Kinetic studies of plasma free fatty acid and triglyceride metabolism in man

Eaton, R. Philip; Berman, Mones; Steinberg, Daniel

doi:10.1172/jci106122

Cited by 129 publications

(82 citation statements)

References 35 publications

(30 reference statements)

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“…However, no attempt was made to separate individual lipoproteins before performing the labeling procedure; in fact, the authors reported that radiolabeled TG was found in all lipoprotein fractions before injection of the processed sample. In a recent elegant study, Sidossis and coworkers (3) used in vivo labeling of VLDL-TGs using [U- 13 C 3 ]glycerol, plasmapheresis, and isolation of 13 C-labeled VLDL-TGs followed by traditional isotope dilution technique (primed constant infusion and steady-state equations). Such studies require the availability of mass spectrometry facilities.…”

Section: Discussionmentioning

confidence: 99%

“…These methods do not allow one to determine the metabolic fate of the fatty acid moiety of the TG molecule and are dependent upon the validity of the mathematical model for the given experimental setting. Another approach is to collect and isolate in vivo-labeled VLDL particles and reinfuse them into the same subject at a later time (13). However, using this approach, only a small amount of labeled VLDL-TG can been obtained for reinfusion; consequently, the specific activity (SA) of circulating VLDL-TG after reinjection has been sufficiently low that it is sometimes difficult to obtain accurate kinetic estimates.…”

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confidence: 99%

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Measuring VLDL-triglyceride turnover in humans using ex vivo-prepared VLDL tracer

Gormsen

Jensen

Nielsén

2006

Journal of Lipid Research

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There has been more interest in VLDL-triglyceride (TG) kinetics during the last decade. Unfortunately, robust measurement methods are elaborate and not readily available. Here, we describe a method using unique, ex vivo labeling of the fatty acid moiety of VLDL-TG followed by intravenous bolus infusion in the same person. We found that plasma disappearance of ex vivo-labeled VLDL-TG was comparable to that of in vivo-labeled VLDL-TG and that turnover rates can be safely estimated from the log linear decay of VLDL-TG specific activity. We found minor labeling of the plasma FFA (oleate) pool, which was largely attributable to coinfusion of free [14 C]triolein; VLDL-TG did not contribute substantially to the plasma FFA pool. The plasma decay curve of VLDL-TG was not affected by the presence of tracer in the FFA pool, provided that the data from 2 h after the VLDL tracer bolus infusion was used. The FFA contamination problem was circumvented by minor modification of the VLDL-TG tracer preparation. The approach we describe should expand the opportunity to study processes that cannot be assessed if the FFA precursor pool is labeled. This method for VLDL-TG tracer preparation can allow measurement of VLDL turnover, tissue uptake of VLDL-TG, and oxidation of VLDL-TG.-Gormsen L. C., M. D. Jensen, and S. Nielsen. Measuring VLDLtriglyceride turnover in humans using ex vivo-prepared VLDL tracer. J. Lipid Res. 2006. 47: 99-106. Supplementary key words very low density lipoprotein . lipoproteins . free fatty acids Our present understanding of human VLDL-triglyceride (TG) kinetics and metabolism has been limited by the lack of easily available and robust methods. Although the assessment of VLDL production using splanchnic balances is thought to be accurate (1, 2), this procedure requires blood sampling from the arterial bed as well as the hepatic and portal veins in combination with measurement of splanchnic blood flow, which is impractical in human experimental settings. Traditional turnover measurement, based on isotope dilution techniques using constant infusion of labeled VLDL-TGs (3), has not been widely used in human studies because of the lack of appropriate tracers and problems with tracer recycling. Consequently, a variety of alternative approaches have been used, as recently reviewed by Magkos and Sidossis (4). Among the most widely used approaches are labeling of the TG precursor pool with FFA (1-3), glycerol (8-11), or acetate (12), which results in in vivo incorporation of the tracer into the VLDL-TG complex. Frequent blood sampling and mathematical modeling of the data are needed to calculate the plasma VLDL-TG decay. These methods do not allow one to determine the metabolic fate of the fatty acid moiety of the TG molecule and are dependent upon the validity of the mathematical model for the given experimental setting. Another approach is to collect and isolate in vivo-labeled VLDL particles and reinfuse them into the same subject at a later time (13). However, using this approach, only a small amount ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Measuring VLDL-triglyceride turnover in humans using ex vivo-prepared VLDL tracer

Gormsen

Jensen

Nielsén

2006

Journal of Lipid Research

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“…Early studies of FFA kinetics used the approach of measuring FFA radioactivity and concentrations. FFAs were isolated from plasma with extraction (27)(28)(29)(30), and separate aliquots were assayed for radioactivity (dpm/ml) and fatty acid content (nmol/ml). By dividing the former by the latter, FFA SA (dpm/nmol) was calculated.…”

mentioning

confidence: 99%

Thematic review series: Patient-Oriented Research. Free fatty acid metabolism in human obesity

Koutsari

Jensen

2006

Journal of Lipid Research

181

106

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Adipose tissue lipolysis provides circulating FFAs to meet the body's lipid fuel demands. FFA release is well regulated in normal-weight individuals; however, in upperbody obesity, excess lipolysis is commonly seen. This abnormality is considered a cause for at least some of the metabolic defects (dyslipidemia, insulin resistance) associated with upper-body obesity. ''Normal'' lipolysis is sex-specific and largely determined by the individual's resting metabolic rate. Women have greater FFA release rates than men without higher FFA concentrations or greater fatty acid oxidation, indicating that they have greater nonoxidative FFA disposal, although the processes and tissues involved in this phenomenon are unknown. Therefore, women have the advantage of having greater FFA availability without exposing their tissues to higher and potentially harmful FFA concentrations. Upperbody fat is more lipolytically active than lower-body fat in both women and men. FFA released by the visceral fat depot contributes only a small percentage of systemic FFA delivery. Upper-body subcutaneous fat is the dominant contributor to circulating FFAs and the source of the excess FFA release in upper-body obesity. We believe that abnormalities in subcutaneous lipolysis could be more important than those in visceral lipolysis as a cause of peripheral insulin resistance. Understanding the regulation of FFA availability will help to discover new approaches to treat FFA-induced abnormalities in obesity. Obesity is a global public health concern (1-3). It is well established that obesity, particularly upper-body obesity, is a major contributor to chronic disease and disability, such as dyslipidemia, hypertension, type 2 diabetes, and cardiovascular disease (4). A major link between upper-body obesity and metabolic complications is excessive adipose tissue lipolysis. Under normal conditions, FFA release from adipose tissue is well regulated, allowing appropriate availability of FFAs to meet the energy requirements of the tissues. Increased adiposity can result in excess FFA release relative to tissue needs. The resultant higher FFA concentrations can induce muscle (5) and hepatic (6) insulin resistance, endothelial (7) and pancreatic b-cell (8) dysfunction, and increased VLDL triglyceride production (9). Thus, although adipose tissue is an excellent site for storage of energy and can provide FFAs at times of lipid fuel demands, appropriate regulation of its function is necessary for optimal health in humans.Although upper-body obesity has been associated with a number of metabolic abnormalities, lower-body adiposity has been associated with a more favorable metabolic profile (10-13). It is currently unknown whether the accumulation of subcutaneous fat in the lower-body region exerts a direct protective effect against the unfavorable consequences of obesity or merely serves as a marker for the "healthy" regulation of other fat stores. However, these observations illustrate the complexity of the links between obesity, body fat distributio...

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“…We speculate, first, that other fat depots in the body may have been responsible for the increase in FFA levels after LPS in the diabetic group. Thus, while the abdominal subcutaneous fat depot is usually considered the main source of FFA into plasma [29], a small proportion arises from leg and intra-abdominal adipose tissue [30][31][32]. Secondly, we propose that the attenuated LPL and HSL expression response in the subcutaneous adipose tissue in patients with T2DM encompasses compensatory mechanism that serves to limit the systemic levels of FFA upon pro-inflammatory stimuli.…”

Section: Genmentioning

confidence: 87%

Altered Subcutaneous Adipose Tissue Response to Systemic LPS Administration in Patients with Type 2 Diabetes

Mathur

Rmg

et al. 2012

J Diabetes Metab

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Aim: Inflammation is thought to play a major role in impaired metabolism. However, the metabolic and inflammatory response of adipose tissue, to a pro-inflammatory stimulus is poorly defined in patients with Type 2 Diabetes Mellitus (T2DM). We therefore aimed to investigate whether adipose tissue in T2DM would display an altered response to E. coli LipoPolySaccharide (LPS). Materials and methods:Twelve patients with T2DM and 12 control subjects received an intravenous bolus injection of LPS (0.3 ng/kg). Abdominal subcutaneous adipose tissue biopsies, serum and plasma were obtained at 0, 2, 4, 6 and 8 hours after LPS. The gene expression of Tumour Necrosis Factor-α (TNF), InterLeukin-6 (IL-6), lipoprotein lipase (LPL), hormone sensitive lipase (HSL), fatty acid synthase (FASN), adiponectin and peroxisome proliferator-activated recptor γ (PPARγ) was analysed by real time reverse transcription Polymerase Chain Reaction (PCR). Results:The expression of TNF and IL-6 in adipose tissue increased after LPS administration without any difference between groups (2-way ANOVA, effect of time: p<0.001 and p=0.0001, respectively). In contrast, the expression of LPL, HSL and adiponectin in adipose tissue increased only in control subjects (2-way ANOVA, effect of time X group: p=0.03; p=0.02 and p=0.02, respectively). There was no effect of LPS on FASN or PPARγ in either group. Conclusion:Patients with T2DM demonstrate a resistance to LPS in terms of inducing important mediators of lipolysis and lipogenesis, although the expression of TNF and IL-6 in adipose tissue increased in both groups. And thus, adipose tissue may contribute to the acute inflammation-related metabolic complications seen in T2DM.

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Kinetic studies of plasma free fatty acid and triglyceride metabolism in man

Cited by 129 publications

References 35 publications

Measuring VLDL-triglyceride turnover in humans using ex vivo-prepared VLDL tracer

Measuring VLDL-triglyceride turnover in humans using ex vivo-prepared VLDL tracer

Thematic review series: Patient-Oriented Research. Free fatty acid metabolism in human obesity

Altered Subcutaneous Adipose Tissue Response to Systemic LPS Administration in Patients with Type 2 Diabetes

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