An Induction in Hepatic HDL Secretion Associated with Reduced ATPase Expression

Pandey, Nihar R.; Renwick, Joanna; Rabaa, Seham; Misquith, Ayesha; Kouri, Lara; Twomey, Erin; Sparks, Daniel L.

doi:10.2353/ajpath.2009.090082

Cited by 9 publications

(11 citation statements)

References 60 publications

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“…F 1 -ATPase is inhibited by mitochondrial inhibitory factor 1 (IF1) [34] and serum IF1 levels have been shown to be positively correlated with HDL-cholesterol levels and negatively correlated with serum triglyceride levels in normolipidemic subjects [39]. This is consistent with other work, which suggested that therapeutic modulation of circulating HDL levels may be associated with the expression of F 1 -ATPase, ADP production and purinergic signaling [19,40,41]. …”

Section: Nucleotides and Diseasesupporting

confidence: 80%

“…Niacin reduces cell surface levels of F 1 -ATPase in hepatocytes and thereby blocks the production of extracellular ADP [40]. Linoleic acid phospholipids also block ADP production by inhibiting the cell surface expression of F 1 -ATPase and thereby stimulate HDL secretion from liver cells [41]. These phospholipids appear to mute purinergic signaling and cellular autophagy by stimulating Akt phosphorylation and blocking MAPK activation [19].…”

Section: Resultsmentioning

confidence: 99%

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Purinergic Signaling, Dyslipidemia and Inflammatory Disease

Sparks

Chatterjee

2012

Cell Physiol Biochem

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Metabolic syndrome is a compound obesity disorder, wherein the abnormal metabolism of glucose and lipid is associated with the development of chronic inflammatory diseases. The prevalence of this disease is increasing in the developed world, but the causative linkage between these metabolic disorders has remained obscure. Metabolic disease may be associated with chronic nucleotide secretion, purinergic signaling and activation of inflammatory pathways. Purinergic signaling has been implicated in impaired glucose metabolism and inflammatory disease and may contribute to dyslipidemia. Our research shows that purinergic signaling disrupts hepatic lipoprotein metabolism by blocking insulin receptor signaling and by activating cellular autophagic pathways. Chronic stimulation of purinergic signaling may therefore be causative to glucose and lipid metabolic disorders and associated with the development of cardiovascular disease.

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Section: Nucleotides and Diseasesupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Purinergic Signaling, Dyslipidemia and Inflammatory Disease

Sparks

Chatterjee

2012

Cell Physiol Biochem

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“…As in the circulation, HL in hepatocyte medium is primarily associated with larger HDL complexes containing both ApoA-I and ApoA-II. Phospholipid treatment increases the secretion of both ApoA-I and ApoA-II 43,45 and, as shown by Boucher et al, 31 the association of HL with ApoA-II-enriched HDL directly inhibits HL hydrolytic activity.…”

Section: Regulation Of Hl Secretion From the Livermentioning

confidence: 82%

“…43 Instead, PLs stimulate PPAR␣ expression 44 and inhibit membrane nucleotide signaling events on the cell surface to block retroendocytic degradative pathways. 45 The data suggest that PLs block membrane recycling pathways that promote the reuptake and degradation of cell surface proteins such as HL (Figure 2). Hepatic lipase degradation has been shown to be rate-limiting to HL secretion, and associated with the dimerization of the enzyme.…”

Section: Regulation Of Hl Secretion From the Livermentioning

confidence: 99%

Hepatic Lipase, High Density Lipoproteins, and Hypertriglyceridemia

Chatterjee

Sparks

2011

The American Journal of Pathology

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109

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Hepatic lipase (HL) is a lipolytic enzyme that contributes to the regulation of plasma triglyceride (TG) levels. Elevated TG levels may increase the risk of developing coronary heart disease, and studies suggest that mutations in the HL gene may be associated with elevated TG levels and increased risk of coronary heart disease. Hepatic lipase facilitates the clearance of TG from the very low density lipoprotein (VLDL) pool, and this function is governed by the composition and quality of high density lipoprotein (HDL) particles. In humans, HL is a liver resident enzyme regulated by factors that release it from the liver and activate it in the bloodstream. HDL regulates the release of HL from the liver and HDL structure controls HL transport and activation in the circulation. Alterations in HDL-apolipoprotein composition can perturb HL function by inhibiting the release and activation of the enzyme. HDL structure may therefore affect plasma TG levels and coronary heart disease risk. Triglycerides and Heart DiseaseElevated plasma triglyceride (TG) levels have been viewed as a risk factor for coronary heart disease (CHD) for more than a decade.1,2 Plasma TG levels are regulated by both synthesis and degradation of both very low density lipoprotein (VLDL) and chylomicron particles. The clearance of TG-rich lipoproteins from the circulation is controlled by the actions of lipoprotein lipase (LPL) and hepatic lipase (HL) and by the interlipoprotein exchange of TG by cholesteryl ester transfer protein. Lipoprotein lipase is the predominant TG lipase and is responsible for hydrolyzing TG in chylomicrons and VLDL, whereas HL is both a phospholipase and a TG lipase and plays an important role in HDL metabolism and in the conversion of VLDL to LDL.3 Single nucleotide polymorphisms (SNPs) in the HL gene (LIPC) have been shown to associate with plasma lipid concentrations and increased CHD risk. 4,5 Hepatic lipase deficiency is a result of relatively rare LIPC mutations that give rise to a loss in circulating HL activity (due to impaired secretion or inactive enzyme) and cause an increase in TG-rich HDL and VLDL remnants and increased CHD risk.

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“…Similarly, niacin appears to regulate the recycling/reuptake of newly secreted apo A-I (Pandey et al, 2009) through the effects of a novel G-protein coupled receptor, P2Y13. This pathway may be central to the HDL raising effects of niacin (Jacquet et al, 2005;Zhang et al, 2008).…”

Section: Introductionmentioning

confidence: 97%