共轭型亚油酸对B（a）P诱导小鼠前胃癌的抑制作用

目的 研究共轭型亚油酸(CAL)的抑癌作用,并为进一步探讨CLA的抑癌机制提供线索。方法 以B(a)P诱导建立小鼠前胃癌动物模型,观察CLA对小鼠前胃癌促长阶段的抑制效果,共分5组,即色拉油阴性对照组、CLA阴性对照组、B(a)P阳性对照组、B(a)P CLA高剂量实验组和B(a)P CLA低剂量实验组。整个实验期为23周,检测细胞增殖、Pan-ras P21蛋白表达和氧化还原酶等指标。结果 短期给予CLA对B(a)P诱导的小鼠前胃癌促长阶段具有明显的抑制作用,B(a)P阳性对照组、B(a)P CLA高剂量实验组和B(a)P CLA低剂量实验组的肿瘤发生率分别为100％、60％和69％。其抑癌机制与其对细胞增殖活力的抑制及对机体GSH-Px、GST和SOD酶活力的诱导作用有关,而并不依赖于对Pan-ras P21蛋白表达的调节途径。结论 提示共轭型亚油酸是一种很有前途的化学预防剂,其抑癌机制可能与影响机体氧化还原体系密切相关。     

轭型亚油酸对B(a)P诱导小鼠前胃癌的抑制作用

目的　研究共轭型亚油酸 (CAL)的抑癌作用 ,并为进一步探讨CLA的抑癌机制提供线索。方法　以B(a)P诱导建立小鼠前胃癌动物模型 ,观察CLA对小鼠前胃癌促长阶段的抑制效果 ,共分 5组 ,即色拉油阴性对照组、CLA阴性对照组、B(a)P阳性对照组、B(a)P CLA高剂量实验组和B(a)P CLA低剂量实验组。整个实验期为 2 3周 ,检测细胞增殖、Pan rasP2 1蛋白表达和氧化还原酶等指标。结果　短期给予CLA对B(a)P诱导的小鼠前胃癌促长阶段具有明显的抑制作用 ,B(a)P阳性对照组、B(a)P CLA高剂量实验组和B(a)P CLA低剂量实验组的肿瘤发生率分别为 10 0 %、6 0 %和6 9 %。其抑癌机制与其对细胞增殖活力的抑制及对机体GSH Px、GST和SOD酶活力的诱导作用有关 ,而并不依赖于对Pan rasP2 1蛋白表达的调节途径。结论　提示共轭型亚油酸是一种很有前途的化学预防剂 ,其抑癌机制可能与影响机体氧化还原体系密切相关     

胃癌中P16、Rb蛋白表达分析

目的：研究p16和Rb基因表达产物P16、Rb蛋白与胃癌发生发展的关系及分析胃癌组织中p16、Rb基因表达的相互关系。方法：运用链霉菌抗生物素蛋白－过氧化物酶（S－P）免疫组织化学方法检测胃癌、癌前病变及正常胃粘膜组织中P16、RB蛋白的表达。结果：P16、Rb蛋白表达阳性率分别为：正常胃粘膜96．25％（77／80）、98．75％（79／80），不典型增生92．00％（46／50）、80．00％（40／50）；胃癌47．54％（58／122）、59．84％（73／122），胃癌组中P16、Rb蛋白表达低于正常胃粘膜及不典型增生（P＜0．05）；胃癌中P16、Rb蛋白的表达的相互关系；P16、Rb蛋白均为阳性15．56＄（14／90），P16、Rb蛋白 均为阴性7．78％（7／90），P17蛋白阳性、Rb蛋白阴性33．33％（30／90），P16蛋白阴性、Rb蛋白阳性43．33％（39／90），P16、Rb蛋白表达呈负相关（P＜0．05）。结论：P16、Rb蛋白表达缺失与胃癌的发生发展有关；胃癌组织中P16蛋白与Rb蛋白表达呈负相关关系。     

苯并[a]芘单独以及与雌二醇联合染毒对小鼠肺组织雌激素受体-β表达的影响

目的研究苯并[a]芘(benzo[a]pyrene,B[a]P)单独以及与雌二醇联合染毒对小鼠肺组织雌激素受体-β(estrogen receptor,ER-β)表达的影响,探讨雌激素在B[a]P所致小鼠肺癌中的作用。方法雌性昆明种小鼠125只,随机分为5组,每组25只,正常对照组(橄榄油灌胃和皮下注射)、雌二醇组(900μg/kg雌二醇)、B[a]P组(75μmol/kgB[a]P),B[a]P+高剂量雌二醇组(75μmol/kgB[a]P和900μg/kg雌二醇)和B[a]P+低剂量雌二醇组(75μmol/kgB[a]P和300μg/kg雌二醇),B[a]P灌胃,雌二醇皮下注射,灌胃和注射每周一次,持续8周,之后给予8周的恢复期,共16周。手术切除全肺,采用实时定量PCR(Realtime-PCR)和蛋白质印迹(Westernblotting)技术测定小鼠肺组织中ER-β的表达水平。结果B[a]P组和B[a]P+低剂量雌二醇组ER-β基因和蛋白的表达量明显高于正常对照组,差异有统计学意义(P<0.05)。雌二醇组ER-β基因表达高于正常对照组,差异有统计学意义(P<0.05)。B[a]P+高剂量雌二醇组和...     

胃癌组织中幽门螺杆菌感染与PCNA、COX-2蛋白表达的相关性

目的：探讨胃癌组织中增殖细胞核抗原（PCNA）、环氧合酶-2（COX-2）蛋白的表达及其与幽门螺杆菌感染的关系。方法：应用Warthin—Starry银染色观察胃癌组织中幽门螺杆菌（HP）感染情况、免疫组化染色检测胃癌中PCNA、COX-2蛋白的表达情况,并与慢性胃炎、胃黏膜上皮内瘤变标本检测结果相比较。结果：胃癌、慢性胃炎和胃黏膜上皮内瘤变组织中HP感染率分别为：84．5％、42．9％、66．7％;PCNA阳性表达率分别86．2％、47．6％、72．2％;COX一2阳性表达率为84．5％、28．6％、72．2％。在同一病变中HP阳性组PCNA、COX-2阳性表达率高于HP阴性组,胃癌组有显著差异（Fisher’s ExaCt Test：前者P=0．000,后者P=-0．025）。胃癌中HP感染与PCNA与COX-2蛋白表达呈正相关（r=0．521。P=0．000及r=0．342,P＝0．009）。结论：胃癌组织中PCNA与COX-2蛋白表达及HP感染共同参与胃癌的发生、发展。     

小鼠前胃癌诱导过程中组织学与脂质过氧化

诱导小鼠前胃癌的化学物有多种 ,如苯并 (a)芘 [B(a)P]、甲基苄基亚硝胺、亚硝基肌氨酸乙酯等。其中用B(a)P诱导小鼠前胃癌的方法已经被多位学者用于抗癌物质的研究 ,证明抗癌物能抑制或延缓胃癌的发生〔1～ 4〕。为研究B(a)P诱导小鼠前胃癌过程中胃组织形态学的发展变化 ,本实验用B(a)P诱导小鼠前胃癌 ,观察胃组织形态学在胃癌形成过程中的变化。同时检测不同阶段血浆中丙二醛 (MDA)含量和超氧化物歧化酶 (SOD)活力 ,并探讨胃癌与脂质过氧化之间的关系。1　材料与方法1 1　实验动物和分组　昆明种雌性小白鼠 2 10只 ,体重 17～ 2 0g …     

幽门螺杆菌感染对胃癌组织miR-19a表达的影响

目的探讨幽门螺杆菌(Hp)感染对胃癌组织microRNA-19a(miR-19a)表达的影响。方法选择2018年5月-2020年5月在南阳医学高等专科学校第一附属医院接受手术治疗的135例胃癌患者,根据是否存在Hp感染,分为Hp阳性组(n=87)和Hp阴性组(n=48)。记录患者年龄、肿瘤直径、分化程度、TNM分期、浸润深度和淋巴结转移等临床特征。术前检测血清白细胞介素6(IL-6)、IL-8、肿瘤坏死因子α(TNF-α)、C-反应蛋白(CRP)水平。荧光定量PCR检测癌组织miR-19a水平,蛋白印迹法(WB)检测Ki67、周期蛋白依赖性激酶1(CDK1)、基质金属蛋白酶2(MMP-2)、金属蛋白酶组织抑制因子(TIMP-2)、核因子κB(NF-κB)和磷酸化NF-κB(p-NF-κB)蛋白表达。结果胃癌患者Hp阳性与肿瘤TNM分期、浸润深度和淋巴结转移有关(P0.05); Hp阳性组患者癌组织和癌旁组织中miR-19a水平均高于Hp阴性组(P0.05),且癌组织中miR-19a水平与肿瘤TNM分期、浸润深度和淋巴结转移有关(P0.05); Hp阳性组患者血清IL-6、IL-8、TNF-α和CRP水平均高于Hp阴性组(P0.05),癌组织中Ki67、CDK1、MMP-2、p-NF-κB/NF-κB蛋白均高于Hp阴性组(P0.05),TIMP-2蛋白低于Hp阴性组(P0.05)。结论 Hp感染可以促进miR-19a表达,激活NF-кB信号通路,促进胃癌细胞的增殖和侵袭,促进胃癌的恶性进展。     

共轭亚油酸对人胃腺癌细胞中环氧合酶的影响

目的采用体外细胞培养方法,研究不同浓度c9,t11-共轭亚油酸(CLA)对人胃腺癌细胞(SGC-7901)的亚油酸代谢途径中限速酶-环氧合酶(COX)表达的影响.方法采用逆转录聚合酶链反应(RT-PCR)和蛋白免疫印迹(Western blot)方法检测不同浓度c9,t11-CLA处理后的SGC-7901细胞中环氧合酶(COX)-1、(COX)-2mRNA和蛋白的表达.结果在200,100,50和25μmol/L浓度时,c9,t11-CLA均可下调COX-2 mRNA和蛋白的表达,与共轭亚油酸(CLA)浓度呈负相关;上调COX-1 mRNA的表达,并与CLA浓度呈正相关.结论 c9,t11-CLA的抗癌活性与其影响COX的表达有关.     

c9,t11-共轭亚油酸对巨噬细胞因子表达的影响

目的 研究c9，t11-共轭亚油酸(Conjugated linoleic acid，CLA)对C57小鼠巨噬细胞杀伤黑色索瘤细胞(B16-MB)能力的影响。方法用0，25，50，75，100μmol／L CLA处理巨噬细胞24h后，分别用MTT法检测CLA处理的巨噬细胞对B16-MB细胞的杀伤能力；RT-PCR方法检测C57小鼠巨噬细胞细胞因子IL-6、TNF-α和iNOS mRNA表达。结果 在100，75μmol／L CLA处理后，巨噬细胞对肿瘤的杀伤率分别为18％和14．5％：同时，IL-6、TNF-α和iNOS mRNA表达增加。结论 c9，tll-CLA增强C57小鼠巨噬细胞对B16-MB细胞的杀伤能力，并与其诱导IL-6、TNF-α和iNOS mRNA的表达有关。推测CLA发挥抗肿瘤作用可能与其参与机体免疫调节作用有关．     

共轭亚油酸对小鼠巨噬细胞杀伤肿瘤能力的影响

目的　研究c9,t11 共轭亚油酸 (CLA)对C5 7小鼠巨噬细胞杀伤黑色素瘤 (B16 MB)细胞能力的影响并探讨其可能机制。方法　用 0、2 5、5 0、75、10 0 μmol/LCLA处理巨噬细胞 2 4h后 ,分别用四甲基偶氮唑盐法检测CLA处理的巨噬细胞对B16 MB细胞的杀伤能力 ;逆转录聚合酶链式反应方法检测C5 7小鼠巨噬细胞细胞因子IL 6、TNF α和iNOSmRNA表达 ;免疫印迹法 (Westernblot)检测细胞外信号调节蛋白激酶 (Erk)的表达情况。结果　c9,t11 CLA处理后 ,巨噬细胞对肿瘤抑制率随剂量的升高而升高 ,同时 ,白细胞介素 (IL 6 )、肿瘤坏死因子 (TNF α)和一氧化氮合酶 (iNOS)mRNA表达增加 ;Erk的表达下降。结论　c9,t11 CLA增强C5 7小鼠巨噬细胞对B16 MB细胞的杀伤能力 ,并与其诱导IL 6、TNF α和iNOSmRNA的表达有关。推测CLA发挥抗肿瘤作用可能与其参与机体免疫调节作用有关 ,并且CLA对小鼠巨噬细胞IL 6的影响与促裂原活化蛋白激酶 细胞外信号调节蛋白激酶途径无关     

Conjugated linoleic acid isomers and cancer

We reviewed the literature regarding the effects of conjugated linoleic acid (CLA) preparations enriched in specific isomers, cis9, trans11-CLA (c9, t11-CLA) or trans10, cis12-CLA (t10, c12-CLA), on tumorigenesis in vivo and growth of tumor cell lines in vitro. We also examined the potential mechanisms by which CLA isomers may alter the incidence of cancer. We found no published reports that examined the effects of purified CLA isomers on human cancer in vivo. Incidence of rat mammary tumors induced by methylnitrosourea was decreased by c9, t11-CLA in all studies and by t10, c12-CLA in just a few that included it. Those 2 isomers decreased the incidence of forestomach tumors induced by benzo (a) pyrene in mice. Both isomers reduced breast and forestomach tumorigenesis. The c9, t11-CLA isomer did not affect the development of spontaneous tumors of the intestine or mammary gland, whereas t10, c12-CLA increased development of genetically induced mammary and intestinal tumors. In vitro, t10, c12-CLA inhibited the growth of mammary, colon, colorectal, gastric, prostate, and hepatoma cell lines. These 2 CLA isomers may regulate tumor growth through different mechanisms, because they have markedly different effects on lipid metabolism and regulation of oncogenes. In addition, c9, t11-CLA inhibited the cyclooxygenase-2 pathway and t10, c12-CLA inhibited the lipooxygenase pathway. The t10, c12-CLA isomer induced the expression of apoptotic genes, whereas c9, t11-CLA did not increase apoptosis in most of the studies that assessed it. Several minor isomers including t9, t11-CLA; c11, t13-CLA; c9, c11-CLA; and t7, c11-CLA were more effective than c9, t11-CLA or t10, c12-CLA in inhibiting cell growth in vitro. Additional studies with purified isomers are needed to establish the health benefit and risk ratios of each isomer in humans.     

Dietary trans-10, cis-12 and cis-9,trans-11 conjugated linoleic acids induce apoptosis in the colonic mucosa of rats treated with 1,2-dimethylhydrazine

We have previously shown that a diet containing a mixture of conjugated linoleic acid (CLA) isomers reduces the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine (DMH). The present study examined which of the two main CLA isomers, trans-10,cis-12 CLA (t10c12) or cis-9,trans-11 CLA (c9t11), decreases colon tumor numbers and the mechanisms for this effect. Six-week-old, male Sprague-Dawley rats were intramuscularly injected with 15 mg/kg of DMH twice per week for 6 weeks and fed a control diet, 1% t10c12, or 1% c9t11 for 30 weeks. The experimental diets were initiated simultaneously with DMH injection. The tumor numbers were decreased and the apoptotic index was significantly increased in the colonic mucosa of the t10c12 and c9t11 groups, when the results were compared with those of the control group. The protein levels of Bcl-2 and cyclooxygenase-2 were significantly decreased, but Bax levels were increased in both of the CLA isomer groups. The thromboxane B(2) levels in colonic mucosa were substantially lower in the two CLA isomer groups than in the control group. However, there was no difference in these parameters between the CLA isomer groups. We have demonstrated that diets containing 1% t10c12 and c9t11 were equally effective in reducing tumor numbers and inducing apoptosis in the colonic mucosa of rats treated with DMH. These results indicate that Bcl-2 family protein levels are associated with CLA-induced apoptosis in the colonic mucosa of DMH-treated rats.     

Control of Rat Mammary Epithelium Proliferation by Conjugated Linoleic Acid

Past research showed that mammary gland morphogenesis in the pubescent rat was retarded by the feeding of conjugated linoleic acid (CLA). A major objective of the present study was to examine the proliferative activity and the expression of cell cycle regulatory proteins in the developing mammary epithelium of rats fed a mixture of CLA isomers (primarily as free fatty acid c9,t11-CLA and t10,c12-CLA) or a highly enriched natural source of c9,t11-CLA (as triacylglycerol in butterfat). In both experiments, the diets, with or without CLA, were started at weaning and continued for four weeks. The two CLA preparations were equally effective in suppressing bromodeoxyuridine labeling and the expression of cyclin D1 and cyclin A (determined by immunohistochemistry) in the terminal end buds and alveolar clusters of the mammary epithelium while it undergoes extensive ductal branching during pubescence. There was a trend of an increase, although not statistically significant, in the proportion of cells expressing the p16 and p27 cdk inhibitors. A separate experiment was designed to evaluate the effect of c9,t11-CLA (as a free fatty acid of >90% purity) treatment on the rate of proliferation of the mammary epithelium as the animal matured from weanling to adult. The bromodeoxyuridine labeling data indicated that the mammary epithelium appeared to lose its sensitivity to CLA control of proliferation as it completely filled the fat pad and became quiescent. These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status.     

Control of rat mammary epithelium proliferation by conjugated linoleic acid.

Past research showed that mammary gland morphogenesis in the pubescent rat was retarded by the feeding of conjugated linoleic acid (CLA). A major objective of the present study was to examine the proliferative activity and the expression of cell cycle regulatory proteins in the developing mammary epithelium of rats fed a mixture of CLA isomers (primarily as free fatty acid c9, t11-CLA and t10,c12-CLA) or a highly enriched natural source of c9,t11-CLA (as triacylglycerol in butterfat). In both experiments, the diets, with or without CLA, were started at weaning and continued for four weeks. The two CLA preparations were equally effective in suppressing bromodeoxyuridine labeling and the expression of cyclin D1 and cyclin A (determined by immunohistochemistry) in the terminal end buds and alveolar clusters of the mammary epithelium while it undergoes extensive ductal branching during pubescence. There was a trend of an increase, although not statistically significant, in the proportion of cells expressing the p16 and p27 cdk inhibitors. A separate experiment was designed to evaluate the effect of c9,t11-CLA (as a free fatty acid of > 90% purity) treatment on the rate of proliferation of the mammary epithelium as the animal matured from weanling to adult. The bromodeoxyuridine labeling data indicated that the mammary epithelium appeared to lose its sensitivity to CLA control of proliferation as it completely filled the fat pad and became quiescent. These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status.     

Conjugated linoleic acid isomers inhibit platelet-derived growth factor-induced NF-κB transactivation and collagen formation in human vascular smooth muscle cells

Background Atherosclerosis is characterized by extensive thickening of the arterial intima partially resulting from deposition of collagen by vascular smooth muscle cells (SMCs). Polyunsaturated fatty acids stimulate collagen formation through NF-κB activation. Aim of the study The present study aimed to explore the effect of conjugated linoleic acids (CLAs) which are known to inhibit NF-κB activation on collagen formation by SMCs. Methods Vascular SMCs were cultured with 50 μmol/l of CLA isomers (c9t11-CLA, t10c12-CLA) or linoleic acid (LA) and analysed for collagen formation and NF-κB p50 transactivation. Results Treatment with CLA isomers but not LA significantly reduced PDGF-stimulated [³H] proline incorporation into cell layer protein of SMCs without altering cell proliferation. Simultaneous treatment with the PPARγ inhibitor T0070907 abrogated this effect. Treatment of SMCs with c9t11-CLA and t10c12-CLA significantly reduced PDGF-induced NF-κB p50 activation. Conclusions CLA isomers inhibit PDGF-stimulated collagen production by vascular SMCs, which is considered to be a hallmark of atherosclerosis, in a PPARγ-dependent manner. Whether inhibition of the NF-κB-pathway is of significance for the reduction of collagen formation by CLA isomers needs further investigation.     

Daily intake of conjugated linoleic acid-enriched yoghurts: effects on energy metabolism and adipose tissue gene expression in healthy subjects

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. The present study was designed to determine whether 14-week CLA supplementation as triacylglycerols (3.76 g) with a 50 : 50 combination of the two main isomers (35 % cis-9, trans-11 and 35 % trans-10, cis-12) added to flavoured yoghurt-like products was able to alter body composition in healthy subjects and to alter the expression of several key adipose tissue genes (PPAR gamma, lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and uncoupling protein 2 (UCP-2)). Forty-four healthy subjects were randomly assigned to consume daily either a CLA-supplemented yoghurt-like product or a placebo yoghurt for 98 d. There were no significant effects of CLA supplementation on body weight, fat mass or free fat mass. Basal energy expenditure expressed as kg free fat mass increased significantly in the CLA group (123.3 (SEM 2.5) kJ/kg free fat mass per d on day 98 v. 118.7 (SEM 2.3) kJ/kg free fat mass per d on day 0, P = 0.03). PPAR gamma mRNA gene expression increased significantly with CLA supplementation (53 (SEM 20) %, P < 0.01) and a significant reduction in mRNA levels of HSL was observed ( - 42 (SEM 7) %, P = 0.01). The levels of UCP-2 and LPL mRNA were not affected. The present results suggest that a 98 d supplementation diet with a 50 : 50 mixture of the two CLA isomers cis-9, trans-11 and trans-10, cis-12 in a dairy product was unable to alter body composition, although a significant increase in the RMR has been induced. Moreover, changes in mRNA PPAR gamma and HSL in adipose tissue were recorded.     

Effects of conjugated linoleic acid (CLA) isomers on lipid levels and peroxisome proliferation in the hamster

Effects of the conjugated linoleic acid (CLA) isomers cis-9, trans-11 (c9,t11 CLA) and trans-10, cis-12 (t10,c12 CLA) on lipid metabolism and markers of peroxisome proliferation were investigated in hamsters fed on purified diets containing 30% energy as fat and 0.1 g cholesterol/kg for 8 weeks. Four groups (n 32 each) received diets without CLA (control), with a mixture of equal amounts of c9,t11 and t10,c12 CLA (CLA mix), with c9,t11 CLA, and with t10,c12 CLA. The total amount of CLA isomers was 1.5% energy of 6.6g/ kg diet. CLA was incorporated into glycerides and exchanged for linoleic acid in the diet. Compared with the control, the CLA mix and t10,c12 CLA decreased fasting values of LDL- (21 and 18% respectively) and HDL-cholesterol (8 and 11%), increased VLDL-triacylglycerol (80 and 61%, and decreased epididymal fat pad weights (9 and 16%), whereas c9,t11 CLA had no significant effects. All CLA preparations increased liver weight, but not liver lipids. However, the increase in liver weight was much less in the c9,t11 CLA group (8%) than in the other two groups (25%) and might have been caused by the small amount of t10,c12 CLA present in the c9,t11 CLA preparation. Liver histology revealed that increased weight was due to hypertrophy. Markers of peroxisome proliferation, such as cyanide-insensitive palmitoyl CoA oxidase (EC 1.3.3.6) and carnitine acetyl transferase (EC 2.3.1.7) activities, were not increased by CLA. Both c9,t11 CLA and t10,c12 CLA were incorporated into phospholipids and triacylglycerols, but t10,c12 CLA only about half as much as c9,t11 CLA. In addition, linoleic acid and linolenic acid concentrations were lower in lipids of the t10,c12 CLA group compared with the c9,t11 CLA group. These data suggest that t10,c12 CLA stimulated the oxidation of all C18 polyunsaturated fatty acids. The results indicate that the t10,c12 CLA isomer, and not the so-called natural CLA isomer (c9,t11), is the active isomer affecting lipid levels in hamsters.     

Effects of three different conjugated linoleic acid preparations on insulin signalling, fat oxidation and mitochondrial function in rats fed a high-fat diet

To investigate the effects of three different conjugated linoleic acid (CLA) preparations containing different ratios of CLA isomers on insulin signalling, fatty acid oxidation and mitochondrial function, Sprague-Dawley rats were fed a high-fat diet either unsupplemented or supplemented with one of three CLA preparations at 1 % of the diet for 8 weeks. The first CLA preparation contained approximately 30 % cis-9, trans-11 (c9, t11)-CLA isomer and 40 % trans-10, cis-12 (t10, c12)-CLA isomer (CLA-mix). The other two preparations were an 80:20 mix (c9, t11-CLA-mix) or a 10:90 mix of two CLA isomers (t10, c12-CLA-mix). Insulin resistance was decreased in all three supplemented groups based on the results of homeostasis model assessment and the revised quantitative insulin-sensitivity check index. The phosphorylation of insulin receptor substrate-1 on serine decreased in the livers of all three supplemented groups, while subsequent Akt phosphorylation increased only in the t10, c12-CLA-mix group. Both the c9, t11-CLA-mix and the t10, c12-CLA-mix increased the expression of hepatic adiponectin receptors R1 and 2, which are thought to enhance insulin sensitivity and fat oxidation. The c9, t11-CLA-mix increased protein and mRNA levels of PPAR alpha, acyl-CoA oxidase and uncoupling protein, which are involved in fatty acid oxidation and energy dissipation. The c9, t11-CLA-mix enhanced mitochondrial function and protection against oxidative stress by increasing the activities of cytochrome c oxidase, manganese-superoxide dismutase, glutathione peroxidase, and glutathione reductase and the level of GSH. In conclusion, all three CLA preparations reduced insulin resistance. Among them, the c9, t11-CLA-mix was the most effective based on the parameters reflecting insulin resistance and fat oxidation, and mitochondrial antioxidative enzyme activity in the liver.     

Trans10,cis12-18:2 is a more potent inhibitor of de novo fatty acid synthesis and desaturation than cis9,trans11-18:2 in the mammary gland of lactating mice

To investigate the effects of 2 conjugated linoleic acid (CLA) isomers and trans11-18:1 (TVA) on de novo lipogenesis and desaturation in liver and mammary gland, lactating mice were fed diets containing 3% canola oil (control) or 2% canola oil plus 1% stearic acid (SA), TVA, cis9,trans11 CLA (c9t11), or trans10,cis12 CLA (t10c12). In mammary tissue, TVA and CLA isomers reduced mRNA for acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) compared with control, but only c9t11 and t10c12 reduced mammary ACC activity. Of the 2 CLA isomers, t10c12 caused a greater reduction in mammary ACC activity. Hepatic ACC or FAS activity and mRNA abundance were not affected by dietary treatments. Feeding TVA, c9t11, or t10c12 reduced mammary stearoyl-CoA desaturase 1 (SCD) mRNA and activity. Reduction was greater due to feeding t10c12 compared with c9t11. Hepatic SCD mRNA was not affected by dietary treatments, but both CLA isomers depressed hepatic SCD activity. Results indicated that t10c12 is a more potent inhibitor of mammary lipogenesis and desaturation than is c9t11. A net gain of 77 and 1690 micro g of c9t11 in liver and mammary tissue, respectively, was found in the TVA-fed group over the control and SA-fed group. However, reduced mammary SCD mRNA or activity due to feeding TVA may indicate a limited capacity for desaturation of dietary TVA to c9t11 in vivo.