Functional analysis of rat liver citrate carrier promoter: differential responsiveness to polyunsaturated fatty acids

2008 ◽  
Vol 417 (2) ◽  
pp. 561-571 ◽  
Author(s):  
Fabrizio Damiano ◽  
Gabriele V. Gnoni ◽  
Luisa Siculella

CiC (citrate carrier), a mitochondrial membrane protein, plays an important metabolic role by transporting acetyl-CoA into the cytosol for fatty acid and cholesterol synthesis. Several studies showed that CiC activity and expression is regulated by dietary fatty acids. In the present study we report data on the structural and functional characterization of the 5′-flanking region of the rat Cic gene. By transient transfection assays in H4IIE rat hepatoma cells, a PUFA (polyunsaturated fatty acids) response region has been identified within the CiC promoter. A cluster of putative binding sites for several transcription factors, composed of a NF-Y (nuclear factor-Y) site, an E-box-like site, a SRE1 (sterol regulatory element 1)-like site and four Sp1 (stimulatory protein 1) sites, was localized in the promoter region. Luciferase reporter gene and gel mobility shift assays indicated that a functional E-box-like, essential to the basal CiC promoter activity, confers responsiveness to activation by SREBP (SRE-binding protein)-1c. This study provides evidence for SREBP-1c as a principal target for PUFA regulation of CiC transcription. In H4IIE cells, overexpression of nSREBP (nuclear SREBP)-1c over-rides arachidonic acid (C20:4, n-6) suppression, but does not prevent the repression by docosahexaenoic acid (C22:6, n-3). ChIP (chromatin immunoprecipitation) assays in H4IIE cells showed that docosahexaenoic acid affects the binding of NF-Y, Sp1 and SREBP-1 to the PUFA response region of CiC promoter, whereas arachidonic acid alters only the binding of SREBP-1. Our data show that PUFA inhibition of hepatic Cic gene transcription is mediated not only by the nuclear level of SREBP-1c, but also might involve a reduction in Sp1 and NF-Y DNA binding, suggesting differential mechanisms in the Cic gene regulation by different PUFA.

2019 ◽  
Vol 59 (4) ◽  
pp. 1763-1766 ◽  
Author(s):  
Yasutake Tomata ◽  
Susanna C. Larsson ◽  
Sara Hägg

Abstract Purpose Observational studies have suggested that polyunsaturated fatty acids (PUFAs) may decrease Alzheimer’s disease (AD) risk. In the present study, we examined this hypothesis using a Mendelian randomization analysis. Methods We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of n-6 PUFAs (linoleic acid, arachidonic acid) and n-3 PUFAs (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid), and the corresponding data for AD from a genome-wide association meta-analysis of 63,926 individuals (21,982 diagnosed AD cases, 41,944 controls). Results None of the genetically predicted PUFAs was significantly associated with AD risk; odds ratios (95% confidence interval) per 1 SD increase in PUFA levels were 0.98 (0.93, 1.03) for linoleic acid, 1.01 (0.98, 1.05) for arachidonic acid, 0.96 (0.88, 1.06) for alpha-linolenic acid, 1.03 (0.93, 1.13) for eicosapentaenoic acid, 1.03 (0.97, 1.09) for docosapentaenoic acid, and 1.01 (0.81, 1.25) for docosahexaenoic acid. Conclusions This study did not support the hypothesis that PUFAs decrease AD risk.


2021 ◽  
pp. 089033442199346
Author(s):  
Adriana V. Gaitán ◽  
JodiAnne T. Wood ◽  
Yingpeng Liu ◽  
Lipin Ji ◽  
Spyros P. Nikas ◽  
...  

Background Dietary long-chain polyunsaturated fatty acids are known to benefit infant development. After birth, human milk provides arachidonic, eicosapentaenoic, and docosahexaenoic acids to the infant. Endocannabinoids are endogenous lipid mediators derived from the long-chain polyunsaturated fatty acids. Although the roles and the mechanisms of action are not fully understood, previous researchers have suggested that endocannabinoids might play a role in infant feeding behavior. Research Aims To assess (i) maternal dietary intake of long-chain polyunsaturated fatty acids and (ii) their relationship to concentrations of fatty acids and derived endocannabinoids in human milk. Methods For this exploratory-longitudinal study, participants ( N = 24) provided dietary intake data and milk samples. Fatty acids and derived endocannabinoids: Arachidonylethanolamide, arachidonoylglycerol, docosahexaenoyl glycerol, eicosapentaenoyl ethanolamide, and eicosapenaenoyl glycerol were identified in their milk by liquid chromatography-mass spectrometry and correlations to dietary fatty acids were assessed. Results Participants were not consuming recommended amounts of docosahexaenoic acid. Significant correlations ( p ≤ .05) were only found between dietary docosahexaenoic and eicosapentaenoic acids and the concentrations of these in human milk. Moreover, only dietary docosahexaenoic acid was correlated ( p = .031) with its corresponding endocannabinoid, docosahexaenoyl glycerol. Conclusions To the best of our knowledge, this may be one of the first studies evaluating relationships between dietary long-chain polyunsaturated fatty acids and multiple endocannabinoids in human milk. Our findings suggest that endocannabinoid concentrations could be modulated by dietary precursors. Future research studies can be designed based on these data to better elucidate the roles of endocannabinoids in human milk for infant health and development.


2003 ◽  
Vol 56 (1-2) ◽  
pp. 50-53 ◽  
Author(s):  
Vanja Ristic ◽  
Gordana Ristic

Introduction Hyperlipoproteinemia is a key factor in development of atherosclerosis, whereas regression of atherosclerosis mostly depends on decreasing the plasma level of total and LDL-cholesterol. Many studies have reported the hypocholesterolemic effect of linolenic acid. Types of polyunsaturated fatty acids (PUFA) Linoleic and ?-linolenic acids are essential fatty acids. The main sources of linoleic acid are vegetable seeds and of ?-linolenic acid - green parts of plants. ?-linolenic acid is converted to eicosapentaenoic and docosahexaenoic acid. Linoleic acid is converted into arachidonic acid competing with eicosapentaenoic acid in the starting point for synthesis of eicosanoids, which are strong regulators of cell functions and as such, very important in physiology and pathophysiology of cardiovascular system. Eicosanoids derived from eicosapentaenoic acid have different biological properties in regard to those derived from arachidonic acid, i.e. their global effects result in decreased vasoconstriction platelet aggregation and leukocyte toxicity. Role and significant of PUFA The n-6 to n-3 ratio of polyunsaturated fatty acids in the food is very important, and an optimal ratio 4 to 1 in diet is a major issue. Traditional western diets present absolute or relative deficiency of n-3 polyunsaturated fatty acids, and a ratio 15-20 to 1. In our diet fish and fish oil are sources of eicosapentaenoic and docosahexaenoic acid. Refined and processed vegetable oils change the nature of polyunsaturated fatty acids and obtained derivates have atherogenic properties.


2011 ◽  
Vol 236-238 ◽  
pp. 2516-2522
Author(s):  
Xiang Hua Chai ◽  
Ke Gang Wu ◽  
Ruo Hui Lin ◽  
Xiao Li Liu

To evaluate oxidative stability of microencapsulated oils rich in polyunsaturated fatty acids, the change of peroxide value (POV) during storage was investigated. Microencapsulated oils were prepared by spray drying emulsions containing oils rich in docosahexaenoic acid or arachidonic acid, caseinate, modified starch and maltodextrin. Results showed that oxidative stability and initial POV of oils, packing and storage temperature all affected markedly oxidative stability of microencapsulated oils. It is necessary for obtaining stable microencapsulated oils to choose oils of high oxidative stability and low initial POV, reduce oxygen content in wrapper and lower storage temperature. Basing on our findings, six stages of the oxidation of microencapsulated oils were suggested as compared with three stages of the oxidation of oils. It is very important for the oxidative stability and shelf-life to extend the first and the forth stages, shorten the second and the third stages, and avoid the fifth and the sixth stages during oxidation of microencapsulated oils.


2021 ◽  
Author(s):  
Xiaodan Lu ◽  
Rongbin Zhong ◽  
Ling Hu ◽  
Luyao Huang ◽  
Lijiao Chen ◽  
...  

Abstract Large yellow croaker roe phospholipids (LYCRPLs) has great nutritional value because of containing rich docosahexaenoic acid (DHA), which is a kind of n-3 polyunsaturated fatty acids (n-3 PUFAs). In...


Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 113
Author(s):  
Marine Remize ◽  
Yves Brunel ◽  
Joana L. Silva ◽  
Jean-Yves Berthon ◽  
Edith Filaire

N-3 polyunsaturated fatty acids (n-3 PUFAs), and especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential compounds for human health. They have been proven to act positively on a panel of diseases and have interesting anti-oxidative, anti-inflammatory or anti-cancer properties. For these reasons, they are receiving more and more attention in recent years, especially future food or feed development. EPA and DHA come mainly from marine sources like fish or seaweed. Unfortunately, due to global warming, these compounds are becoming scarce for humans because of overfishing and stock reduction. Although increasing in recent years, aquaculture appears insufficient to meet the increasing requirements of these healthy molecules for humans. One alternative resides in the cultivation of microalgae, the initial producers of EPA and DHA. They are also rich in biochemicals with interesting properties. After defining macro and microalgae, this review synthesizes the current knowledge on n-3 PUFAs regarding health benefits and the challenges surrounding their supply within the environmental context. Microalgae n-3 PUFA production is examined and its synthesis pathways are discussed. Finally, the use of EPA and DHA in food and feed is investigated. This work aims to define better the issues surrounding n-3 PUFA production and supply and the potential of microalgae as a sustainable source of compounds to enhance the food and feed of the future.


Membranes ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 479
Author(s):  
Souvik Mukerjee ◽  
Abdulaziz S. Saeedan ◽  
Mohd. Nazam Ansari ◽  
Manjari Singh

Particular dramatic macromolecule proteins are responsible for various cellular events in our body system. Lipids have recently recognized a lot more attention of scientists for understanding the relationship between lipid and cellular function and human health However, a biological membrane is formed with a lipid bilayer, which is called a P–L–P design. Our body system is balanced through various communicative signaling pathways derived from biological membrane proteins and lipids. In the case of any fatal disease such as cancer, the biological membrane compositions are altered. To repair the biological membrane composition and prevent cancer, dietary fatty acids, such as omega-3 polyunsaturated fatty acids, are essential in human health but are not directly synthesized in our body system. In this review, we will discuss the alteration of the biological membrane composition in breast cancer. We will highlight the role of dietary fatty acids in altering cellular composition in the P–L–P bilayer. We will also address the importance of omega-3 polyunsaturated fatty acids to regulate the membrane fluidity of cancer cells.


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