Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Age-associated decrease in plasma cholesterol and changes in cholesterol metabolism in homozygous Watanabe heritable

M Shiomi1, T Ito, T Fujioka

  • 1Institute for Experimental Animals, Kobe University School of Medicine, Japan.

Metabolism: Clinical and Experimental
|April 25, 2000
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

MRI study of atherosclerotic plaque progression using ultrasmall superparamagnetic iron oxide in Watanabe heritable hyperlipidemic rabbits.

The British journal of radiology·2015
Same author

A case of severe progressive early-onset epileptic encephalopathy: unique GABAergic interneuron distribution and imaging.

Journal of the neurological sciences·2013
Same author

Morphological Study of Carotid Artery of WHHL Rabbit after Balloon Dilatation.

Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences·2010
Same author

Determinants of outcomes following acute child encephalopathy and encephalitis: pivotal effect of early and delayed cooling.

Archives of disease in childhood·2010
Same author

Acute encephalitis with refractory, repetitive partial seizures (AERRPS): a peculiar form of childhood encephalitis.

Acta neurologica Scandinavica·2009
Same author

[Current topics of acute encephalitis and encephalopathy in Japanese children].

No to hattatsu = Brain and development·2009

This study investigates why cholesterol levels drop as Watanabe heritable hyperlipidemic rabbits age. Researchers found that both reduced production of cholesterol-carrying particles by the liver and faster clearance of these particles from the blood contribute to this decline.

Area of Science:

  • Lipid metabolism research within cardiovascular medicine
  • Watanabe heritable hyperlipidemic rabbit models in metabolic physiology

Background:

The physiological mechanisms driving age-related shifts in lipid profiles remain poorly characterized in specific genetic models. Prior research has shown that Watanabe heritable hyperlipidemic rabbits exhibit severe hypercholesterolemia due to inherited receptor deficiencies. That uncertainty drove this investigation into why these animals experience a significant decline in plasma cholesterol as they mature. No prior work had resolved how hepatic enzyme activities and lipoprotein kinetics interact during this specific aging process. It was already known that these rabbits serve as a standard proxy for human familial hypercholesterolemia. This gap motivated a detailed longitudinal analysis of lipid metabolism across multiple developmental stages. Researchers sought to bridge the disconnect between observed phenotypic changes and underlying biochemical pathways. Understanding these dynamics provides a clearer picture of how lipid homeostasis evolves in the absence of standard clearance pathways.

Purpose Of The Study:

Keywords:
Lipid kineticsHepatic enzymesLDL receptorsVLDL secretion

Frequently Asked Questions

The researchers propose that the decline in plasma cholesterol results from a combination of reduced secretion of very-low-density lipoprotein from the liver and an accelerated catabolic rate of these particles in the circulation.

The study utilized the Triton WR-1339 injection technique to determine the secretion rate of very-low-density lipoprotein cholesterol, allowing for a precise evaluation of hepatic output across different age groups.

The researchers note that the oldest group of rabbits exhibited a catabolic rate of very-low-density lipoprotein cholesterol that was approximately 2-fold higher than that observed in the younger cohorts.

Related Experiment Videos

The aim of this study was to elucidate the biological drivers behind the age-related decline in plasma cholesterol observed in a specific genetic rabbit model. Researchers sought to clarify why these animals, which lack functional low-density lipoprotein receptors, exhibit such a pronounced shift in lipid profiles over time. This investigation addressed the uncertainty regarding whether hepatic production or peripheral clearance is responsible for the observed reduction. By examining rabbits at various life stages, the team intended to map the progression of lipid metabolism from weaning to advanced age. The study specifically targeted the interaction between microsomal enzyme activity and lipoprotein secretion rates. This effort was motivated by the need to understand the physiological properties of this model beyond its initial hyperlipidemic state. The researchers hypothesized that age-dependent changes in liver function might compensate for the underlying receptor deficiency. Ultimately, the work provides a detailed analysis of the metabolic pathways that modulate lipid levels in this unique animal system.

Main Methods:

Review Approach framing involves a longitudinal assessment of rabbits at four distinct developmental milestones. The team monitored subjects from weaning at three months through sexual maturity at six months. Further observations occurred at twelve and twenty-four months to capture long-term physiological shifts. Investigators quantified plasma levels of total cholesterol, triglycerides, and phospholipids to track systemic lipid changes. The research team utilized liver microsomal fractions to evaluate specific enzymatic activities, including reductase and transferase functions. They applied Triton WR-1339 injections to isolate and measure the secretion rate of very-low-density lipoprotein particles. This systematic design allowed for a direct comparison of metabolic kinetics between young and aged cohorts. The methodology prioritized tracking the LDL fraction to determine its contribution to overall plasma lipid reductions.

Main Results:

Key Findings From the Literature indicate that plasma total cholesterol, triglyceride, and phospholipid levels declined by approximately 45% throughout the aging period. These reductions were primarily attributed to a significant decrease in the LDL fraction. Within the liver, 3-hydroxy-3-methylglutaryl coenzyme A reductase activity increased, while acyl-coenzyme A:cholesterol acyltransferase activity showed a marked decrease. Hepatic cholesterol concentration and cholesterol 7alpha-hydroxylase activity remained unchanged across all examined age groups. The secretion rate of very-low-density lipoprotein cholesterol decreased significantly as the rabbits reached older ages. Conversely, the catabolic rate of very-low-density lipoprotein cholesterol was found to be 2-fold higher in the oldest group compared to younger animals. Lipolytic activity displayed variable patterns throughout the study duration. These results demonstrate that multiple metabolic pathways are involved in the age-associated drop in circulating lipids.

Conclusions:

Synthesis and Implications framing suggests that the observed drop in circulating cholesterol levels stems from a dual-action process. The authors propose that reduced hepatic output of very-low-density lipoprotein particles plays a primary role. They also highlight that enhanced clearance rates of these particles from the bloodstream contribute to the overall reduction. These findings indicate that aging significantly alters the metabolic handling of lipids in this specific animal model. The researchers emphasize that these shifts occur independently of changes in cholesterol 7alpha-hydroxylase activity. They suggest that the observed enzymatic adjustments in the liver reflect a complex adaptation to long-term hyperlipidemia. This work clarifies the physiological factors governing lipid fluctuations in the absence of functional low-density lipoprotein receptors. The study provides a framework for interpreting age-dependent lipid changes in similar clinical contexts.

The authors observed that 3-hydroxy-3-methylglutaryl coenzyme A reductase activity increased, whereas acyl-coenzyme A:cholesterol acyltransferase activity decreased in the liver microsomal fraction as the rabbits aged.

While plasma total cholesterol, triglyceride, and phospholipid levels dropped by approximately 45% with aging, the cholesterol concentration and cholesterol 7alpha-hydroxylase activity within the liver microsomes remained stable.

The authors conclude that the age-associated lipid reduction is driven by a synergistic effect of decreased hepatic secretion and increased peripheral clearance, rather than a single metabolic event.