Body Composition and Very-Low-Density-Lipoprotein-Triglycerides (VLDL-TG) Kinetics

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00646698
Recruitment Status : Completed
First Posted : March 28, 2008
Last Update Posted : March 28, 2008
The Danish Medical Research Council
The Novo Nordic Foundation
Information provided by:
University of Aarhus

Brief Summary:

Context: Upper body obese (UBO) subjects are more likely to develop cardiovascular disease (CVD) than lower body obese (LBO) or lean. This may in part be caused by greater hepatic secretion of very-low-density-lipoprotein-triglycerides (VLDL-TG).

Objective: To assess the impact of body composition and insulin sensitivity on basal VLDL-TG turnover in women.

Condition or disease
Obesity Insulin Resistance

Detailed Description:

Body composition is an important predictor of obesity related life-style diseases. Thus, preferential accumulation of adipose tissue in the abdominal region has been demonstrated to be associated with greater risk of developing CVD and insulin resistance than accumulation in lower body depots. The reason for this is not yet fully understood, but there are indications that upper body fat depots contain larger and more lipolytically active adipocytes resulting in an excess hepatic delivery of FFAs in upper body obese individuals. As several lines of experimental evidence as well as cross-sectional studies have demonstrated, elevated levels of FFAs affect the cardiovascular system unfavourably and are most likely a major contributor to insulin resistance. A prominent feature of insulin resistance is hypertriglyceridemia, primarily caused by increased levels of very-low-density-lipoprotein (VLDL)-TG.

Even though lipolysis in subcutaneous adipose tissue accounts for the majority (~75 %) of FFAs delivered to the liver, it is conceivable that excess release from visceral adipocytes in UBO individuals impacts VLDL-TG secretion. The reason for this is two-sided: First, upon entry into the liver, FFAs are reesterified to form VLDL-TG which is subsequently secreted. Studies in cell lines as well as whole body investigations in humans have demonstrated, that perturbations of FFA levels may directly affect VLDL-TG output by the liver. Second, elevated levels of FFAs may induce hepatic insulin resistance resulting in increased VLDL-TG output due to a loss of the inhibitory effect of insulin on VLDL-TG secretion. In theory, this combination of excess substrate availability coupled with an unfavorable hormonal milieu (hepatic insulin resistance) could result in increased VLDL-TG production in UBO subjects. A recent study by Mittendorfer et. al. support this notion, since weight loss in UBO women resulted in decreased VLDL-TG production, presumably caused primarily by a decrease in the supply of visceral fatty acids.

Although findings from previous studies have been contradictory as to whether body fat distribution directly affects VLDL-TG clearance, in vitro findings suggest regional differences in lipoprotein lipase (LPL) activity between UBO and LBO women, and VLDL-TG clearance could also be modulated by differences in VLDL associated fatty acid oxidation. To our knowledge, the latter point has not previously been addressed.

The purpose of this study was therefore to investigate differences in VLDL-TG kinetics in women with different body composition phenotypes. Our preliminary hypothesis was that UBO women produce and secrete greater amounts of VLDL-TG than their lower body obese (LBO) or lean counterparts. We also hypothesized, that peripheral clearance would be similar in all groups. Lastly, we wanted to investigate whether the more benevolent lipid profile seen in lean women could in part be a result of a more efficient channeling of VLDL derived fatty acids towards oxidation.

Study Type : Observational
Actual Enrollment : 30 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Impact of Body Composition on Very-Low-Density-Lipoprotein-Triglycerides Kinetics
Study Start Date : April 2006
Actual Primary Completion Date : February 2007
Actual Study Completion Date : June 2007

Premenopausal Upper Body Obese (UBO) women with waist-hip ratio > 0.85 and BMI > 28
Premenopausal Lower Body Obese (LBO) women with waist hip ratio < 0.8 and BMI > 28
Premenopausal lean women with BMI < 25

Primary Outcome Measures :
  1. VLDL-TG kinetics were assessed using a bolus injection of ex-vivo labeled [1-14C]VLDL-TG [ Time Frame: Hours ]

Secondary Outcome Measures :
  1. fractional VLDL-TG derived fatty acid oxidation was measured by 14CO2 trapping from expired air [ Time Frame: Hours ]
  2. VLDL-TG fat deposition by adipose tissue biopsies [ Time Frame: Hours ]
  3. Insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique [ Time Frame: 2 hours ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Community sample

Inclusion Criteria:

  • Woman
  • Premenopausal
  • Healthy
  • Not taking medication

Exclusion Criteria:

  • Diabetes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00646698

Medical Research Laboratories
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
The Danish Medical Research Council
The Novo Nordic Foundation
Principal Investigator: Lars C Gormsen, MD PhD Aarhus University Hospital, Department M

Responsible Party: Soren Nielsen, MD DMsc, Aarhus University Hospital Identifier: NCT00646698     History of Changes
Other Study ID Numbers: 2004-0217
First Posted: March 28, 2008    Key Record Dates
Last Update Posted: March 28, 2008
Last Verified: March 2008

Keywords provided by University of Aarhus:
VLDL-TG kinetics
Body composition
Tissue biopsies

Additional relevant MeSH terms:
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases