ApoA-IV modulates the secretory trafficking of apoB and the size of triglyceride-rich lipoproteins

Weinberg, Richard B.; Gallagher, James W.; Fabritius, Melissa A.; Shelness, Gregory S.

doi:10.1194/jlr.m019992

Cited by 51 publications

(58 citation statements)

References 57 publications

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“…Pan et al ( 78 ) showed that this increase in MTP might involve transcription factors FoxO1 and FoxA2. In contrast to these studies, other studies suggest no increase in MTP after apoAIV overexpression ( 75,79 ). Thus, how apoAIV assists in fat absorption at was signifi cantly reduced.…”

Section: Mtpcontrasting

confidence: 48%

Circadian regulators of intestinal lipid absorption

Hussain

Pan

2015

Journal of Lipid Research

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Journal of Lipid Research Volume 56, 2015 761(MTP), to transport dietary and endogenous lipids, respectively ( 7-9 ). Therefore, it is possible that a major reason for the circadian regulation of plasma triglyceride depends on their assembly and secretion by the intestine and the liver. Circadian rhythms are centrally orchestrated by a set of clock genes expressed in the suprachiasmatic nuclei (SCN) of the brain. These genes are also expressed in other cells and their expression is entrained by various stimuli emanating from the SCN. Additionally, they are regulated by external stimuli such as food availability. Several intestinal functions, including lipid absorption, show diurnal variations. We will briefl y introduce clock genes and their regulation and intestinal lipid absorption, and then discuss three proteins that have been shown to be involved in the diurnal regulation of lipid absorption ( Fig. 1 ). LIGHT AND FOOD ENTRAINMENT OF CIRCADIAN RHYTHMSConstant periodicity of sunrise and sunset affects every organism. Some wake up with the sunrise while others go to sleep. However, wakefulness is always associated with physical activity aimed at gathering food. In contrast, sleep is associated with low locomotor activity and fasting. The information about the sunlight is transmitted from the eye via retino-hypothalamic neurons to bilateral SCN in the brain ( 10-12 ). These photic signals are deciphered in the SCN resulting in the increased expression of a clock gene, brain and muscle arylhydrocarbon receptor nuclear translocator ( Several behavioral and physiologic activities show circadian rhythms that are attuned to changes in light within a 24 h day. Plasma triacylglycerols exhibit diurnal variations in humans and rodents ( 1-6 ). Due to their hydrophobic nature, these lipids are transported in the plasma as major core constituents of apoB-containing lipoproteins. These lipoproteins are assembled in the endoplasmic reticulum and Golgi of enterocytes and hepatocytes with the assistance of a dedicated chaperone, microsomal triglyceride transfer protein Abbreviations: ARNT, arylhydrocarbon receptor nuclear translocator; Bmal1, brain and muscle ARNT -like protein 1; Clock, circadian locomotor output cycles kaput; CREBH, cAMP responsive element-binding protein H; Cry, cryptochrome; ER, endoplasmic reticulum; HNF, hepatic nuclear factor; MTP, microsomal triglyceride transfer protein; Per, period; PGC1 ␣ , PPAR ␥ coactivator 1-␣ ; Rev-erb ␣ , reverse erythroblastosis virus ␣ ; Ror ␣ , retinoic acid receptor-related orphan receptor ␣ ; SCN, suprachiasmatic nuclei; Shp, small heterodimer partner .

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Section: Mtpcontrasting

confidence: 48%

Circadian regulators of intestinal lipid absorption

Hussain

Pan

2015

Journal of Lipid Research

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“…ApoAIV enters the circulation on the surface of nascent CMs. It has been suggested that apoAIV enhances particle expansion and increases triglyceride secretion [62]. In the circulation, apoAIV is displaced from CMs by HDL-associated apoC, and the exchange facilitates the activation of LPL by its cofactor apoCII [63].…”

Section: Apolipoproteins and Chylomicron Synthesismentioning

confidence: 99%

Recent advances in physiological lipoprotein metabolism

Ramasamy

2014

Clinical Chemistry and Laboratory Medicine (CCLM)

182

159

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Abstract:Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the synthesis and secretion of triglyceride rich lipoproteins, chylomicrons (CM) and very low density lipoproteins (VLDL). These included the identification of microsomal transfer protein, the cotranslational targeting of apoproteinB (apoB) for degradation regulated by the availability of lipids, and the characterization of transport vesicles transporting primordial apoB containing particles to the Golgi. The lipase maturation factor 1, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 and an angiopoietin-like protein play a role in lipoprotein lipase (LPL)-mediated hydrolysis of secreted CMs and VLDL so that the right amount of fatty acid is delivered to the right tissue at the right time. Expression of the low density lipoprotein (LDL) receptor is regulated at both transcriptional and posttranscriptional level. Proprotein convertase subtilisin/ kexin type 9 (PCSK9) has a pivotal role in the degradation of LDL receptor. Plasma remnant lipoproteins bind to specific receptors in the liver, the LDL receptor, VLDL receptor and LDL receptor-like proteins prior to removal from the plasma. Reverse cholesterol transport occurs when lipid free apoAI recruits cholesterol and phospholipid to assemble high density lipoprotein (HDL) particles. The discovery of ABC transporters (ABCA1 and ABCG1) and scavenger receptor class B type I (SR-BI) provided further information on the biogenesis of HDL. In humans HDLcholesterol can be returned to the liver either by direct uptake by SR-BI or through cholesteryl ester transfer protein exchange of cholesteryl ester for triglycerides in apoB lipoproteins, followed by hepatic uptake of apoB containing particles. Cholesterol content in cells is regulated by several transcription factors, including the liver X receptor and sterol regulatory element binding protein. This review summarizes recent advances in knowledge of the molecular mechanisms regulating lipoprotein metabolism.Keywords: ABCA1; angiopoietin-like proteins; apoC; apoAI; apolipoprotein E (apoE); cholesterol ester transfer protein; chylomicron; LDL receptor; lecithin cholesterol acyl transferase; lipoprotein(a); lipoprotein lipase; microsomal transfer protein; propertin convertase subtilisin/ kexin type 9; SR-BI; phospholipid transfer protein; very low density lipoproteins (VLDL). Abstract 1695

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“…Because APOL1 is abundantly expressed in the liver, which is likely the primary source of circulating APOL1 ( 8 ), McA rat hepatoma cells were stably transfected with APOL1 G0, G1, and G2 variants under the control of a Tet-inducible promoter, using methods described previously ( 14,15 ). When cells were induced with Dox for 16 h and metabolically radiolabeled with […”

Section: Apol1 May Be Targeted For Proteasomal Degradationmentioning

confidence: 99%

Biogenesis and cytotoxicity of APOL1 renal risk variant proteins in hepatocytes and hepatoma cells

Cheng¹,

Weckerle²,

Yu³

et al. 2015

Journal of Lipid Research

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reduced levels of calcifi ed atherosclerotic plaque in coronary and carotid arteries ( 3,4 ).APOL1 nephropathy risk variants have undergone positive selection in sub-Saharan Africa due to protection from Trypanosoma brucei rhodesiense , a cause of African sleeping sickness ( 5 ). The mechanism whereby APOL1 risk variant (G1 and G2) proteins kill trypanosomes is well-understood, and refl ects APOL1 protein uptake by parasites, traffi cking to the lysosome, and an acidic pH-induced conformational change with subsequent APOL1 protein insertion into lysosomal membranes. Chloride transport ensues via the APOL1 channel with osmotic swelling and eventual lysosomal rupture leading to parasite death. In contrast, the mechanism(s) whereby APOL1 renal risk variants produce progressive nondiabetic nephropathy remain poorly understood. Moreover, the basic biology of APOL1 proteins has not yet been elucidated and will be of utmost importance to defi ne its role in human diseases. We and others have shown that APOL1 mRNA and protein are present in podocytes, renal tubule cells, and glomerular endothelial cells, but not in mesangial cells ( 6, 7 ). APOL1 protein is also present in the circulation ( 8 ) and may thus play an important role in its pathology.Although APOL1 is produced by several cell types ( 9, 10 ), few details regarding its production and secretion are known. APOL1 is reported to bind to HDL ( 8 ). Because the liver is a major source of HDL production ( 11 ) and circulating apolipoproteins, and is likely an important contributor to the circulating pool of APOL1, the present study was performed using a hepatoma cell line and primary hepatocytes. These studies have revealed novel traffi cking behavior of APOL1 and identify potential pathways involved in APOL1-induced cell injury and death.Abstract Two APOL1 gene variants, which likely evolved to protect individuals from African sleeping sickness, are strongly associated with nondiabetic kidney disease in individuals with recent African ancestry. Consistent with its role in trypanosome killing, the pro-death APOL1 protein is toxic to most cells, but its mechanism of cell death is poorly understood and little is known regarding its intracellular traffi cking and secretion. Because the liver appears to be the main source of circulating APOL1, we examined its secretory behavior and mechanism of toxicity in hepatoma cells and primary human hepatocytes. APOL1 is poorly secreted in vitro, even in the presence of chemical chaperones; however, it is effi ciently secreted in wild-type transgenic mice, suggesting that APOL1 secretion has specialized requirements that cultured cells fail to support. In hepatoma cells, inducible expression of APOL1 and its risk variants promoted cell death, with the G1 variant displaying the highest degree of toxicity. To explore the basis for APOL1-mediated cell toxicity, endoplasmic reticulum stress, pyroptosis, autophagy, and apoptosis were examined. Our results suggest that autophagy represents the predominant mechanism of APOL1-mediated ce...

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ApoA-IV modulates the secretory trafficking of apoB and the size of triglyceride-rich lipoproteins

Cited by 51 publications

References 57 publications

Circadian regulators of intestinal lipid absorption

Circadian regulators of intestinal lipid absorption

Recent advances in physiological lipoprotein metabolism

Biogenesis and cytotoxicity of APOL1 renal risk variant proteins in hepatocytes and hepatoma cells

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