.79) than ND/NAO. Dynapenic and D/AO individuals had higher prevalence of heart disease (OR = 2.05, 95%CI: 1.17-3.59 and OR = 1.92, 95%CI: 1.06-3.48, respectively) than ND/NAO. D/AO was associated with high prevalence of lipid and glucose metabolism disorders and metabolic syndrome while dynapenia and D/AO were associated with high prevalence of heart disease. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  9. A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid.

    Science.gov (United States)

    Castro, Maite A; Beltrán, Felipe A; Brauchi, Sebastián; Concha, Ilona I

    2009-07-01

    In this review, we discuss a novel function of ascorbic acid in brain energetics. It has been proposed that during glutamatergic synaptic activity neurons preferably consume lactate released from glia. The key to this energetic coupling is the metabolic activation that occurs in astrocytes by glutamate and an increase in extracellular [K(+)]. Neurons are cells well equipped to consume glucose because they express glucose transporters and glycolytic and tricarboxylic acid cycle enzymes. Moreover, neuronal cells express monocarboxylate transporters and lactate dehydrogenase isoenzyme 1, which is inhibited by pyruvate. As glycolysis produces an increase in pyruvate concentration and a decrease in NAD(+)/NADH, lactate and glucose consumption are not viable at the same time. In this context, we discuss ascorbic acid participation as a metabolic switch modulating neuronal metabolism between rest and activation periods. Ascorbic acid is highly concentrated in CNS. Glutamate stimulates ascorbic acid release from astrocytes. Ascorbic acid entry into neurons and within the cell can inhibit glucose consumption and stimulate lactate transport. For this switch to occur, an ascorbic acid flow is necessary between astrocytes and neurons, which is driven by neural activity and is part of vitamin C recycling. Here, we review the role of glucose and lactate as metabolic substrates and the modulation of neuronal metabolism by ascorbic acid.

  10. Regional differences in brain glucose metabolism determined by imaging mass spectrometry

    OpenAIRE

    André Kleinridders; Heather A. Ferris; Michelle L. Reyzer; Michaela Rath; Marion Soto; M. Lisa Manier; Jeffrey Spraggins; Zhihong Yang; Robert C. Stanton; Richard M. Caprioli; C. Ronald Kahn

    2018-01-01

    Objective: Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). Metho...

  11. Interaction between leucine and phosphodiesterase 5 inhibition in modulating insulin sensitivity and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Fu L

    2015-05-01

    Full Text Available Lizhi Fu,1 Fenfen Li,1 Antje Bruckbauer,2 Qiang Cao,1 Xin Cui,1 Rui Wu,1 Hang Shi,1 Bingzhong Xue,1 Michael B Zemel21Department of Biology, Center for Obesity Reversal, Georgia State University, Atlanta, GA, 2NuSirt Biopharma Inc., Nashville, TN, USA Purpose: Leucine activates SIRT1/AMP-activated protein kinase (AMPK signaling and markedly potentiates the effects of other sirtuin and AMPK activators on insulin signaling and lipid metabolism. Phosphodiesterase 5 inhibition increases nitric oxide–cGMP signaling, which in turn exhibits a positive feedback loop with both SIRT1 and AMPK, thus amplifying peroxisome proliferator-activated receptor γ co-activator α (PGC1α-mediated effects. Methods: We evaluated potential synergy between leucine and PDE5i on insulin sensitivity and lipid metabolism in vitro and in diet-induced obese (DIO mice. Results: Leucine (0.5 mM exhibited significant synergy with subtherapeutic doses (0.1–10 nM of PDE5-inhibitors (sildenafil and icariin on fat oxidation, nitric oxide production, and mitochondrial biogenesis in hepatocytes, adipocytes, and myotubes. Effects on insulin sensitivity, glycemic control, and lipid metabolism were then assessed in DIO-mice. DIO-mice exhibited fasting and postprandial hyperglycemia, insulin resistance, and hepatic steatosis, which were not affected by the addition of leucine (24 g/kg diet. However, the combination of leucine and a subtherapeutic dose of icariin (25 mg/kg diet for 6 weeks reduced fasting glucose (38%, P<0.002, insulin (37%, P<0.05, area under the glucose tolerance curve (20%, P<0.01, and fully restored glucose response to exogenous insulin challenge. The combination also inhibited hepatic lipogenesis, stimulated hepatic and muscle fatty acid oxidation, suppressed hepatic inflammation, and reversed high-fat diet-induced steatosis. Conclusion: These robust improvements in insulin sensitivity, glycemic control, and lipid metabolism indicate therapeutic potential for

  12. L-carnitine: a partner between immune response and lipid metabolism ?

    Directory of Open Access Journals (Sweden)

    Giuseppe Famularo

    1993-01-01

    Full Text Available The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

  13. Effects of coumestrol on lipid and glucose metabolism as a farnesoid X receptor ligand

    International Nuclear Information System (INIS)

    Takahashi, Miki; Kanayama, Tomohiko; Yashiro, Takuya; Kondo, Hidehiko; Murase, Takatoshi; Hase, Tadashi; Tokimitsu, Ichiro; Nishikawa, Jun-ichi; Sato, Ryuichiro

    2008-01-01

    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-4α. Through these actions, coumestrol is expected to exert beneficial effects on lipid and glucose metabolism

  14. Systematic Review of Chinese Traditional Exercise Baduanjin Modulating the Blood Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Lijuan Mei

    2012-01-01

    Full Text Available Background. Baduanjin exercise is considered to be beneficial to modulate the blood lipid metabolism. The purpose of the systematic review was to assess the potential efficacy and safety of Baduanjin exercise. Methods. MEDLINE, EMBASE, CBM, CNKI, VIP, Chinese Important Conference Papers Database, and Chinese Dissertation Database were searched for all prospective-controlled trials of Baduanjin exercise from their inception to December 31, 2011. Results. A total of 14 studies were included. Comparing with no treatment, Baduanjin exercise significantly reduced the levels of TC, TG, LDL-C in plasma, and elevated plasma HDL-C level for healthy participants, and the pooled MD (95% confidence interval, CI was −0.58 mmol/L (−0.86, −0.30 mmol/L, −0.22 mmol/L (−0.31, −0.13 mmol/L, −0.35 mmol/L (−0.54, −0.17 mmol/L, 0.13 mmol/L (0.06, 0.21 mmol/L, respectively. Baduanjin exercise also obviously decreased the levels of TG, LDL-C in plasma comparing with no treatment for patients, and the pooled MD (95% CI was −0.30 mmol/L (−0.40, −0.19 mmol/L, −0.38 mmol/L (−0.63, −0.13 mmol/L, but there was not obvious to decrease plasma TC level or elevate plasma HDL-C level in patients with the pooled MD (95%CI, −0.39 mmol/L (−1.09, 0.31 mmol/L and 0.22 mmol/L (−0.11, 0.55 mmol/L, respectively. In addition, the obvious advantage was not observed to modulate the blood lipid metabolism in comparing Baduanjin exercise with other exercises, regardless for health participants or patients. Conclusion. Studies indicated that Baduanjin exercise could significantly decrease the levels of TC, TG, LDL-C levels in plasma and elevate plasma HDL-C level for the healthy people. It also was helpful that Baduanjin exercise modulated the blood lipid metabolism for patients. Moreover, the Baduanjin exercise did not have an obvious advantage on modulating the lipid metabolism comparing with other exercises. But the

  15. Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood-brain barrier function

    DEFF Research Database (Denmark)

    Bailey, D M; Evans, K A; James, P E

    2008-01-01

    We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood-brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O...... developed clinical AMS (AMS+) and were more hypoxaemic relative to subjects without AMS (AMS-). A more marked increase in the venous concentration of the ascorbate radical (A(*-)), lipid hydroperoxides (LOOH) and increased susceptibility of low-density lipoprotein (LDL) to oxidation was observed during...

  16. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Evaluation of the hemostatic state, carbohydrate and lipid metabolism in young women with abdominal obesity and hypertension

    Directory of Open Access Journals (Sweden)

    Veronika Andreevna Sumerkina

    2015-09-01

    Full Text Available Aim of this study was to determine the characteristics of the laboratory parameters of hemostasis, carbohydrate and lipid metabolism in women with metabolic syndrome, isolated abdominal obesity or with hypertension. Materials and methods. The study included 71 women aged 30 – 44 years and was conducted at laboratory study of hemostasis system, carbohydrate and lipid metabolism. Results. In women with abdominal obesity and arterial hypertension we found an increased levels of glucose, total cholesterol, LDL-C and triglycerides and a decrease in a concentration of HDL-C compared to healthy women. The study of hemostasis revealed prothrombotic changes in the form of activation of coagulation hemostasis and fibrinolysis system activity. Conclusions. The disorders of carbohydrate and lipid metabolism are very prevalent in young women with abdominal obesity and hypertension with every second woman meeting the criteria for the metabolic syndrome. The most pronounced signs of activation of blood coagulation markes was seen in women with abdominal obesity and hypertension. In women with the individual components of the metabolic syndrome there were no significant changes in carbohydrate and lipid metabolism, although we saw an early signs of activation of hemocoagulation.

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

    Science.gov (United States)

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

    2017-06-22

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Manal Mused Almatrafi

    2017-06-01

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

  1. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Shu-Hui [Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan (China); Wen, Chih-Jen; Yen, Tzu-Chen [Animal Molecular Imaging Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan (China); Al-Suwayeh, S A; Fang, Jia-You [Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh (Saudi Arabia); Chang, Hui-Wen, E-mail: fajy@mail.cgu.edu.tw [Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan 333, Taiwan (China)

    2010-10-08

    Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

  2. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

    International Nuclear Information System (INIS)

    Hsu, Shu-Hui; Wen, Chih-Jen; Yen, Tzu-Chen; Al-Suwayeh, S A; Fang, Jia-You; Chang, Hui-Wen

    2010-01-01

    Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

  3. Dynamics of a lipid and metabolic imbalance on the background of a complex programs of rehabilitation at metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Kotenko К.V.

    2013-12-01

    Full Text Available The study aimed the development and assessment of features of corrective action of a medical complex on a lipid imbalance at patients with obesity. Material and methods. For an assessment of features of corrective action of a medical complex on a lipid imbalance at patients with obesity in research I was 50 male patients with obesity and frustration of the reproductive sphere aged from 24 to 68 years were included, middle age was 38,5±6,1 years and 7 healthy persons, men of comparable age without any pathological states, results of which all researches were accepted to values of norm. To all patients included in research, except all-clinical inspection calculation of an index of body weight and the relation of a circle of a waist to a circle of hips, measurement of arterial pressure were applied questioning concerning food and food behavior, anthropometry (growth the body weight, a circle of a waist and hips. Besides all patients conducted laboratory methods the researches including definition of atherogenic fractions of lipids (the general cholesterol, triglycerides, LPNPand LPVP. Researches were conducted before treatment and after a course of treatment. Results. The effective complex program for restoration of reproductive function at patients with obesity is developed. Conclusion. Application of the developed comprehensive program more than its separate components caused the expressed reduction of body weight, mainly due to reduction of fatty tissue and manifestations of visceral obesity in patients with obesity and violation of reproductive function, including due to elimination of metabolic imbalance.

  4. Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

    International Nuclear Information System (INIS)

    Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

    2017-01-01

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. - Highlights: • Aspirin inhibits the levels of liquid droplets, triglyceride and cholesterol in HCC cells. • Aspirin is able to down-regulate ACSL1 in HCC cells. • NF-κB inhibitor PDTC can down-regulate ACSL1 and reduces lipogenesis in HCC cells. • Aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling.

  5. Effect of rosuvastatin intensification therapy on blood lipid metabolism, adipocytokines and plaque stability after PCI in ACS patients

    Directory of Open Access Journals (Sweden)

    Xiu-Quan Sun

    2017-10-01

    Full Text Available Objective: To explore the effect of rosuvastatin intensification therapy on blood lipid metabolism, adipocytokines and plaque stability after PCI in ACS patients. Methods: ACS patients who received PCI in the hospital between July 2015 and January 2017were reviewed and divided into the routine dose group (n=60 who received rosuvastatin routine dose therapy after PCI and the intensification therapy group (n=46 who received rosuvastatin intensification therapy after PCI. The differences in blood lipid metabolism, adipocytokines and plaque stability were compared between the two groups before and after treatment. Results: Before PCI, the differences in blood lipid metabolism, adipocytokines and plaque stability were not statistically significant between the two groups. 1 month after PCI, lipid metabolism indexes HDL-C and ApoA1 levels in peripheral blood of intensification therapy group were higher than those of routine dose group while LDL-C and ApoB levels were lower than those of routine dose group; adipocytokines APN and Leptin levels in serum were higher than those of routine dose group while Resistin level was lower than that of routine dose group; plaque stability- related indexes ICAM-1, MMP-1 and TIMP-1 levels were lower than those of routine dose group. Conclusion: Rosuvastatin intensification therapy after PCI could effectively regulate the lipid metabolism and increase the plaque stability in ACS patients.

  6. Brain glucose metabolism in an animal model of depression.

    Science.gov (United States)

    Detka, J; Kurek, A; Kucharczyk, M; Głombik, K; Basta-Kaim, A; Kubera, M; Lasoń, W; Budziszewska, B

    2015-06-04

    An increasing number of data support the involvement of disturbances in glucose metabolism in the pathogenesis of depression. We previously reported that glucose and glycogen concentrations in brain structures important for depression are higher in a prenatal stress model of depression when compared with control animals. A marked rise in the concentrations of these carbohydrates and glucose transporters were evident in prenatally stressed animals subjected to acute stress and glucose loading in adulthood. To determine whether elevated levels of brain glucose are associated with a change in its metabolism in this model, we assessed key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase), products of glycolysis, i.e., pyruvate and lactate, and two selected enzymes of the tricarboxylic acid cycle (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the hippocampus and frontal cortex. Additionally, we assessed glucose-6-phosphate dehydrogenase activity, a key enzyme in the pentose phosphate pathway (PPP). Prenatal stress increased the levels of phosphofructokinase, an important glycolytic enzyme, in the hippocampus and frontal cortex. However, prenatal stress had no effect on hexokinase or pyruvate kinase levels. The lactate concentration was elevated in prenatally stressed rats in the frontal cortex, and pyruvate levels remained unchanged. Among the tricarboxylic acid cycle enzymes, prenatal stress decreased the level of pyruvate dehydrogenase in the hippocampus, but it had no effect on α-ketoglutarate dehydrogenase. Like in the case of glucose and its transporters, also in the present study, differences in markers of glucose metabolism between control animals and those subjected to prenatal stress were not observed under basal conditions but in rats subjected to acute stress and glucose load in adulthood. Glucose-6-phosphate dehydrogenase activity was not reduced by prenatal stress but was found to be even higher in animals exposed to

  7. The Role of Lipid and Lipoprotein Metabolism in Non‐Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Francesco Massimo Perla

    2017-06-01

    Full Text Available Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a “multiple-hit process” where the first “hit” is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD.

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

    Science.gov (United States)

    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 (pPea protein-fed rats displayed higher hepatic mRNA levels of LDL receptor versus those fed casein (ppea protein-fed rats than in rats fed casein (ppea 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.

  9. Application of metabolic controls for the maximization of lipid production in semicontinuous fermentation.

    Science.gov (United States)

    Xu, Jingyang; Liu, Nian; Qiao, Kangjian; Vogg, Sebastian; Stephanopoulos, Gregory

    2017-07-03

    Acetic acid can be generated through syngas fermentation, lignocellulosic biomass degradation, and organic waste anaerobic digestion. Microbial conversion of acetate into triacylglycerols for biofuel production has many advantages, including low-cost or even negative-cost feedstock and environmental benefits. The main issue stems from the dilute nature of acetate produced in such systems, which is costly to be processed on an industrial scale. To tackle this problem, we established an efficient bioprocess for converting dilute acetate into lipids, using the oleaginous yeast Yarrowia lipolytica in a semicontinuous system. The implemented design used low-strength acetic acid in both salt and acid forms as carbon substrate and a cross-filtration module for cell recycling. Feed controls for acetic acid and nitrogen based on metabolic models and online measurement of the respiratory quotient were used. The optimized process was able to sustain high-density cell culture using acetic acid of only 3% and achieved a lipid titer, yield, and productivity of 115 g/L, 0.16 g/g, and 0.8 g⋅L -1 ⋅h -1 , respectively. No carbon substrate was detected in the effluent stream, indicating complete utilization of acetate. These results represent a more than twofold increase in lipid production metrics compared with the current best-performing results using concentrated acetic acid as carbon feed.

  10. Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism

    Science.gov (United States)

    Kim, Hyunbae; Mendez, Roberto; Chen, Xuequn; Fang, Deyu

    2015-01-01

    Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH acetylation in mouse livers in a time-dependent manner, and this event is critical for CREBH transcriptional activity in regulating hepatic lipid homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH acetylation states under fasting conditions. Site-directed mutagenesis and functional analyses revealed that the lysine (K) residue at position 294 (K294) within the bZIP domain of the CREBH protein is the site where fasting-induced acetylation/deacetylation occurs. Introduction of the acetylation-deficient (K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH transcriptional activity, respectively. Importantly, CREBH acetylation at lysine 294 was required for the interaction and synergy between CREBH and peroxisome proliferator-activated receptor α (PPARα) in activating their target genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294 mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals under prolonged fasting. In summary, our study reveals a molecular mechanism by which fasting or glucagon stimulation modulates lipid homeostasis through acetylation of CREBH. PMID:26438600

  11. Relation of dietary carbohydrates to lipid metabolism and the status of zinc and chromium in rabbits.

    Science.gov (United States)

    Moersen, T J; Borgman, R F

    1984-06-01

    Rabbits were fed a purified ration known to produce alterations in lipid metabolism and cholelithiasis. During a 14-week period, group 1 was fed sucrose as the sole dietary carbohydrate, whereas group 2 was fed corn starch; the rations were equicaloric and the carbohydrate provided 43% of the calories. Serum cholesterol and triglyceride concentrations increased when the purified rations were fed, and these concentrations were often greater (toward the end of the trial) in rabbits fed the sucrose than in rabbits fed corn starch. Liver weight was increased by the sucrose feeding, but there were no differences as to concentrations of lipid, cholesterol, Cr, or Zn between treatments. The aortas of the sucrose group contained more lipid, and the cholesterol concentrations tended to be greater; but dietary carbohydrate had no effect on concentrations of Cr or Zn. A reduction in hair Cr concentration was noticed over time in the rabbits fed sucrose, but changes were not noticed in the Zn concentrations. Cholelithiasis tended to be more severe in rabbits fed sucrose.

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

    Science.gov (United States)

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

    2015-12-01

    The oleaginous fungus Mucor circinelloides is of industrial interest because it can produce high levels of polyunsaturated fatty acid γ-linolenic acid. M. circinelloides CBS 277.49 is able to accumulate less than 15% of cell dry weight as lipids, while M. circinelloides WJ11 can accumulate lipid up to 36%. In order to better understand the mechanisms behind the differential lipid accumulation in these two strains, tracer experiments with (13)C-glucose were performed with the growth of M. circinelloides and subsequent gas chromatography-mass spectrometric detection of (13)C-patterns in proteinogenic amino acids was carried out to identify the metabolic network topology and estimate intracellular fluxes. Our results showed that the high oleaginous strain WJ11 had higher flux of pentose phosphate pathway and malic enzyme, lower flux in tricarboxylic acid cycle, higher flux in glyoxylate cycle and ATP: citrate lyase, together, it might provide more NADPH and substrate acetyl-CoA for fatty acid synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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    Martina Gsell

    Full Text Available 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.

  14. New avenues for regulation of lipid metabolism by thyroid hormones and analogs.

    Science.gov (United States)

    Senese, Rosalba; Lasala, Pasquale; Leanza, Cristina; de Lange, Pieter

    2014-01-01

    Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3'-triiodo-L-thyronine (T3) acts predominantly by binding to nuclear receptors termed TH receptors (TRs), that recognize TH response elements (TREs) on the DNA, and so regulate transcription. T3 also acts through "non-genomic" pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TRα. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2), that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism.

  15. New Avenues for Regulation of Lipid Metabolism by Thyroid Hormones and Analogs

    Directory of Open Access Journals (Sweden)

    Rosalba eSenese

    2014-12-01

    Full Text Available Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs. The classic, active TH, 3,5,3’-triiodo-L-thyronine (T3 acts predominantly by binding to nuclear receptors termed TH receptors (TRs, that recognize TH response elements (TREs on the DNA, and so regulate transcription. T3 also acts through non-genomic pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TR alpha. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2, that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism.

  16. Erectile dysfunction and diabetes: Association with the impairment of lipid metabolism and oxidative stress.

    Science.gov (United States)

    Belba, Arben; Cortelazzo, Alessio; Andrea, Giansanti; Durante, Jacopo; Nigi, Laura; Dotta, Francesco; Timperio, Anna Maria; Zolla, Lello; Leoncini, Roberto; Guerranti, Roberto; Ponchietti, Roberto

    2016-01-01

    To test the hypothesis that exists an association of non-diabetic and diabetic patients suffering from erectile dysfunction (ED) with lipid metabolism and oxidative stress. Clinical and laboratory characteristics in non-diabetic (n = 30, middle age range: 41–55.5 years; n = 25, old age range: 55.5–73), diabetic ED patients (n = 30, age range: 55.5–75 years) and diabetic patients (n = 25, age range: 56–73.25), were investigated. Proteomic analysis was performed to identify differentially expressed plasma proteins and to evaluate their oxidative posttranslational modifications. A decreased level of high-density lipoproteins in all ED patients (P < 0.001, C.I. 0.046–0.10), was detected by routine laboratory tests. Proteomic analysis showed a significant decreased expression (P < 0.05) of 5 apolipoproteins (i.e. apolipoprotein H, apolipoprotein A4, apolipoprotein J, apolipoprotein E and apolipoprotein A1) and zinc-alpha-2-glycoprotein, 50% of which are more oxidized proteins. Exclusively for diabetic ED patients, oxidative posttranslational modifications for prealbumin, serum albumin, serum transferrin and haptoglobin markedly increased. Showing evidence for decreased expression of apolipoproteins in ED and the remarkable enhancement of oxidative posttranslational modifications in diabetes-associated ED, considering type 2 diabetes mellitus and age as independent risk factors involved in the ED pathogenesis, lipid metabolism and oxidative stress appear to exert a complex interplay in the disease.

  17. Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae

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    Zhenting Zhou

    2017-01-01

    Full Text Available Alcoholic liver disease (ALD is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wild-type and transgenic line with liver-specific eGFP expression Tg (lfabp10α:eGFP zebrafish larvae (4 dpf. The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45αa, and edem1. In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism.

  18. Effect of Phellinus baumii-Biotransformed Soybean Powder on Lipid Metabolism in Rats.

    Science.gov (United States)

    Kim, Dae Ik; Kim, Kil Soo; Kang, Ji Hyuk; Kim, Hye Jeong

    2013-06-01

    In this study, we evaluated the hypolipidemic and antioxidative effects of biotransformed soybean powder (BTS; Phellinus baumii-fermented soybean) on lipid metabolism in rats. Sprague-Dawley (SD) male rats were divided into basal diet group (BA), high fat diet group (HF), high fat diet containing 10% BTS group (10 BTS), and high fat diet containing 20% BTS group (20 BTS). Changes in the content of various isoflavones, including daidzein and genistein, within the soybean after fermentation to BTS were investigated. The levels of daidzein and genistein were 149.28 μg/g and 364.31 μg/g, respectively. After six weeks experimental period, Food efficiency ratio in the 10 and 20 BTS group was significantly lower than the HF group (PBTS group were significantly lower than the HF group. The levels of alanine aminotransferase, aspartate aminotransferase and thiobarbituric acid reactive substance were significantly lower in the groups that received 10% and 20% BTS than the HF. The activities of SOD and CAT were significantly higher in the 10 and 20 BTS group than the HF group. The activity of XO in the 10 and 20 BTS group was significantly lower than in the HF group by 20% and 23%, respectively. In conclusion, these data suggest that BTS is an effective agent in improving lipid metabolism and antioxidant enzyme system.

  19. Lipid metabolism in streptozotocin induced experimental diabetes and it’s correction with niacin-oxyethylidendiphosphonatogermanate

    Directory of Open Access Journals (Sweden)

    N. V. Kresyun

    2017-08-01

    Full Text Available Introduction. The development of approaches for effective control of diabetes-induced deterioration of lipid metabolism and plasma glucose level could be implemented by the applying of germanium-contained biologically active substances. Among others such compound as niacin – oxyethylidendiphosphonatogermanate (MIGU-4 should be mentioned, which is able to correct effectively the lipid layers of liver mitochondrial membranes on models of streptozotocin – induced diabetes. Aim. To investigate the dynamic changes of the total cholesterol, total phospholipids level along with their molar ratio; fractions of phospholipids of both erythrocyte membranes and liver mitochondria membranes in experimental diabetes mellitus and to investigate the mentioned indices under conditions of complex correction by MIGU-4 and insulin. Materials and Methods. Diabetes was induced in male Wistar rats with streptozotocin injection (50.0 mg/kg., i. p.. ED50 of MIGU-4 (25.0 mg/kg, i. p. was used. Cellular membranes were obtained from erythrocytes, and mitochondrial membranes were obtained through differential centrifugation of liver tissue. Lipid extracts were isolated from 1 g of erythrocyte mass and from 200 mg of liver tissue; phospholipids fractionation was carried out by method of ascending one-dimensional thin-layer chromatography. Content of certain phospholipids was estimated by method of spots “burning out” using the 72 % chloride acid at 200 0С up to their complete bleaching with the consequent determination of lipids phosphate. The level of total phospholipids was calculated by summing up all fractions content. Results. The total cholesterol level substantially elevated along with the decreasing of phospholipids content in both erythrocyte and mitochondrial membranes obtained from liver tissue in two weeks after experimental streptozotocin diabetes induction in rats. It resulted in an increase of the cholesterol/ phospholipids ratio. These changes

  20. Toxoplasma gondii infection induces lipid metabolism alterations in the murine host

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    Ivan Milovanović

    2009-03-01

    Full Text Available Host lipids have been implicated in the pathogenesis of Toxoplasma gondiiinfection. To determine if Toxoplasmainfection influences the lipid status in the normal host, we assessed serum lipids of Swiss-Webster mice during infection with the BGD-1 strain (type-2 at a series of time points. Mice were bled at days zero and 42 post-infection, and subgroups were additionally bled on alternating weeks (model 1, or sacrificed at days zero, 14 and 42 (model 2 for the measurement of total cholesterol (Chl, high density lipoproteins (HDL, low density lipoproteins (LDL and triglycerides and adiponectin. At day 42, brains were harvested for cyst enumeration. A significant decrease (p = 0.02 in HDL and total Chl was first noted in infected vs. control mice at day 14 and persisted to day 42 (p = 0.013. Conversely, LDL was unaltered until day 42, when it increased (p = 0.043. Serum LDL levels at day 42 correlated only with cyst counts of above 300 (found in 44% mice, while the change in HDL between days zero and 42 correlated with both the overall mean cyst count (p = 0.041 and cyst counts above 300 (p = 0.044. Calculated per cyst, this decrease in HDL in individual animals ranged from 0.1-17 µmol/L, with a mean of 2.43 ± 4.14 µmol/L. Serum adiponectin levels remained similar between infected and control mice throughout the experiment.

  1. Traumatic brain injury alters methionine metabolism: implications for pathophysiology

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    Pramod K Dash

    2016-04-01

    Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

  2. The human hepatocyte cell lines IHH and HepaRG: models to study glucose, lipid and lipoprotein metabolism.

    Science.gov (United States)

    Samanez, Carolina Huaman; Caron, Sandrine; Briand, Olivier; Dehondt, Hélène; Duplan, Isabelle; Kuipers, Folkert; Hennuyer, Nathalie; Clavey, Véronique; Staels, Bart

    2012-07-01

    Metabolic diseases reach epidemic proportions. A better knowledge of the associated alterations in the metabolic pathways in the liver is necessary. These studies need in vitro human cell models. Several human hepatoma models are used, but the response of many metabolic pathways to physiological stimuli is often lost. Here, we characterize two human hepatocyte cell lines, IHH and HepaRG, by analysing the expression and regulation of genes involved in glucose and lipid metabolism. Our results show that the glycolysis pathway is activated by glucose and insulin in both lines. Gluconeogenesis gene expression is induced by forskolin in IHH cells and inhibited by insulin in both cell lines. The lipogenic pathway is regulated by insulin in IHH cells. Finally, both cell lines secrete apolipoprotein B-containing lipoproteins, an effect promoted by increasing glucose concentrations. These two human cell lines are thus interesting models to study the regulation of glucose and lipid metabolism.

  3. Comparative analysis of changes in protein and lipid metabolism, lipid peroxidation, and hemostasis under the effects of polychlorinated dibenzo-p-dioxins and radiation

    International Nuclear Information System (INIS)

    Kuntsevich, A.D.; Baulin, S.I.; Golovkov, V.F.; Rembovskii, V.R.; Smirnova, L.A.; Troshkin, N.M.

    1994-01-01

    Polychlorinated dibenzo-p-dioxins (PCDD) and ionizing radiation are among the most hazardous environmental factors causing ecological catastrophes and mass afflications in various accidents involving nuclear power plants and chemical industrial enterprises. The authors previously established that the simultaneous action of a toxic dose of PCDD and ionizing radiation increases the combined toxic effect. The effects of these chemical and physical factors were superadditive (the biological potentiation effect). Here, the authors compare the effects of PCDD and irradiation on protein and lipid metabolism, lipid peroxidation, and hemostasis in order to learn more about biochemical mechanisms mediating the potentiation effect. The experimental evidence suggests that PCDD can modify the biological effects of ionizing radiation through the generation of free radicals and activation of the chain reactions of free-radical lipid peroxidation, such as the formation of peroxides or malonic dialdehyde. The toxic effects of PCDD and ionizing radiation are based on free-radical reactions and chemical pathology. In other words, the chemical and physical factors directly and selectively hit the same biological target, thereby increasing their combined toxic effects. The results can partially explain the observed potentiating effect of the combined action of ionizing radiation and PCDD on the body. This phenomenon is based on biochemical processes generating an abundance of products of lipid peroxidation and the decrease in the body's defenses caused by disorders in protein and lipid metabolism and blood coagulation

  4. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

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    Varsha Agarwal

    2008-06-01

    Full Text Available Cytochrome P450 (P450 is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

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

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    Amber J Marty

    2015-06-01

    Full Text Available 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.

  6. Blockade of oestrogen biosynthesis in peripubertal boys: effects on lipid metabolism, insulin sensitivity, and body composition.

    Science.gov (United States)

    Hero, Matti; Ankarberg-Lindgren, Carina; Taskinen, Marja-Riitta; Dunkel, Leo

    2006-09-01

    In males, the pubertal increase in sex hormone production has been associated with proatherogenic changes in lipid and carbohydrate metabolism. Aromatase inhibitors, a novel treatment modality for some growth disorders, may significantly influence these risk factors for cardiovascular disease by suppressing oestrogen biosynthesis and stimulating gonadal androgen production. In the current study, we explored the effects of aromatase inhibition on lipid metabolism, insulin sensitivity, body composition and serum adiponectin in peripubertal boys. Prospective, double-blind, randomised, placebo-controlled clinical study. Thirty-one boys, aged 9.0-14.5 years, with idiopathic short stature were treated with the aromatase inhibitor letrozole (2.5 mg/day) or placebo for 2 years. During the treatment, the concentrations of sex hormones, IGF-I, lipids, lipoproteins and adiponectin were followed-up. The percentage of fat mass (FM) was assessed by skinfold measurements and insulin resistance by homeostasis model assessment (HOMA) index. In pubertal boys, who received letrozole, high-density lipoprotein cholesterol (HDL-C) decreased by 0.47 mmol/l (P<0.01) during the study. Simultaneously, their percentage of FM decreased from 17.0 to 10.5 (P<0.001), in an inverse relationship with serum testosterone. The concentrations of low-density lipoprotein cholesterol, triglycerides and HOMA index remained at pretreatment level in both groups. Serum adiponectin decreased similarly in letrozole- and placebo-treated pubertal boys (2.9 and 3.3 mg/l respectively). In males, aromatase inhibition reduces HDL-C and decreases relative FM after the start of puberty. The treatment does not adversely affect insulin sensitivity in lean subjects.

  7. Study on the correlation of serum lipid metabolism and central retinal artery hemodynamics with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Ran-Yang Guo

    2016-01-01

    Objective:To explore the correlation of serum lipid metabolism and central retinal artery (CRA) hemodynamics with diabetic retinopathy (DR).Methods:A total of 120 patients with type 2 diabetes who were admitted in our hospital from May, 2015 to May, 2016 were included in the study and divided into NDR group (non-diabetic retinopathy), NPR group (non-proliferative retinopathy), and PR group (proliferative retinopathy) with 40 cases in each group according to DR clinical staging. Moreover, 50 healthy individuals who came for physical examinations were served as the control group. The full automatic biochemical analyzer was used to detect the levels of TG, TC, LDL-C, and HDL-C. The color Doppler flow imaging (CDFI) was used to detect EDV, PSV, RI, and PI of CRA and OA.Results:The levels of TG, TC, and LDL-C in NDG, NPR, and PR groups were gradually increased with the aggravation of retinopathy, HDL-C was reduced, the comparison among the three groups was statistically significant, and the comparison with the control group was statistically significant. EDV, PSV, and PI of CRA and OA in NDG, NPR, and PR groups were gradually increased with the aggravation of retinopathy, RI was reduced, the comparison among the three groups was statistically significant, and the comparison with the control group was statistically significant. Conclusions: The lipid metabolism disorder can promote the occurrence and development of DR. The change of CRA and OA hemodynamics is an important pathological basis for developing DR. Clinical detection of serum lipid level and monitoring of the changes of fundus artery hemocynamic parameters are of great significance in early detecting DR.

  8. Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population

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    M. Hannich

    2018-01-01

    Full Text Available Objective. Aldosterone and high-density lipoprotein cholesterol (HDL-C are involved in many pathophysiological processes that contribute to the development of cardiovascular diseases. Previously, associations between the concentrations of aldosterone and certain components of the lipid metabolism in the peripheral circulation were suggested, but data from the general population is sparse. We therefore aimed to assess the associations between aldosterone and HDL-C, low-density lipoprotein cholesterol (LDL-C, total cholesterol, triglycerides, or non-HDL-C in the general adult population. Methods. Data from 793 men and 938 women aged 25–85 years who participated in the first follow-up of the Study of Health in Pomerania were obtained. The associations of aldosterone with serum lipid concentrations were assessed in multivariable linear regression models adjusted for sex, age, body mass index (BMI, estimated glomerular filtration rate (eGFR, and HbA1c. Results. The linear regression models showed statistically significant positive associations of aldosterone with LDL-C (β-coefficient = 0.022, standard error = 0.010, p=0.03 and non-HDL-C (β-coefficient = 0.023, standard error = 0.009, p=0.01 as well as an inverse association of aldosterone with HDL-C (β-coefficient = −0.022, standard error = 0.011, p=0.04. Conclusions. The present data show that plasma aldosterone is positively associated with LDL-C and non-HDL-C and inversely associated with HDL-C in the general population. Our data thus suggests that aldosterone concentrations within the physiological range may be related to alterations of lipid metabolism.

  9. Physiological Aldosterone Concentrations Are Associated with Alterations of Lipid Metabolism: Observations from the General Population.

    Science.gov (United States)

    Hannich, M; Wallaschofski, H; Nauck, M; Reincke, M; Adolf, C; Völzke, H; Rettig, R; Hannemann, A

    2018-01-01

    Aldosterone and high-density lipoprotein cholesterol (HDL-C) are involved in many pathophysiological processes that contribute to the development of cardiovascular diseases. Previously, associations between the concentrations of aldosterone and certain components of the lipid metabolism in the peripheral circulation were suggested, but data from the general population is sparse. We therefore aimed to assess the associations between aldosterone and HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, or non-HDL-C in the general adult population. Data from 793 men and 938 women aged 25-85 years who participated in the first follow-up of the Study of Health in Pomerania were obtained. The associations of aldosterone with serum lipid concentrations were assessed in multivariable linear regression models adjusted for sex, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), and HbA1c. The linear regression models showed statistically significant positive associations of aldosterone with LDL-C ( β -coefficient = 0.022, standard error = 0.010, p = 0.03) and non-HDL-C ( β -coefficient = 0.023, standard error = 0.009, p = 0.01) as well as an inverse association of aldosterone with HDL-C ( β -coefficient = -0.022, standard error = 0.011, p = 0.04). The present data show that plasma aldosterone is positively associated with LDL-C and non-HDL-C and inversely associated with HDL-C in the general population. Our data thus suggests that aldosterone concentrations within the physiological range may be related to alterations of lipid metabolism.

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

    Science.gov (United States)

    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.

  11. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    Science.gov (United States)

    Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

    2016-04-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

  12. Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

    Science.gov (United States)

    Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

    1998-11-01

    Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

  13. Effect of dietary poly unsaturated fatty acids on total brain lipid concentration and anxiety levels of electron beam irradiated mice

    International Nuclear Information System (INIS)

    Suchetha Kumari; Bekal, Mahesh

    2013-01-01

    The whole brain irradiation causes injury to the nervous system at various levels. Omega-3 poly unsaturated fatty acids are very much essential for the growth and development of nervous system. Dietary supplementation of these nutrients will promote the development of injured neuronal cells. Therefore this study was undertaken to establish the role of Omega-3 poly unsaturated fatty acids on total brain lipid concentration, lipid peroxidation and anxiety levels in the irradiated mice. The effect of Electron Beam Radiation (EBR) on total brain lipid concentration, lipid peroxidation and anxiety level were investigated in male Swiss albino mice. The study groups were subjected to a sub-lethal dose of EBR and also the flax seed extract and fish oil were given orally to the irradiated mice. Irradiated groups show significant elevation in anxiety levels when compared to control group, indicating the acute radiation effects on the central nervous system. But the oral supplementation of dietary PUFA source decrees the anxiety level in the irradiated group. The analysis of lipid peroxidation showed a significant level of changes when compared between control and radiation groups. Dietary PUFA supplementation showed a significant level of decrease in the lipid peroxidation in the irradiated groups. The observation of total lipids in brain shows decrease in concentration in the irradiated groups, the differences in the variables follow the similar patterns as of that the MDA levels. This study suggests that the dietary intake of PUFAs may help in prevention and recovery of the oxidative stress caused by radiation. (author)

  14. An acetone bio-sniffer (gas phase biosensor) enabling assessment of lipid metabolism from exhaled breath.

    Science.gov (United States)

    Ye, Ming; Chien, Po-Jen; Toma, Koji; Arakawa, Takahiro; Mitsubayashi, Kohji

    2015-11-15

    Several volatile organic compounds (VOCs) are released from human breath or skin. Like chemical substances in blood or urine, some of these vapors can provide valuable information regarding the state of the human body. A highly sensitive acetone biochemical gas sensor (bio-sniffer) was developed and used to measure exhaled breath acetone concentration, and assess lipid metabolism based on breath acetone analysis. A fiber-optic biochemical gas sensing system was constructed by attaching a flow-cell with nicotinamide adenine dinucleotide (NADH)-dependent secondary alcohol dehydrogenase (S-ADH) immobilized membrane onto a fiber-optic NADH measurement system. The NADH measurement system utilizes an ultraviolet-light emitting diode with peak emission of 335 nm as an excitation light source. NADH is consumed by the enzymatic reaction of S-ADH, and the consumption is proportional to the concentration of acetone vapor. Phosphate buffer which contained NADH was circulated into the flow-cell to rinse products and the excessive substrates from the optode. The change of fluorescent emitted from NADH is analyzed by the PMT. Hence, fluorescence intensity decreased as the acetone concentration increased. The relationship between fluorescence intensity and acetone concentration was identified from 20 ppb to 5300 ppb. This interval included the concentration of acetone vapor in the breath of healthy people and those suffering from disorders of carbohydrate metabolism. Finally, the acetone bio-sniffer was used to measure breath acetone during an exercise stress test on an ergometer after a period of fasting. The concentration of acetone in breath was shown to significantly increase after exercise. This biosensor allows rapid, highly sensitive and selective measurement of lipid metabolism. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans.

    Science.gov (United States)

    Kullmann, Stephanie; Heni, Martin; Hallschmid, Manfred; Fritsche, Andreas; Preissl, Hubert; Häring, Hans-Ulrich

    2016-10-01

    Ever since the brain was identified as an insulin-sensitive organ, evidence has rapidly accumulated that insulin action in the brain produces multiple behavioral and metabolic effects, influencing eating behavior, peripheral metabolism, and cognition. Disturbances in brain insulin action can be observed in obesity and type 2 diabetes (T2D), as well as in aging and dementia. Decreases in insulin sensitivity of central nervous pathways, i.e., brain insulin resistance, may therefore constitute a joint pathological feature of metabolic and cognitive dysfunctions. Modern neuroimaging methods have provided new means of probing brain insulin action, revealing the influence of insulin on both global and regional brain function. In this review, we highlight recent findings on brain insulin action in humans and its impact on metabolism and cognition. Furthermore, we elaborate on the most prominent factors associated with brain insulin resistance, i.e., obesity, T2D, genes, maternal metabolism, normal aging, inflammation, and dementia, and on their roles regarding causes and consequences of brain insulin resistance. We also describe the beneficial effects of enhanced brain insulin signaling on human eating behavior and cognition and discuss potential applications in the treatment of metabolic and cognitive disorders. Copyright © 2016 the American Physiological Society.

  16. Brain metabolic impairment of OSAS: evidence from MRS

    International Nuclear Information System (INIS)

    Shen Jie; Long Miaomiao; Shen Wen; Qi Ji

    2011-01-01

    Objective: To evaluate the impact of obstructive sleep apnea syndrome (OSAS) on human cerebral metabolism by using magnetic resonance spectroscopy (MRS). Materials and methods: Twenty-one severe OSAS patients, 14 mild-moderate OSAS patients, and 15 healthy control subjects were included. All subjects underwent MRS using the point-resolved echo spin spectroscopy (PRESS). Proton volumes of interest were placed in the bilateral frontal lobes and left temporal -parietal-occipital cortex, and left hippocampus. Results: 1. Compared to the controls, the NAA/Cr ratio was significantly decreased in the left frontal lobe in the severe OSAS group (P=0.004), and in the right frontal lobe in the severe (P=0.002) and mild-moderate (P=0.007) OSAS patients. The NAA/Cr ratio trended to be decreased in the left hippocampus in the OSAS patients compared to controls. 2. A significant increase in the ml/Cr ratio was detected in the right frontal regions in the severe (P=0.008) and mild-moderate (P<0.001) OSAS groups. 3. Clx/Cr ratio values were significantly smaller than controls in the left (P=0.006) and right (P=0.027) frontal regions. Conclusion: Bilateral frontal lobes are the vulnerable location in patients with OSAS. MRS can be used to screen the brain metabolic impairment. (authors)

  17. Tween 80 containing lipid nanoemulsions for delivery of indinavir to brain

    Directory of Open Access Journals (Sweden)

    Kandadi Prabhakar

    2013-09-01

    Full Text Available Indinavir is a protease inhibitor used in the treatment of HIV infection. However, it has limited efficacy in eradicating the virus in the brain due to efflux by P-glycoprotein (P-gp expressed at the blood–brain barrier (BBB. The objective of this work was to develop an o/w lipid nanoemulsion (LNE of indinavir using Tween 80 as co-emulsifier to improve its brain specific delivery. LNEs were prepared with different compositions and were characterized for globule size, polydispersity index, zeta potential and in vitro drug release. Five formulations were then evaluated for drug content, entrapment efficiency and stability after which brain uptake studies were carried out using fluorescent labeled LNEs and pharmacokinetic (PK and tissue distribution studies were conducted after intravenous administration in mice. Brain uptake of indinavir was shown to be improved for a 1% Tween 80 containing formulation (F5 compared to a formulation containing 0.3% cholesterol (F2. In PK studies, the brain level of indinavir subsequent to administration of F5 was significantly (P<0.05 higher than produced by administration of a drug solution (2.44-fold or a control nanoemulsion (F1 (1.48-fold or formulation F2 (1.6-fold. The increased brain specific accumulation of indinavir from F5 is probably due to enhanced low density lipoprotein-mediated endocytosis and P-gp inhibition by Tween 80 at the BBB. These results suggest Tween 80 containing LNEs could provide a simple but effective means of delivering indinavir to brain.

  18. A remedy against obesity? The role of lactoferrin in the metabolism of glucose and lipids

    Directory of Open Access Journals (Sweden)

    Jolanta Artym

    2012-11-01

    Full Text Available Obesity, dyslipidemia, hyperglycemia/type II diabetes and hypertension together constitute the so-called metabolic syndrome. Frequency of occurrence of these serious metabolic disturbances is associated with life style and is on the rise in prosperous industrialized countries. These diseases represent not only a serious health problem but also social and economic ones, and involve in prophylaxis and treatment various specialists (physicians, dieticians and psychologists. For about two decades research has been conducted on the possibility to apply milk-derived proteins in prevention and treatment of the above mentioned metabolic diseases. Lactoferrin (LF, a protein present in milk and excretory fluids of mammals, is one of the most intensively studied milk proteins for therapeutic application. Initial trials revealing an advantageous effect of LF on lipid metabolism and obesity enrolled only a few volunteers and were performed in Japan in 2003. Subsequent trials were conducted on animals as well as in clinics, and the positive results were supported by in vitro tests. After oral administration of LF, decreases of body weight, waist measurement, visceral fat tissue, plasma and liver fatty acid concentrations, triglycerides and cholesterol were registered. The mechanism of LF action may involve several processes, such as inhibition of adipogenesis, decrease of dietary triglyceride absorption, elevation of HDL cholesterol possessing anti-atherogenic properties, inhibition of accumulation of oxidized LDL cholesterol forms in macrophages and protection against formation of foam cells. LF also increases the susceptibility of cells to insulin action, including in conditions when the response to insulin is lowered (during inflammation. In addition, LF regulates activity of insulin-like growth factor (IGF. The data collected to date indicate that LF is a promising, completely nontoxic, natural remedy which (as for example a food supplement may be applied

  19. Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies.

    Science.gov (United States)

    El-Zaafarany, Ghada M; Soliman, Mahmoud E; Mansour, Samar; Awad, Gehanne A S

    2016-04-30

    Lipid-based nanovectors offer effective carriers for brain delivery by improving drug potency and reducing off-target effects. Emulsomes are nano-triglyceride (TG) carriers formed of lipid cores supported by at least one phospholipid (PC) sheath. Due to their surface active properties, PC forms bilayers at the aqueous interface, thereby enabling encapsulated drug to benefit from better bioavailability and stability. Emulsomes of oxcarbazepine (OX) were prepared, aimed to offer nanocarriers for nasal delivery for brain targeting. Different TG cores (Compritol(®), tripalmitin, tristearin and triolein) and soya phosphatidylcholine in different amounts and ratios were used for emulsomal preparation. Particles were modulated to generate nanocarriers with suitable size, charge, encapsulation efficiency and prolonged release. Cytotoxicity and pharmacokinetic studies were also implemented. Nano-spherical OX-emulsomes with maximal encapsulation of 96.75% were generated. Stability studies showed changes within 30.6% and 11.2% in the size and EE% after 3 months. MTT assay proved a decrease in drug toxicity by its encapsulation in emulsomes. Incorporation of OX into emulsomes resulted in stable nanoformulations. Tailoring emulsomes properties by modulating the surface charge and particle size produced a stable system for the lipophilic drug with a prolonged release profile and mean residence time and proved direct nose-to-brain transport in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Interaction of IFNL3 with insulin resistance, steatosis and lipid metabolism in chronic hepatitis C virus infection.

    Science.gov (United States)

    Eslam, Mohammed; Booth, David R; George, Jacob; Ahlenstiel, Golo

    2013-11-07

    Metabolic changes are inextricably linked to chronic hepatitis C (CHC). Recently polymorphisms in the IFNL3 (IL28B) region have been shown to be strongly associated with spontaneous and treatment induced recovery from hepatitis C virus (HCV) infection. Further, circumstantial evidence suggests a link between IFNL3 single nucleotide polymorphisms and lipid metabolism, steatosis and insulin resistance in CHC. The emerging picture suggests that the responder genotypes of IFNL3 polymorphisms are associated with a higher serum lipid profile, and less frequent steatosis and insulin resistance. This review analyzes the current data regarding this interaction and its meaning for HCV pathogenesis and disease progression.

  1. Direct-acting antiviral agents against hepatitis C virus and lipid metabolism.

    Science.gov (United States)

    Kanda, Tatsuo; Moriyama, Mitsuhiko

    2017-08-21

    Hepatitis C virus (HCV) infection induces steatosis and is accompanied by multiple metabolic alterations including hyperuricemia, reversible hypocholesterolemia and insulin resistance. Total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels are increased by peginterferon and ribavirin combination therapy when a sustained virologic response (SVR) is achieved in patients with HCV. Steatosis is significantly more common in patients with HCV genotype 3 but interferon-free regimens are not always effective for treating HCV genotype 3 infections. HCV infection increases fatty acid synthase levels, resulting in the accumulation of fatty acids in hepatocytes. Of note, low-density lipoprotein receptor, scavenger receptor class B type I and Niemann-Pick C1-like 1 proteins are candidate receptors that may be involved in HCV. They are also required for the uptake of cholesterol from the external environment of hepatocytes. Among HCV-infected patients with or without human immunodeficiency virus infection, changes in serum lipid profiles are observed during interferon-free treatment and after the achievement of an SVR. It is evident that HCV affects cholesterol metabolism during interferon-free regimens. Although higher SVR rates were achieved with interferon-free treatment of HCV, special attention must also be paid to unexpected adverse events based on host metabolic changes including hyperlipidemia.

  2. Metabolic mapping of the effects of the antidepressant fluoxetine on the brains of congenitally helpless rats

    OpenAIRE

    Shumake, Jason; Colorado, Rene A.; Barrett, Douglas W.; Gonzalez-Lima, F.

    2010-01-01

    Antidepressants require adaptive brain changes before efficacy is achieved, and they may impact the affectively disordered brain differently than the normal brain. We previously demonstrated metabolic disturbances in limbic and cortical regions of the congenitally helpless rat, a model of susceptibility to affective disorder, and we wished to test whether administration of fluoxetine would normalize these metabolic differences. Fluoxetine was chosen because it has become a first-line drug for...

  3. The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

    NARCIS (Netherlands)

    Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

    2017-01-01

    BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients

  4. Lipid and fatty acid metabolism in Ralstonia eutropha: relevance for the biotechnological production of value-added products.

    Science.gov (United States)

    Riedel, Sebastian L; Lu, Jingnan; Stahl, Ulf; Brigham, Christopher J

    2014-02-01

    Lipid and fatty acid metabolism has been well studied in model microbial organisms like Escherichia coli and Bacillus subtilis. The major precursor of fatty acid biosynthesis is also the major product of fatty acid degradation (β-oxidation), acetyl-CoA, which is a key metabolite for all organisms. Controlling carbon flux to fatty acid biosynthesis and from β-oxidation allows for the biosynthesis of natural products of biotechnological importance. Ralstonia eutropha can utilize acetyl-CoA from fatty acid metabolism to produce intracellular polyhydroxyalkanoate (PHA). R. eutropha can also be engineered to utilize fatty acid metabolism intermediates to produce different PHA precursors. Metabolism of lipids and fatty acids can be rerouted to convert carbon into other value-added compounds like biofuels. This review discusses the lipid and fatty acid metabolic pathways in R. eutropha and how they can be used to construct reagents for the biosynthesis of products of industrial importance. Specifically, how the use of lipids or fatty acids as the sole carbon source in R. eutropha cultures adds value to these biotechnological products will be discussed here.

  5. Dietary Tributyrin Supplementation Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Suckling Piglets with Intrauterine Growth Retardation

    Science.gov (United States)

    He, Jintian; Dong, Li; Xu, Wen; Bai, Kaiwen; Lu, Changhui; Wu, Yanan; Huang, Qiang; Zhang, Lili; Wang, Tian

    2015-01-01

    Intrauterine growth retardation (IUGR) is associated with insulin resistance and lipid disorder. Tributyrin (TB), a pro-drug of butyrate, can attenuate dysfunctions in body metabolism. In this study, we investigated the effects of TB supplementation on insulin resistance and lipid metabolism in neonatal piglets with IUGR. Eight neonatal piglets with normal birth weight (NBW) and 16 neonatal piglets with IUGR were selected, weaned on the 7th day, and fed basic milk diets (NBW and IUGR groups) or basic milk diets supplemented with 0.1% tributyrin (IT group, IUGR piglets) until day 21 (n = 8). Relative parameters for lipid metabolism and mRNA expression were measured. Piglets with IUGR showed higher (P insulin in the serum, higher (P insulin, HOMA-IR, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the serum, and the concentrations of TG and NEFA in the liver, and increased (P insulin signal transduction pathway and hepatic lipogenic pathway (including transcription factors and nuclear factors) was significantly (P insulin resistance and abnormal lipid metabolism in IUGR piglets by increasing enzyme activities and upregulating mRNA expression, leading to an early improvement in the metabolic efficiency of IUGR piglets. PMID:26317832

  6. Regulation of Brain Glucose Metabolic Patterns by Protein Phosphorlyation and Drug Therapy

    Science.gov (United States)

    2007-03-30

    Tymoczko et al. 2002). Both cardiac muscle and brain contain the necessary enzymes to metabolize either glucose or ketone bodies . The enzymes... metabolic phenotype of astrocytes and neurons in vitro; and to determine whether antipsychotic drug administration affects glucose metabolites in...Cortical Astrocytes and Neurons 20 Abstract 21 v Introduction ~ 22 Results 24 Enriched Astrocyte and Neuronal Cultures Display Unique Metabolic

  7. Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

    Science.gov (United States)

    Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

    2011-01-01

    OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

  8. Anatomy and metabolism of the normal human brain studied by magnetic resonance at 1.5 Tesla

    International Nuclear Information System (INIS)

    Bottomley, P.A.; Hart, H.R. Jr.; Edelstein, W.A.; Schenck, J.F.; Smith, L.S.; Leue, W.M.; Mueller, O.M.; Redington, R.W.

    1984-01-01

    Proton magnetic resonance (MR) images were obtained of the human head in magnetic fields as high as 1.5 Tesla (T) using slotted resonator high radio-frequency (RF) detection coils. The images showed no RF field penetration problems and exhibited an 11 (+/-1)-fold improvement in signal-to-noise ratio over a .12-T imaging system. The first localized phosphorus 31, carbon 13, and proton MR chemical shift spectra recorded with surface coils from the head and body in the same instrument showed relative concentrations of phosphorus metabolites, triglycerides, and, when correlated with proton images, negligible lipid (-CH 2 -) signal from brain tissue on the time scale of the imaging experiment. Sugar phosphate and phosphodiester concentrations were significantly elevated in the head compared with muscle. This method should allow the combined assessment of anatomy, metabolism, and biochemistry in both the normal and diseased brain

  9. ROLE OF PHYSICAL EXERCISE, FITNESS AND AEROBIC TRAINING IN TYPE 1 DIABETIC AND HEALTHY MEN IN RELATION TO THE LIPID PROFILE, LIPID PEROXIDATION AND THE METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    David E. Laaksonen

    2003-06-01

    Full Text Available Dyslipidemia and possibly lipid peroxidation play important roles in the development of macro- and microvascular disease in type 1 diabetes mellitus. Little is known, however, of the role of aerobic exercise in dyslipidemia and resting and exercise-induced lipid peroxidation in type 1 diabetes. Despite the well-known effect of leisure-time physical activity (LTPA on components of the metabolic syndrome, little is known of the association of LTPA and cardiorespiratory fitness (maximal oxygen consumption, VO2max with development of the metabolic syndrome itself. A randomized controlled trial assessing the effect of a 12-16 week aerobic exercise program on VO2max and the lipid profile was carried out in otherwise healthy young men with type 1 diabetes. The effect of acute physical exercise on oxidative stress and antioxidant defenses and the relation to VO2max in men with type 1 diabetes was also evaluated. To test four recently proposed definitions by the World Health Organization (WHO and National Cholesterol Education Program (NCEP of the metabolic syndrome, the sensitivity and specificity of the definitions for prevalent and incident diabetes were assessed in a population-based cohort of middle-aged men. We also studied the associations of LTPA and cardiorespiratory fitness with prevalent and incident cases of the metabolic syndrome. A 12-16 week endurance exercise program produced antiatherogenic changes in lipid, lipoprotein and apolipoprotein levels in 20 type 1 diabetic men who for the most part were already physically active at baseline. The most favorable training-induced changes in the high-density lipoprotein cholesterol (HDL/low-density lipoprotein cholesterol (LDL and apolipoprotein A-I/apolipoprotein B ratios were in patients with low baseline HDL/LDL levels, likely the group with the most benefit to be gained by such changes. Plasma thiobarbituric acid reactive substances (TBARS, a measure of lipid peroxidation, was higher in nine

  10. Some Lipid Droplets Are More Equal Than Others: Different Metabolic Lipid Droplet Pools in Hepatic Stellate Cells.

    Science.gov (United States)

    Molenaar, Martijn R; Vaandrager, Arie B; Helms, J Bernd

    2017-01-01

    Hepatic stellate cells (HSCs) are professional lipid-storing cells and are unique in their property to store most of the retinol (vitamin A) as retinyl esters in large-sized lipid droplets. Hepatic stellate cell activation is a critical step in the development of chronic liver disease, as activated HSCs cause fibrosis. During activation, HSCs lose their lipid droplets containing triacylglycerols, cholesteryl esters, and retinyl esters. Lipidomic analysis revealed that the dynamics of disappearance of these different classes of neutral lipids are, however, very different from each other. Although retinyl esters steadily decrease during HSC activation, triacylglycerols have multiple pools one of which becomes transiently enriched in polyunsaturated fatty acids before disappearing. These observations are consistent with the existence of preexisting "original" lipid droplets with relatively slow turnover and rapidly recycling lipid droplets that transiently appear during activation of HSCs. Elucidation of the molecular machinery involved in the regulation of these distinct lipid droplet pools may open new avenues for the treatment of liver fibrosis.

  11. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.

    2016-01-01

    Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat...... is similar to the overflow metabolism observed in many other microorganisms, e.g. ethanol production by Sacchromyces cerevisiae at nitrogen limitation....

  12. Lipid peroxidation in neonatal mouse brain subjected to two different types of hypoxia.

    Science.gov (United States)

    Hasegawa, K; Yoshioka, H; Sawada, T; Nishikawa, H

    1991-01-01

    To elucidate the role of free radicals in the pathogenesis of neonatal hypoxic encephalopathy, we determined the content of thiobarbituric acid reactants (TBARs), as an index of lipid peroxidation related with a free radical reaction, in the brains of newborn mice during hypoxia and recovery from hypoxia. Hypoxic stress was induced by 100% nitrogen gas breathing (N2 group) or 100% carbon dioxide gas breathing (CO2 group). TBARs increased with 20 minutes of hypoxia and returned to the control level during the recovery period in both groups. The increase in TBARs in the CO2 group was greater than that in the N2 group. These results may suggest that free radical reaction occurs during the hypoxic period and that CO2 hypoxia is more effective on free radical production in the newborn brain than N2 hypoxia.

  13. Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle

    DEFF Research Database (Denmark)

    Langfort, Jozef; Jagsz, Slawomir; Dobrzyn, Pawel

    2010-01-01

    tissue suggests that testosterone regulates HSL activity. To test whether this is also true in the heart, we measured HSL activity in the left ventricle of sedentary male rats that had been treated with testosterone supplementation or orchidectomy with or without testosterone substitution. Left ventricle...... HSL activity against TG was significantly elevated in intact rats supplemented with testosterone. HSL activity against both TG and diacylglyceride was reduced by orchidectomy, whereas testosterone replacement fully reversed this effect. Moreover, testosterone increased left ventricle free fatty acid...... levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid...

  14. A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy.

    Science.gov (United States)

    Zhang, Ren; Abou-Samra, Abdul B

    2014-09-13

    Metabolic syndrome includes glucose intolerance and dyslipidemia, both of which are strong risk factors for developing diabetes and atherosclerotic cardiovascular diseases. Recently, multiple groups independently studied a previously uncharacterized gene, officially named C19orf80 (human) and Gm6484 (mouse), but more commonly known as RIFL, Angptl8, betatrophin and lipasin. Both exciting and conflicting results have been obtained, and significant controversy is ongoing. Accumulating evidence from genome wide association studies and mouse genetic studies convincingly shows that lipasin is involved in lipid regulation. However, the mechanism of action, the identity of transcription factors mediating its nutritional regulation, circulating levels, and relationship among lipasin, Angptl3 and Angptl4, remain elusive. Betatrophin represents a promising drug target for replenishing β-cell mass, but current results have not been conclusive regarding its potency and specificity. Here, we summarize the consensus and controversy regarding functions of lipasin/betatrophin based on currently available evidence.

  15. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    Science.gov (United States)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  16. Effect of fenitrothion and disulfoton on lipid metabolism in tissues of white leghorn chicks (Gallus domesticus)

    International Nuclear Information System (INIS)

    Gopal, P.K.; Chopra, Arvind; Ahuja, S.P.

    1990-01-01

    The effects of acute and chronic toxicity due to Disulfoton (diethyl S-(2-ehtyl thio) ethyl phosphorothionate) and Fenitrothion (dimethyl P-3-methyl-4 nitrophenyl phosphorothionate) on the lipid metabolism in tissues of white leghorn chicks (Gallus domesticus) was studied by using 32 P-phosphate, 2- 14 C-acetate and U- 14 C-glucose as precursors. During acute toxicity, the biosynthesis of fatty acids and aerobic oxidation of glucose appear to be inhibited in nervous tissues. However, during chronic toxicity, the biosynthesis of fatty acids is not inhibited. The biosynthesis of phospholipids is depressed in certain tissues due to decreased availability of diglyceride precursors during acute toxicity. During chronic toxicity, the formation of diglyceride from phosphatidic acid appears to be inhibited. (author). 14 refs., 4 tabs

  17. A20 modulates lipid metabolism and energy production to promote liver regeneration.

    Directory of Open Access Journals (Sweden)

    Scott M Damrauer

    2011-03-01

    Full Text Available Liver regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice.We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20 and rAd.βgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV.This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings

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

    Science.gov (United States)

    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...

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Castelli, Martina Galatea [Norwegian Polar Institute, Fram Centre, 9296 Tromsø (Norway); University of Bergen, Department of Biology, 5020 Bergen (Norway); Rusten, Marte; Goksøyr, Anders [University of Bergen, Department of Biology, 5020 Bergen (Norway); Routti, Heli, E-mail: heli.routti@npolar.no [Norwegian Polar Institute, Fram Centre, 9296 Tromsø (Norway)

    2014-01-15

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