Body Composition and Very-Low-Density-Lipoprotein-Triglycerides (VLDL-TG) Kinetics
Condition: Obesity; Insulin Resistance
MeSH terms: Insulin Resistance
Study type: Observational

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.
    

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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Community sample
      
Keywords: VLDL-TG kinetics; Obesity; Body composition; Tracers; Tissue biopsies