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1.
Fatty Acids and Antioxidants in Multiple Sclerosis: Therapeutic Role of GEMSP.
Ahumada-Pascual, P, Gañán, DG, Montero, YEB, Velasco, A
Current pharmaceutical design. 2019;(4):376-380
Abstract
Multiple sclerosis is a high-frequency neurological disorder in young adults. Although there are some genetic and environmental factors that have been related to the onset of the disease, these are still not completely understood and nowadays multiple sclerosis can neither be prevented, nor its symptom effectively treated due to disease heterogeneity. For this reason, the search of prognostic factors and new therapeutic compounds for MS has long aroused among clinicians and researchers. Among these therapeutic compounds, GEMSP, which consists of a mixture of functional constituents as fatty acids, antioxidants, free radical scavengers and amino acids linked individually to poly-L-Lysine (PL), is emerging as a promising drug for MS treatment. Pre-clinical studies using GEMSP have demonstrated that this drug strongly inhibits brain leukocyte infiltration and completely abolishes experimental autoimmune encephalomyelitis. In addition, in an open clinical trial in humans treated with GEMSP, in 72% of the cases, a positive evolution of the state of the MS patients treated with GMSP was observed. In this review a biochemical characterization of main constituents of GEMSP, which include fatty acids as oleic acid, linoleic acid or azelaic acid and the antioxidants alpha-tocopherol or ascorbic acid, will be provided in order to understand their proved therapeutic effects in MS.
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2.
FabG: from a core to circumstantial catalyst.
Shanbhag, AP
Biotechnology letters. 2019;(6-7):675-688
Abstract
Core biochemical pathways such as Fatty-acid synthesis II (FAS II) is ascribed to the synthesis of fatty-acids, biotin and lipoic acid in prokaryotes. It has two dehydrogenases namely, FabG and FabI which interact with the fatty-acid chain bound to Acyl-carrier protein (ACP), a well-studied enzyme which binds to substrates of varying lengths. This protein-protein interaction 'broadens' the active site of these dehydrogenases thus, contributing to their flexible nature. This property is exploited for catalysing numerous chiral synthons, alkanes, long-chain alcohols and secondary metabolites in industries especially with FabG. FASI relegates FASII in eukaryotes making it a 'relic gene pool' and an antibacterial drug target with diverse inhibitor and substrate markush. FabG often substitutes other dehydrogenases for producing secondary metabolites in nature. This redundancy is probably due to gene duplication or addition events possibly making FabG, a progenitor to some of the complex short-chain dehydrogenases used in organisms and industries today.
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3.
Dietary total fat, fatty acids intake, and risk of cardiovascular disease: a dose-response meta-analysis of cohort studies.
Zhu, Y, Bo, Y, Liu, Y
Lipids in health and disease. 2019;(1):91
Abstract
BACKGROUND Several epidemiological studies have investigated the association between dietary fat intake and cardiovascular disease. However, dietary recommendations based on systematic review and meta-analysis might be more credible. METHODS AND RESULTS Pubmed, Embase and Cochrane library were searched up to July 1st 2018 for cohort studies reporting associations of dietary fat intake and risk of CVDs. By comparing the highest vs. the lowest categories of fat or fatty acids intake, we found that higher dietary trans fatty acids (TFA) intake was associated with increased risk of CVDs [RR:1.14(1.08-1.21)]. However, no association was observed between total fat, monounsaturated fatty acids (MUFA), saturated fatty acids (SFA), and polyunsaturated fatty acids (PUFA), and risk of CVDs. Subgroup analysis found a cardio-protective effect of PUFA in the studies that has been followed up more than 10 years [0.95(0.91-0.99), I2 = 62.4%]. Dose-response analysis suggested that the risk of CVDs increased 16% [1.16 (1.07-1.25), Plinearity = 0.033] for an increment of 2% energy/day of TFA intake. CONCLUSIONS This current meta-analysis of cohort studies suggested that total fat, SFA, MUFA, and PUFA intake were not associated with the risk of cardiovascular disease. However, we found that higher TFA intake is associated with greater risk of CVDs in a dose-response fashion. Furthermore, the subgroup analysis found a cardio-protective effect of PUFA in studies followed up for more than 10 years.
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4.
Influence of surfactants on anaerobic digestion of waste activated sludge: acid and methane production and pollution removal.
He, Q, Xu, P, Zhang, C, Zeng, G, Liu, Z, Wang, D, Tang, W, Dong, H, Tan, X, Duan, A
Critical reviews in biotechnology. 2019;(5):746-757
Abstract
The objective of this study is to summarize the effects of surfactants on anaerobic digestion (AD) of waste activated sludge (WAS). The increasing amount of WAS has caused serious environmental problems. Anaerobic digestion, as the main treatment for WAS containing three stages (i.e. hydrolysis, acidogenesis, and methanogenesis), has been widely investigated. Surfactant addition has been demonstrated to improve the efficiency of AD. Surfactant, as an amphipathic substance, can enhance the efficiency of hydrolysis by separating large sludge and releasing the encapsulated hydrolase, providing more substance for subsequent acidogenesis. Afterwards, the short chain fatty acids (SCFAs), as the major product, have been produced. Previous investigations revealed that surfactant could affect the transformation of SCFA. They changed the types of acidification products by promoting changes in microbial activity and in the ratio of carbon to nitrogen (C/N), especially the ratio of acetic and propionic acid, which were applied for either the removal of nutrient or the production of polyhydroxyalkanoate (PHA). In addition, the activity of microorganisms can be affected by surfactant, which mainly leads to the activity changes of methanogens. Besides, the solubilization of surfactant will promote the solubility of contaminants in sludge, such as organic contaminants and heavy metals, by increasing the bioavailability or desorbing of the sludge.
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5.
Applications of Innovative Lipidomic Methods for Blood Lipid Biomarkers.
Stark, KD
Journal of oleo science. 2019;(6):503-510
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Abstract
Assessing dietary intake is critical for understanding the relationship between diet and health. Fatty acid blood biomarkers have been particularly useful in determining dietary intakes and assessing the risk of chronic disease. However, fatty acid analysis involves the removal of fatty acids from their complex lipid structures resulting in a loss of potentially useful biological information. "Lipidomics" involves the use of mass spectrometry to identify lipids in their native form. Lipidomic approaches present challenges as an alternative to fatty acid analysis. This includes different types of lipidomic approaches and a lack of consensus on the lipids reported in different studies. Distinguishing between macrolipidomic approaches to characterize highly abundant lipids and microlipidomic approaches examining low abundant bioactive lipids and the use of brutto, medio, genio, and infinio to describe the level of information of lipidomic data can provide clarity to the field. Using lipidomic measurements for understanding docosahexaenoic acid metabolism during pregnancy will also be examined.
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6.
Production of conjugated fatty acids: A review of recent advances.
Gong, M, Hu, Y, Wei, W, Jin, Q, Wang, X
Biotechnology advances. 2019;(8):107454
Abstract
Conjugated fatty acids (CFAs) have received a deal of attention due to the increasing understanding of their beneficial physiological effects, especially the anti-cancer effects and metabolism-regulation activities. However, the production of CFAs is generally difficult. Several challenges are the low CFAs content in natural sources, the difficulty to chemically synthesize target CFA isomers in high purity, and the sensitive characteristics of CFAs. In this article, the current technologies to produce CFAs, including physical, chemical, and biotechnical approaches were summarized, with a focus on the conjugated linoleic acids (CLAs) and conjugated linolenic acids (CLNAs) which are the most common investigated CFAs. CFAs usually demonstrate stronger physiological effects than other non-conjugated fatty acids; however, they are more sensitive to heat and oxidation. Consequently, the quality control throughout the entire production process of CFAs is significant. Special attention was given to the micro- or nano-encapsulation which presented as an emerging technique to improve the bioavailability and storage stability of CFAs. The current applications of CFAs and the potential research directions were also discussed.
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7.
Management and diagnosis of mitochondrial fatty acid oxidation disorders: focus on very-long-chain acyl-CoA dehydrogenase deficiency.
Yamada, K, Taketani, T
Journal of human genetics. 2019;(2):73-85
Abstract
Mitochondrial fatty acid oxidation disorders (FAODs) are caused by defects in β-oxidation enzymes, including very long-chain acyl-CoA dehydrogenase (VLCAD), trifunctional protein (TFP), carnitine palmitoyltransferase-2 (CPT2), carnitine-acylcarnitine translocase (CACT) and others. During prolonged fasting, infection, or exercise, patients with FAODs present with hypoglycemia, rhabdomyolysis, cardiomyopathy, liver dysfunction, and occasionally sudden death. This article describes the diagnosis, newborn screening, and treatment of long-chain FAODs with a focus on VLCAD deficiency. VLCAD deficiency is generally classified into three phenotypes based on onset time, but the classification should be comprehensively determined based on genotype, residual enzyme activity, and clinical course, due to a lack of apparent genotype-phenotype correlation. With the expansion of newborn screening for FAODs, several issues have arisen, such as missed detection, overdiagnosis (including detection of benign/asymptomatic type), and poor prognosis of the neonatal-onset form. Meanwhile, dietary management and restriction of exercise have been unnecessary for patients with the benign/asymptomatic type of VLCAD deficiency with a high fatty acid oxidation flux score. Although L-carnitine therapy for VLCAD/TFP deficiency has been controversial, supplementation with L-carnitine may be accepted for CPT2/CACT and multiple acyl-CoA dehydrogenase deficiencies. Recently, a double-blind, randomized controlled trial of triheptanoin (seven-carbon fatty acid triglyceride) versus trioctanoin (regular medium-chain triglyceride) was conducted and demonstrated improvement of cardiac functions on triheptanoin. Additionally, although the clinical efficacy of bezafibrate remains controversial, a recent open-label clinical trial showed efficacy of this drug in improving quality of life. These drugs may be promising for the treatment of FAODs, though further studies are required.
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8.
FADS1 and FADS2 Polymorphisms Modulate Fatty Acid Metabolism and Dietary Impact on Health.
Koletzko, B, Reischl, E, Tanjung, C, Gonzalez-Casanova, I, Ramakrishnan, U, Meldrum, S, Simmer, K, Heinrich, J, Demmelmair, H
Annual review of nutrition. 2019;:21-44
Abstract
Variants in the FADS gene cluster modify the activity of polyunsaturated fatty acid (PUFA) desaturation and the lipid composition in human blood and tissue. FADS variants have been associated with plasma lipid concentrations, risk of cardiovascular diseases, overweight, eczema, pregnancy outcomes, and cognitive function. Studies on variations in the FADS genecluster provided some of the first examples for marked gene-diet interactions in modulating complex phenotypes, such as eczema, asthma, and cognition. Genotype distribution differs markedly among ethnicities, apparently reflecting an evolutionary advantage of genotypes enabling active long-chain PUFA synthesis when the introduction of agriculture provided diets rich in linoleic acid but with little arachidonic and eicosapentaenoic acids. Discovering differential effects of PUFA supply that depend on variation of FADS genotypes could open new opportunities for developing precision nutrition strategies based either on an individual's genotype or on genotype distributions in specific populations.
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Sensing Mitochondrial Acetyl-CoA to Tune Respiration.
Mills, CA, Trub, AG, Hirschey, MD
Trends in endocrinology and metabolism: TEM. 2019;(1):1-3
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Abstract
Fatty acid synthesis (FAS) in mitochondria produces a key metabolite called lipoic acid. However, a new study by Van Vranken et al.[1] (Mol. Cell 2018;71:567-580) shows that mitochondrial FAS regulates the assembly of oxidative phosphorylation complexes, thereby functioning as a nutrient sensor for mitochondrial respiration.
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The Impact of Dairy Products in the Development of Type 2 Diabetes: Where Does the Evidence Stand in 2019?
Guo, J, Givens, DI, Astrup, A, Bakker, SJL, Goossens, GH, Kratz, M, Marette, A, Pijl, H, Soedamah-Muthu, SS
Advances in nutrition (Bethesda, Md.). 2019;(6):1066-1075
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Abstract
The prevalence of type 2 diabetes (T2D) has increased rapidly. Adopting a heathy diet is suggested as one of the effective behaviors to prevent or delay onset of T2D. Dairy consumption has been recommended as part of a healthy diet, but there remains uncertainty in both the scientific community and the public about the effect of different dairy products on T2D risk. In a recent workshop, the evidence on dairy products and T2D risk was presented and discussed by a group of experts. The main conclusions from the workshop are presented in this position paper and are as follows. 1) Available evidence from large prospective cohort studies and limited randomized controlled trials (RCTs) suggests that total dairy consumption has a neutral or moderately beneficial effect on T2D risk. 2) Increasing evidence from prospective cohort studies indicates that yogurt is most strongly associated with a lower T2D risk, but evidence from RCTs is scarce. 3) Fatty acids from dairy (medium-chain, odd, and very long-chain SFAs as well as trans-palmitoleic acid) are associated with lower T2D risk and improved metabolic health, but more research is needed on studies that explore cause and effect relations to exclude the possibility that the dairy fatty acids simply serve as markers of overall dairy consumption. 4) The food matrix can be a stronger determinant of health effects than SFA content. This review further identifies research gaps in the existing knowledge and highlights key research questions that need to be addressed to better understand the impact of dairy consumption on future T2D risk.