Oxidized LDL Modify the Human Adipocyte Phenotype to an Insulin Resistant, Proinflamatory and Proapoptotic Profile

Santiago‐Fernández, Concepción; Martín‐Reyes, Flores; Tomé, Mónica; Ocaña-Wilhelmi, Luis; Rivas-Becerra, Jose; Tatzber, Franz; Pursch, Edith; Tinahones, Francisco J.; Garcı́a-Fuentes, Eduardo; Garrido‐Sánchez, Lourdes

doi:10.3390/biom10040534

Cited by 17 publications

(14 citation statements)

References 71 publications

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“…In a recent study, Ampuero's team found that the levels of oxidized LDL cholesterol antibodies/HDL cholesterol were significantly higher in lean NAFLD patients [38]. When the body has elevated levels of oxidized LDL cholesterol antibodies, oxidized LDL cholesterol reduces insulin sensitivity by inhibiting signaling kinase and/or activating the nuclear factor-κB subunit 1 complex responsible for the cellular response to insulin, resulting in IR [39,40]. High oxidized LDL cholesterol levels will also increase the secretion of the proinflammatory adipocytokines TNF-α and IL6 [40], and the inflammatory response will further lead to IR, which will lead to lipid accumulation and form a vicious cycle [41].…”

Section: Discussionmentioning

confidence: 99%

“…When the body has elevated levels of oxidized LDL cholesterol antibodies, oxidized LDL cholesterol reduces insulin sensitivity by inhibiting signaling kinase and/or activating the nuclear factor-κB subunit 1 complex responsible for the cellular response to insulin, resulting in IR [39,40]. High oxidized LDL cholesterol levels will also increase the secretion of the proinflammatory adipocytokines TNF-α and IL6 [40], and the inflammatory response will further lead to IR, which will lead to lipid accumulation and form a vicious cycle [41]. In addition, previous studies have shown that in hepatic steatosis, an alteration in the activity of the transcription factors SREBP-1c and PPAR-alpha is observed.…”

Section: Discussionmentioning

confidence: 99%

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LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study

Zou

Zhong

et al. 2021

Lipids Health Dis

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Background Low-density lipoprotein to high density lipoprotein (LDL/HDL) cholesterol ratio has been reported to predict the risk of many metabolic diseases. However, the association between the LDL/HDL cholesterol ratio and nonalcoholic fatty liver disease (NAFLD) has not been established. Methods A longitudinal cohort design was adopted in this study; 9767 non-obese subjects without NAFLD were included and analyzed. The subjects were grouped according to the quintile of LDL/HDL cholesterol ratio. The cumulative incidence of NAFLD and the independent effect of the LDL/HDL cholesterol ratio on NAFLD during 5 years of follow-up were calculated using the Kaplan-Meier method and Cox proportional-hazards regression model. Results During the 5-year follow-up period, 841 subjects were diagnosed with new-onset NAFLD, and the 1-, 2-, 3-, 4-, and 5-year cumulative incidence rates of NAFLD were 1.16, 4.65, 8.33, 12.43, and 25.14%, respectively. In the multivariable-adjusted Cox proportional-hazards regression model, the LDL/HDL cholesterol ratio was significantly associated with the risk for NAFLD (HR: 1.66, 95% CI: 1.38–1.99, P trend< 0.001), especially among young people (HR: 3.96, 95% CI: 1.50–10.46, P interaction< 0.05). Additionally, receiver operating characteristic curve analysis showed that the LDL/HDL cholesterol ratio was better than HDL cholesterol and LDL cholesterol in predicting new-onset NAFLD. Conclusions LDL/HDL cholesterol ratio is an independent predictor of NAFLD in Chinese non-obese people with normal lipids, and its predictive value is higher than that of other lipoproteins. In clinical practice, the LDL/HDL cholesterol ratio can be used to identify people at high risk of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study

Zou

Zhong

et al. 2021

Lipids Health Dis

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“…In cultured murine adipocytes, oxLDLs inhibited the expression of leptin, an effect that was prevented by anti-CD36 antibodies and the ROS inhibitor N-acetylcysteine [ 160 ]; moreover, exposure to oxLDLs reduced the recruitment of glucose transporter 4 (GLUT4) to the plasma membrane, resulting in impaired insulin signaling [ 161 ]. Data obtained with human visceral fat from nonobese subjects strengthened this evidence, indicating that adipocytes exposed to oxLDLs assume an inflammatory phenotype with decreased leptin secretion, low insulin-induced glucose uptake, and altered expression of genes involved in apoptosis, autophagy, necrosis, and mitophagy [ 162 ].…”

Section: The Oxldl Signalingmentioning

confidence: 99%

Oxidized LDLs as Signaling Molecules

2021

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Levels of oxidized low-density lipoproteins (oxLDLs) are usually low in vivo but can increase whenever the balance between formation and scavenging of free radicals is impaired. Under normal conditions, uptake and degradation represent the physiological cellular response to oxLDL exposure. The uptake of oxLDLs is mediated by cell surface scavenger receptors that may also act as signaling molecules. Under conditions of atherosclerosis, monocytes/macrophages and vascular smooth muscle cells highly exposed to oxLDLs tend to convert to foam cells due to the intracellular accumulation of lipids. Moreover, the atherogenic process is accelerated by the increased expression of the scavenger receptors CD36, SR-BI, LOX-1, and SRA in response to high levels of oxLDL and oxidized lipids. In some respects, the effects of oxLDLs, involving cell proliferation, inflammation, apoptosis, adhesion, migration, senescence, and gene expression, can be seen as an adaptive response to the rise of free radicals in the vascular system. Unlike highly reactive radicals, circulating oxLDLs may signal to cells at more distant sites and possibly trigger a systemic antioxidant defense, thus elevating the role of oxLDLs to that of signaling molecules with physiological relevance.

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“…It is known that ox-LDL is uptaken by visceral in vitro-differentiated adipocytes, and its increase stimulates the proinflammatory profile of these visceral adipocytes [ 18 ]. These effects are mediated by the binding of ox-LDL to its receptors, the SRs.…”

Section: Introductionmentioning

confidence: 99%

“…The aims of this study were to analyze in human visceral adipocytes (a) whether morbid obesity modified SRs expression, (b) whether hypoxia could produce an increase of SRs expression, as we had previously demonstrated for ox-LDL [ 18 ], (c) the effect of hypoxia on inflammation markers and (d) whether ox-LDL could increase the inflammatory response produced by hypoxia.…”

Section: Introductionmentioning

confidence: 99%

Oxidized LDL Increase the Proinflammatory Profile of Human Visceral Adipocytes Produced by Hypoxia

et al. 2021

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Background: Little is known about the effects of hypoxia on scavenger receptors (SRs) levels in adipocytes. We analyzed the effect of morbid obesity and hypoxia on SRs and inflammation markers in human visceral adipocytes and whether ox-LDL modify the inflammatory profile produced by hypoxia. Methods: We studied in 17 non-obese and 20 subjects with morbid obesity (MO) the mRNA expression of HIF-1α, SRs (LOX-1, MSR1, CL-P1 and CXCL16), IL6 and TNFα in visceral adipocytes and the effect of hypoxia with or without ox-LDL on visceral in vitro-differentiated adipocytes (VDA). Results: HIF-1α, TNFα, IL6, LOX-1, MSR1 and CXCL16 expression in adipocytes was increased in MO when compared with those in non-obese subjects (p < 0.05). The expression of most of the inflammatory markers and SRs gene correlated with HIF-1α. In VDA, hypoxia increased TNFα, IL6, MSR1, CXCL16 and CL-P1 (p < 0.05) in non-obese subjects, and TNFα, IL6, MSR1 and CXCL16 (p < 0.05) in MO. Silencing HIF-1α prevented the increase of TNFα, IL6, LOX-1, MSR1, CL-P1 and CXCL16 expression (p < 0.05). The combination of hypoxia and ox-LDL produced higher TNFα expression (p = 0.041). Conclusions: Morbid obesity and hypoxia increased SRs and inflammatory markers in visceral adipocytes. In a hypoxic state, ox-LDL increased the proinflammatory response of visceral adipocytes to hypoxia.

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Oxidized LDL Modify the Human Adipocyte Phenotype to an Insulin Resistant, Proinflamatory and Proapoptotic Profile

Cited by 17 publications

References 71 publications

LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study

LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study

Oxidized LDLs as Signaling Molecules

Oxidized LDL Increase the Proinflammatory Profile of Human Visceral Adipocytes Produced by Hypoxia

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