Very Low Density Lipoprotein Turnover in Young and Elderly Individuals

Study Overview
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Brief Summary
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Intrahepatic and intramyocellular lipid concentrations are elevated in elderly individuals relative to young people, despite no significant difference in fasting plasma TAG concentrations. Our general hypothesis is that the increase in intrahepatic fat with age results from reduced VLDL turnover, and therefore elderly individuals in this study will display lower VLDL turnover rates than young individuals. The aims of this study are a) to compare VLDL turnover in young and elderly individuals, and b) to compare a bolus method and a constant infusion method of assessing VLDL turnover.

Detailed Description
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Several studies have shown an association between hypertriacylglycerolaemia and coronary artery disease. Additionally, ectopic fat distribution, in particular, deposition of excess lipid within the liver and skeletal muscle, has been shown to correlate negatively with insulin sensitivity, thus presenting a metabolic milieu in which risk of developing type 2 diabetes is elevated. Previous research from our group has shown that the triacylglycerol (TAG) concentration within the liver, and within skeletal muscle fibres IMCLs (intramyocellular lipids), is increased in elderly individuals compared with young people. The elevation of lipids in these particular tissues for the elderly group was observed despite no statistically significant difference in fasting plasma TAG concentration. As the plasma TAG concentration during the postabsorptive state is largely determined by the production and clearance rates of very low density lipoprotein triacylglycerol (VLDL-TAG), and increased liver fat content has been shown to drive production of large VLDL particles, it is important to gain an understanding of whether VLDL synthesis and breakdown differs between young and elderly individuals. Such new knowledge may offer an insight into why tissue lipids are elevated in the elderly. At present, no data exist in the literature describing VLDL turnover in elderly people. We hypothesise that very low density lipoprotein turnover will be reduced in elderly individuals compared with young people. The aims of this study are a) to determine whether fractional synthesis and breakdown rates of both the protein and lipid parts of the VLDL are different between young and elderly individuals, and b) to determine whether VLDL turnover values appear different when calculated using a constant infusion tracer method as compared with a bolus tracer method. Eight young men, eight young women, eight elderly men and eight elderly women will each participate in an 8-hour infusion study. Stable isotopes of glycerol, amino acids and fatty acids will be infused, and blood samples will be drawn in intervals during the study.

Official Title
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Very Low Density Lipoprotein Turnover in Young and Elderly Individuals

Conditions
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Aging

Intervention / Treatment
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* Procedure: Stable Isotope Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 35 years, or 60 to 75 years. Body mass index ≤ 27 kg•m2 Ability to sign informed consent. Score of ≥26 for Mini-Mental State Exam Exclusion Criteria: Diabetics (plasma glucose concentration >200 mg/dl at 2 hr after oral intake of 75 g glucose). Fasting plasma triacylglycerol concentration above 500 mg/dl Kidney disease. Liver disease. Bleeding disorders. Anaemia (Hb < 13 g/dl in males or < 12 g/dl in females). Endocrine disease (with the exception of well-regulated hypothyroidism). Positive hepatitis or HIV screens. Alcohol (CAGE questionnaire; abnormal liver enzyme values) or drug abuse (amphetamines, cocaine, opioids, marijuana). Lipid altering agents. Score of <26 for Mini-Mental State Exam

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Young Males<br>Males, age 18-35 years. 9-hour Stable isotope infusion | Procedure: Stable Isotope Infusion<br>* 9-hour infusion of stable isotope tracers<br>|
| Young Females<br>Females, age 18-35 years. 9-hour Stable isotope infusion | Procedure: Stable Isotope Infusion<br>* 9-hour infusion of stable isotope tracers<br>|
| Older Males<br>Males, age 60-75. 9-hour Stable isotope infusion | Procedure: Stable Isotope Infusion<br>* 9-hour infusion of stable isotope tracers<br>|
| Older Females<br>Females, age 60-75. 9-hour Stable isotope infusion | Procedure: Stable Isotope Infusion<br>* 9-hour infusion of stable isotope tracers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Very Low Density Lipoprotein (VLDL) Turnover | Turnover rates of VLDL-triglycerides and VLDL-ApoB (apolipoprotein B)-100, including synthesis and breakdown rates, measured during a 9-hour infusion trial. | 9-hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aging, lipid metabolism, very low density lipoproteins