Oxidised LDL up‐regulate CD36 expression by the Nrf2 pathway in 3T3‐L1 preadipocytes

D’Archivio, Massimo; Scazzocchio, Beatrice; Filesi, Carmelina; Varı̀, Rosaria; Maggiorella, Maria Teresa; Sernicola, Leonardo; Giovannini, Claudio; Masella, Roberta

doi:10.1016/j.febslet.2008.05.029

Cited by 44 publications

(43 citation statements)

References 37 publications

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“…This was related to the PPARg activation due to thiazolidinedione. What makes the present study different is that in our system PPARg was not activated, but oxLDL decreased its level also in agreement with our previous papers (56). Summarizing, we provided evidence that oxLDL lowered the sensitivity of adipocytes to insulin by impairing GLUT4 translocation and glucose uptake.…”

Section: Oxldl Impair Insulin Signaling In Adipocytes 839supporting

confidence: 78%

“…We have recently demonstrated that oxLDL can be actively taken up by 3T3-L1 preadipocytes through a CD36-mediated transport and that they can induce a significant increase in membrane receptor content. This enables oxLDL to interfere with the homeostasis of adipose tissue by altering the normal balance between differentiation and proliferation in preadipocytes, thus potentially contributing to the appearance of insulin resistance (55,56). Furthermore, oxLDL are a causative factor in lowering insulin sensitivity in cultured cells, possibly by inhibiting the signaling kinases responsible for the cellular response to insulin (57) and/or by activating the NF-kB complex, responsible for the regulation of genes involved in inflammation and cell survival (58).…”

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confidence: 99%

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Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

Scazzocchio

Varı̀

D’Archivio

et al. 2009

Journal of Lipid Research

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Oxidized LDL (oxLDL) increase in patients affected by type-2 diabetes, obesity, and metabolic syndrome. Likewise, insulin resistance, an impaired responsiveness of target tissues to insulin, is associated with those pathological conditions. To investigate a possible causal relationship between oxLDL and the onset of insulin resistance, we evaluated the response to insulin of 3T3-L1 adipocytes treated with oxLDL. We observed that oxLDL inhibited glucose uptake (240%) through reduced glucose transporter 4 (GLUT4) recruitment to the plasma membrane (270%), without affecting GLUT4 gene expression. These findings were associated to the impairment of insulin signaling. Specifically, in oxLDL-treated cells insulin receptor (IR) substrate-1 (IRS-1) was highly degraded likely because of the enhanced Ser 307 phosphorylation. This process was largely mediated by the activation of the inhibitor of kB-kinase b (IKKb) and the c-Jun NH 2 -terminal kinase ( JNK). Moreover, the activation of IKKb positively regulated the nuclear content of nuclear factor kB (NF-kB), by inactivating the inhibitor of NF-kB (IkBa). The activated NF-kB further impaired per se GLUT4 functionality. Specific inhibitors of IKKb, JNK, and NF-kB restored insulin sensitivity in adipocytes treated with oxLDL. These data provide the first evidence that oxLDL, by activating serine/threonine kinases, impaired adipocyte response to insulin affecting pathways involved in the recruitment of GLUT4 to plasma membranes (PM). This suggests that oxLDL might participate in the development of insulin resistance.-Scazzocchio, B., R. Varì, M. DʼArchivio, C. Santangelo, C. Filesi, C. Giovannini, and R. Masella. Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases. J. Lipid Res. 2009. 50: 832-845.

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Section: Oxldl Impair Insulin Signaling In Adipocytes 839supporting

confidence: 78%

mentioning

confidence: 99%

Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

Scazzocchio

Varı̀

D’Archivio

et al. 2009

Journal of Lipid Research

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“…A chronic inhibitory effect of apoB-lipoproteins/LDL was revealed ex vivo and in vitro as i ) plasma apoB was inversely related to in situ LPL activity and NEFA storage in women's WAT and ii ) LDL-differentiated 3T3-L1 adipocytes had decreased in situ LPL activity and NEFA storage. In addition, LDL had a direct acute inhibitory effect on TRL clearance as i ) LDL treatment of WAT for 4 h reduced the hydrolysis of synthetic TRL and increased the accumulation of LPL-derived to bind and be internalized by CD36 in mouse 3T3-L1 cells, causing the upregulation of preadipocyte factor-1 (Pref-1), whose suppression is key for the expression of peroxisome proliferator-activated receptor ␥ and adipocyte differentiation (21)(22)(23). Although higher oxidized LDL levels are likely more abundant in women with high apoB and their effects on adipocytes function cannot be excluded; our data demonstrate that LDL taken from women with both low and high apoB induced equivalent negative effects on WAT function ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms responsible for delayed plasma clearance of postprandial TRL by WAT are not fully understood. However, the uptake of LDL, albeit oxidized, by 3T3-L1 adipocytes was reported to increase cell proliferation and decrease cell differentiation (21)(22)(23). Moreover, multiple clinical studies have demonstrated that statin therapy, which reduces plasma concentrations of apoBlipoproteins, also improves plasma clearance of triglyceride (TG) (24)(25)(26)(27).…”

Section: Postprandial In Vivo Fat Clearancementioning

confidence: 99%

Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue

Bissonnette

Salem

Wassef

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org among the most common is reduced triglyceride-rich lipoprotein (TRL) clearance by peripheral tissue. White adipose tissue (WAT) is a major regulator of TRL clearance, particularly in the postprandial state ( 2-6 ). Following a meal, dietary fat enters the circulation in the form of chylomicrons, TRL with apoB48. Effi cient clearance of chylomicrons by WAT requires three sequential steps: i ) the hydrolysis of chylomicrons by endothelial lipoprotein lipase (LPL); ii ) the uptake of LPL-generated nonesterifi ed fatty acid (NEFA) by underlying adipocytes; and iii ) the utilization or storage of NEFA ( 3, 5 ). Dietary TRL remnants and NEFA that are not cleared by peripheral tissue are then taken up by the liver for utilization and resecretion as VLDL (TRL with apoB100).Healthy WAT is able to respond promptly to postprandial signals, such as insulin increasing the hydrolysis of dietary TRL and the uptake and storage of generated NEFA, thus reestablishing the homeostasis in plasma lipids. The storage versus the release of TRL-generated NEFA in human subcutaneous WAT was reported to be almost absent in the fasting state, to increase to 100% 1 h after the ingestion of a meal, and to decrease to 10-30% 6 h after the meal ( 5 ). Accordingly, delayed plasma clearance of postprandial TRL by WAT is believed to increase the infl ux of dietary TRL remnants and NEFA into nonadipose peripheral tissues, including muscle, pancreas, and liver, inducing lipotoxicity and insulin resistance ( 6-8 ). In the liver, this also leads to increased synthesis and secretion of VLDL, which further reduces chylomicron clearance due to competitive binding to LPL ( 9-14 ). Altogether, this increases the plasma concentrations of apoB-lipoproteins, which is measured as plasma apoB and represents mostly LDL particles (>90%) ( 14-16 ). Dysfunctional WAT is thus Postprandial hypertriglyceridemia is an independent risk factor for cardiometabolic disease ( 1 ). Many factors have been implicated in the etiology of hyperlipidemia;

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“…A study reported that hyperinsulinemia and impaired glycaemic control independent of lipid level were associated with increased in vivo LDL oxidation, as reflected by the higher prevalence of highly oxidized LDL [5]. Ox-LDL is reported to interfere with the homeostasis of adipose tissue by altering the normal balance between differentiation and proliferation in preadipocyte, which potentially contributes to the appearance of insulin resistance [38].…”

Section: Discussionmentioning

confidence: 99%

Circulating Oxidized Low Density Lipoprotein and Non-High Density Lipoprotein Cholesterol Concentrations in Metabolic Syndrome Egyptian Women Before and After Specific Nutritional Therapy

2012

Maced J Med Sci

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Aim: To investigate the relation between the metabolic syndrome (MetS), and oxidized low density lipoprotein (ox-LDL) and non-high density lipoprotein cholesterol (non-HDL-C), and to evaluate a dietary therapy composed of a balanced hypocaloric regimen plus a supplement prepared from whole wheat and tigernut flour (Cyperus Esculentus). Material and Methods:Forty two obese Egyptian female volunteers (their mean age was 47.76± 0.90) were given a low caloric balanced diet (900-1000 kcal) for 4 weeks, and then the supplement was used to replace Baladi bread during the next four weeks. The metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. Results:The prevalence rate of MetS was found to be 76.2%.The metabolic syndrome was significantly associated with higher levels of total cholesterol (T.cholesterol), LDL-C, ox-LDL and non HDL-C. Significant and sustained reduction in the levels of fasting blood glucose and HbA1c, normalization of lipid profile, and decrease in the levels of ox-LDL were observed after the end of the two periods of the dietary therapy. Conclusion:Metabolic syndrome is associated with higher levels of circulating ox-LDL and non-HDLC. The use of the dietary therapy composed of balanced hypocaloric regimen plus a supplement rich in antioxidants and anti-inflammatory components, reduced obesity and the risky biochemical markers of the MetS.

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Oxidised LDL up‐regulate CD36 expression by the Nrf2 pathway in 3T3‐L1 preadipocytes

Cited by 44 publications

References 37 publications

Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue

Circulating Oxidized Low Density Lipoprotein and Non-High Density Lipoprotein Cholesterol Concentrations in Metabolic Syndrome Egyptian Women Before and After Specific Nutritional Therapy

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