Non-alcoholic fatty liver disease: understanding the role of aging, fatty acid transport and epigenetics

Fareeba Sheedfar

Non-alcoholic fatty liver disease: understanding the role of aging, fatty acid transport and epigenetics

Vertaalde titel van de bijdrage: Niet-alcoholische leververvetting: het begrijpen van de rol van ouderdom, vetzuur transport en epigenetica

Fareeba Sheedfar

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Overgewicht, een gezondheidstoestand waarbij de inname van energie groter is dan het verbruik ervan, vormt een wereldwijd probleem in de huidige maatschappij. De toename in overgewicht gaat gepaard met een stijging in overgewicht gerelateerde ziekten, zoals type 2 diabetes (T2D) en niet-alcoholische leververvetting (NAFLD). NAFLD is wereldwijd de grootste veroorzaker van leverziekte. Het begint met vet ophoping in de lever, beter bekend als lever steatose. Deze goedaardige en omkeerbare toestand van NAFLD kan echter uitgroeien tot een leverontsteking ofwel een niet-alcoholische steatohepatitis (NASH), welke vervolgens kan doorgroeien tot fibrose, cirrose en uiteindelijk een hepatocellulair carcinoom (HCC). Toch worden de pathogenese van NAFLD en de mechanismen, die verantwoordelijk zijn voor de progressie van de ziekte, onvoldoende begrepen. Het in dit proefschrift beschreven onderzoek werd uitgevoerd om meer inzicht te krijgen in de etiologie, het verloop van de ziekte en het effect van risicofactoren zoals ouderdom en laaggradige chronische ontsteking op de ontwikkeling van NAFLD. Daarnaast beschrijven we de rol van macroH2A1 en de vetzuurtransporteur CD36 in de ontwikkeling van NAFLD met behulp van diermodellen en een dieet interventiestrategie. Onze gegevens suggereren dat een breed spectrum van genetische en milieu afhankelijke factoren betrokken zijn bij de ontwikkeling van NAFLD. Echter meer onderzoek en begrip over deze factoren is vereist om de weg vrij te banen voor een nieuwe behandeling van NAFLD.

Vertaalde titel van de bijdrage	Niet-alcoholische leververvetting: het begrijpen van de rol van ouderdom, vetzuur transport en epigenetica
Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Hofker, Marten, Supervisor Koonen, Debby, Co-supervisor
Datum van toekenning	12-jan.-2015
Plaats van publicatie	[S.l.]
Uitgever	[S.n.]
Gedrukte ISBN's	978-90-367-7573-1
Elektronische ISBN's	978-90-367-7572-4
Status	Published - 2015

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Title and contents Final publisher's version, 884 KB
Chapter 1Final publisher's version, 1,68 MB
Chapter 2Final publisher's version, 1,75 MB
Chapter 3 Publisher's versionFinal publisher's version, 2,03 MB
Chapter 4 publisher's versionFinal publisher's version, 2,93 MB
Chapter 5Final publisher's version, 3,89 MB
Chapter 6Final publisher's version, 4,76 MB
Chapter 7Final publisher's version, 2,34 MB
Chapter 8Final publisher's version, 1,02 MB
Chapter 9Final publisher's version, 1,03 MB
Chapter 10Final publisher's version, 1,02 MB
Chapter 11Final publisher's version, 1,14 MB
Chapter 12Final publisher's version, 1,18 MB
PropositionsFinal publisher's version, 1,86 MB

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title = "Non-alcoholic fatty liver disease: understanding the role of aging, fatty acid transport and epigenetics",

abstract = "Obesity is a problem of positive energy balance, favoring an increase in energy storage over energy utilization. Parallel with increase in obesity, there is an increase in obesity-associated diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common cause of liver disease worldwide. The early stage of NAFLD starts with lipid accumulation in the liver also known as hepatic steatosis. This benign state of NAFLD may, however, evolve into non-alcoholic steatohepatitis (NASH), a condition of inflamed liver, which can further progress to liver fibrosis, cirrhosis and ultimately hepatocellular carcinoma (HCC). However, the pathogenesis of NAFLD and the mechanisms responsible for disease progression remain inadequately understood. The research described in this thesis was performed to gain more insights into the etiology, progression and effect of risk factors in the development of NAFLD. We focus on the relationship between old age and inflammation, both of which are risk factors for the development of NAFLD and highlight the role of target gene ablations such as macroH2A1 and the fatty acid transporter CD36 in the development of NAFLD. Using animal models and a diet intervention strategy, we show the influence of parameters such as chronic obesity, aging, CD36, and macroH2A1 in the development of NAFLD. Our data clearly suggest that a broad spectrum of genetically and environmentally originated factors are involved in the development of NAFLD. These factors, however, require more research and understanding to pave a path to treatment for NAFLD.",

author = "Fareeba Sheedfar",

year = "2015",

language = "English",

isbn = "978-90-367-7573-1",

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T2 - understanding the role of aging, fatty acid transport and epigenetics

AU - Sheedfar, Fareeba

PY - 2015

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N2 - Obesity is a problem of positive energy balance, favoring an increase in energy storage over energy utilization. Parallel with increase in obesity, there is an increase in obesity-associated diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common cause of liver disease worldwide. The early stage of NAFLD starts with lipid accumulation in the liver also known as hepatic steatosis. This benign state of NAFLD may, however, evolve into non-alcoholic steatohepatitis (NASH), a condition of inflamed liver, which can further progress to liver fibrosis, cirrhosis and ultimately hepatocellular carcinoma (HCC). However, the pathogenesis of NAFLD and the mechanisms responsible for disease progression remain inadequately understood. The research described in this thesis was performed to gain more insights into the etiology, progression and effect of risk factors in the development of NAFLD. We focus on the relationship between old age and inflammation, both of which are risk factors for the development of NAFLD and highlight the role of target gene ablations such as macroH2A1 and the fatty acid transporter CD36 in the development of NAFLD. Using animal models and a diet intervention strategy, we show the influence of parameters such as chronic obesity, aging, CD36, and macroH2A1 in the development of NAFLD. Our data clearly suggest that a broad spectrum of genetically and environmentally originated factors are involved in the development of NAFLD. These factors, however, require more research and understanding to pave a path to treatment for NAFLD.

AB - Obesity is a problem of positive energy balance, favoring an increase in energy storage over energy utilization. Parallel with increase in obesity, there is an increase in obesity-associated diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common cause of liver disease worldwide. The early stage of NAFLD starts with lipid accumulation in the liver also known as hepatic steatosis. This benign state of NAFLD may, however, evolve into non-alcoholic steatohepatitis (NASH), a condition of inflamed liver, which can further progress to liver fibrosis, cirrhosis and ultimately hepatocellular carcinoma (HCC). However, the pathogenesis of NAFLD and the mechanisms responsible for disease progression remain inadequately understood. The research described in this thesis was performed to gain more insights into the etiology, progression and effect of risk factors in the development of NAFLD. We focus on the relationship between old age and inflammation, both of which are risk factors for the development of NAFLD and highlight the role of target gene ablations such as macroH2A1 and the fatty acid transporter CD36 in the development of NAFLD. Using animal models and a diet intervention strategy, we show the influence of parameters such as chronic obesity, aging, CD36, and macroH2A1 in the development of NAFLD. Our data clearly suggest that a broad spectrum of genetically and environmentally originated factors are involved in the development of NAFLD. These factors, however, require more research and understanding to pave a path to treatment for NAFLD.

M3 - Thesis fully internal (DIV)

SN - 978-90-367-7573-1

PB - [S.n.]

CY - [S.l.]

ER -

Non-alcoholic fatty liver disease: understanding the role of aging, fatty acid transport and epigenetics

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