Receptor-independent low density lipoprotein transport in the rat in vivo. Quantitation, characterization, and metabolic consequences

D. K. Spady, S. D. Turley, J. M. Dietschy

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Abstract

Receptor-independent low density lipoprotein (LDL) transport plays a critical role in the regulation of plasma cholesterol levels; hence, these studies were done to characterize this process in the tissues of the rat. High rates of receptor-independent clearance were found in the spleen, but other organs, like liver, gastrointestinal tract, and endocrine glands manifested lower clearance rates that varied from 3 to 9 μl/h per g, while the rates in nervous tissue, muscle, and adipose tissue were <1 μl/h per g. Receptor-dependent uptake was much higher in liver (85 μl/h per g) and adrenal gland (219 μl/h per g), but was also low in most other tissues. At normal plasma LDL concentrations, 67% of the receptor-dependent transport in the whole animal was accounted for by LDL uptake in the liver. In contrast, the receptor-independent uptake found in the whole animal took place in many organs, including skeletal muscle (20%), liver (16%), small bowel (15%), skin (10%), and spleen (7%). Furthermore, in liver, the rate of cholesterol synthesis could be varied 11-fold, yet the rate of receptor-independent LDL clearance remained constant at ~8 μl/h per g. When the circulating levels of LDL were systematically increased, receptor-independent LDL clearance also remained constant, so that hepatic LDL-cholesterol uptake by this mechanism increased linearly, from 1 to 20 μg/h per g, as the plasma LDL-cholesterol level was increased from 10 to 250 mg/dl. Finally, when equal amounts of LDL-cholesterol were delivered into the liver by either the receptor-dependent or receptor-independent mechanism, there was significant suppression of cholesterol synthesis and an increase in cholesteryl esters. Thus, in any situation in which receptor-dependent LDL degradation is lost, cholesterol balance in the whole animal and across individual organs is maintained by receptor-independent mechanisms, although when the new steady state is achieved, circulating levels of LDL must necessarily be very much increased.

Original languageEnglish (US)
Pages (from-to)1113-1122
Number of pages10
JournalJournal of Clinical Investigation
Volume76
Issue number3
StatePublished - 1985

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LDL Receptors
Liver
LDL Lipoproteins
Cholesterol
LDL Cholesterol
Spleen
Endocrine Glands
Nerve Tissue
Cholesterol Esters
Adrenal Glands
Gastrointestinal Tract
Adipose Tissue
Skeletal Muscle
Muscles
Skin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Receptor-independent low density lipoprotein transport in the rat in vivo. Quantitation, characterization, and metabolic consequences. / Spady, D. K.; Turley, S. D.; Dietschy, J. M.

In: Journal of Clinical Investigation, Vol. 76, No. 3, 1985, p. 1113-1122.

Research output: Contribution to journalArticle

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abstract = "Receptor-independent low density lipoprotein (LDL) transport plays a critical role in the regulation of plasma cholesterol levels; hence, these studies were done to characterize this process in the tissues of the rat. High rates of receptor-independent clearance were found in the spleen, but other organs, like liver, gastrointestinal tract, and endocrine glands manifested lower clearance rates that varied from 3 to 9 μl/h per g, while the rates in nervous tissue, muscle, and adipose tissue were <1 μl/h per g. Receptor-dependent uptake was much higher in liver (85 μl/h per g) and adrenal gland (219 μl/h per g), but was also low in most other tissues. At normal plasma LDL concentrations, 67{\%} of the receptor-dependent transport in the whole animal was accounted for by LDL uptake in the liver. In contrast, the receptor-independent uptake found in the whole animal took place in many organs, including skeletal muscle (20{\%}), liver (16{\%}), small bowel (15{\%}), skin (10{\%}), and spleen (7{\%}). Furthermore, in liver, the rate of cholesterol synthesis could be varied 11-fold, yet the rate of receptor-independent LDL clearance remained constant at ~8 μl/h per g. When the circulating levels of LDL were systematically increased, receptor-independent LDL clearance also remained constant, so that hepatic LDL-cholesterol uptake by this mechanism increased linearly, from 1 to 20 μg/h per g, as the plasma LDL-cholesterol level was increased from 10 to 250 mg/dl. Finally, when equal amounts of LDL-cholesterol were delivered into the liver by either the receptor-dependent or receptor-independent mechanism, there was significant suppression of cholesterol synthesis and an increase in cholesteryl esters. Thus, in any situation in which receptor-dependent LDL degradation is lost, cholesterol balance in the whole animal and across individual organs is maintained by receptor-independent mechanisms, although when the new steady state is achieved, circulating levels of LDL must necessarily be very much increased.",
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