Lack of interleukin-1α in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice

Olteanu, Sarita; Kandel-Kfir, Michal; Shaish, Aviv; Almog, Tal; Shemesh, Shay; Barshack, Iris; Apte, Ron N.; Harats, Dror; Kamari, Yehuda

doi:10.1016/j.dld.2014.01.156

Cited by 39 publications

(38 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the liver of HFD-induced obese mice, lipid accumulation activates Kupffer cells to release a large amounts of proinflammatory cytokines, such as TNFα, IL-1β, and IL-6 [56,57]. The effects of cytokines could be attenuated with clodronate to deplete Kupffer cells, resulting in a reduction of IL-1β, TG, and lipogenic enzyme expression levels.…”

Section: Discussionmentioning

confidence: 99%

Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet–induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles

Wang

Yen

Cheng

et al. 2017

Food & Nutrition Research

View full text Add to dashboard Cite

Obesity, the excessive accumulation of lipids in the body, is closely associated with many prevalent human disorders. Continued efforts to identify plant extracts that exhibit anti-obesity effects have drawn much attention. This study investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity activity and how PTE may affect liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet–induced obese mouse model to determine the effects of PTE on lipid accumulation. Next-generation sequencing analysis of liver gene expression and gut microbiota profiles following PTE treatment were conducted to elucidate possible mechanisms. We found that treatment of fully differentiated 3T3-L1 adipocytes with PTE inhibited lipid accumulation in the cells through reducing lipid formation and triglyceride content and by increasing lipase activity. No cytotoxicity was observed from the PTE treatment. After 5 weeks of treatment with PTE, the increased body weight, elevated serum triglyceride content, and liver steatosis in the high-fat diet–induced obese mice were each reduced. Liver transcriptomic analysis revealed that expression of genes involved in lipid and cholesterol metabolism was significantly altered. The low-grade chronic inflammation of obesity caused by a high-fat diet was also decreased after PTE treatment. In addition, treatment with PTE improved the relatively low Bacteroidetes/Firmicutes ratio in the gut of high-fat diet–fed mice through enrichment of the Proteobacteria population and reduction of the Deferribacteres population. In conclusion, treatment with PTE inhibited lipid accumulation by inducing the expression of the master transcription factor PPARα, attenuated the low-grade chronic inflammation of obesity, and also altered gut microbiota profiles. These results indicate that PTE has the potential to be developed into an anti-obesity food supplement and therapy. Abbreviations: Abcg5: ATP-binding cassette subfamily G member 5; ALT: alanine aminotransferase; AMPK: adenosine monophosphate-activated protein kinase; AST: aspartate aminotransferase; B/F: Bacteroidetes to Firmicutes [ratio]; C/EBPα: CCAAT/enhancer-binding protein alpha; CR: creatinine; Cyp51: cytochrome P450 family 51; DMEM: Dulbecco’s modified Eagle’s medium; Fabp5: fatty acid-binding protein 5; FBS: fetal bovine serum; Fdps: farnesyl diphosphate synthase; Glc: Glucose; HFD: high-fat diet; GO: gene ontology; HPRT: hypoxanthine guanine phosphoribosyl transferase; IBMS: 3-isobutyl-1-methylxanthine; Idi1: isopentenyl-diphosphate delta isomerase 1; IL-1β: interleukin-1-beta; Lpin1: phosphatidic acid phosphohydrolase; LPS: lipopolysaccharide; Mvd: mevalonate diphosphate decarboxylase; ND: normal diet; OTU: operational taxonomic units; Pcsk9: proprotein convertase subtilisin/kexin 9; Pctp: phosphatidylcholine transfer protein; PPARα: peroxisome proliferator-activated receptor alpha; PPARγ: peroxisome proliferator-activated receptor gamma; PTE: Polygala tenuifolia extract; Saa1: serum amyloid A1; SD: ...

show abstract

Section: Discussionmentioning

confidence: 99%

Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet–induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles

Wang

Yen

Cheng

et al. 2017

Food & Nutrition Research

View full text Add to dashboard Cite

show abstract

“…of Pages 9 D.A. Rubenstein et al / Molecular Immunology xxx (2015) xxx-xxx 7 for particular formulations tested, has also been associated with increased inflammation that may cause cardiovascular disease generation (Olteanu et al, 2014). Furthermore, Valatas et al (2004) has shown that the Kupffer cell cytokine release profile in response to octreotide can lead to liver inflammation through the actions of TNF␣, IL6, IL12 and IL13.…”

Section: Cytokine Releasementioning

confidence: 96%

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses

Rubenstein

Hom

Ghebrehiwet

2015

Molecular Immunology

View full text Add to dashboard Cite

“…[34] Recent studies have indicated that deficiency of IL-1α in KC reduces liver inflammation and expression of inflammatory cytokines, which may implicate KC-derived IL-1α in steatohepatitis development. [35] Obesity, especially visceral adiposity, is a major risk factor for NASH in humans. [36] Adipose tissue is a source of free fatty acids (FFA) that are delivered to the liver and a depot for triglycerides that are synthesized by hepatocytes and released into the blood.…”

Section: Structural Organization Of the Liver And Cytokines Potentialmentioning

confidence: 99%

Physiological potential of cytokines and liver damages

Mannaa¹,

Abdel-Wahhab²

2016

View full text Add to dashboard Cite

Cytokines are soluble extracellular small molecular weight protein or peptide. They are produced by virtually every nucleated cell type in response to injurious stimuli to control body metabolism, infection, inflammation and tissue or neuronal damage; therefore acting as messengers between tissues and the immune system; and participating in many physiological processes through their either anti-inflammatory or pro-inflammatory characteristics. Many cytokines have multiple cellular sources and targets, as well as many natural inducers and inhibitors. In pathophysiological conditions and during the early phase of chronic liver diseases, agent like virus, bacteria, parasites, ethanol, or toxins, induce secretion of cytokines at high levels. The presence of cytokine antagonists and soluble cytokine receptors, often released in concert with their respective cytokine agonist, presents additional complexity to interpretation.

show abstract

Lack of interleukin-1α in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice

Cited by 39 publications

References 26 publications

Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet–induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles

Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet–induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses

Physiological potential of cytokines and liver damages

Contact Info

Product

Resources

About