Identification of potential serum biomarkers of inflammation and lipid modulation that are altered by fish oil supplementation in healthy volunteers

Long chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) lower risk of coronary heart disease (CHD), but mechanisms are not well understood. We used proteomics to identify human serum proteins that are altered by n-3 LCPUFA. Such proteins could identify pathways whereby they affect CHD. Eighty-one healthy volunteers entered a double blind randomised trial to receive 3.5 g of fish oil or 3.5 g of high oleic sunflower oil daily. Serum was collected before and after 6 wk of intervention. Serum was analysed by proteomics using 2-DE. Proteins that were differentially regulated were identified by MS. We also analysed serum apolipoprotein A1 (apo A1), high-density lipoprotein (HDL) particle size and haptoglobin. Serum levels of apo A1, apo L1, zinc-alpha-2-glycoprotein, haptoglobin precursor, alpha-1-antitrypsin precursor, antithrombin III-like protein, serum amyloid P component and haemopexin were significantly downregulated (all p<0.05) by fish oil compared with high oleic sunflower oil supplementation. Fish oil supplementation caused a significant shift towards the larger, more cholesterol-rich HDL(2) particle. The alterations in serum proteins and HDL size imply that fish oil activates anti-inflammatory and lipid modulating mechanisms believed to impede the early onset of CHD. These proteins are potential diagnostic biomarkers to assess the mechanisms whereby fish oil protects against CHD in humans.     

Dehydroabietic acid, a phytochemical, acts as ligand for PPARs in macrophages and adipocytes to regulate inflammation

Obesity is characterized by an enhanced infiltration of macrophages to adipose tissues, which is closely associated with the low-grade inflammatory state and obesity-related pathologies such as type 2 diabetes and cardiovascular diseases. We showed here that dehydroabietic acid (DAA) is a potent PPARα/γ dual activator. Furthermore, we examined the anti-inflammatory effects of DAA in stimulated macrophages and in the coculture of macrophages and adipocytes. DAA significantly suppressed the production of proinflammatory mediators such as MCP-1, TNF-α, and NO in stimulated RAW 264 macrophages and in the coculture of RAW 264 macrophages and 3T3-L1 adipocytes. These results suggest that DAA is a valuable medicinal and food component for improving inflammatory changes associated with obesity-related diabetes.     

Docosahexaenoic acid: membrane properties of a unique fatty acid

Docosahexaenoic acid (DHA) with 22-carbons and 6 double bonds is the extreme example of an omega-3 polyunsaturated fatty acid (PUFA). DHA has strong medical implications since its dietary presence has been positively linked to the prevention of numerous human afflictions including cancer and heart disease. The PUFA, moreover, is essential to neurological function. It is remarkable that one simple molecule has been reported to affect so many seemingly unrelated biological processes. Although details of a molecular mode of action remain elusive, DHA must be acting at a fundamental level common to many tissues that is related to the high degree of conformational flexibility that the multiple double bonds have been identified to confer. One likely target for DHA action is at the cell membrane where the fatty acid is known to readily incorporate into membrane phospholipids. Once esterified into phospholipids DHA has been demonstrated to significantly alter many basic properties of membranes including acyl chain order and "fluidity", phase behavior, elastic compressibility, permeability, fusion, flip-flop and protein activity. It is concluded that DHA's interaction with other membrane lipids, particularly cholesterol, may play a prominent role in modulating the local structure and function of cell membranes.     

大肠埃希菌脂多糖对高脂饮食动物血脂及炎性反应的影响

目的研究大肠埃希菌脂多糖对高脂饮食兔血脂和炎性反应的影响。方法给含0．5％胆固醇的饲料,3周后,分别在第4、8、12周采用耳动脉内、颈部、腹股沟处肌肉注射大肠埃希菌脂多糖（LPS）,并设立正常组和单纯高脂组。16周后观察兔的一般状态,取血清检查血脂六项、C-反应蛋白和TNF—α,取耳动脉、颈动脉、主动脉弓、胸主动脉、腹主动脉、髂动脉、肝脏,放置4％多聚甲醛中过夜,常规行HE染色,检查血管病变和相关脏器病变情况。结果单纯高脂组血清中胆固醇和LDL-C较正常组增加,复合模型组动物血清中胆固醇和LDL-C均明显高于单纯高脂组,单纯高脂组TNF-α较正常组高,复合模型组TNF-α比单纯高脂组高。病理显示主动脉弓变化明显,复合模型组内膜斑块弥漫,而单纯高脂组内膜只出现单个小斑块,单纯高脂组和复合模型组心脏病变区别不大,均见轻度水肿和小脂肪滴;单纯模型组肝脏细胞轻度水肿,而复合模型组肝脏脂肪滴明显。结论大肠埃希菌脂多糖加重了内膜斑块的形成,加剧了血脂代谢的紊乱和炎性反应。     

A water-soluble extract from Cucurbita moschata shows anti-obesity effects by controlling lipid metabolism in a high fat diet-induced obesity mouse model

During the screening of a variety of plant sources for their anti-obesity activity, it was found that a water-soluble extract, named PG105, prepared from stem parts of Cucurbita moschata, contains potent anti-obesity activities in a high fat diet-induced obesity mouse model. In this animal model, increases in body weight and fat storage were suppressed by 8-week oral administration of PG105 at 500 mg/kg, while the overall amount of food intake was not affected. Furthermore, PG105 protected the development of fatty liver and increased the hepatic beta-oxidation activity. Results from blood analysis showed that the levels of triglyceride and cholesterol were significantly lowered by PG105 administration, and also that the level of leptin was reduced, while that of adiponectin was increased. To understand the underlying mechanism at the molecular level, the effects of PG105 were examined on the expression of the genes involved in lipid metabolism by Northern blot analysis. In the liver of PG105-treated mice, the mRNA level of lipogenic genes such as SREBP-1c and SCD-1 was decreased, while that of lipolytic genes such as PPARalpha, ACO-1, CPT-1, and UCP-2 was modestly increased. Our data suggest that PG105 may have great potential as a novel anti-obesity agent in that both inhibition of lipid synthesis and acceleration of fatty acid breakdown are induced by this reagent.     

PPARalpha gene expression is up-regulated by LXR and PXR activators in the small intestine

LXR, PXR, and PPARα are members of a nuclear receptor family which regulate the expression of genes involved in lipid metabolism. Here, we show the administration of T0901317 stimulates PPARα gene expression in the small intestine but not in the liver of both normal and FXR-null mice. The administration of LXR specific ligand GW3965, or PXR specific ligand PCN has the same effect, indicating that ligand-dependent activation of LXR and PXR, but not FXR, is responsible for the increased gene expression of PPARα in the mouse small intestine.     

去卵巢小鼠肠道菌群和血脂的变化

目的 探讨去卵巢对小鼠肠道菌群和血脂的影响。 方法 12只10周龄C57BL/6小鼠随机分为2组:假手术组(SHAM组)和去卵巢组(OVX组),每组6只,进行12周的喂养。每2周测定小鼠体质量,12周后测肝脏指数、血清三酰甘油水平和游离脂肪酸水平,小肠进行病理学检查,收集小鼠粪便并在Illumina MiSeq测序平台进行16S rRNA基因测序检测。 结果 与SHAM组相比,OVX组小鼠体质量、肝脏指数、血清三酰甘油水平和游离脂肪酸水平明显增加(t=4.745,t=15.090,t=11.140,t=4.038,均P结论 去卵巢小鼠血脂升高和肠道菌群失衡,提示肠道菌群可能是预防和治疗雌激素缺乏后脂质代谢异常的潜在靶点。     

Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism

On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen.     

Identification of a potential bottleneck in branched chain fatty acid incorporation into triacylglycerol for lipid biosynthesis in agronomic plants

In plant, unusual fatty acids are produced by a limited number of species. The industrial benefits of these unusual structures have led several groups to study their production in transgenic plants. Their research results led to very modest accumulation in seeds which was largely due to a limited knowledge of the lipid metabolism and fatty acid transfer in plants. More specifically we need to better understand the substrate specificity and selectivity of acyltransferases which are required for the incorporation of these unusual fatty acids into storage triacylglycerols. In our studies we have compared the incorporation of [¹⁴C] Oleoyl-CoA and Branched Chain Acyls-CoA into [³H] LPA-C18:1 by the Lysophosphatidic acid Acyltransferase (LPAAT) from developing seeds of agronomic plants (flax (Linum usitatissimum) and rape (Brassica napus)) and from a plant capable of producing high amounts of hydroxy fatty acids (castor bean (Ricinus communis)). Our assays demonstrate that LPAATs of the three studied species (1) incorporated preferentially oleyl-CoA, (2) could incorporate cyclopropane acyl-CoA when added alone as a substrate, however very weakly for rapeseed and castor bean seeds, (3) presented a low capacity to incorporate methyl branched acyl-CoA when added alone as a substrate (4) weakly incorporated cyclopropane acyl-CoA and was unable to incorporate methyl branched acyl-CoA when presented with an equimolar mix of oleyl-CoA and branched chain acyl-CoA. In all cases, the LPAAT had a low affinity for branched chain acyl-CoAs. The results show that LPAAT activity from agronomic plants constitutes a bottleneck for the incorporation of branched Chain acyl-CoA into PA.     

CD36调控脂质代谢作用及机制

脂质代谢是机体的重要代谢过程,其紊乱会导致众多疾病的发生。人类白细胞分化抗原36(cluster of differentiation 36,CD36)是一种在单核细胞、巨噬细胞、平滑肌细胞以及脂肪细胞高度表达的清道夫受体,是识别氧化低密度脂蛋白及长链脂肪酸的主要受体和转运蛋白,在脂质代谢过程中发挥着重要作用。本文综述了CD36基因及蛋白的结构和生理功能,阐述了清道夫受体CD36在脂质代谢过程中发挥的作用,并系统地总结了其级联AMPK、mTOR和MAPK信号通路参与脂质代谢过程的分子机制,为相关生物学研究提供了理论基础。     

The effects of chromium picolinate on glucose and lipid metabolism in running rats

BackgroundChromium picolinate (CrPic) is commonly used to reduce muscle fatigue after exercise. We aimed to elucidate the effects of CrPic on glucose and lipid metabolism and the expression of glucose transporters in exercised rats.MethodsForty-two male Wistar rats (8-week-old) were distributed into six groups (n = 7) as follows: Control, CrPic, Chronic Exercise (CEx), CEx + CrPic, Acute Exercise (AEx), and AEx + CrPic. CEx consists of 30 m/min, 30 min/day, and 5 days/week for 6 weeks. CrPic was supplemented at 400 μg elemental Cr/kg of diet for 6 weeks. In the AEx groups, animals were run on the treadmill at 30 m/min until exhaustion.ResultsCEx significantly lowered blood glucose (BG), total cholesterol (TC) and triglyceride (TG) levels, but elevated insulin concentration (IC), compared with control (P < 0.05). CEx significantly decreased the level of malondialdehyde (MDA) in the serum, liver, and muscle while AEx elevated it (P < 0.001 for all). CrPic significantly decreased BG, TC, TG levels, and increased IC with a remarkable effect in CEx rats (P < 0.01). CrPic also significantly reduced serum, liver, and muscle MDA levels (P < 0.001). Both AEx and CEx increased the expression of liver glucose transporter 2 (GLUT-2) and muscle GLUT-4 with the highest level in CEx rats (P < 0.05). Moreover, CrPic supplementation significantly elevated GLUT-2 and GLUT-4 expressions in the liver and muscle of sedentary and exercise-treated rats (P < 0.05).ConclusionCrPic improves various metabolic parameters and reduces oxidative stress in CEx and AEx rats by decreasing BG, TC, TG, MDA levels in serum and elevating GLUT-2 and GLUT-4 expression in the liver and muscle samples. The efficacy of CrPic was more pronounced in CEx rats.