Related Experiment Video

Updated: Oct 4, 2026

Quantification of Atherosclerosis in Mice
06:59

Quantification of Atherosclerosis in Mice

Published on: June 12, 2019

Decreased hepatic accumulation and enhanced esterification of cholesterol in mice deficient in mdr1a and mdr1b

G D Luker1, J L Dahlheimer, R E Ostlund

  • 1Laboratory of Molecular Radiopharmacology, Washington University School of Medicine, 510 S. Kingshighway Blvd., St. Louis, MO 63110, USA.

Journal of Lipid Research
|August 24, 2001
PubMed

Insights

Class I P-glycoproteins (Pgp) do not affect overall cholesterol absorption in mice. However, Pgp influences cholesterol

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Class I P-glycoproteins (Pgp), including MDR1 (ABCB1) in humans and mdr1a/mdr1b in mice, are known for conferring drug resistance.
  • Their precise role in normal physiological processes, particularly sterol metabolism, is not well understood.
  • Previous cell culture studies suggest a potential involvement of Pgp in sterol absorption and intracellular transport.

Purpose of the Study:

  • To investigate the in vivo role of Class I Pgp in cholesterol absorption and esterification.
  • To determine if the absence of mdr1a and mdr1b genes affects cholesterol metabolism in mice.

Main Methods:

  • Utilized wild-type and mdr1a(-/)-/1b(-/)- mice models.
  • Employed a dual-isotope protocol to track radiolabeled cholesterol absorption and distribution.
  • Analyzed cholesterol and esterified cholesterol levels in serum and liver tissue.

Main Results:

  • Class I Pgp is not essential for the overall intestinal absorption of cholesterol.
  • Mice lacking mdr1a/mdr1b showed a decreased ratio of oral to intravenous labeled cholesterol in the liver.
  • Deletion of Class I Pgp enhanced the kinetics of hepatic esterification of orally administered cholesterol, but not intravenously administered cholesterol.

Conclusions:

  • Class I P-glycoproteins play a role in regulating the kinetics of hepatic cholesterol accumulation from oral administration.
  • Pgp appears to decrease the esterification rate of orally absorbed cholesterol in the liver.
  • These findings elucidate a novel physiological function of Class I Pgp in cholesterol metabolism in vivo.

More Related Videos

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction03:42

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction

Published on: March 29, 2024

Cholesterol Efflux Assay07:54

Cholesterol Efflux Assay

Published on: March 6, 2012

Related Concept Videos

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion, mediated...
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...