Formation of cholesteryl ester-rich particulate lipid during metabolism of chylomicrons

Redgrave, Trevor G.

doi:10.1172/jci106255

Cited by 483 publications

(169 citation statements)

References 29 publications

(28 reference statements)

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“…Specifically, a significantly higher degree of lipid accumulation, together with impaired liver function, widespread ballooning degeneration, moderate inflammatory cell infiltration, and mild fibrosis, was exhibited in the livers of the offspring of rats exposed to BPA when they consumed a HFD immediately after weaning. A study conducted on rats demonstrated that dietary fats taken up in the intestine could be packaged into TG-rich chylomicrons and 20% of TGs in chylomicrons were then delivered to the liver (Redgrave 1970). Extrapolating from these experiments, the HFD (20 g food per day) could furnish the liver with a significantly higher amount of fat (approximately 0.53 g fat each day) than the SD (approximately 0.18 g fat each day).…”

Section: Discussionmentioning

confidence: 99%

Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

Jie¹,

Sun²,

Chen³

et al. 2014

Journal of Endocrinology

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Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA contributes to metabolic syndrome. In this study, we examined whether perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50 mg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after weaning. Effects of BPA were assessed by examination of hepatic morphology, biochemical analysis, and the hepatic expression of genes and/or proteins involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to BPA exhibited moderate hepatic steatosis and altered expression of insulin signaling elements in the liver, but with normal liver function. On a HFD, the offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like phenotype, characterized by extensive accumulation of lipids, large lipid droplets, profound ballooning degeneration, impaired liver function, increased inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA worsened the hepatic damage caused by the HFD in the rat offspring. The additive effects of BPA correlated with higher levels of hepatic oxidative stress. Collectively, exposure to BPA may be a new risk factor for the development of fatty liver disease and further studies should assess whether this finding is also relevant to the human population.

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Section: Discussionmentioning

confidence: 99%

Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

Jie¹,

Sun²,

Chen³

et al. 2014

Journal of Endocrinology

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“…The surface remnants consist of the phospholipid, free cholesterol, and apolipoprotein that are removed from the chylomicron surface in the course of chylomicron metabolism. The core remnants are removed from the plasma by the liver, whereas the surface remnants become components of HDL (25)(26)(27). Hepatic uptake of rat chylomicron core remnants is effectively inhibited by competition with an HDL particle that contains only apoE (apoE,.…”

Section: Discussionmentioning

confidence: 99%

Regulation of serum apolipoprotein E metabolism: role of chylomicron metabolism.

DeLamatre¹,

Krause²,

Roheim³

1982

Proc. Natl. Acad. Sci. U.S.A.

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The mechanism by which high-fat, high-cholesterol diets lower serum apolipoprotein E (apoE) concentration was studied in rats by feeding a single high-fat, high-cholesterol meal and by intravenously infusing chylomicrons containing low and high amounts of cholesterol. Serum apoE concentrations were unchanged 9 hours after an olive oil meal but were decreased by 35% after an olive oil/cholesterol-enriched meal. The decrease in serum apoE concentrations with the olive oil/cholesterol meal was accompanied by a decrease in apoE concentration in the high density lipoprotein fraction. Three hours after the intravenous infusion of cholesterol-enriched chylomicrons, serum apoE concentrations decreased 40%, whereas serum apoE concentrations decreased by only 10% when chylomicrons with low cholesterol concentrations or saline were infused. It is concluded that the metabolism of cholesterol-enriched chylomicrons results in an increased removal of serum apoE and that the cholesterol content of chylomicrons is a determinant of serum apoE removal.Apolipoprotein E (apoE) plays a role in lipoprotein recognition and removal by the liver and is also thought to be the hepatic recognition site on chylomicron remnants (1-5). This concept is supported by the fact that high density lipoprotein (HDL) particles (density, 1.063-1.21) that contain only apoE (apoE, HDLc) compete effectively for hepatic binding with rat chylomicron remnants in a rat liver perfusion system (1). We have demonstrated that plasma apoE concentrations decreased in euthyroid rats fed a high-fat, high-cholesterol diet for several weeks. We postulated that the decrease of serum apoE concentrations was associated with the removal of chylomicron remnants (6). Because chylomicrons are rapidly removed from the plasma (7, 8), we tested whether the decrease in serum apoE concentrations would occur acutely. Therefore, we studied the effects of a single high-fat, high-cholesterol meal and of the intravenous infusion of chylomicrons with different cholesterol contents on serum apoE concentrations. Chylomicrons collected from the mesenteric lymph ofa normal rat contain apoE, whereas nascent chylomicrons do not (9, 10). To accurately assess the effect that chylomicrons have on serum apoE concentrations, it is necessary to infuse chylomicrons that do not contain apoE. It is possible to obtain chylomicrons with no apoE from a rat treated with 17a-ethynylestradiol (EE) because EE treatment lowers serum apoE concentrations dramatically (10, 11). Therefore, chylomicrons collected from the mesenteric lymph of EE-treated rats were used so that apoE would not be introduced into the serum during the chylomicron infusion and interfere with the results. The present study demonstrates that the metabolism of cholesterol-enriched chylomicrons is associated with serum apoE removal.MATERIALS AND METHODS Animals. Male, Sprague-Dawley rats (275-300 g) were maintained on laboratory rat chow on a 12-hr-light/12-hr-dark cycle (6 a.m.-6 p.m.). At 3 p.m. on the day before an experiment, the...

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“…For the HepX model, a functional hepatectomy was performed using a modification of the method described by Redgrave. 25 The abdomen was opened with a midline incision, and the common bile duct (proximal to the pancreatic duct) was ligated. The inferior vena cava, proximal and distal to the junction of the hepatic veins, as well as the portal vein and the hepatic artery, were ligated.…”

Section: Methodsmentioning

confidence: 99%

Extrahepatic deposition and cytotoxicity of lithocholic acid: Studies in two hamster models of hepatic failure and in cultured human fibroblasts

et al. 1998

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Effects of bile acids on tissues outside of the enterohepatic circulation may be of major pathophysiological significance under conditions of elevated serum bile acid concentrations, such as in hepatobiliary disease. Two hamster models of hepatic failure, namely functional hepatectomy (HepX), and 2-day bile duct ligation (BDL), as well as cultured human fibroblasts, were used to study the comparative tissue uptake, distribution, and cytotoxicity of lithocholic acid (LCA) in relation to various experimental conditions, such as binding of LCA to low-density lipoprotein (LDL) or albumin as protein carriers. Fifteen minutes after iv infusion of [24-14 C]LCA, the majority of LCA in shamoperated control animals was recovered in liver, bile, and small intestine. After hepatectomy, a significant increase in LCA was found in blood, muscle, heart, brain, adrenals, and thymus. In bile duct-ligated animals, significantly more LCA was associated with blood and skin, and a greater than twofold increase in LCA was observed in the colon. In the hepatectomized model, the administration of LCA bound to LDL resulted in a significantly higher uptake in the kidneys and skin.

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Formation of cholesteryl ester-rich particulate lipid during metabolism of chylomicrons

Cited by 483 publications

References 29 publications

Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

Regulation of serum apolipoprotein E metabolism: role of chylomicron metabolism.

Extrahepatic deposition and cytotoxicity of lithocholic acid: Studies in two hamster models of hepatic failure and in cultured human fibroblasts

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