Reciprocal regulation of inflammation and lipid metabolism by liver X receptors

Joseph, Sean B.; Castrillo, Antonio; Laffitte, Bryan; Mangelsdorf, David J.; Tontonoz, Peter

doi:10.1038/nm820

Cited by 1,098 publications

(1,097 citation statements)

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“…Accumulation of cholesterol crystals in the cytoplasm of macrophages was also proposed to stimulate a proinflammatory cascade 37. Alternatively, lipoprotein‐derived oxysterols are natural liver X receptor ligands, which can counter‐regulate induction of inflammatory gene expression by NF‐κB by recruiting corepressors to the promoters of inflammatory genes 37, 38, 39. Thus, we asked whether increases in plasma cholesterol that significantly accelerate atherosclerosis development would actually affect the inflammatory balance of lesional foam cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate‐Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation

Goo

Son

Yechoor

et al. 2016

JAHA

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BackgroundFoam cells are central to two major pathogenic processes in atherogenesis: cholesterol buildup in arteries and inflammation. The main underlying cause of cholesterol deposition in arteries is hypercholesterolemia. This study aimed to assess, in vivo, whether elevated plasma cholesterol also alters the inflammatory balance of foam cells.Methods and ResultsApolipoprotein E–deficient mice were fed regular mouse chow through the study or were switched to a Western‐type diet (WD) 2 or 14 weeks before death. Consecutive sections of the aortic sinus were used for lesion quantification or to isolate RNA from foam cells by laser‐capture microdissection (LCM) for microarray and quantitative polymerase chain reaction analyses. WD feeding for 2 or 14 weeks significantly increased plasma cholesterol, but the size of atherosclerotic lesions increased only in the 14‐week WD group. Expression of more genes was affected in foam cells of mice under prolonged hypercholesterolemia than in mice fed WD for 2 weeks. However, most transcripts coding for inflammatory mediators remained unchanged in both WD groups. Among the main players in inflammatory or immune responses, chemokine (C‐X‐C motif) ligand 13 was induced in foam cells of mice under WD for 2 weeks. The interferon‐inducible GTPases, guanylate‐binding proteins (GBP)3 and GBP6, were induced in the 14‐week WD group, and other GBP family members were moderately increased.ConclusionsOur results indicate that acceleration of atherosclerosis by hypercholesterolemia is not linked to global changes in the inflammatory balance of foam cells. However, induction of GBPs uncovers a novel family of immune modulators with a potential role in atherogenesis.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate‐Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation

Goo

Son

Yechoor

et al. 2016

JAHA

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“…Modified PS and stanols have been shown to modify the cholesterol influx and efflux from cells by altering nuclear hormone receptor activity, although it is still under discussion whether such a direct effect on the gene level can be considered one of the key mechanisms of action of PS (Plat and Mensink, 2002;Kaneko et al, 2003;Plosch et al, 2004;Calpe-Berdiel et al, 2005). The potential effect on nuclear hormone receptors could also influence gene expression of inflammatory mediators such as iNOS, COX-2 and IL-6 (Joseph et al, 2003). PS or stanols could thus directly have an impact on inflammation and plasma markers of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Dose-response effects of different plant sterol sources in fat spreads on serum lipids and C-reactive protein and on the kinetic behavior of serum plant sterols

et al. 2007

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Objective: To test the dose-response effect on low-density lipoprotein cholesterol (LDL-c) of plant sterols (PS) from different sources in a low-fat spread. Methods: Dose responses of soybean oil (BO), tall oil (TO) and a mix of tall oil and rapeseed oil (TO/RP) as fatty acid esters were tested in a parallel design in free-living subjects recruited from the general community who had elevated cholesterol concentrations. Subjects received either control for 6 weeks or 1.6 g PS per day for 3 weeks, then 3.0 g/day for 3 weeks. Results: LDL-c was lowered significantly by consumption of 1.6 g/day of PS (À10.4%, range À7.3 to À11.4%). Increasing the dose to 3.0 g/day modestly reduced LDL-c concentrations further to À14.7%. TO, containing 78% sitosterol, produced an increase in serum sitosterol of 6.5 nmol/ml, while BO, containing only 27% campesterol, produced an increase in serum campesterol of 9.5 nmol/ml in 6 weeks. After PS withdrawal, serum sterols declined by 50% within 2 weeks. Conclusion: Different PS sources were equally effective in lowering serum LDL-c concentrations. The decrease in absolute concentrations of LDL-c was dependent on the baseline concentrations. IntroductionA large number of human intervention studies have been performed using plant sterols (PS) or stanols incorporated into different food matrices to study their cholesterollowering effects. These studies are based on unesterified (free) or esterified PS or stanols, where the esterification is mostly based on vegetable-oil-derived fatty acids. Since the first publications of Mattson et al. in 1977 and1982, in which the efficacy of the ester format was shown, the interest in enriching foods with PS or stanol esters as an effective means of lowering total cholesterol (TC) and lowdensity lipoprotein-cholesterol (LDL-c) has increased. Quite a number of different food formats are now available, such as spreads, yogurts or milks, which can be taken on a daily basis. These foods formats typically provide between 1.5 and 2.5 g/day of PS or stanols from one or more servings, which have been proven to result in a 10-15% LDL-c lowering.From these studies considered collectively, the effective dose range can be established. It was stated in a recent metaanalysis of 41 studies that increasing the dose of PS or stanols to above 2.5 g/day results in little additional effects on lowering cholesterol (Katan et al., 2003). A few studies using specific PS sources and formats have also shown a dose response in smaller groups (Weststrate and Meijer, 1998;Hendriks et al., 1999). However, these studies were based on parallel groups or random assignment to the order of PS dose. One study has examined using PS the effect of four Correspondence: Dr PM Clifton, CSIRO Human Nutrition, Gate 13 Kintore Ave, Adelaide, SA 5000, Australia. E-mail: peter.clifton@csiro.au Guarantor: PM Clifton. Contributors: PMC and GSMJED designed the study; the intervention part was organized and monitored by PMC. PMC and MM coordinated the serum analysis. HCMvdK performed the data analysis ...

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“…In mice model, it has been reported that inflammation can insult many different metabolic pathways, ultimately affect the growth of animals (Joseph et al, 2003). Skeletal muscle as a major mass peripheral tissue accounts for 40% of total BW, and is the main product of animals for slaughter.…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

Sun

Huang

Yin

et al. 2016

Animal

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Most previous studies on the effects of lipopolysaccharide (LPS) in pigs focused on the body's immune response, and few reports paid attention to body metabolism changes. To better understand the glucose metabolism changes in skeletal muscle following LPS challenge and to clarify the possible mechanism, 12 growing pigs were employed. Animals were treated with either 2 ml of saline or 15 µg/kg BW LPS, and samples were collected 6 h later. The glycolysis status and mitochondrial function in the longissimus dorsi (LD) muscle of pigs were analyzed. The results showed that serum lactate content and NADH content in LD muscle significantly increased compared with the control group. Most glycolysis-related genes expression, as well as hexokinase, pyruvate kinase and lactic dehydrogenase activity, in LD muscle was significantly higher compared with the control group. Mitochondrial complexes I and IV significantly increased, while mitochondrial ATP concentration markedly decreased. Significantly increased calcium content in the mitochondria was observed, and endoplasm reticulum (ER) stress has been demonstrated in the present study. The results showed that LPS treatment markedly changes glucose metabolism and mitochondrial function in the LD muscle of pigs, and increased calcium content induced by ER stress was possibly involved. The results provide new clues for clarifying metabolic diseases in muscle induced by LPS.Keywords: lipopolysaccharide, mitochondria, glycolysis, pig, inflammation ImplicationsSkeletal muscle is the primary tissue responsible for wholebody energy metabolism. In the current study, we designed the experiment to investigate the effect of lipopolysaccharide (LPS) treatment on muscle energy metabolism in pigs. The results indicated that LPS treatment significantly changed glycolysis level and mitochondrial function in the longissimus dorsi (LD) muscle of pigs, and increased calcium content induced by endoplasm reticulum stress was possibly involved. Understanding these underlying mechanisms may provide new therapeutic strategies for treating metabolic diseases induced by LPS in muscle.

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Reciprocal regulation of inflammation and lipid metabolism by liver X receptors

Cited by 1,098 publications

References 40 publications

Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate‐Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation

Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate‐Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation

Dose-response effects of different plant sterol sources in fat spreads on serum lipids and C-reactive protein and on the kinetic behavior of serum plant sterols

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

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