Control of cholesterol homeostasis by entero-hepatic bile transport – the role of feedback mechanisms

Mishra, Shekhar; Somvanshi, Pramod R.; Venkatesh, Kareenhalli V.

doi:10.1039/c4ra09397f

Cited by 14 publications

(8 citation statements)

References 41 publications

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“…This model is coded in the Systems Biology Markup Language and archived in the BioModels Database, a repository for models encased in Systems Biology Markup Language exchange framework (http://www.ebi.ac.uk/biomodelsmain/BIOMD0000000434). This means the model is straightforward to update and adapt, a feature exploited by other groups working in this area (122) . We recently implemented significant updates to the model described earlier for the following reasons (123) .…”

Section: Applying Systems Biology To Our Understanding Of Cholesterolmentioning

confidence: 99%

Investigating cholesterol metabolism and ageing using a systems biology approach

et al. 2016

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CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.

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Section: Applying Systems Biology To Our Understanding Of Cholesterolmentioning

confidence: 99%

Investigating cholesterol metabolism and ageing using a systems biology approach

et al. 2016

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“…Biomolecules 2021, 11, 1470 2 of 15 regulator of cholesterol synthesis and metabolism, cholesterol degradation to bile acids, and ultimate excretion to bile [6,7]. Excess cholesterol in extrahepatic tissues is subjected to the reverse cholesterol transport (RCT) process and transported by high-density lipoprotein (HDL) or LDL molecules back to the liver for metabolism and excretion [8].…”

Section: Introductionmentioning

confidence: 99%

Rosmarinic Acid Exhibits a Lipid-Lowering Effect by Modulating the Expression of Reverse Cholesterol Transporters and Lipid Metabolism in High-Fat Diet-Fed Mice

Nyandwi

Jin

et al. 2021

Biomolecules

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Hyperlipidemia is a potent risk factor for the development of cardiovascular diseases. The reverse cholesterol transport (RCT) process has been shown to alleviate hyperlipidemia and protect against cardiovascular diseases. Recently, rosmarinic acid was reported to exhibit lipid-lowering effects. However, the underlying mechanism is still unclear. This study aims to investigate whether rosmarinic acid lowers lipids by modulating the RCT process in high-fat diet (HFD)-induced hyperlipidemic C57BL/6J mice. Our results indicated that rosmarinic acid treatment significantly decreased body weight, blood glucose, and plasma total cholesterol and triglyceride levels in HFD-fed mice. Rosmarinic acid increased the expression levels of cholesterol uptake-associated receptors in liver tissues, including scavenger receptor B type 1 (SR-B1) and low-density lipoprotein receptor (LDL-R). Furthermore, rosmarinic acid treatment notably increased the expression of cholesterol excretion molecules, ATP-binding cassette G5 (ABCG5) and G8 (ABCG8) transporters, and cholesterol 7 alpha-hydroxylase A1 (CYP7A1) as well as markedly reduced cholesterol and triglyceride levels in liver tissues. In addition, rosmarinic acid facilitated fatty acid oxidation through AMP-activated protein kinase (AMPK)-mediated carnitine palmitoyltransferase 1A (CPT1A) induction. In conclusion, rosmarinic acid exhibited a lipid-lowering effect by modulating the expression of RCT-related proteins and lipid metabolism-associated molecules, confirming its potential for the prevention or treatment of hyperlipidemia-derived diseases.

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“…This makes the model straightforward to adapt and update. The adaptable nature of this model was emphasized recently by Mishra, Somvanshi & Venkatesh (2014), who used this model in tandem with another model (Demirezen and Barlas, 2008). Their combined model included the variables body weight, diet and exercise and they analysed the feedback mechanisms of enterohepatic circulation of bile acids; specifically, bile acid synthesis, interactions with dietary lipids, and excretion.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years however, several groups have adopted a systems level approach to investigating lipid metabolism Mooney et al, 2016). The majority of these models have centred on specific metabolic processes, including those directed at lipoprotein metabolism (Hubner et al, 2008;Shorten and Upreti, 2005;Sips et al, 2014), cholesterol biosynthesis (Bhattacharya et al, 2014;Kervizic and Corcos, 2008;Mazein et al, 2013;Watterson et al, 2013), reverse cholesterol transport (Lu et al, 2014), adipocyte metabolism (Micheloni et al, 2015), hepatocyte metabolism (Jerby et al, 2010), cholesterol regulatory enzymes (Chapman et al, 2010), whole-body plasma cholesterol metabolism (van de Pas et al, 2012) and enterohepatic circulation of bile acids (Mishra et al, 2014). These models all have noteworthy features and have added to our understanding of lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Mathematically modelling the dynamics of cholesterol metabolism and ageing

et al. 2016

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Control of cholesterol homeostasis by entero-hepatic bile transport – the role of feedback mechanisms

Abstract: Cholesterol homeostasis is achieved through a tight regulation between synthesis, dietary absorption, utilization of bile salts, and excretion in the entero-hepatic compartment.

Cited by 14 publications

References 41 publications

Investigating cholesterol metabolism and ageing using a systems biology approach

Investigating cholesterol metabolism and ageing using a systems biology approach

Rosmarinic Acid Exhibits a Lipid-Lowering Effect by Modulating the Expression of Reverse Cholesterol Transporters and Lipid Metabolism in High-Fat Diet-Fed Mice

Mathematically modelling the dynamics of cholesterol metabolism and ageing

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