Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential for murine CD4 T cell metabolic activation

Glycerol-3-phosphate acyltransferase-1 is the first rate limiting step in de novo glycerophospholipid synthesis. We have previously demonstrated that GPAT-1 deletion can significantly alter T cell function resulting in a T cell phenotype similar to that seen in aging. Recent studies have suggested that changes in the metabolic profile of T cells are responsible for defining specific effector functions and T cell subsets. Therefore, we determined whether T cell dysfunction in GPAT-1 ^−/− CD4⁺ T cells could be explained by changes in cellular metabolism. We show here for the first time that GPAT-1 ^−/− CD4⁺ T cells exhibit several key metabolic defects. Striking decreases in both the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) were observed in GPAT-1 ^−/− CD4⁺ T cells following CD3/CD28 stimulation indicating an inherent cellular defect in energy production. In addition, the spare respiratory capacity (SRC) of GPAT-1 ^−/− CD4 + T cells, a key indicator of their ability to cope with mitochondrial stress was significantly decreased. We also observed a significant reduction in mitochondrial membrane potential in GPAT-1 ^−/− CD4⁺ T cells compared to their WT counterparts, indicating that GPAT-1 deficiency results in altered or dysfunctional mitochondria. These data demonstrate that deletion of GPAT-1 can dramatically alter total cellular metabolism under conditions of increased energy demand. Furthermore, altered metabolic response following stimulation may be the defining mechanism underlying T cell dysfunction in GPAT-1 ^−/− CD4⁺ T cells. Taken together, these results indicate that GPAT-1 is essential for the response to the increased metabolic demands associated with T cell activation.     

Fatty acid-induced angiogenesis in first trimester placental trophoblast cells: Possible roles of cellular fatty acid-binding proteins

Angiogenesis is involved in the growth of new blood vessels from the existing one. Consequently, angiogenesis plays an indispensable role in tissue growth and repair including early placentation processes. Besides angiogenic growth factors (vascular endothelial growth factor (VEGF), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), platelet derived growth factor (PDGF), fibroblast growth factors (FGF)), dietary fatty acids (c>16) also directly or indirectly modulate angiogenic processes in tumors and other cell systems. Usually n − 3 fatty acids inhibit whereas n − 6 fatty acids stimulate angiogenesis in tumors and other cells. Contrary to this, docosahexaenoic acid, 22:6n − 3 (DHA) and other fatty acids including conjugated linoleic acid stimulate angiogenesis in placental first trimester cells. In addition to the stimulation of expression of major angiogenic factors such as VEGF and ANGPTL4, fatty acids also stimulate expression of intracellular fatty acid-binding proteins (FABPs) FABP-4 and FABP-3 those are known to directly modulate angiogenesis. Emerging data indicate that FABPs may be involved in the angiogenesis process. This paper reviews the fatty acid mediated angiogenesis process and the involvement of their binding proteins in these processes.     

Fatty Acid Composition of Human Myelin Proteolipid Protein in Peroxisomal Disorders

Myelin proteolipid protein (PLP) is an acylated protein which contains approximately 2 mol of ester-bound fatty acids. In this study, the amount and composition of fatty acids covalently bound to human myelin PLP were determined during development and in peroxisomal disorders. Palmitic, oleic, and stearic acids accounted for most of the PLP acyl chains. However, in contrast to PLP in other species, human PLP contains relatively more very long chain fatty acids (VLCFA). The fatty acid composition remained essentially unchanged between 1 day and 74 years of age. The total amount of fatty acid bound to PLP was not altered in any of the pathological cases examined. However, in the peroxisomal disorder adrenoleukodystrophy, the proportions of saturated and, to a lesser extent, monounsaturated VLCFA bound to PLP were increased at the expense of oleic acid. Smaller, but significant, changes were observed in adrenomyeloneuropathy. The reduction in the levels of oleic acid was also observed in two other peroxisomal disorders, the cerebrohepatorenal (Zellweger) syndrome and neonatal adrenoleukodystrophy, as well as in the lysosomal disorder Krabbe globoid cell leukodystrophy. However, in these disorders, the decrease in oleic acid occurred at the expense of stearic acid, and not VLCFA. The results indicate that, although a characteristic PLP fatty acid pattern is normally maintained, changes in the acyl chain pool can ultimately be reflected in the fatty acid composition of the protein. The altered PLP-acyl chain pattern in peroxisomal disorders may contribute to the pathophysiology of these devastating disorders.     

冷冻干燥条件下酿酒酵母细胞脂肪酸组成变化的研究

以气相色谱法测定酿酒酵母(Saccharomyces cereuisiae) F159细胞膜类脂中脂肪酸的组成。结果表明,在低温干燥条件下,酿酒酵母细胞能自身调节脂肪酸的不饱和度,出现C_(16:1)脂肪酸含量增加,C_(16:0)脂肪酸含量略有所增,而C_(18:0)脂肪酸含量却有下降,不饱和直链脂肪酸之和与饱和直链脂肪酸之和的比值增加。说明这些变化使酿酒酵母细胞膜保持流动状态而维持细胞的稳定性和活性。初步探讨了冷冻干燥对酿酒酵母细胞脂肪酸组成的影响,为进一步探索和研究微生物抗冷冻干燥生理生化机制提供了依据。     

Steroids,fatty acids and ceramide from the mushroom Stropharia rugosoannulata Farlow apud Murrill

Stropharia rugosoannulata Farlow apud Murrill is an edible mushroom. Phytochemical investigation of the sporophore of Stropharia rugosoannulata resulted in isolation and identification of 16 compounds, including steroids (1-6), steroidal saponins (7), fatty acids (8–10), alkanes (11), ceramides (12), esters (13), pyrimidines (14), vitamins (15) and flavonoids (16). The structure elucidation of isolated compounds was achieved on the basis of NMR and mass spectral data. Compounds 4–16 were isolated for the first time from this genus and their chemotaxonomic significance was discussed. The isolation of steroids (4–5) and ceramides (12) might be used as chemotaxonomic markers for the genus of Stropharia.     

Selective ϖ-1 oxidation of fatty acids by CYP147G1 from Mycobacterium marinum

Background

Cyp147G1 is one of 47 cytochrome P450 encoding genes in Mycobacterium marinum M, a pathogenic bacterium with a high degree of sequence similarity to Mycobacterium tuberculosis and Mycobacterium ulcerans. Cyp147G1 is one of only two of these cyp genes which are closely associated with a complete electron transfer system.

Enhanced acetoin production by Bacillus amyloliquefaciens through improved acetoin tolerance

Acetoin production by Bacillus amyloliquefaciens was used as a model of product feedback to develop a strategy to enhance the production of acetoin. To enhance the resistance of B. amyloliquefaciens to acetoin, an acetoin-tolerant mutant E-11 was screened by using adaptive evolution with acetoin stress as the selection pressure. When compared with the parent FMME044, the mutant E-11 exhibited superior fermentation performance as follows: (1) the mutant E-11 exhibited increased tolerance to high concentration of acetoin, and the specific growth rate was 265.2% higher than that of the parent FMME044 in medium containing 80 g/L acetoin; (2) acetoin production by the mutant E-11 reached 71.5 g/L at 44 h when cultured in a 7-L fermentor with 173 g/L glucose, and the acetoin concentration and productivity of the mutant E-11 were 39.6% and 14.4% higher than those of the parent FMME044, respectively; (3) the unsaturated fatty acid contents in the mutant E-11 were 64.8%, 37.8%, and 18.4% higher than those in the parent FMME044 when cultured in 0, 40, and 60 g/L acetoin, whereas the saturated fatty acid contents in the mutant E-11 were 9.5%, 13.9%, and 14.1% lower than those in the parent FMME044, respectively.     

两种海桐属植物种子油脂肪酸组成的分析评价

采用有机溶剂抽提了海桐属 2种植物 (海桐和皱叶海桐 )的籽油 ,使用气相色谱法 (GC)分析鉴定了其油脂的脂肪酸组分。 2种籽油均含有 6种脂肪酸 ,主要脂肪酸成分均为软脂酸 (C16∶0 )和油酸 (C18∶1)。其含量 ( % )分别为 :软脂酸 (C16∶0 ) 2 9.66,3 4 .72 ;油酸 (C18∶1) 66.4 3 ,62 .54。这两种油脂中 ,单不饱和脂肪酸油酸占优势 ,因而品质优良。提示海桐属植物籽油可作为保健型食用油研究和开发利用     

Effects of weight loss on erythrocyte membrane composition and fluidity in overweight and moderately obese women

A previous study showed chemical and physical impairment of the erythrocyte membrane of overweight and moderately obese women. The present study investigated the effects of a low-calorie diet (800 kcal/day deficit for 8 weeks) on erythrocyte membrane properties in 70 overweight and moderately obese (body mass index, 25-33 kg/m²) normotensive, nondiabetic women. At the end of dietary intervention, 24.3% of women dropped out, 45.7% lost less than 5% of their initial weight (Group I) and only 30% of patients lost at least 5% of their initial body weight (Group II). Group I showed no significant changes in erythrocyte membrane composition and function. The erythrocyte membranes of Group II showed significant reductions in malondialdehyde, lipofuscin, cholesterol, sphingomyelin, palmitic acid and nervonic acid and an increase in di-homo-γ-linolenic acid, arachidonic acid and membrane fluidity. Moreover, Group II showed an improvement in total cholesterol, low-density lipoprotein cholesterol, glycemia and insulin resistance. These changes in erythrocyte membrane composition could reflect a virtuous cycle resulting from the reduction in insulin resistance associated with increased membrane fluidity that, in turn, results in a sequence of metabolic events that concur to further improve membrane fluidity.     

植物种子油合成的调控与遗传修饰

植物种子油含有多种脂肪酸,是一种重要的种子贮藏化舍物。种子油既是人类的食品,又是重要的工业原料。代谢物组学的发展加深了对种子油生物合成途径的全景式认识,应用基因工程改良种子油品质和价值的研究已取得长足的进展。本文分析了种子油及脂肪酸合成调控机制的复杂性,论述了转基因提高种子油及高营养品质脂肪酸含量和培育能大量合成积累工业用脂肪酸的油料作物的技术策略、存在问题和发展前景。