| 1. |
- Feng, Dan, et al.
(författare)
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Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression
- 2010
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Curcumin is a polyphenol and the one of the principle curcuminoids of the spice turmeric. Its antioxidant, anti-cancer and anti-inflammatory effects have been intensively studied. Previous in vivo studies showed that administration of curcumin also decreased cholesterol levels in the blood, and the effects were considered to be related to upregulation of LDL receptor. However, since plasma cholesterol levels are also influenced by the uptake of cholesterol in the gut, which is mediated by a specific transporter Niemann-Pick Cl-like 1 (NPC1L1) protein, the present study is to investigate whether curcumin affects cholesterol uptake in the intestinal Caco-2 cells. Methods: Caco-2 cells were cultured to confluence. The micelles composed of bile salt, monoolein, and C-14-cholesterol were prepared. We first incubated the cells with the micelles in the presence and absence of ezetimibe, the specific inhibitor of NPC1L1, to see whether the uptake of the cholesterol in the cells was mediated by NPC1L1. We then pretreated the cells with curcumin at different concentrations for 24 h followed by examination of the changes of cholesterol uptake in these curcumin-treated cells. Finally we determined whether curcumin affects the expression of NPC1L1 by both Western blot analysis and qPCR quantification. Results: We found that the uptake of radioactive cholesterol in Caco-2 cells was inhibited by ezetimibe in a dose-dependent manner. The results indicate that the uptake of cholesterol in this study was mediated by NPC1L1. We then pretreated the cells with 25-100 mu M curcumin for 24 h and found that such a treatment dose-dependently inhibited cholesterol uptake with 40% inhibition obtained by 100 mu M curcumin. In addition, we found that the curcumin-induced inhibition of cholesterol uptake was associated with significant decrease in the levels of NPC1L1 protein and NPC1L1 mRNA, as analyzed by Western blot and qPCR, respectively. Conclusion: Curcumin inhibits cholesterol uptake through suppression of NPC1L1 expression in the intestinal cells.
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| 2. |
- Haugaard, Steen B., et al.
(författare)
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Skeletal muscle structural lipids improve during weight-maintenance after a very low calorie dietary intervention
- 2009
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The objective was to investigate in a group of obese subjects the course in skeletal muscle phospholipid (SMPL) fatty acids (FA) during a 24-weeks weight maintenance program, which was preceded by a successful very low calorie dietary intervention (VLCD). Special focus was addressed to SMPL omega-3 FA, which is a lipid entity that influences insulin action. Methods: Nine obese subjects (BMI = 35.7 +/- 1.0 kg/m(2)), who had completed an 8 weeks VLCD (weight-loss = -9.7 +/- 1.6 kg, P < 0.001), had obtained skeletal muscle biopsies (vastus lateralis) before and after a dietician-guided 24-weeks weight-maintenance program (-1.2 +/- 1.5 kg, P = ns). SMPL FA composition was determined by gas liquid chromatography. During the preceding VLCD, insulin sensitivity (HOMA-IR) and glycemic control (HbA1c) improved but no change in SMPL omega-3 FA was observed. During the weight-maintenance program five subjects received the pancreas lipase inhibitor Orlistat 120 mg t.i.d. versus placebo. Results: HOMA-IR and HbA1c stabilized and SMPL total omega-3 FA, docosahexaenoic acid and ratio of n-3/n-6 polyunsaturated FA increased by 24% (P < 0.01), 35% (P < 0.02) and 26% (P < 0.01), respectively, whereas saturated and monounsaturated FA did not change. Plasma total-cholesterol and LDL-cholesterol, which decreased during the VLCD, reverted to pre-VLCD levels (P < 0.01). Orlistat therapy was associated with weight-loss (P < 0.05), trends for better glycemic control (P = 0.15) and greater increase in SMPL docosahexaenoic acid (P = 0.12) but similar reversal of plasma cholesterols compared to placebo. Conclusion: The data are consistent with the notion that greater SMPL omega-3 FA obtained during a weight-maintenance program may play a role for preserving insulin sensitivity and glycemic control being generated during a preceding VLCD.
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| 3. |
- Jiang, Jingting, et al.
(författare)
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Increased plasma apoM levels in the patients suffered from hepatocellular carcinoma and other chronic liver diseases
- 2008
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine plasma apolipoprotein M ( apoM) levels and other lipid profiles in hepatocellular carcinoma ( HCC) patients compared to other chronic liver diseases and normal subjects. Materials and methods: 36 HCC, 68 chronic hepatitis, 29 liver cirrhosis patients and 64 normal controls were subjected in the present study. Serum lipids, lipoproteins, apolipoprotein AI ( apoAI) and apoB were determined by the conventional methods. Plasma apoM levels were semiquantitatively determined by both dot- blotting and western blotting analysis. Results: Serum levels of triglycerides ( TG), HDL- cholesterol, apoAI and lipoprotein ( a) ( Lp( a)) were significantly lower in the HCC patients than in the normal subjects, whereas there were no obvious differences on serum total cholesterol, LDL- cholesterol and apoB between HCC patients and normal subjects. However, plasma apoM levels in HCC patients were significantly increased than those in the normal subjects, but lower than those in the chronic hepatitis and cirrhosis patients. Conclusion: It is concluded that serum TG, apoAI, HDL- C and Lp( a) were significantly decreased in HCC patients than in controls, whereas plasma apoM levels were significantly increased in the HCC patients. Decreased serum TG, apoAI, HDL- C and Lp( a) may reflect the liver damage in HCC patients, whereas the clinical significance of increased plasma apoM levels in relation to HCC is not clear.
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| 4. |
- Jiang, Jingting, et al.
(författare)
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Influence of liver cancer on lipid and lipoprotein metabolism
- 2006
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC) is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx) that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL). Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG), cholesterol, free fatty acids (FFA), HDL, low-density lipoproteins (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (apoAI) and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a) might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents.
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| 5. |
- Luo, Guanghua, et al.
(författare)
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Apolipoprotein M
- 2004
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 3
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Forskningsöversikt (refereegranskat)abstract
- Apolipoprotein M (apoM) is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL) in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP) and low-density lipoproteins (LDL). Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse). Human apoM cDNA (734 base pairs) encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that apoM is only expressed in liver and in kidney and small amounts are found in fetal liver and kidney. In situ apoM mRNA hybridization demonstrates that apoM is exclusively expressed in the hepatocytes and in the tubule epithelial cells in kidney. Expression of apoM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF) and leptin in vivo and/or in vitro. It has been demonstrated that apoM expression is dramatically decreased in apoA-I deficient mouse. Hepatocyte nuclear factor-1alpha (HNF-1alpha) is an activator of apoM gene promoter. Deficiency of HNF-1alpha mouse shows lack of apoM expression. Mutations in HNF-1alpha (MODY3) have reduced serum apoM levels. Expression of apoM is significantly decreased in leptin deficient (ob/ob) mouse or leptin receptor deficient (db/db) mouse. ApoM concentration in plasma is positively correlated to leptin level in obese subjects. These may suggest that apoM is related to the initiation and progression of MODY3 and/or obesity.
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| 6. |
- Luo, Guanghua, et al.
(författare)
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Expression and localization of apolipoprotein M in human colorectal tissues
- 2010
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been well documented that apolipoprotein M (apoM) is principally expressed in the liver and kidney. However we found that there was weak apoM expression in other tissues or organs too, which could not be ignored. In the present study, we therefore examined apoM expression in human colorectal tissues including cancer tissues, cancer adjacent normal tissues, polyp tissues and normal mucosa as well as inflammatory mucosa. Methods: Tissue samples were collected from patients who underwent surgical resection or endoscopic examination. ApoM mRNA levels were determined by the real-time RT-PCR and apoM protein mass were examined by the immunohistochemistry. Results: ApoM protein can be detected in all colorectal tissues. However, apoM protein mass were significantly lower in the cancer tissues than its matched adjacent normal tissues, polyp tissues, normal mucosa and inflammatory mucosa. In parallel, apoM mRNA levels in the colorectal cancer tissues (0.0536 +/- 0.0131) were also significantly lower than those in their adjacent normal tissues (0.1907 +/- 0.0563) (P = 0.033). Interestingly, apoM mRNA levels in colorectal cancer tissues were statistic significant higher in the patients with lymph node metastasis than the patients without lymph node metastasis (P = 0.008). Patients under Dukes' C and D stages had much higher apoM mRNA levels than patients under Dukes' A and B stages (P = 0.034). Conclusion: It is concluded that apoM could also be expressed in human colorectal tissues besides liver and kidney. ApoM mRNA levels in the colorectal cancer tissues were significantly increased in the patients with lymph node metastasis. Whether increased apoM expression in the patients with lymph node metastasis being related to patients' prognosis and the physiopathological importance of apoM expression in colorectal tissues need further investigation.
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| 7. |
- Luo, Libo, et al.
(författare)
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Impaired plasma lipid profiles in acute hepatitis
- 2010
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The present study examined plasma lipid profiles in thirty patients suffered from acute viral hepatitis. Patients' blood samples were collected at both the debut and recovery of diseases. Thirty sex and age matched normal subjects were included as controls. Plasma total triglycerides (TG), total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), lipoprotein (a) (Lp(a)), blood coagulation status including prothrombin complex activity and activated partial tromboplastin time (APTT), and hepatic functions were determined by the automatic biochemical analytical instrument. It demonstrated that plasma levels of total cholesterol, HDL-C and apoAI were significantly lower in the patients at the acute phase of hepatitis than those in normal subjects, whereas plasma levels of TG and LDL-C were obviously higher in the patients than in normal subjects (P < 0.05). Moreover, we demonstrated that patients' plasma levels of total cholesterol, LDL-C, HDL-C and apoAI were lower at the active phase of the diseases than at the recovering phase, which indicating that acute liver damage could significant influence lipid metabolism in vivo. No pathological changes of blood coagulation status occurred in these patients during the study as all selected patients had moderate hepatitis. It may conclude that examinations of plasma lipid profile could be considered as a clinical index to reflect liver damage in the active phase of hepatitis.
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| 8. |
- Ohlsson, Lena, et al.
(författare)
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Long term effects on human plasma lipoproteins of a formulation enriched in butter milk polar lipid.
- 2009
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 8:Oct 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sphingolipids (SL), in particular sphingomyelin (SM) are important components of milk fat polar lipids. Dietary SM inhibits cholesterol absorption in rats (Nyberg et al. J Nutr Biochem. 2000) and SLs decrease both cholesterol and TG concentrations in lipid- and cholesterol fed APOE*3Leiden mice (Duivenvoorden et al. Am J Clin Nutr. 2006). This human study examines effects of a butter milk formulation enriched in milk fat globule membrane material, and thereby in SLs, on blood lipids in healthy volunteers. In a four week parallel group study with 33 men and 15 women we examined the effects of an SL-enriched butter milk formulation (A) and an equivalent control formulation (B) on plasma lipid levels. Plasma concentrations of HDL and LDL cholesterol, triacylglycerols (TG), apolipoproteins AI and B, and lipoprotein (a) were measured. The daily dose of SL in A was 975 mg of which 700 mg was SM. The participants registered food and drink intake four days before introducing the test formula and the last four days of the test period. RESULTS: A daily increase of SL intake did not significantly influence fasting plasma lipids or lipoproteins. In group B TG, cholesterol, LDL, HDL and apolipoprotein B concentrations increased, however, but not in group A after four weeks. The difference in LDL cholesterol was seen primarily in women and difference in TG primarily in men. No significant side effects were observed. CONCLUSION: The study did not show any significant decrease on plasma lipids or lipoprotein levels of an SL-enriched formulation containing 2-3 times more SL than the normal dietary intake on cholesterol, other plasma lipids or on energy intake. The formulation A may, however, have counteracted the trend towards increased blood lipid concentrations caused by increased energy intake that was seen with the B formulation.
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| 9. |
- Persson, Jenny, et al.
(författare)
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Cytokine response to lipoprotein lipid loading in human monocyte-derived macrophages
- 2006
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 5:17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Macrophage foam cell formation is a prominent feature of human atherosclerotic plaques, usually considered to be correlated to uptake of and inflammatory response to oxidized low density lipoproteins (OxLDL). However, there are alternative pathways for formation of macrophage foam cells and the effect of such lipid loading on macrophage function remains to be fully characterized. In the present study we investigated basal and inducible cytokine expression in primary human macrophages either loaded with triglycerides through incubation with very low density lipoproteins (VLDL) or with cholesterol through incubation with aggregated LDL (AgLDL). We then analyzed how foam cell lipid content affected secretion of three pro-inflammatory cytokines: interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and of one chemokine: interleukin-8 (IL-8), all of which are considered pro-inflammatory, pro-atherosclerotic, and are expressed by cells in atherosclerotic tissue. RESULTS: Formation of triglyceride-loaded foam cells resulted in a four-fold increase in basal IL-1beta secretion, whereas cholesterol loading lacked significant effect on IL-1beta secretion. In contrast, secretion of TNF-alpha and IL-6 decreased significantly following both cholesterol and triglyceride loading, with a similar trend for secretion of IL-8. Lipid loading did not affect cell viability or expression of caspase-3, and did not significantly affect macrophage ability to respond to stimulation with exogenous TNF-alpha. CONCLUSION: Lipid loading of primary human macrophages resulted in altered cytokine secretion from cells, where effects were similar regardless of neutral lipid composition of cells. The exception was IL-1beta, where triglyceride, but not cholesterol, lipid loading resulted in a stimulation of basal secretion of the cytokine. It is apparent that macrophage cytokine secretion is affected by lipid loading by lipoproteins other than OxLDL. As both VLDL and AgLDL have been found in the vessel wall, macrophage cytokine response to uptake of these lipoproteins may have a direct effect on atherosclerotic development in vivo. However, macrophage neutral lipid amount and composition did not affect cellular activation by exogenous TNF-alpha, making it likely that lipoprotein lipid loading can affect foam cell cytokine secretion during basal conditions but that the effects can be overruled by TNF-alpha during acute inflammation.
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| 10. |
- Skoog, Maria, et al.
(författare)
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Lipid synthesis and secretion in HepG2 cells is not affected by ACTH
- 2010
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein B (apoB) containing lipoproteins, i.e. VLDL, LDL and Lp(a), are consequently lowered by ACTH treatment in humans. This is also seen as reduced plasma apoB by 20-30% and total cholesterol by 30-40%, mostly accounted for by a decrease in LDL-cholesterol. Studies in hepatic cell line (HepG2) cells showed that apoB mRNA expression is reduced in response to ACTH incubation and is followed by a reduced apoB secretion, which may hypothesize that ACTH lowering apoB containing lipoproteins in humans may be mediated by the inhibition of hepatic apoB synthesis. This was recently confirmed in vivo in a human postprandial study, where ACTH reduced transient apoB48 elevation from the small intestine, however, the exogenic lipid turnover seemed unimpaired. In the present study we investigated if lipid synthesis and/or secretion in HepG2 cells were also affected by pharmacological levels of ACTH to accompany the reduced apoB output. HepG2 cells were incubated with radiolabelled precursors ([C-14] acetate and [H-3] glycerol) either before or during ACTH stimuli. Cellular and secreted lipids were extracted with chloroform: methanol and separated by the thin layer chromatography (TLC), and [C-14] labelled cholesterol and cholesteryl ester and [H-3] labelled triglycerides and phospholipids were quantitated by the liquid scintillation counting. It demonstrated that ACTH administration did not result in any significant change in neither synthesis nor secretion of the studied lipids, this regardless of presence or absence of oleic acid, which is known to stabilize apoB and enhance apoB production. The present study suggests that ACTH lowers plasma lipids in humans mainly mediated by the inhibition of apoB synthesis and did not via the reduced lipid synthesis.
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