Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells

Wang, Yanan; Tuin, Sam van der; Tjeerdema, Nathanja; Dam, Anke; Rensen, Sander S.; Hendrikx, Tim; Berbée, Jimmy F.P.; Atanasovska, Biljana; Fu, Jingyuan; Hoekstra, Menno; Bekkering, Siroon; Riksen, Niels P.; Buurman, Wim A.; Greve, Jan; Hofker, Marten H.; Shiri-Sverdlov, R.; Meijer, Onno C.; Smit, Johannes; Havekes, Louis M.; Dijk, Ko Willems van; Rensen, Patrick C.N.

doi:10.1002/hep.27985

Cited by 70 publications

(63 citation statements)

References 49 publications

(84 reference statements)

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“…APOE*3-Leiden.CETP (E3L.CETP) mice were obtained as previously described21 and housed under standard conditions in conventional cages with free access to chow diet and water unless indicated otherwise. At the age of 10–12 weeks, male mice were used for experiments in accordance with the regulations of Dutch law on animal welfare.…”

Section: Methodsmentioning

confidence: 99%

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit

Katiraei

et al. 2017

Gut

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394

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Section: Methodsmentioning

confidence: 99%

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit

Katiraei

et al. 2017

Gut

Self Cite

485

394

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“…A recent study also showed that TNFα increased apoB secretion in mouse hepatocytes in vitro and promoted hepatic VLDL secretion in mice [19], indicating a link between hepatic TNFα and elevated plasma triglycerides. Moreover, Kupffer cells were identified as the predominant source of plasma CETP, a protein which mediates the exchange of cholesteryl esters for triglycerides between lipoproteins and is associated with dyslipidemia [20]. In obesity-associated NAFLD, hepatic Kupffer cell content and plasma CETP are increased, concomitant with atherogenic dyslipidemia characterized by small dense LDL, elevated triglycerides and reduced HDL [20].…”

Section: Hepatic Macrophages and Kupffer Cellsmentioning

confidence: 99%

“…Moreover, Kupffer cells were identified as the predominant source of plasma CETP, a protein which mediates the exchange of cholesteryl esters for triglycerides between lipoproteins and is associated with dyslipidemia [20]. In obesity-associated NAFLD, hepatic Kupffer cell content and plasma CETP are increased, concomitant with atherogenic dyslipidemia characterized by small dense LDL, elevated triglycerides and reduced HDL [20]. These findings suggest that activation of liver macrophages in NAFLD may alter lipoprotein metabolism and secretion to promote increased plasma LDL-C and triglycerides, and reduced HDL-C, contributing to an atherogenic lipid profile during NAFLD progression.…”

Section: Hepatic Macrophages and Kupffer Cellsmentioning

confidence: 99%

Non-parenchymal hepatic cell lipotoxicity and the coordinated progression of non-alcoholic fatty liver disease and atherosclerosis

Peters¹,

Wilson²,

Borradaile³

2018

Current Opinion in Lipidology

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Purpose of reviewNon-alcoholic fatty liver disease (NAFLD) appears to be independently associated with the development of atherosclerosis. The biological mechanisms underlying this association are complex, and likely involve liver-resident cell types other than hepatocytes. Thus, we review recent evidence that non-parenchymal hepatic cell responses to lipid excess contribute to the pathogenesis of both NAFLD and atherosclerosis.Recent findingsSignificant independent associations between NAFLD and atherosclerosis have been identified through cross-sectional studies and meta-analyses. Mechanistic studies in cell cultures and in rodent models suggest that liver-resident macrophages, activated hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) mount lipotoxic responses under NAFLD conditions which can contribute to the progression of both NAFLD and atherosclerosis.SummaryNon-parenchymal hepatic cell types exhibit some similarity in their responses to lipid excess, and in their pathogenic mechanisms, which likely contribute to the coordinated progression of NAFLD and atherosclerosis. In response to lipotoxic conditions, macrophages, Kupffer cells and HSC initiate robust inflammatory responses, whereas LSEC generate excess reactive oxygen species (ROS). The extent to which inflammatory cytokines and ROS produced by non-parenchymal cells contribute to the progression of both NAFLD and atherosclerosis warrants further investigation.

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“…Liver fat accumulation per se proportionally increases the hepatic secretion rate of large VLDL1, which exchanges triglycerides with cholesterol contained in circulating LDL and HDL particles, resulting in small LDL and HDL3 formation (55). Furthermore, recent studies demonstrated that circulating cholesteryl ester transfer protein (CETP) derives largely from hepatic Kupffer cells, and its levels parallel the severity of histological necroinflammations in NASH (111). Of note, CETP inhibitors alleviate high-fat diet-induced steatohepatitis and fibrosis, possibly by reducing oxidized LDL uptake by hepatic Kupffer and stellate cells (112), and represent a potential therapeutic target for the treatment of both NAFLD and CKD (Table 2).…”

Section: Nafld As a Determinant Of Ckd: Targeting The Liver To Improvmentioning

confidence: 99%

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities

et al. 2016

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Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferatoractivated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium-glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium. EPIDEMIOLOGICAL EVIDENCE LINKING NAFLD AND CKDChronic kidney disease (CKD) affects up to 8% of the world's adult population, with its prevalence increasing in an aging population beset by lifestyle-associated diseases such as obesity, the metabolic syndrome, diabetes, hypertension, and smoking (1). CKD may progress to end-stage renal disease (ESRD) and is an important cardiovascular disease (CVD) risk factor. Importantly, most patients with CKD die as a result of CVD before renal replacement therapy is initiated (1).There is potential for improving recognition and treatment of CKD. In the Third National Health and Nutrition Survey, awareness among patients with stage 3 CKD was ,8% (1). Furthermore, ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and all-cause mortality remains unchanged in the CKD population (2). These data suggest that key pathogenetic mechanisms underlying

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Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells

Cited by 70 publications

References 49 publications

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit

Non-parenchymal hepatic cell lipotoxicity and the coordinated progression of non-alcoholic fatty liver disease and atherosclerosis

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities

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