Lipocalin-2 (LCN2) regulates PLIN5 expression and intracellular lipid droplet formation in the liver

Asimakopoulou, Anastasia; Borkham-Kamphorst, Erawan; Henning, Marc; Yagmur, Eray; Gaßler, Nikolaus; Liedtke, Christian; Berger, Thorsten; Mak, Tak W.; Weiskirchen, Ralf

doi:10.1016/j.bbalip.2014.07.017

Cited by 47 publications

(53 citation statements)

References 60 publications

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“…The lipocalin family plays a role in antimicrobial and antiinflammatory response and Lcn2 has been shown to be expressed mainly in liver upon acute-phase response [40]. Lcn2 has been linked to obesity and insulin resistance and was recently proposed to be a key modulator of hepatic lipid homeostasis by controlling intracellular lipid droplet formation [41]. Furthermore, Lcn2 is an indicator of liver damage and Lcn2 expression in liver correlates with steatosis in obese human subjects [42].…”

Section: Lingonberry and Bilberry Intake Have Antiinflammatory Effectsmentioning

confidence: 98%

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

Heyman-Lindén

Seki

Storm

et al. 2016

The Journal of Nutritional Biochemistry

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The liver is a critical organ for regulation of energy homeostasis and fatty liver disease is closely associated with obesity and insulin resistance. We have previously found that lingonberries, blackcurrants and bilberries prevent, whereas açai berries exacerbate, the development of hepatic steatosis and obesity in the high-fat (HF)-fed C57BL/6J mouse model. In this follow-up study, we investigated the mechanisms behind these effects. Genome-wide hepatic gene expression profiling indicates that the protective effects of lingonberries and bilberries are accounted for by several-fold downregulation of genes involved in acute-phase and inflammatory pathways (e.g. Saa1, Cxcl1, Lcn2). In contrast, açai-fed mice exhibit marked upregulation of genes associated with steatosis (e.g. Cfd, Cidea, Crat) and lipid and cholesterol biosynthesis, which is in line with the exacerbation of HF-induced hepatic steatosis in these mice. In silico transcription factor analysis together with immunoblot analysis identified NF-κB, STAT3 and mTOR as upstream regulators involved in mediating the observed transcriptional effects. To gain further insight into mechanisms involved in the gene expression changes, the HELP-tagging assay was used to identify differentially methylated CpG sites. Compared to the HF control group, lingonberries induced genome-wide hypermethylation and specific hypermethylation of Ncor2, encoding the corepressor NCoR/SMRT implicated in the regulation of pathways of metabolic homeostasis and inflammation. We conclude that the beneficial metabolic effects of lingonberries and bilberries are associated with downregulation of inflammatory pathways, whereas for blackcurrants, exerting similar metabolic effects, different mechanisms of action appear to dominate. NF-κB, STAT3 and mTOR are potential targets of the health-promoting effects of berries.

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Section: Lingonberry and Bilberry Intake Have Antiinflammatory Effectsmentioning

confidence: 98%

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

Heyman-Lindén

Seki

Storm

et al. 2016

The Journal of Nutritional Biochemistry

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“…LCN2 induces adiponectin expression in adipocytes [7]. LCN2 is upregulated in murine adipose tissue and liver in obesity [7,8]. LCN2 is also induced in human NASH liver when compared to normal liver [9].…”

Section: Introductionmentioning

confidence: 95%

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis

et al. 2016

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“…Total RNA was isolated from cells using Trizol (Invitrogen) according to the manufacturer's instructions [19,20]. RNA was quantified using a GeneQuant pro RNA/DNA Calculator spectrophotometer (Amersham Biosciences, Freiburg, Germany), and then first-strand cDNA was synthesized from 1 μg RNA in a 20 μl reaction volume using a PrimeScriptTM RT reagent Kit with gDNA Eraser (RR047A; Takara, Shiga, Japan) according to the manufacturer's instructions.…”

Section: Rna Isolation and Real-time Pcrmentioning

confidence: 99%

Lipocalin 2 Upregulation Protects Hepatocytes from IL1-β-Induced Stress

Xue

Yang

et al. 2015

Cell Physiol Biochem

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Background: Lipocalin 2 (LCN2), a protein primarily produced by hepatocytes, is highly upregulated under various conditions that induce cellular stress, such as intoxication, infection or inflammation. However, the precise biological functions and underlying mechanisms of LCN2 in hepatocytes remains unknown. Methods: Hepatocyte stress was successfully induced by treating Huh7 cells with interleukin-1β (IL-1β). Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and LCN2 levels were measured in IL-1β treated Huh7 cells and supernatant. Additionally, microarray analysis was conducted to identify genes differentially expressed in LCN2-silenced and control Huh7 cells. Results: TNF-α, IL-6 and LCN2 were significantly elevated in Huh7 cells after IL-1β) treatment. In LCN2-silenced Huh7 cells, expression of IL-6 and TNF-α was significantly increased when compared with the expression levels of control Huh7 cells. Furthermore, differentially expressed genes were observed between the LCN2-silenced and control cells. Microarray analysis indicated that LCN2 acted by influencing genes involved in protein metabolism, stress response, cell cycle and proliferation. Conclusions: Our results suggest that LCN2 upregulation protects hepatocytes from IL-1β-induced stress. Additionally, our microarray analysis of LCN2-silenced and control cells provides a better understanding of the mechanisms that may be influenced by LCN2 induction.

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Lipocalin-2 (LCN2) regulates PLIN5 expression and intracellular lipid droplet formation in the liver

Cited by 47 publications

References 60 publications

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis

Lipocalin 2 Upregulation Protects Hepatocytes from IL1-β-Induced Stress

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