Role Of Unsaturated Fatty Acids Research Articles

A metabolic map and artificial intelligence-aided identification of nasopharyngeal carcinoma via a single-cell Raman platform.

Nasopharyngeal carcinoma (NPC) is a complex cancer influenced by various factors. This study explores the use of single-cell Raman spectroscopy as a potential diagnostic tool for investigating biomolecular changes associated with NPC carcinogenesis. Seven NPC cell lines, one immortalised nasopharyngeal epithelial cell line, six nasopharyngeal mucosa tissues and seven NPC tissue samples were analysed by performing confocal Raman spectroscopic measurements and imaging. The single-cell Raman spectral dataset was used to quantify relevant biomolecules and build machine learning classification models. Metabolomic profiles were investigated using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). By generating a metabolic map of seven NPC cell lines, we identified an interplay of altered metabolic processes involving nucleic acids, amino acids, lipids and sugars. The results from spatially resolved Raman maps and UPLC-MS/MS metabolomics were consistent, revealing an increase of unsaturated fatty acids in cancer cells, particularly in highly metastatic 5-8F and poorly differentiated CNE2 cells. The classification model achieved a nearly perfect classification when identifying NPC and non-NPC cells with an ROC-AUC of 0.99 and a value of 0.97 when identifying 13 tissue samples. This study unveils a complex interplay of metabolic network and highlights the potential roles of unsaturated fatty acids in NPC progression and metastasis. This renders further research to provide deeper insights into NPC pathogenesis, identify new metabolic targets and improve the efficacy of targeted therapies in NPC. Artificial intelligence-aided analysis of single-cell Raman spectra has achieved high accuracies in the classification of both cancer cells and patient tissues, paving the way for a simple, less invasive and accurate diagnostic test.

Efficacy and Biomedical Roles of Unsaturated Fatty Acids as Bioactive Food Components

Abstract: Unsaturated fatty acids (UFAs) as bioactive compounds possess a wide range of biomedical functions and a lack or shortage of them may cause serious harm to human body health. Biochemically, UFAs have attracted growing interest, and this attention arises not only from biomedical reasons but also economic ones. Among these fatty acids, omega-3 and omega-6 fatty acids are considered the most efficient and safe compounds which can be used for expanding and identification of novel functionalities. They are considered essential membrane components and are associated with a variety of biological processes. For example, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as polyunsaturated fatty acids (PUFAs) play a central role in the proper functioning of the nervous system like anti-atherogenic properties and improve the functioning of the cardiovascular system. Briefly, understanding the relationship between these properties and potential biomedical applications of UFAs may help to elucidate and facilitate the development of novel pathogenesis strategies regarding their disorders in human health and diseases. This review provides the most suitable functional roles and potential mechanisms of UFAs associated with human health and nutrition.

C24:0 avoids cold exposure-induced oxidative stress and fatty acid β-oxidation damage

SummaryLow temperatures can cause severe growth inhibition and mortality in fish. Previous studies about the cold resistance of fish mainly focused on the role of unsaturated fatty acids, rather than saturated fatty acids (SFAs). In this study, the role of very-long-chain SFA synthetized by fatty acyl elongase 1 gene (elovl1) in cold resistance was explored. Both an aggravated liver oxidative stress and a mitochondrial metabolism disorder were observed in elovl1a–/– and elovl1b–/– zebrafish with cold stress. In vitro studies confirmed that high levels of C20:0 and C22:0 obviously increased the hepatocyte oxidative stress and activated the extracellular signal-regulated kinases 1/2 (Erk1/2) pathway to further induce apoptosis and inflammation. We further demonstrated that C24:0 could promote mitochondrial β-oxidation to improve the cold resistance of zebrafish. Overall, our results define a positive role of C24:0 fatty acids synthetized by elovl1 in the cold resistance of fish.

C24:0 Avoids Cold Exposure-Induced Oxidative Stress and Impaired Fatty Acid β -Oxidation

As we know, low temperatures can cause severe growth inhibition and mortality in fish. Previous studies about cold resistance of fish mainly focused on the role of unsaturated fatty acids, rather than saturated fatty acids (SFA). In this study, the role of very long chain SFA synthetized by through fatty acid elongase 1 gene (elovl1) in cold resistance was explored. The aggravated liver oxidative stress and the disorder of mitochondrial metabolism were found in elovl1a-/- and elovl1b-/- zebrafish with cold stress. In vitro experiments confirmed that high levels of C20:0 and C22:0 significantly increased the hepatocytes oxidative stress and activated mitogen-activated protein kinase (Mapk) pathway to further induce apoptosis and inflammation. We further demonstrated that C24:0 promoted mitochondrial β-oxidation through ceramide synthetase to produce Cer24:0 to improve cold resistance. Overall, our results define a positive role of C24:0 fatty acids synthetized by through elovl1 in cold resistance of fish.

Adherence to the Mediterranean diet and body composition of breast-feeding mothers: the potential role of unsaturated fatty acids.

A paucity of evidence is available regarding the impact of diet's quality during pregnancy and lactation on the body composition of breast-feeding mothers. The purpose of the present study was to evaluate the association between maternal degree of adherence to the Mediterranean diet (MD) and body composition measures specifically those relating to body fat, in the lactation period. A cross-sectional study on healthy mothers of full-term babies has been conducted. At 30 ± 10 d after delivery, anthropometric measurements and body composition were assessed. A food frequency questionnaire was performed to compute the Italian Mediterranean Index (IMI) score as an index of adherence to the MD. Data related to pregnancy such as pre-pregnancy weight, gestational weight gain and morbidities were also collected. The 147 mothers included were categorised in IMI-1 (IMI score < 5; n 92) and IMI-2 (IMI score ≥ 5; n 55) groups. IMI-2 mothers showed higher daily energy, total carbohydrates, starch and fibre intakes than IMI-1. The dietary habits of IMI-2 mothers reflect the typical characteristics of MD: they consumed higher quantities of proteins and lipids of vegetal origin, higher amounts of monounsaturated and polyunsaturated fatty acids (PUFAs) and lower saturated to PUFAs ratio. The IMI-2 group showed lower absolute fat mass and fat mass index compared to IMI-1 [(20⋅2 ± 5⋅9) v. (22⋅9 ± 8⋅4) kg; P 0⋅036 and (7⋅5 ± 2⋅2) v. (8⋅5 ± 3⋅1) kg/m2; P 0⋅036, respectively], whereas body weight [(61⋅1 ± 8⋅0) v. (63⋅3 ± 9⋅2) kg] and body mass index [(22⋅4 ± 2⋅6) v. (23⋅3 ± 3⋅5) kg/m2] were similar. The degree of adherence to the MD during pregnancy and lactation is positively associated with lower maternal fat deposition in the breast-feeding period. The higher quality of dietary lipids, probably in synergy with the assumption of starchy carbohydrates and fibre, could influence maternal body fat.

Factors promoting nuclear envelope assembly independent of the canonical ESCRT pathway.

The nuclear envelope (NE) undergoes dynamic remodeling to maintain NE integrity, a process involving the inner nuclear membrane protein LEM2 recruiting CHMP7/Cmp7 and then ESCRT-III. However, prior work has hinted at CHMP7/ESCRT-independent mechanisms. To identify such mechanisms, we studied NE assembly in Schizosaccharomyces japonicus, a fission yeast that undergoes partial mitotic NE breakdown and reassembly. S. japonicus cells lacking Cmp7 have compromised NE sealing after mitosis but are viable. A genetic screen identified mutations that promote NE integrity in cmp7Δ cells. Unexpectedly, loss of Lem2 or its interacting partner Nur1 suppressed cmp7Δ defects. In the absence of Cmp7, Lem2 formed aggregates that appear to interfere with ESCRT-independent NE sealing. A gain-of-function mutation implicated a membrane and ESCRT-III regulator, Alx1, in this alternate pathway. Additional results suggest a potentially general role for unsaturated fatty acids in NE integrity. These findings establish the existence of mechanisms for NE sealing independent of the canonical ESCRT pathway.

Exploring the Physiological Roles of Unsaturated Fatty Acids Using C. elegans

Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), classified broadly as unsaturated fatty acids, are macronutrients that have a wide range of physiological effects. It is known that unsaturated fatty acids play a crucial role in a diet, but it is unclear which specific MUFAs and PUFAs are required and what the physiological consequences of having different amounts of these fatty acids and their metabolites in the body are. Specific omega‐3 and omega‐6 PUFAs have been shown to be beneficial to human diseases, such as cardiovascular disease, inflammatory conditions, and certain cognitive impairments. This study aims to investigate the physiological roles of individual MUFAs and PUFAs. From this study, we will gain the preliminary knowledge for making dietary and treatment suggestions for patients with various disease states and in normal aging. To do this, we will use the model organism C. elegans because of its short lifespan and abundance of genetic tools available (including single and multiple genetic knockouts of fatty acid desaturase enzymes). Additionally, findings from studies in C. elegans reliably translate to human disease. Preliminary data suggests that specific MUFAs and PUFAs are essential for normal lifespan, physiological functions, and neurodevelopment. This study will expand on this by examining every available genetic knockout of fatty acid desaturase enzyme in the worm. We will conduct lifespan assays in order to observe changes in the median and maximum lifespans of different genetic knockouts compared to the wild type as well as thrashing assays, a measure of physical fitness. We hypothesize that certain unsaturated fatty acids play more important physiologic roles than others and the corresponding downstream metabolites are important lipid signaling molecules. Preliminary results from the lab confirm these hypotheses, as the genetic strains tested thus far show variations in lifespan and fitness.Support or Funding InformationThis project was funded by the MSU Startup Fund, NIEHS ‐ R00 ES024806, and NSF ‐DMS‐1761320.

Prevention of arachidonic acid-induced liver injury by controlling oxidative stress-mediated transglutaminase activation with garlic extracts.

Garlic and its sulfur constituents have numerous biological functions, such as antioxidant, anti-inflammatory, anti-microbial, anticancer, antidiabetic and cardioprotective effects. Fatty liver diseases, such as non-alcoholic steatohepatitis, which is characterized by the accumulation of lipids and oxidative stress in hepatocytes and continual liver damage, has attracted much attention, and it is believed that it will become the leading etiology of liver cancer. We have previously reported that the growth-suppressive effects of arachidonic acid (AA), an unsaturated fatty acid known to be a pro-inflammatory precursor, is accompanied by the production of reactive oxygen species followed by the nuclear accumulation and activation of the protein crosslinking enzyme, transglutaminase (TG)2. In this study, we examined the potential role of garlic extracts in preventing the growth-suppressive effects of AA on human hepatic cells. We also aimed to provide a mechanistic insight regarding the association between the hepatoprotective effects of garlic extract and the inhibition of the TG-related crosslinking of nuclear proteins, which is not associated with hepatic lipid partitioning mediated by stearoyl-CoA desaturase-1. Given the critical roles of unsaturated fatty acids in the regulation of cancer cell stemness and immune surveillance in the context of chronic injury, we propose that garlic extracts may serve as a therapeutic option for the prevention of chronic liver injury and inflammation, as well as for the prevention of the carcinogenesis of fatty livers.

New insights into acute pancreatitis.

The incidence of acute pancreatitis continues to increase worldwide, and it is one of the most common gastrointestinal causes for hospital admission in the USA. In the past decade, substantial advancements have been made in our understanding of the pathophysiological mechanisms of acute pancreatitis. Studies have elucidated mechanisms of calcium-mediated acinar cell injury and death and the importance of store-operated calcium entry channels and mitochondrial permeability transition pores. The cytoprotective role of the unfolded protein response and autophagy in preventing sustained endoplasmic reticulum stress, apoptosis and necrosis has also been characterized, as has the central role of unsaturated fatty acids in causing pancreatic organ failure. Characterization of these pathways has led to the identification of potential molecular targets for future therapeutic trials. At the patient level, two classification systems have been developed to classify the severity of acute pancreatitis into prognostically meaningful groups, and several landmark clinical trials have informed management strategies in areas of nutritional support and interventions for infected pancreatic necrosis that have resulted in important changes to acute pancreatitis management paradigms. In this Review, we provide a summary of recent advances in acute pancreatitis with a special emphasis on pathophysiological mechanisms and clinical management of the disorder.

Modulation of Membrane Fluidity Performed on Model Phospholipid Membrane and Live Cell Membrane: Revealing through Spatiotemporal Approaches of FLIM, FAIM, and TRFS.

We have elucidated the role of unsaturated fatty acid in the in vitro model phospholipid membrane and in vivo live cell membrane. Fluorescence microscopy and time-resolved fluorescence spectroscopy have been employed to uncover how modulation of vesicle bilayer fluidity persuades structural transformation. This unsaturation induced structural transformation due to packing disorder in bilayer has been delineated through spatially resolved fluorescence lifetime imaging microscopy (FLIM) and fluorescence polarization or anisotropy imaging microscopy (FPIM/FAIM). Structure-function relationship of phospholipid vesicle is also investigated by monitoring intervesicular water dynamics behavior, which has been demonstrated by temporally resolved fluorescence spectroscopy (TRFS) techniques. Nevertheless, it has also been manifested from this study that loss of rigidity in bilayer breaks down the strong hydrogen bond (H-bond) network around the charged lipid head groups. The disruption of this H-bond network increases the bilayer elasticity, which helps to evolve various kinds of vesicular structure. Furthermore, the significant influence of unsaturated fatty acid on membrane bilayer has been ratified through in vivo live cell imaging.

The differentiation of preadipocytes and gene expression related to adipogenesis in ducks (Anas platyrhynchos).

Meat quality is closely related to adipose tissues in ducks, and adipogenesis is controlled by a complex network of transcription factors tightly acting at different stages of differentiation especially in ducks. The aim of this study was to establish the preadipocyte in vitro culture system and understand the biological characteristics of expansion of duck adipocyte tissue at the cellular and molecular level. We isolated pre-adipocytes from the subcutaneous fat of three breeds of duck and differentiated them into mature adipocytes using a mixture of insulin, rosiglitazone, dexamethasone, 3-isobutyl-1-methylxanthine, and oleic acid over 0,2, 4, 6, and 8 days. Successful differentiation was confirmed from the development of lipid droplets and their response to Oil Red O, and increasing numbers of lipid droplets were stained red over time. The expression of key marker genes, including peroxisome proliferator activated receptor γ (PPARγ), CCAAT/enhancer binding protein-α (C/EBPα), adipocyte fatty acid binding protein 4 (FABP4), and fatty acid synthetase (FAS), gradually increased during pre-adipocyte differentiation. Furthermore, it was verified by interference experiments that the knockdown of PPARγ directly reduced lipid production. Meanwhile we analyzed the role of unsaturated fatty acids in the production of poultry fat using different concentrations of oleic acid and found that lipid droplet deposition was highest when the concentration of oleic acid was 300 μM. We also compared the level of differentiated pre-adipocytes that were isolated from Jianchang ducks (fatty-meat duck), Cherry Valley ducks (lean-meat duck) and White-crested ducks (egg-producing duck). The proliferation and differentiation rate of pre-adipocytes derived from Jianchang ducks was higher than that of White-crested ducks. These results provide the foundation for further research into waterfowl adipogenesis.

A Role of Unsaturated Fatty Acid in Animal Reproductive Cells and Biology

As a one of unsaturated fatty acid, polyunsaturated fatty acids (PUFAs) have multiple actions: as precursor of prostaglandins (PGs), steroid hormone synthesis and energy production in animal reproduction. PUFAs, which include omega-3 (n-3) and omega-6 (n-6), are derived from the diet and changed by diet, species, breed and season. The plasma membrane of spermatozoa in mammals contain various PUFAs. These composition of PUFAs regulate the membrane fluidity and cause lipid peroxidation via generation of reactive oxygen species (ROS). Induced lipid peroxidation by ROS decreased viability and motility of spermatozoa, and it is reduced by addition of antioxidant and low concentration of PUFAs. Because oocytes of animal have a high lipid components, process of oocyte maturation and embryo development are influenced by PUFAs. In in vitro study, oocyte maturation, embryo development, intracellular cAMP and MAPK activity were increased by treatment of n-3 α-linolenic acid (ALA) during maturation, whereas n-6 linoleic acid (LA) negatively influenced. Also, inhibition of fatty acid metabolism in oocyte influenced blastocyst formation of cattle. PGs are synthesized from PUFAs and various PUFAs influence PGs via regulation of PG-endoperoxide synthase (PTGS). Steroid hormone synthesis from cholesterol is regulated by expression of steroid acute regulator (StAR) protein and mRNA. Exogenous n-3 and n-6 PUFAs altered sex hormone in animal through stimulate or inhibit StAR activity. Because PUFAs altered PG and steroid hormone synthesis, follicular development was influenced by PUFAs. This effect of unsaturated fatty acid could provide information for improvement of reproductive ability in animals.

Oleic acid enhances the motility of umbilical cord blood derived mesenchymal stem cells through EphB2-dependent F-actin formation

The role of unsaturated fatty acids (UFAs) is essential for determining stem cell functions. Eph/Ephrin interactions are important for regulation of stem cell fate and localization within their niche, which is significant for a wide range of stem cell behavior. Although oleic acid (OA) and Ephrin receptors (Ephs) have critical roles in the maintenance of stem cell functions, interrelation between Ephs and OA has not been explored. Therefore, the present study investigated the effect of OA-pretreated UCB-MSCs in skin wound-healing and underlying mechanism of Eph expression. OA promoted the motility of UCB-MSCs via EphB2 expression. OA-mediated GPR40 activation leads to Gαq-dependent PKCα phosphorylation. In addition, OA-induced phosphorylation of GSK3β was followed by β-catenin nuclear translocation in UCB-MSCs. Activation of β-catenin was blocked by PKC inhibitors, and OA-induced EphB2 expression was suppressed by β-cateninsiRNA transfection. Of those Rho-GTPases, Rac1 was activated in an EphB2-dependent manner. Accordingly, knocking down EphB2 suppressed F-actin expression. In vivo skin wound-healing assay revealed that OA-treated UCB-MSCs enhanced skin wound repair compared to UCB-MSCs pretreated with EphB2siRNA and OA. In conclusion, we showed that OA enhances UCB-MSC motility through EphB2-dependent F-actin formation involving PKCα/GSK3β/β-catenin and Rac1 signaling pathways.

Raman microspectroscopy of noncancerous and cancerous human breast tissues. Identification and phase transitions of linoleic and oleic acids by Raman low-temperature studies.

We present the results of Raman studies in the temperature range of 293-77 K on vibrational properties of linoleic and oleic acids and Raman microspectroscopy of human breast tissues at room temperature. Our results confirmed the significant role of unsaturated fatty acids in differentiation of noncancerous and cancerous breast tissues and the role of vibrational spectroscopy in phase transition identification. We have found that vibrational properties are very sensitive indicators to specify phases and phase transitions typical of unsaturated fatty acids at the molecular level. Using Raman spectroscopy we have identified high-temperature, middle-temperature and low-temperature phases of linoleic acid. Results obtained for linoleic acid were compared with parameters characteristic of α and γ phases of oleic acid - the parent compound of polyunsaturated fatty acids.

Stearoyl-CoA Desaturase 1 Activity Is Required for Autophagosome Formation

Autophagy is one of the major degradation pathways for cytoplasmic components. The autophagic isolation membrane is a unique membrane whose content of unsaturated fatty acids is very high. However, the molecular mechanisms underlying formation of this membrane, including the roles of unsaturated fatty acids, remain to be elucidated. From a chemical library consisting of structurally diverse compounds, we screened for novel inhibitors of starvation-induced autophagy by measuring LC3 puncta formation in mouse embryonic fibroblasts stably expressing GFP-LC3. One of the inhibitors we identified, 2,5-pyridinedicarboxamide, N2,N5-bis[5-[(dimethylamino)carbonyl]-4-methyl-2-thiazolyl], has a molecular structure similar to that of a known stearoyl-CoA desaturase (SCD) 1 inhibitor. To determine whether SCD1 inhibition influences autophagy, we examined the effects of the SCD1 inhibitor 28c. This compound strongly inhibited starvation-induced autophagy, as determined by LC3 puncta formation, immunoblot analyses of LC3, electron microscopic observations, and p62/SQSTM1 accumulation. Overexpression of SCD1 or supplementation with oleic acid, which is a catalytic product of SCD1 abolished the inhibition of autophagy by 28c. Furthermore, 28c suppressed starvation-induced autophagy without affecting mammalian target of rapamycin activity, and also inhibited rapamycin-induced autophagy. In addition to inhibiting formation of LC3 puncta, 28c also inhibited formation of ULK1, WIPI1, Atg16L, and p62/SQSTM1 puncta. These results suggest that SCD1 activity is required for the earliest step of autophagosome formation.

Salt-induced photoinhibition of PSII is alleviated in halophyte Thellungiella halophila by increases of unsaturated fatty acids in membrane lipids

The effect of salinity on plant growth, chlorophyll content, photosynthetic parameters, photochemical efficiency of PSII, membrane lipid content and fatty-acid composition of halophyte Thellungiella halophila and glycophyte Arabidopsis thaliana was investigated to examine the possible role of unsaturated fatty acids in photosynthesis under saline conditions. The growth of Arabidopsis was significantly decreased by the 100 and 200 mM NaCl treatments; however, there was no significant difference in the fresh and dry weight of Thellungiella at different concentrations of NaCl. Exposure of Arabidopsis to salt resulted in a progressive decline in chlorophyll content, while there was no significant change in that of Thellungiella. The net photosynthetic rate, maximal photochemical efficiency of PSII (Fv/Fm) and actual PSII efficiency were significantly reduced in Arabidopsis but remained unaffected in Thellungiella. Arabidopsis under NaCl treatment showed decreased PG levels and decreased values for the unsaturated fatty acid content and the double bond index (DBI) of monogalactosyldiacylglycerols and phosphatidylglycerols; these values significantly increased in Thellungiella under NaCl treatment, as did the DBI values of digalactosyldiacylglycerols and sulphoquinovosyldiacylglycerols. These results suggest that Thellungiella under salt stress displays high resistance to photoinhibition and that increased concentrations of unsaturated fatty acids in membrane lipids enhances the tolerance of photosystem II to salt stress.

Impact of maternal dietary n-3 and n-6 fatty acids on milk medium-chain fatty acids and the implications for neonatal liver metabolism

Levels of n-6, n-3, and medium-chain fatty acids (MCFA) in milk are highly variable. Higher carbohydrate intakes are associated with increased mammary gland MCFA synthesis, but the role of unsaturated fatty acids for milk MCFA secretion is unclear. This study addressed whether n-6 and n-3 fatty acids, which are known to inhibit hepatic fatty acid synthesis, influence MCFA in rat and human milk and the implications of varying MCFA, n-6, and n-3 fatty acids in rat milk for metabolic regulation in the neonatal liver. Rats were fed a low-fat diet or one of six higher-fat diets, varying in 16:0, 18:1n-9, 18:2n-6, 18:3n-3, and long-chain (LC) n-3 fatty acids. Higher maternal dietary 18:2n-6 or 18:3n-3 did not influence milk MCFA, but lower maternal plasma triglycerides, due to either a low-fat or a high-fat high-LC n-3 diet led to higher milk MCFA. MCFA levels were inversely associated with 18:1n-9, 18:2n-6, and 18:3n-3 in human milk, likely reflecting the association between dietary total fat and unsaturated fatty acids. High LC n-3 fatty acid in rat milk was associated with lower hepatic Pklr, Acly, Fasn, and Scd1 and higher Hmgcs2 in the milk-fed rat neonate, with no effect of milk 18:1n-9, 18:2n-6, or MCFA. These studies show that the dietary fatty acid composition does not impact MCFA secretion in milk, but the fatty acid composition of milk, particularly the LC n-3 fatty acid, is relevant to hepatic metabolic regulation in the milk-fed neonate.

Increase in unsaturated fatty acids in membrane lipids of Suaeda salsa L. enhances protection of photosystem II under high salinity

In order to examine the possible role of unsaturated fatty acids in photosynthesis of halophytes under high salinity, the effect of salinity on plant growth, chlorophyll (Chl) content, photochemical efficiency of PSII, membrane lipid content and fatty acids composition of a C3 euhalophyte Suaeda salsa L. was investigated. Salt stress induced a slight increase of the maximal photochemical efficiency of PSII (Fv/Fm), actual PSII efficiency (&Phi;PSII), Chl a content and Chl a/b ratio. The unsaturated fatty acid content also increased under salt stress. The proportion of MGDG, DGDG, SQDG, and PC decreased, while the proportion of PG increased from 10.9% to 26.9% under salt stress. These results suggest that S. salsa displays high resistance to photoinhibition under salt stress and that increased concentration of unsaturated fatty acids in membrane lipids of S. salsa enhances the tolerance of photosystem II to salt stress.

Cytochrome b 5 null mouse: a new model for studying inherited skin disorders and the role of unsaturated fatty acids in normal homeostasis

Microsomal cytochrome b 5 is a ubiquitous, 15.2 kDa haemoprotein implicated in a number of cellular processes such as fatty acid desaturation, drug metabolism, steroid hormone biosynthesis and methaemoglobin reduction. As a consequence of these functions this protein has been considered essential for life. Most of the ascribed functions of cytochrome b 5, however, stem from in vitro studies and for this reason we have carried out a germline deletion of this enzyme. We have unexpectedly found that cytochrome b 5 null mice were viable and fertile, with pups being born at expected Mendelian ratios. However, a number of intriguing phenotypes were identified, including altered drug metabolism, methaemoglobinemia and disrupted steroid hormone homeostasis. In addition to these previously identified roles for this protein, cytochrome b 5 null mice displayed skin defects closely resembling those observed in autosomal recessive congenital ichthyosis and retardation of neonatal development, indicating that this protein, possibly as a consequence of its role in the de novo biosynthesis of unsaturated fatty acids, plays a central role in skin development and neonatal nutrition. Results from fatty acid profile analysis of several tissues suggest that cytochrome b 5 plays a role controlling saturated/unsaturated homeostasis. These data demonstrate that regional concentrations of unsaturated fatty acids are controlled by endogenous metabolic pathways and not by diet alone.Electronic supplementary materialThe online version of this article (doi:10.1007/s11248-010-9426-1) contains supplementary material, which is available to authorized users.

Striatal dopamine in the response of brain and liver unsaturated and saturated free fatty acids following administration of C75 in CD-1 mice

In order to clarify the mechanism of action of cerulenin analog, C75, known to suppress feeding behavior, food intake was measured in adult CD-1 male mice n=5 per group, treated i.p. with 10 and 20mg/kg of C75. Animals in both treatment groups had significantly lower 24h food consumption rate relative to the control group injected with vehicle. Striatal monoamine neurotransmitters and striatal as well as liver long chain free fatty acids concentrations were subsequently evaluated in another group treated i.p. with 20mg/kg C75. Acute exposure to C75 at 20mg/kg led to approximately 50% increase in the striatal dopamine levels and a decrease in dopamine turnover for up to 24h following the injection. The concentration of serotonin remained unchanged. Concentration of saturated fatty acids in the liver and striatum did not change, while striatal unsaturated myristoleic acid (cis-9-tetradecenoic acid) levels were significantly higher as early as 2h post-injection and remained elevated at 24h post-injection. These preliminary data suggest a central regulatory role of unsaturated fatty acids under dopaminergic control in the C75-induced anorexia. Pharmacological alterations in fatty acid metabolism may prove beneficial in the treatment of obesity.