Cited by 265Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthLipid metabolism and disorders

Human HDL cholesterol levels are determined by apoA-I fractional catabolic rate, which correlates inversely with estimates of HDL particle size. Effects of gender, hepatic and lipoprotein lipases, triglyceride and insulin levels, and body fat distribution.

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Brinton, E A, Eisenberg, S, Breslow, J L·1994·Arteriosclerosis and Thrombosis: A Journal of Vascular Biology

Abstract

High-density lipoprotein (HDL) cholesterol (HDL-C) levels are a strong inverse predictor of atherosclerosis risk, but the physiological determinants of HDL-C levels are poorly understood. We selected 57 human subjects (30 women and 27 men) with a broad range of HDL-C levels and performed turnover studies of apolipoprotein (apo)A-I and apoA-II, the two major apolipoproteins of HDL, to measure the fractional catabolic rate (FCR) and production or transport rate (TR) of these proteins. We also measured several other parameters known to correlate with HDL-C levels to test for their interrelations and to postulate mechanisms of regulation of HDL-C levels. As expected, the women had higher levels of HDL-C (56.7 +/- 21.4 versus 45.1 +/- 16.3 mg/dL, mean +/- SD; P = .03) and apoA-I (147 +/- 32 versus 126 +/- 29 mg/dL, P = .01) than men and did not differ in apoA-II levels (34.5 +/- 7.4 versus 33.3 +/- 7.5 mg/dL, P > .2). The FCR of apoA-I tended to be lower in the women (0.248 +/- 0.077 versus 0.277 +/- 0.069 pools/d, P = .1), although the difference was not statistically significant. The FCR of apoA-II was also lower (0.184 +/- 0.043 versus 0.216 +/- 0.056 pools/d, P = .02). In contrast, the apoA-I TR was equal in women and men (12.0 +/- 1.6 versus 12.1 +/- 2.8 mg/kg per day, P > .2), and there was a trend toward lower apoA-II TR in women (2.19 +/- .62 versus 2.61 +/- 1.06 mg/kg per day, P = .07). Linear regression analysis revealed a strong inverse correlation between HDL-C levels and the FCRs of apoA-I and apoA-II (r = -.81 and -.76, respectively; P < .0001 for both). In contrast, there was little or no association between HDL-C and the TRs of apoA-I and apoA-II (r = .06 and -.35, P = not significant and .01, respectively). In stepwise multiple linear regression analysis, apoA-I FCR alone accounted for 66% of the variability in HDL-C; two other variables accounted for an additional 7%. Due to the importance of apoA-I FCR, its determinants were sought among the remaining variables.(ABSTRACT TRUNCATED AT 400 WORDS)

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Crossref · 10.1161/01.atv.14.5.707

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  • Small HDL in hypertriglyceridemia is associated with hypercatabolism of apolipoprotein A-I and seems related to elevated hepatic lipase activity in central obesity and insulin resistance.

    “Small HDL in hypertriglyceridemia is associated with hypercatabolism of apolipoprotein A-I (47, 48), and it seems to be related to elevated hepatic lipase activity in central obesity and insulin resistance (49).”

    From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [48]

    The Discussion links HDL size to hepatic lipase activity and suggests that abdominal fat may influence that activity. The Results report a positive association between abdominal fat distribution and hepatic lipase, but no significant association between fasting insulin and hepatic lipase. Thus, the central-obesity link is supported, while elevated hepatic lipase in insulin resistance is not established by this paper. Page numbers are unavailable in our copy. (LLM, conf=0.85)

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  • Catabolism rather than production is the major determinant of HDL apoA-I levels.

    “These data suggest that catabolism rather than production is the major determinant of HDL apoA-I levels, as suggested by previous studies (43)(44)(45).”

    From Plasma turnover of HDL apoC-I, apoC-III, and apoE in humans (2003) · cites this paper as [45]

    The Discussion (page not available in our copy) says apoA-I fractional catabolic rate predicts variation in HDL cholesterol better than apoA-I production or transport rate. The claim instead concerns apoA-I levels; the same section notes a study suggesting that production rate may predict those levels better than catabolic rate. This paper therefore supports the comparison for HDL cholesterol, but not for the stated outcome. (LLM, conf=0.85)

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1 of the 36 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Miller NE. High density lipoprotein as a predictor of clinical coronary heart disease. In: Fidge NH, Nestel PJ, eds. Athero- sclerosis VII. Amsterdam, the Netherlands: Elsevier; 1986:61.
  2. National Health and Nutrition Examination Survey. Dietary intake source data, 11. Hyattsville, Md: National Center for Health Statistics; Office of Health Research Statistics and Technology; 1983:48-52.
  3. Sadur CN, Eckel RH. Insulin stimulation of adipose tissue lipo- protein lipase. J Clin Invest. 1982;69:1119-1125.

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Authors
Brinton, E. A., Eisenberg, S., & Breslow, J. L.
Affiliations
Rockefeller University (US)
Venue
Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
Published
1994-05
Volume
14
Issue
5
Pages
707-720
ISSN
1049-8834 (ISSN-L)
OpenAlex
W2155588817
Cited by
265
References
36
Citations by year
2026: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 6 · 2014: 5 · 2013: 9 · 2012: 3
FWCI
16.95
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis and Thrombosis A Journal of Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Pew Charitable Trusts
  • Memorial Sloan-Kettering Cancer Center
  • National Institutes of Health (5r01hl033714-17, 5r37hl036461-09)
  • National Heart, Lung, and Blood Institute (HL 33714, R01HL032435, HL-36461, HL32435)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
HDL cholesterol, apolipoprotein A-I, apolipoprotein A-II, fractional catabolic rate, HDL particle size, sex differences, hepatic lipase, lipoprotein lipase, triglycerides, insulin, body fat distribution, atherosclerosis risk
MeSH terms
Adipose Tissue, Adult, Aged, Female, Humans, Insulin, Lipase, Lipoprotein Lipase, Lipoproteins, HDL, Cholesterol, HDL, Liver, Male, Middle Aged, Particle Size, Regression Analysis, Sex Factors, Triglycerides, Apolipoprotein A-I, Apolipoprotein A-II

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