Features of cholesterol structure that regulate the clearance of chylomicron-like lipid emulsions.

Mortimer, B-C.; Tso, P.; Phan, Cam T; Beveridge, Dianne J.; Wen, Ja-Yan; Redgrave, Trevor G.

doi:10.1016/s0022-2275(20)41121-6

Cited by 25 publications

(9 citation statements)

References 35 publications

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“…6) was greater for emulsions containing sterols with an alkyl side chain with 4 carbon atoms or with an unsaturated bond at the terminal carbon (n-C4-1-u) compared with emulsions prepared with cholesterol or other sterols. However, other sterols had little effect on lipolysis consistent with previous evidence that emulsion sterols have little influence on lipolysis in vivo (5,6). Although sterol side-chain structure did not affect the amount of apoE3 bound to emulsions, we found that in cell culture studies the binding of the n-C3 emulsions to HepG2 cells was markedly reduced (Fig.…”

Section: Discussionsupporting

confidence: 90%

“…We have previously shown that for the physiological clearance of chylomicron-like emulsions, the presence of a hydroxyl group in either the ␣ and ␤ configuration at the 3 position and an alkyl side chain of undefined length and degree of saturation at the C-17 position of cholesterol are essential (6). To determine the importance of the structure and length of the isooctyl side chain at the C-17 position, the present clearance studies were performed with various synthetic sterols using emulsion models of lymph chylomicrons.…”

Section: Discussionmentioning

confidence: 99%

“…When cholesterol is omitted, emulsions are substrates for lipoprotein lipase but the remnants, traced by emulsion cholesteryl oleate (CO), remain circulating in the plasma for a protracted time (2,5). We also found that for the physiological clearance of chylomicron-like emulsions, the presence of a hydroxyl group at the 3 position and an alkyl side chain at C-17 of cholesterol are essential (6).…”

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confidence: 99%

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Sterol side chain length and structure affect the clearance of chylomicron-like lipid emulsions in rats and mice

Martins

Vilchèze

Mortimer

et al. 1998

Journal of Lipid Research

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In previous work we found that sterols such as cholesterol were essential for physiological plasma clearance of lipid emulsions mimicking the structure of mammalian triglyceride-rich lipoproteins. In the present study we compared the clearances of emulsions prepared with sterols of varying alkyl chain length (straight chains, n -C3 to n -C7, or branched chains, i -C5 to i -C10) at the C-17 position. Our studies show that the length of the alkyl chain at the C-17 position of sterols markedly affects the removal of remnant particles from the plasma of rats traced by emulsion cholesteryl oleate label. An alkyl chain of 7 carbons or more was needed for normal remnant clearance. Straight and branched chains of similar length were cleared similarly, showing that the presence of a branch at the end of the alkyl chain had no effect on remnant clearance. For side chains of 7 carbons or less, substitution of sterols with an unsaturation in the alkyl chain close to the terminal carbon markedly decreased the clearance of remnants. Triolein label was used to estimate lipolysis of the injected emulsions. Lipolysis was little affected by the structure of the sterol side chain, except that lipolysis was markedly higher with emulsions containing sterols with an alkyl chain having 4 carbon atoms ( n -C4) or with an unsaturation in the 4 carbon alkyl chain.We conclude that the length of the alkyl side chain is an important element in the essentiality of cholesterol as a regulator of metabolism of lipid emulsion models of triglyceride-rich lipoproteins.-Martins, I. J., C. Vilchèze, B-C. Mortimer, R. Bittman, and T. G. Redgrave. Sterol side chain length and structure affect the clearance of chylomicron-like lipid emulsions in rats and mice.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Sterol side chain length and structure affect the clearance of chylomicron-like lipid emulsions in rats and mice

Martins

Vilchèze

Mortimer

et al. 1998

Journal of Lipid Research

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“…Dietary oxysterols also have the potential to effect the metabolism of lipoproteins. They may, for example, exacerbate the atherogenicity of postprandial lipoproteins by delaying their clearance from plasma and enhancing arterial uptake (26,27). Oxysterols could also influence the kinetics and arterial retention of hepatic-derived lipoproteins after transfer from chylomicrons (26,27).…”

mentioning

confidence: 99%

“…They may, for example, exacerbate the atherogenicity of postprandial lipoproteins by delaying their clearance from plasma and enhancing arterial uptake (26,27). Oxysterols could also influence the kinetics and arterial retention of hepatic-derived lipoproteins after transfer from chylomicrons (26,27). Moreover, others have suggested that ingestion of lipid oxidation products may increase metabolic oxidative stress in vivo (28,29).…”

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confidence: 99%

Dietary oxysterols are incorporated in plasma triglyceriderich lipoproteins, increase their susceptibility to oxidation and increase aortic cholesterol concentration of rabbits

Vine

Mamo

Beilin

et al. 1998

Journal of Lipid Research

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Early fatty streaks and advanced lesions are characterized by the deposition of cholesterol and cholesterol oxidation products (oxysterols). Oxysterols have been shown to be cytotoxic and pro-atherogenic compared to cholesterol and are found in cholesterol-rich processed foods. The consumption of dietary oxysterols may be significant in the onset and development of vascular disease. In order to study the short term effects of low levels of ingested dietary oxysterols on lipoprotein and aortic cholesterol and oxysterol levels, rabbits were fed either standard chow, chow supplemented with 1.0% oxidized cholesterol (containing 6% oxysterols), or 1.0% purified cholesterol (control). To determine the distribution and uptake of oxysterols after a 2-week dietar y period, triglyceride-rich plasma lipoproteins, low density lipoproteins and aorta were analyzed by GC-MS. The concentration of 7 ␤ -hydroxycholesterol was similar in all groups but the oxidized cholesterol-fed animals showed five times the concentration of 5 ␣ ,6 ␣ -epoxycholesterol and double the level of 7-ketocholesterol in triglyceride-rich lipoproteins compared to the purified cholesterol-fed animals. The presence of 7-ketocholesterol in LDL was exclusive to animals fed the oxidized cholesterol diet. In addition, oxidation of triglyceride-rich lipoproteins was significantly greater in rabbits fed oxidized cholesterol compared to the pure cholesterol-fed animals. The oxidized cholesterol-fed animals also had a 64% increase in total aortic cholesterol, despite lower plasma cholesterol levels compared to the pure cholesterol control animals.Taken together these results suggest that dietary oxysterols may substantially increase the atherogenicity of lipoproteins.-Vine, D.

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Methods for Studying Rodent Intestinal Lipoprotein Production and Metabolism

2012

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Lipid absorption begins with the digestion of dietary triacylglycerol and ultimately results in the secretion of triacylglycerol in chylomicrons into the lymphatics. Additionally, the intestine also secretes numerous proteins and peptides involved in lipid and lipoprotein metabolism in response to food. Ultimately, chylomicrons and these proteins, peptides, and hormones are found in lymph. The lymph fistula rat model has traditionally been used to study this intestinal absorption of nutrients, especially lipids, but recently, this model has also been used for studying the secretion of hormones by the small intestine. The protocols described in this article include the lymph fistula rat and mouse model, as well as in vivo chylomicron metabolism studies. These experimental models are helpful for the study of metabolic phenotypes, the characterization of intestinal lipid absorption and transport, and determining peripheral metabolism of intestinally derived lipoproteins.

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Features of cholesterol structure that regulate the clearance of chylomicron-like lipid emulsions.

Cited by 25 publications

References 35 publications

Sterol side chain length and structure affect the clearance of chylomicron-like lipid emulsions in rats and mice

Sterol side chain length and structure affect the clearance of chylomicron-like lipid emulsions in rats and mice

Dietary oxysterols are incorporated in plasma triglyceriderich lipoproteins, increase their susceptibility to oxidation and increase aortic cholesterol concentration of rabbits

Methods for Studying Rodent Intestinal Lipoprotein Production and Metabolism

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