Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans

Weinberg, Richard B.; Geissinger, Brent W.; Kasala, Kalpana; Hockey, Karen J.; Terry, James G.; Easter, Linda; Crouse, John R.

doi:10.1016/s0022-2275(20)32365-8

Cited by 19 publications

(3 citation statements)

References 54 publications

(55 reference statements)

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“…Nonetheless, it is not known whether neural effects of apoA-IV affect gastric emptying in humans or whether apoA-IV polymorphisms could modulate its effect on gastrointestinal function. We have shown that the A-IV-2 allele reduces the efficiency of cholesterol absorption in subjects consuming a polyunsaturated fat diet (40), which suggests that apoA-IV may play a role in modulating chylomicron assembly. However, intestinal lipid absorption is grossly normal in apoA-IV knock-out mice (53); hence, the function of apoA-IV in chylomicron synthesis must be an accessory one.…”

Section: Discussionmentioning

confidence: 89%

“…This allele encodes a Q360H substi-tution (33) that significantly increases the lipid affinity (34), lecithin:cholesterol acyltransferase activation (34), and plasma residence time (35) of the apoA-IV-2 isoprotein. Recently, several studies have observed that the A-IV-2 allele affects the plasma lipoprotein response to dietary fat and cholesterol (36)(37)(38)(39), and may also modulate the efficiency of intestinal cholesterol absorption (40).…”

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confidence: 99%

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Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance

Hockey

Anderson

Cook

et al. 2001

Journal of Lipid Research

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Apolipoprotein (apo)A-IV is synthesized in the small intestine during fat absorption and is incorporated onto the surface of nascent chylomicrons. In circulation, apoA-IV is displaced from the chylomicron surface by high density lipoprotein-associated C and E apolipoproteins; this exchange is critical for activation of lipoprotein lipase and chylomicron remnant clearance. The variant allele A-IV-2 encodes a Q360H polymorphism that increases the lipid affinity of the apoA-IV-2 isoprotein. We hypothesized that this would impede the transfer of C and E apolipoproteins to chylomicrons, and thereby delay the clearance of postprandial triglyceride-rich lipoproteins. We therefore measured triglycerides in plasma, S f Ͼ 400 chylomicrons, and very low density lipoproteins (VLDL) in 14 subjects heterozygous for the A-IV-2 allele (1/2) and 14 subjects homozygous for the common allele (1/1) who were fed a standard meal containing 50 gm fat per m 2 body surface area. All subjects had the apoE-3/3 genotype. Postprandial triglyceride concentrations in the 1/2 subjects were significantly higher between 2-5 h in plasma, chylomicrons, and VLDL, and peaked at 3 h versus 2 h for the 1/1 subjects. The area under the triglyceride time curves was greater in the 1/2 subjects (plasma, P ‫؍‬ 0.045; chylomicrons, P ‫؍‬ 0.027; VLDL, P ‫؍‬ 0.063). A posthoc analysis of the frequency of the apoA-IV T347S polymorphism suggested that it had an effect on triglyceride clearance antagonistic to that of the A-IV-2 allele. We conclude that individuals heterozygous for the A-IV-2 allele display delayed postprandial clearance of triglyceride-rich lipoproteins. -Hockey, K.

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Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance

Hockey

Anderson

Cook

et al. 2001

Journal of Lipid Research

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“…Several mutations have also been described in APOA-IV, although the two most common are a T347S and Q360H aminoacid substitutions (Lohse, Kindt, Rader, & Brewer, 1990a, 1990b. These mutations have been associated with altered lipid profile, including triglyceride clearance, cholesterol absorbance and overall variability of HDL particles (Gomaraschi et al, 2010;Hockey, Anderson, Cook, Hantgan, & Weinberg, 2001;Jansen, Lopez-Miranda, et al, 1997;Weinberg et al, 2000). Although one study indicated a genetic association between the APOA-IV Q360T polymorphism and AD, two other reports failed to confirm this finding (Csaszar, Kalman, Szalai, Janka, & Romics, 1997;Ji, Urakami, et al, 1999;Merched, Xia, Papadopoulou, Siest, & Visvikis, 1998).…”

Section: Apolipoproteinsmentioning

confidence: 99%

High‐density lipoprotein‐related cholesterol metabolism in Alzheimer’s disease

Pedrini

Chatterjee

Hone

et al. 2020

Journal of Neurochemistry

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Alzheimer's disease (AD) is the leading cause of dementia in the elderly and the number of affected individuals is set to increase in the next decades. The two main features of AD are represented by extracellular amyloid plaques of amyloid β (Aβ) in the brain parenchyma and intracellular neurofibrillary tangles of tau protein. In the past decades several lines of evidence have indicated that high-density lipoproteins (HDL) are strongly involved in the aetiology and the progression of the disease, although the overall analysis of HDL levels and their association with cognitive functions somehow lacked consensus. Many of the proteins associated with HDL are also linked to AD and Aβ formation/catabolism, some displaying protective features while others do not, it is not surprising the association between HDL levels and AD provided confounding results. It is therefore possible that components of HDL 'protein cargo', more than the HDL levels alone, are responsible for neuroprotection and affect Aβ formation and/or deposition.

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Simultaneous assessment of cholesterol absorption and synthesis in humans using on‐line gas chromatography/ combustion and gas chromatography/pyrolysis/isotope‐ratio mass spectrometry

Gremaud

Piguet

Baumgartner

et al. 2001

Rapid Comm Mass Spectrometry

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A number of dietary components and drugs are known to inhibit the absorption of dietary and biliary cholesterol, but at the same time can compensate by increasing cholesterol synthesis. It is, therefore, necessary to have a convenient and accurate method to assess both parameters simultaneously. Hence, we validated such a method in humans using on-line gas chromatography(GC)/combustion and GC/pyrolysis/isotope-ratio mass spectrometry (IRMS). Cholesterol absorption was measured using the ratio of [(13)C]cholesterol (injected intravenously) to [(18)O]cholesterol (administered orally). Simultaneously, cholesterol synthesis was measured using the deuterium incorporation method. Our methodology was applied to 12 mildly hypercholesterolemic men that were given a diet providing 2685 +/- 178 Kcal/day (mean +/- SD) and 255 +/- 8 mg cholesterol per day. Cholesterol fractional synthesis rates ranged from 5.0 to 10.5% pool/day and averaged 7.36% +/- 1.78% pool/day (668 +/- 133 mg/day). Cholesterol absorption ranged from 36.5-79.9% with an average value of 50.8 +/- 15.4%. These values are in agreement with already known data obtained with mildly hypercholesterolemic Caucasian males placed on a diet similar to the one used for this study. However, our combined IRMS method has the advantage over existing methods that it enables simultaneous measurement of cholesterol absorption and synthesis in humans, and is therefore an important research tool for studying the impact of dietary treatments on cholesterol parameters.

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Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans

Cited by 19 publications

References 54 publications

Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance

Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance

High‐density lipoprotein‐related cholesterol metabolism in Alzheimer’s disease

Simultaneous assessment of cholesterol absorption and synthesis in humans using on‐line gas chromatography/ combustion and gas chromatography/pyrolysis/isotope‐ratio mass spectrometry

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