Cholesterol synthesis and low density lipoprotein uptake are regulated independently in rat small intestinal epithelium

E. F. Stange, J. M. Dietschy

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Abstract

We have compared the rates of low density lipoprotein (LDL) uptake and cholesterol synthesis in the rat intestine. By using a constant infusion technique, total and receptor-independent uptake was determined with homologous rat LDL (rLDL) and methylated human LDL (Me-hLDL), respectively. The absolute rates of sterol synthesis were measured with [1-14C]octanoate and [3H]water. The rates of rLDL uptake in whole gut segments were similar along the length of the small intestine, whereas the rates of sterol synthesis varied over a 5-fold range and were highest in the duodenum and distal ileum. When the mucosal epithelium was fractionated along the villus/crypt axis, both rLDL and Me-hLDL clearance by the enterocytes increased approximately 3-fold in going from the upper villus to the crypt cell fractions, in both jejunum and ileum. In both the whole gut segments and isolated cells, approximately 60% of LDL uptake was receptor dependent. When the rates of rLDL cholesterol uptake were calculated and related to the absolute rates of sterol synthesis in the same cell fractions in vivo, both processes were found to be distributed similarly along the villus/crypt axis. Furthermore, the majority of mucosal cholesterol (64-86%) was derived from local synthesis rather than from rLDL uptake at all locations along the intestinal villus. Finally, when sterol synthesis in the epithelial cells was varied up to 7-fold by feeding cholesterol, triglyceride, cholestyramine, or surfomer, rLDL uptake was essentially unchanged. Thus, in intestinal epithelial cells in vivo, the rate of LDL uptake was constant under circumstances in which changing needs for cellular cholesterol were met by changes in the rates of sterol synthesis.

Original languageEnglish (US)
Pages (from-to)5739-5743
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume80
Issue number181
StatePublished - 1983

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Intestinal Mucosa
LDL Cholesterol
Sterols
LDL Lipoproteins
Cholesterol
Ileum
Epithelial Cells
Cholestyramine Resin
Enterocytes
Jejunum
Duodenum
Small Intestine
Intestines
Triglycerides
Epithelium
oxidized low density lipoprotein
Water

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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title = "Cholesterol synthesis and low density lipoprotein uptake are regulated independently in rat small intestinal epithelium",
abstract = "We have compared the rates of low density lipoprotein (LDL) uptake and cholesterol synthesis in the rat intestine. By using a constant infusion technique, total and receptor-independent uptake was determined with homologous rat LDL (rLDL) and methylated human LDL (Me-hLDL), respectively. The absolute rates of sterol synthesis were measured with [1-14C]octanoate and [3H]water. The rates of rLDL uptake in whole gut segments were similar along the length of the small intestine, whereas the rates of sterol synthesis varied over a 5-fold range and were highest in the duodenum and distal ileum. When the mucosal epithelium was fractionated along the villus/crypt axis, both rLDL and Me-hLDL clearance by the enterocytes increased approximately 3-fold in going from the upper villus to the crypt cell fractions, in both jejunum and ileum. In both the whole gut segments and isolated cells, approximately 60{\%} of LDL uptake was receptor dependent. When the rates of rLDL cholesterol uptake were calculated and related to the absolute rates of sterol synthesis in the same cell fractions in vivo, both processes were found to be distributed similarly along the villus/crypt axis. Furthermore, the majority of mucosal cholesterol (64-86{\%}) was derived from local synthesis rather than from rLDL uptake at all locations along the intestinal villus. Finally, when sterol synthesis in the epithelial cells was varied up to 7-fold by feeding cholesterol, triglyceride, cholestyramine, or surfomer, rLDL uptake was essentially unchanged. Thus, in intestinal epithelial cells in vivo, the rate of LDL uptake was constant under circumstances in which changing needs for cellular cholesterol were met by changes in the rates of sterol synthesis.",
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T1 - Cholesterol synthesis and low density lipoprotein uptake are regulated independently in rat small intestinal epithelium

AU - Stange, E. F.

AU - Dietschy, J. M.

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N2 - We have compared the rates of low density lipoprotein (LDL) uptake and cholesterol synthesis in the rat intestine. By using a constant infusion technique, total and receptor-independent uptake was determined with homologous rat LDL (rLDL) and methylated human LDL (Me-hLDL), respectively. The absolute rates of sterol synthesis were measured with [1-14C]octanoate and [3H]water. The rates of rLDL uptake in whole gut segments were similar along the length of the small intestine, whereas the rates of sterol synthesis varied over a 5-fold range and were highest in the duodenum and distal ileum. When the mucosal epithelium was fractionated along the villus/crypt axis, both rLDL and Me-hLDL clearance by the enterocytes increased approximately 3-fold in going from the upper villus to the crypt cell fractions, in both jejunum and ileum. In both the whole gut segments and isolated cells, approximately 60% of LDL uptake was receptor dependent. When the rates of rLDL cholesterol uptake were calculated and related to the absolute rates of sterol synthesis in the same cell fractions in vivo, both processes were found to be distributed similarly along the villus/crypt axis. Furthermore, the majority of mucosal cholesterol (64-86%) was derived from local synthesis rather than from rLDL uptake at all locations along the intestinal villus. Finally, when sterol synthesis in the epithelial cells was varied up to 7-fold by feeding cholesterol, triglyceride, cholestyramine, or surfomer, rLDL uptake was essentially unchanged. Thus, in intestinal epithelial cells in vivo, the rate of LDL uptake was constant under circumstances in which changing needs for cellular cholesterol were met by changes in the rates of sterol synthesis.

AB - We have compared the rates of low density lipoprotein (LDL) uptake and cholesterol synthesis in the rat intestine. By using a constant infusion technique, total and receptor-independent uptake was determined with homologous rat LDL (rLDL) and methylated human LDL (Me-hLDL), respectively. The absolute rates of sterol synthesis were measured with [1-14C]octanoate and [3H]water. The rates of rLDL uptake in whole gut segments were similar along the length of the small intestine, whereas the rates of sterol synthesis varied over a 5-fold range and were highest in the duodenum and distal ileum. When the mucosal epithelium was fractionated along the villus/crypt axis, both rLDL and Me-hLDL clearance by the enterocytes increased approximately 3-fold in going from the upper villus to the crypt cell fractions, in both jejunum and ileum. In both the whole gut segments and isolated cells, approximately 60% of LDL uptake was receptor dependent. When the rates of rLDL cholesterol uptake were calculated and related to the absolute rates of sterol synthesis in the same cell fractions in vivo, both processes were found to be distributed similarly along the villus/crypt axis. Furthermore, the majority of mucosal cholesterol (64-86%) was derived from local synthesis rather than from rLDL uptake at all locations along the intestinal villus. Finally, when sterol synthesis in the epithelial cells was varied up to 7-fold by feeding cholesterol, triglyceride, cholestyramine, or surfomer, rLDL uptake was essentially unchanged. Thus, in intestinal epithelial cells in vivo, the rate of LDL uptake was constant under circumstances in which changing needs for cellular cholesterol were met by changes in the rates of sterol synthesis.

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