A mathematical model of fatty acid metabolism and VLDL assembly in human liver

Shorten, Paul R.; Upreti, G.C.

doi:10.1016/j.bbalip.2005.07.007

Cited by 20 publications

(13 citation statements)

References 93 publications

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“…Adiels' model [2] has proven to be a particularly useful tool in determining how physiological features impact VLDL size and dyslipidemia [4,3,39,38]. A more in-depth model of VLDL assembly has been proposed by Shorten and Upreti [50] in which the lipid composition of secreted VLDLs can be determined from uptake of individual free fatty acids after elongation and desaturation by liver enzymes. Another area of mathematical modelling is the hepatic uptake and metabolism of lipoproteins, and the competition between subclasses within this process [46,58].…”

Section: Introductionmentioning

confidence: 99%

Mathematical modelling of hepatic lipid metabolism

Pratt

Wattis

Salter

2015

Mathematical Biosciences

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The aim of this paper is to develop a mathematical model capable of simulating the metabolic response to a variety of mixed meals in fed and fasted conditions with particular emphasis placed on the hepatic triglyceride element of the model. Model validation is carried out using experimental data for the ingestion of three mixed composition meals over a 24-hour period. Comparison with experimental data suggests the model predicts key plasma lipids accurately given a prescribed insulin profile. One counter-intuitive observation to arise from simulations is that liver triglyceride initially decreases when a high fat meal is ingested, a phenomenon potentially explained by the carbohydrate portion of the meal raising plasma insulin.

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Section: Introductionmentioning

confidence: 99%

Mathematical modelling of hepatic lipid metabolism

Pratt

Wattis

Salter

2015

Mathematical Biosciences

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“…Data supporting this finding were recently reported by Chong et al (13 ), who observed a parallel activation of SCD activity estimated from fatty acid ratios as well as conversion of an intravenously infused stable isotope of C16:0 to C16:1 in VLDL-TG with DNL. Because stearate is preferred to palmitate as a substrate of SCD1 (28,29 ), it is surprising that the desaturation activity index of palmitate (16:1/16:0) and not stearate (18:1/18:0) reflects hepatic SCD1 expression more closely. A reason for this result could be the presence of 2 separate triglyceride pools in the liver, as suggested by Donelly et al (30 ).…”

Section: Discussionmentioning

confidence: 99%

Hepatic Lipid Composition and Stearoyl-Coenzyme A Desaturase 1 mRNA Expression Can Be Estimated from Plasma VLDL Fatty Acid Ratios

et al. 2009

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BACKGROUND:Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the limiting step of monounsaturated fatty acid synthesis in humans and is an important player in triglyceride generation. SCD1 has been repeatedly implicated in the pathogenesis of metabolic and inflammatory diseases. Therefore it is of great importance to determine SCD1 activity in human samples. In this study we aimed to evaluate a hepatic SCD1 activity index derived from plasma VLDL triglyceride composition as a tool to estimate hepatic SCD1 expression in humans. Additionally, we further evaluated commonly used fatty acid ratios [elongase, de novo lipogenesis, and ⌬5 and ⌬6 desaturase] in plasma VLDL and hepatic lipid fractions.

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“…Recent models focusing on fatty acid metabolism include a model by Micheloni et al (2014) which includes the key pathways of an adipocyte [112]. VLDL assembly in human liver has also been represented computationally [113]. This model was able to predict the plasma FFA composition required to generate a given alteration in the fatty acid composition of a lipoprotein.…”

Section: Computational Models Of Lipid Metabolismmentioning

confidence: 99%

Computationally Modeling Lipid Metabolism and Aging: A Mini-review

Auley

Mooney

2015

Computational and Structural Biotechnology Journal

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One of the greatest challenges in biology is to improve the understanding of the mechanisms which underpin aging and how these affect health. The need to better understand aging is amplified by demographic changes, which have caused a gradual increase in the global population of older people. Aging western populations have resulted in a rise in the prevalence of age-related pathologies. Of these diseases, cardiovascular disease is the most common underlying condition in older people. The dysregulation of lipid metabolism due to aging impinges significantly on cardiovascular health. However, the multifaceted nature of lipid metabolism and the complexities of its interaction with aging make it challenging to understand by conventional means. To address this challenge computational modeling, a key component of the systems biology paradigm is being used to study the dynamics of lipid metabolism. This mini-review briefly outlines the key regulators of lipid metabolism, their dysregulation, and how computational modeling is being used to gain an increased insight into this system.

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A mathematical model of fatty acid metabolism and VLDL assembly in human liver

Cited by 20 publications

References 93 publications

Mathematical modelling of hepatic lipid metabolism

Mathematical modelling of hepatic lipid metabolism

Hepatic Lipid Composition and Stearoyl-Coenzyme A Desaturase 1 mRNA Expression Can Be Estimated from Plasma VLDL Fatty Acid Ratios

Computationally Modeling Lipid Metabolism and Aging: A Mini-review

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