Anti oxidative acyl CoA Cholesterol acyl transferase Inhibitor Avasimibe reduces the impact of high cholesterol diet on Brain lipid peroxidation in mice

Research output: Contribution to conferenceAbstract

Abstract


Objectives: High fat/high cholesterol diet (HFD) is a risk factor for Alzheimer's Disease (AD). Cholesterol lowering drugs are potential therapies for AD and assessment of the cholesterol-lowering drug Avasimibe was used to assess potential therapeutic effects on liver cholesterol metabolism and its role in the improvement in brain lipid peroxidation and neurodegeneration.
Methods: The anti-oxidative acylCoA cholesterol acyltransferase (ACAT) inhibitor Avasimibe was administered orally (diet) to mice. Diet-induced hypercholesterolemia was used as a model in mice to assess the relationship between steatosis (hepatic dysfunction) and oxidative damage associated with neurodegeneration (brain). Lipid identification and characterization of the brain was conducted with lipidomics.
Results: In mice fed the HFD there was an increase in brain free cholesterol content and an increase in brain cholesterol oxidation (as assessed by 24S-hydroxycholesterol levels). The HFD diet altered phosphatidylinositol turnover in mouse brain membranes. Avasimibe could be detected in the plasma but not in the brain and was found to inhibit ACAT activity in the periphery only yet was associated with therapeutic improvements in brain lipid composition as shown in the image.
Conclusions: The HFD diet induced steatosis (fatty liver) and treatment with Avasimibe reduced liver and brain lipid accumulation and improved brain lipid composition. Avasimibe improved diet-induced brain oxidative stress with reduction of brain cholesterol oxidation and phospholipid peroxidation (vitamin E sensitive) thus preventing neurodegeneration.
Original languageEnglish
Publication statusUnpublished - 6 Mar 2013
EventAD/PD 2013 – The 11th International Conference on Alzheimer’s and Parkinson’s Disease, Florence, Italy - Florence, Italy
Duration: 6 Mar 201310 Mar 2013

Conference

ConferenceAD/PD 2013 – The 11th International Conference on Alzheimer’s and Parkinson’s Disease, Florence, Italy
Abbreviated titleAD/PD 2013
CountryItaly
CityFlorence
Period6/03/1310/03/13

Fingerprint

Acyl Coenzyme A
Transferases
Lipid Peroxidation
Cholesterol
Diet
Brain
High Fat Diet
Sterol O-Acyltransferase
Lipids
Fatty Liver
avasimibe
Liver
Alzheimer Disease
Anticholesteremic Agents
Therapeutic Uses
Phosphatidylinositols
Hypercholesterolemia
Vitamin E
Phospholipids
Oxidative Stress

Cite this

Martins, I. (2013). Anti oxidative acyl CoA Cholesterol acyl transferase Inhibitor Avasimibe reduces the impact of high cholesterol diet on Brain lipid peroxidation in mice. Abstract from AD/PD 2013 – The 11th International Conference on Alzheimer’s and Parkinson’s Disease, Florence, Italy, Florence, Italy.
Martins, Ian. / Anti oxidative acyl CoA Cholesterol acyl transferase Inhibitor Avasimibe reduces the impact of high cholesterol diet on Brain lipid peroxidation in mice. Abstract from AD/PD 2013 – The 11th International Conference on Alzheimer’s and Parkinson’s Disease, Florence, Italy, Florence, Italy.
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title = "Anti oxidative acyl CoA Cholesterol acyl transferase Inhibitor Avasimibe reduces the impact of high cholesterol diet on Brain lipid peroxidation in mice",
abstract = "Objectives: High fat/high cholesterol diet (HFD) is a risk factor for Alzheimer's Disease (AD). Cholesterol lowering drugs are potential therapies for AD and assessment of the cholesterol-lowering drug Avasimibe was used to assess potential therapeutic effects on liver cholesterol metabolism and its role in the improvement in brain lipid peroxidation and neurodegeneration.Methods: The anti-oxidative acylCoA cholesterol acyltransferase (ACAT) inhibitor Avasimibe was administered orally (diet) to mice. Diet-induced hypercholesterolemia was used as a model in mice to assess the relationship between steatosis (hepatic dysfunction) and oxidative damage associated with neurodegeneration (brain). Lipid identification and characterization of the brain was conducted with lipidomics.Results: In mice fed the HFD there was an increase in brain free cholesterol content and an increase in brain cholesterol oxidation (as assessed by 24S-hydroxycholesterol levels). The HFD diet altered phosphatidylinositol turnover in mouse brain membranes. Avasimibe could be detected in the plasma but not in the brain and was found to inhibit ACAT activity in the periphery only yet was associated with therapeutic improvements in brain lipid composition as shown in the image.Conclusions: The HFD diet induced steatosis (fatty liver) and treatment with Avasimibe reduced liver and brain lipid accumulation and improved brain lipid composition. Avasimibe improved diet-induced brain oxidative stress with reduction of brain cholesterol oxidation and phospholipid peroxidation (vitamin E sensitive) thus preventing neurodegeneration.",
author = "Ian Martins",
year = "2013",
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language = "English",
note = "AD/PD 2013 – The 11th International Conference on Alzheimer’s and Parkinson’s Disease, Florence, Italy, AD/PD 2013 ; Conference date: 06-03-2013 Through 10-03-2013",

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Martins, I 2013, 'Anti oxidative acyl CoA Cholesterol acyl transferase Inhibitor Avasimibe reduces the impact of high cholesterol diet on Brain lipid peroxidation in mice' AD/PD 2013 – The 11th International Conference on Alzheimer’s and Parkinson’s Disease, Florence, Italy, Florence, Italy, 6/03/13 - 10/03/13, .

Anti oxidative acyl CoA Cholesterol acyl transferase Inhibitor Avasimibe reduces the impact of high cholesterol diet on Brain lipid peroxidation in mice. / Martins, Ian.

2013. Abstract from AD/PD 2013 – The 11th International Conference on Alzheimer’s and Parkinson’s Disease, Florence, Italy, Florence, Italy.

Research output: Contribution to conferenceAbstract

TY - CONF

T1 - Anti oxidative acyl CoA Cholesterol acyl transferase Inhibitor Avasimibe reduces the impact of high cholesterol diet on Brain lipid peroxidation in mice

AU - Martins, Ian

PY - 2013/3/6

Y1 - 2013/3/6

N2 - Objectives: High fat/high cholesterol diet (HFD) is a risk factor for Alzheimer's Disease (AD). Cholesterol lowering drugs are potential therapies for AD and assessment of the cholesterol-lowering drug Avasimibe was used to assess potential therapeutic effects on liver cholesterol metabolism and its role in the improvement in brain lipid peroxidation and neurodegeneration.Methods: The anti-oxidative acylCoA cholesterol acyltransferase (ACAT) inhibitor Avasimibe was administered orally (diet) to mice. Diet-induced hypercholesterolemia was used as a model in mice to assess the relationship between steatosis (hepatic dysfunction) and oxidative damage associated with neurodegeneration (brain). Lipid identification and characterization of the brain was conducted with lipidomics.Results: In mice fed the HFD there was an increase in brain free cholesterol content and an increase in brain cholesterol oxidation (as assessed by 24S-hydroxycholesterol levels). The HFD diet altered phosphatidylinositol turnover in mouse brain membranes. Avasimibe could be detected in the plasma but not in the brain and was found to inhibit ACAT activity in the periphery only yet was associated with therapeutic improvements in brain lipid composition as shown in the image.Conclusions: The HFD diet induced steatosis (fatty liver) and treatment with Avasimibe reduced liver and brain lipid accumulation and improved brain lipid composition. Avasimibe improved diet-induced brain oxidative stress with reduction of brain cholesterol oxidation and phospholipid peroxidation (vitamin E sensitive) thus preventing neurodegeneration.

AB - Objectives: High fat/high cholesterol diet (HFD) is a risk factor for Alzheimer's Disease (AD). Cholesterol lowering drugs are potential therapies for AD and assessment of the cholesterol-lowering drug Avasimibe was used to assess potential therapeutic effects on liver cholesterol metabolism and its role in the improvement in brain lipid peroxidation and neurodegeneration.Methods: The anti-oxidative acylCoA cholesterol acyltransferase (ACAT) inhibitor Avasimibe was administered orally (diet) to mice. Diet-induced hypercholesterolemia was used as a model in mice to assess the relationship between steatosis (hepatic dysfunction) and oxidative damage associated with neurodegeneration (brain). Lipid identification and characterization of the brain was conducted with lipidomics.Results: In mice fed the HFD there was an increase in brain free cholesterol content and an increase in brain cholesterol oxidation (as assessed by 24S-hydroxycholesterol levels). The HFD diet altered phosphatidylinositol turnover in mouse brain membranes. Avasimibe could be detected in the plasma but not in the brain and was found to inhibit ACAT activity in the periphery only yet was associated with therapeutic improvements in brain lipid composition as shown in the image.Conclusions: The HFD diet induced steatosis (fatty liver) and treatment with Avasimibe reduced liver and brain lipid accumulation and improved brain lipid composition. Avasimibe improved diet-induced brain oxidative stress with reduction of brain cholesterol oxidation and phospholipid peroxidation (vitamin E sensitive) thus preventing neurodegeneration.

UR - https://ec.europa.eu/eip/ageing/events/11th-international-conference-alzheimer-s-and-parkinson-s-diseases_en

M3 - Abstract

ER -

Martins I. Anti oxidative acyl CoA Cholesterol acyl transferase Inhibitor Avasimibe reduces the impact of high cholesterol diet on Brain lipid peroxidation in mice. 2013. Abstract from AD/PD 2013 – The 11th International Conference on Alzheimer’s and Parkinson’s Disease, Florence, Italy, Florence, Italy.