Increased lipid synthesis by liver slice in a superfusion system following raised glucose or insulin concentration

Summary The synthesis of lipid from¹⁴C-glucose and³H-alanine was measured from rat liver slices using a micro-superfusion technique that allows continuous monitoring of the perifusate output. Increase in substrate glucose results in prompt elevation of fatty acid synthesis. Insulin addition also produced an increased¹⁴C incorporation into lipid. The effects were independent. Both these factors may be active in the hypertriglyceridaemia of high carbohydrate intake or diabetes.

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Erhöhte Lipidsynthese von Leberschnitten in einem Superfusionssystem nach erhöhten Konzentrationen von Glucose und Insulin

Zusammenfassung An Rattenleberschnitten wurde mit einer Mikrosuperfusionstechnik, die eine dauernde Kontrolle des Perfusatflusses erlaubt, die Lipidsynthese aus¹⁴C-G-lucose und³H-Alanin gemessen. Eine Erhöhung des Glucosesubstrats führte zu einer sofortigen Steigerung der Fettsäuresynthese. Zugegebenes Insulin erzeugte ebenfalls einen erhöhten¹⁴C-Einbau in die Lipide. Beide Effekte waren unabhängig. — Diese beiden Faktoren können in der Hypertriglycerinämie nach hoher Kohlenhydrataufnahme oder beim Diabetes wirksam sein.

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Augmentation de la synthèse des lipides par des coupes de foie dans un système de superfusion après élévation de la concentration de glucose ou d'insuline

Résumé La synthèse des lipides à partir du¹⁴C-glucose et de la³H-alanine fut mesurée dans des tranches de foie de rat, en utilisant une technique de microsuperfusion qui permettait l'enregistrement continu du débit du périfusat. L'addition de glucose amena une hausse immédiate de la synthèse d'acide gras. L'addition d'insuline provoqua de même une augmentation de l'incorporation de¹⁴C dans les lipides. Les effets étaient indépendants. Ces deux facteurs pourraient être actifs dans l'hypertriglycéridémie après l'absorption importante d'hydrates de carbone ou dans l'état diabétique.

     

IRF5通过对巨噬细胞极化的调节影响脂质摄取及排出的探究

动脉粥样硬化（AS）是严重危害人类生命健康的一类慢性血管疾病,局部胆固醇的大量蓄积和炎症的发生是其主要原因。现已证明许多细胞因子通过调节巨噬细胞向M1及M2型的转化,影响巨噬细胞对脂质的摄取及排出。该文将阐述干扰素调节因子5（IRF5）是否通过调节巨噬细胞的极化而对巨噬细胞的脂质摄取及排出产生影响,从而为以IRF5为作用靶点治疗AS的可能性提供一些前期理论研究。     

Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity

Effector memory T cells (T_M) play a key role in the pathology of certain autoimmune disorders. The activity of effector T_M cells is under the control of Kv1.3 ion channels, which facilitate the Ca²⁺ influx necessary for T cell activation and function, i.e. cytokine release and proliferation. Consequently, the knock-down of Kv1.3 expression in effector T_M's may be utilized as a therapy for the treatment of autoimmune diseases. In this study we synthesized lipid unilamellar nanoparticles (NPs) that can selectively deliver Kv1.3 siRNAs into T_M cells in vitro. NPs made from a mixture of phosphatidylcholine, pegylated/biotinylated phosphoethanolamine and cholesterol were functionalized with biotinylated-CD45RO (cell surface marker of T_M's) antibodies via fluorophore-conjugated streptavidin (CD45RO-NPs). Incubation of T cells with CD45RO-NPs resulted into the selective attachment and endocytosis of the NPs into T_M's. Furthermore, the siRNA against Kv1.3, encapsulated into the CD45RO-NPs, was released into the cytosol. Consequently, the expression of Kv1.3 channels decreased significantly in T_M's, which led to a remarkable decrease in Ca²⁺ influx. Our results can form the basis of an innovative therapeutic approach in autoimmunity.     

Lipidomic profiling of bioactive lipids by mass spectrometry during microbial infections

Bioactive lipid mediators play crucial roles in promoting the induction and resolution of inflammation. Eicosanoids and other related unsaturated fatty acids have long been known to induce inflammation. These signaling molecules can modulate the circulatory system and stimulate immune cell infiltration into the site of infection. Recently, DHA- and EPA-derived metabolites have been discovered to promote the resolution of inflammation, an active process. Not only do these molecules stop the further infiltration of immune cells, they prompt non-phlogistic phagocytosis of apoptotic neutrophils, stimulating the tissue to return to homeostasis. After the rapid release of lipid precursors from the plasma membrane upon stimulation, families of enzymes in a complex network metabolize them to produce a large array of lipid metabolites. With current advances in mass spectrometry, the entire lipidome can be accurately quantified to assess the immune response upon microbial infection. In this review, we discuss the various lipid metabolism pathways in the context of the immune response to microbial pathogens, as well as their complex network interactions. With the advancement of mass spectrometry, these approaches have also been used to characterize the lipid mediator response of macrophages and neutrophils upon immune stimulation in vitro. Lastly, we describe the recent efforts to apply systems biology approaches to dissect the role of lipid mediators during bacterial and viral infections in vivo.     

维生素E对妊娠糖尿病患者血浆C-反应蛋白和血脂水平的影响

目的观察妊娠糖尿病(gestational diabetes mellitus,GDM)患者应用维生素E干预治疗前后血浆C-反应蛋白(CRP)、血脂水平的变化。方法选择符合诊断标准的妊娠糖尿病患者22例,随机分为观察组(n=11)和对照组(n=11),两组均制订个性化的饮食及运动计划并予皮下注射胰岛素,在此基础上观察组口服维生素E 30 mg/d。观察两组治疗前及治疗后2、4周血清CRP、血脂水平并进行比较。结果观察组应用维生素E治疗后2周血清CRP、总胆固醇、甘油三酯、低密度脂蛋白胆固醇浓度较治疗前均显著降低(P0.05),高密度脂蛋白较治疗前显著升高(P0.05),治疗后4周上述改变更为明显(P0.05);对照组治疗后上述指标与治疗前比较无明显变化(P0.05);治疗后2、4周两组上述指标比较差异均有统计学意义(P0.05)。结论维生素E能缓解GDM患者体内炎症反应并降低血脂浓度,从而改善GDM患者的临床症状及减少对胎儿的不良影响。     

正五聚蛋白3在多囊卵巢综合征中的作用研究进展

多囊卵巢综合征（PCOS）是育龄妇女常见的内分泌疾病，是女性不孕的主要原因之一。正五聚蛋白3（PTX3）是一类多功能蛋白质，具有一系列生物活性作用。PTX3参与调节胰岛素分泌及葡萄糖代谢、卵巢卵丘细胞功能、炎症因子活动、雄激素代谢、脂质吸收转运、内皮细胞功能，进而发挥改善胰岛素抵抗、促进卵泡发育与排卵、减弱慢性炎症反应、抑制雄激素水平、改善脂代谢异常和预防动脉粥样硬化及心血管疾病等作用，参与PCOS及其并发症的发生。本文就PTX3在PCOS及其并发症中的作用机制进行综述，以期为PCOS发病机制的深入研究及临床诊疗提供新的思路与方向。     

Opposite fates of fructose in the development of metabolic syndrome

This short review comments on the recently published work of Ishimoto et al regarding the opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice. The framework for the commentary is the preexisting background of epidemiological and experimental data regarding the association between ingestion of fructose, as present in sweetened beverages, and the development of metabolic syndrome. The work of Ishimoto et al clearly confirms the negative effect of fructose on lipid and glucose metabolism, independently from the amount of energy provided by the ingested sugar. It also confirms the absolute requirement of liver fructose metabolism, driven by fructokinase activity, in order to develop the full spectrum of metabolic syndrome alterations.     

Expression of 4-hydroxynonenal in the kidney of diabetic rats and the effect of probucol

Objective To investigate the expression of 4-hydroxynonenal (4-HNE) in the kidney of diabetic rats and the effect of probucol. Methods The rats were being intraperitoneal injected with STZ (60 mg/kg) to establish diabetic models. Then diabetic rats were randomly divided into diabetic group (group D, n＝24), probucol treated group (group P, n＝24). Normal rats were taken as control group (group C, n＝24). Rats in group P were treated by probucol (110 mg·kg-1·d-1); rats in group D and group C were given equal volume water instead. Scr, BUN, triglyceride (TG), total cholesterol (TC) and 24-hour urinary proteinin were measured at the 4th, 8th and 12th week. PAS staining and HE staining were used to evaluate the pathological changes of the kidney. The immunohistochemistry and Western blotting were used to detect the expression of 4-HNE in renal tissue. Results Levels of Scr, BUN, TG, TC and 24-hour urinary protein in group D were higher than those in group C at the 4th, 8th and 12th week(all P＜0.05); Levels of Scr, BUN, TG, TC and 24-huor urinary protein in group P were lower than those in group D at 4th, 8th and 12th week (all P＜0.05). The pathological changes of the kidney in group D were more serious than that in group P. The expression of 4-HNE in group Dwerehigher than group C at the 4th, 8th and 12th week (all P＜0.05); The expression of 4-HNE in the kidneys of group P decreased significantly compared to that of group D at the same time (P＜0.05). Conclusions As an indicator of lipid peroxidation, the expression of 4-HNE significantly increases in the kidney of diabetic rat. Probucol may protect the diabetic kidney through decreasing the expression of 4-HNE and the level of lipidperoxidation.     

Effects of Exogenous Melatonin on Myoglobinuric Acute Renal Failure in the Rats

Free oxygen radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). In this study, we aimed to investigate the effect of melatonin, a potent free radical scavenger, on the myoglobinuric ARF formed by injecting hypertonic glycerol intramuscularly (im). The rats were randomly divided into 4 Groups. Rats in Group 1 were given saline and those in Groups 2, 3, and 4 were injected with glycerol (10 mL/kg) im. Concomitant and 24 hours after glycerol injection Group 3 (5 mg/kg) and Group 4 (10 mg/kg) were administrated melatonin intraperitoneally. Forty‐eight hours after the glycerol injection, the blood and kidneys of the rats were taken under anesthesia. Kidney morphology and the levels of urea, creatinine and nitric oxide metabolites (NO_x) in the plasma and the enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in the kidney were determined. In both groups of melatonin administration, there was no protective effect of melatonin. Moreover, melatonin significantly decreased the level of NO. As a result, we suggest that the decreasing effect of melatonin on NO, which is a strong vasodilatator, may further increase the renal ischemia in this model. Thus, melatonin may have worsening rather than beneficial effects on myoglobinuric ARF.     

Effects of pomegranate extract supplementation on inflammation in overweight and obese individuals: A randomized controlled clinical trial

The study was designed to determine the effect of thirty days of pomegranate extract oral supplementation on plasma inflammatory and oxidative stress biomarkers as well as serum metabolic profiles, in overweight and obese individuals. In this randomized, double-blind, placebo-controlled study 48 obese and overweight participants were randomly assigned to receive either 1000 mg of pomegranate extract, or a placebo, daily for 30 days. At baseline, and after 30 days of treatment, anthropometric parameters, dietary intake, plasma concentrations of malondialdehyde, interleukin-6 and hyper sensitive-C reactive protein and levels of serum lipids, glucose and insulin were assessed. Thirty days of PE supplementation resulted in a significant decrease in mean serum levels of glucose, insulin, total cholesterol, LDL-C, and plasma MDA, IL-6 and hs-CRP. HDL-C significantly increased following the PE versus the PL intervention. Our study suggests that pomegranate extract consumption may reduce complications linked with obesity.