Diet-induced, functional low density lipoprotein receptor deficiency in a healthy young man

P. B. Duell, D. L. Wheaton, D. R. Illingworth, W. E. Connor

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Abstract

Dietary saturated fats and cholesterol (C) promote hypercholesterolemia primarily by downregulating hepatic low density lipoprotein (LDL) receptor activity. Reduced intake of fat and C can induce a maximal 20 to 25 % decrease in plasma LDL-C levels. Preliminary studies in a 34 year old healthy hypercholesterolemic man demonstrated an extraordinary 84% ↓ in plasma LDL-C in response to a low fat diet (20-25% fat) vs very high fat diet (> 50% fat, > 3.3 g C)(table). Plasma sterols were normal; apo E genotype: E3/E3. After 10 days of eating 15 eggs/d, his LDL-C increased 35% (94 → 137 mg/dl). After consuming a high fat diet 5 days/wk for 5 weeks, his LDL-C increased 250% (107 → 267 mg/dl). Further diet studies were declined. His cultured skin fibroblasts revealed 34% downregulation of high affinity 125I-LDL binding at 4° C and 95% ↓ 125I-LDL degradation at 37° C in C-loaded vs lipid-depleted cells. Values for control fibroblasts were 46% and 90%, respectively. Diet Total C (mg/dl) LDL-C(mg/dl) HDL-C(mg/dl) Triglyceride Baseline high fat 704 596 90 88 Low fat x 19 weeks 172 94 68 53 In summary, this man appears to develop unprecedented diet-induced functional LDL-receptor deficiency. We hypothesize that he may hyperabsorb dietary C or could have an abnormality in regulation of hepatic LDL receptor expression, such as defects in sterol regulatory element-binding protein-1 or Sp1 (constitutive) mediated transcription. Further studies are required to test these possibilities.

Original languageEnglish (US)
Pages (from-to)181A
JournalJournal of Investigative Medicine
Volume44
Issue number1
StatePublished - Jan 1 1996

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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