Revisiting the roles of hepatic inflammation and adipokines in metabolic disease

Nanda Gruben

Revisiting the roles of hepatic inflammation and adipokines in metabolic disease

Vertaalde titel van de bijdrage: Herziening van de rollen van leverontsteking en adipokines in metabole ziekten

Nanda Gruben

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Vetzucht is een groot gezondheidsprobleem, omdat er metabole ziekten zoals type 2 diabetes en leververvetting door ontstaan. Er wordt gedacht dat leverontsteking en een veranderde regulatie van adipokines, bioactieve stoffen uitgescheiden door vetweefsel, betrokken zijn bij het ontstaan van deze ziekten. In dit proefschrift is dit nader onderzocht.

De rol van leverontsteking bij type 2 diabetes is onderzocht met behulp van twee muismodellen met leverontsteking. Er is gekeken of deze muizen sneller insulineresistentie (een voorstadium van type 2 diabetes) ontwikkelden dan muizen zonder leverontsteking. In beide modellen bleek leverontsteking geen effect te hebben op het ontstaan van insulineresistentie. Leververvetting wordt ook in verband gebracht met insulineresistentie. Met een literatuuronderzoek is aangetoond dat er weinig bewijs is voor een oorzakelijk verband. In de meeste gevallen kon de relatie verklaard worden door veranderingen in lichaamsgewicht.

Daarnaast is in patiënten onderzocht of de aanwezigheid van verschillende adipokines in vet- en leverweefsel samenhangt met leververvetting. Vooral de aanwezigheid van het adipokine chemerin bleek samen te hangen met verminderde leververvetting. Of chemerin daadwerkelijk beschermt tegen leververvetting is vervolgens onderzocht met muizen die ongevoelig zijn voor chemerin en muizen met een chemerinoverschot. In beide modellen had chemerin geen beschermend effect op het ontstaan van leververvetting.

Uit deze resultaten concluderen we dat leverontsteking, in tegenstelling tot het dogma, niet bijdraagt aan het ontstaan van type 2 diabetes. Daarnaast concluderen we dat chemerin niet beschermt tegen leververvetting. Het is daarom de vraag of medicijnen gericht tegen ontsteking of chemerin zullen helpen bij het bestrijden van deze ziekten.

Vertaalde titel van de bijdrage	Herziening van de rollen van leverontsteking en adipokines in metabole ziekten
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	13-mei-2015
Plaats van publicatie	[Groningen]
Uitgever	University of Groningen
Gedrukte ISBN's	978-90-367-7762-9
Elektronische ISBN's	978-90-367-7761-2
Status	Published - 2015

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Title and contentsFinal publisher's version, 2,81 MB
Chapter 1Final publisher's version, 6,42 MB
Chapter 2Final publisher's version, 9,7 MB
Chapter 3Final publisher's version, 6,8 MB
Chapter 4Final publisher's version, 6 MB
Chapter 5Final publisher's version, 10,1 MB
Chapter 6Final publisher's version, 6,25 MB
Chapter 7Final publisher's version, 5,92 MB
Chapter 8Final publisher's version, 5,56 MB
AppendicesFinal publisher's version, 2,84 MB
Complete dissertationFinal publisher's version, 18,2 MB
PropositionsFinal publisher's version, 527 KB

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title = "Revisiting the roles of hepatic inflammation and adipokines in metabolic disease",

abstract = "Obesity is a major health problem, because it induces type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Hepatic inflammation and an altered secretion of adipokines (bioactive substances secreted by fat tissue) are believed to be involved in the pathogenesis of these diseases. In this thesis their role is further elucidated. The role of hepatic inflammation in the development of T2D was studied in two mouse models with hepatic inflammation. It was investigated if these mice developed insulin resistance (IR, precedes T2D) faster than mice without hepatic inflammation. In both models, hepatic inflammation did not affect the development of IR. NAFLD is also associated with IR. In a review article it was shown that there is little evidence for a causal relationship. In most cases, the relationship was explained by alterations in body weight. In addition, we investigated in patients if the presence of various adipokines in fat and liver tissue is correlated with NAFLD. Especially the adipokine chemerin was correlated with reduced disease severity. To investigate if chemerin actually protects against NAFLD, mice insensitive to chemerin and mice with increased chemerin levels were used. In both models, chemerin did not protect against the development of NAFLD. From these results, we conclude that hepatic inflammation, in contrast to the current dogma, does not contribute to the pathogenesis of T2D. In addition, we conclude that chemerin does not protect against NAFLD. Therefore, this thesis raises the question whether medications directed against inflammation or chemerin will be effective against these diseases.",

author = "Nanda Gruben",

year = "2015",

language = "English",

isbn = "978-90-367-7762-9",

publisher = "University of Groningen",

school = "University of Groningen",

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TY - BOOK

T1 - Revisiting the roles of hepatic inflammation and adipokines in metabolic disease

AU - Gruben, Nanda

PY - 2015

Y1 - 2015

N2 - Obesity is a major health problem, because it induces type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Hepatic inflammation and an altered secretion of adipokines (bioactive substances secreted by fat tissue) are believed to be involved in the pathogenesis of these diseases. In this thesis their role is further elucidated. The role of hepatic inflammation in the development of T2D was studied in two mouse models with hepatic inflammation. It was investigated if these mice developed insulin resistance (IR, precedes T2D) faster than mice without hepatic inflammation. In both models, hepatic inflammation did not affect the development of IR. NAFLD is also associated with IR. In a review article it was shown that there is little evidence for a causal relationship. In most cases, the relationship was explained by alterations in body weight. In addition, we investigated in patients if the presence of various adipokines in fat and liver tissue is correlated with NAFLD. Especially the adipokine chemerin was correlated with reduced disease severity. To investigate if chemerin actually protects against NAFLD, mice insensitive to chemerin and mice with increased chemerin levels were used. In both models, chemerin did not protect against the development of NAFLD. From these results, we conclude that hepatic inflammation, in contrast to the current dogma, does not contribute to the pathogenesis of T2D. In addition, we conclude that chemerin does not protect against NAFLD. Therefore, this thesis raises the question whether medications directed against inflammation or chemerin will be effective against these diseases.

AB - Obesity is a major health problem, because it induces type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Hepatic inflammation and an altered secretion of adipokines (bioactive substances secreted by fat tissue) are believed to be involved in the pathogenesis of these diseases. In this thesis their role is further elucidated. The role of hepatic inflammation in the development of T2D was studied in two mouse models with hepatic inflammation. It was investigated if these mice developed insulin resistance (IR, precedes T2D) faster than mice without hepatic inflammation. In both models, hepatic inflammation did not affect the development of IR. NAFLD is also associated with IR. In a review article it was shown that there is little evidence for a causal relationship. In most cases, the relationship was explained by alterations in body weight. In addition, we investigated in patients if the presence of various adipokines in fat and liver tissue is correlated with NAFLD. Especially the adipokine chemerin was correlated with reduced disease severity. To investigate if chemerin actually protects against NAFLD, mice insensitive to chemerin and mice with increased chemerin levels were used. In both models, chemerin did not protect against the development of NAFLD. From these results, we conclude that hepatic inflammation, in contrast to the current dogma, does not contribute to the pathogenesis of T2D. In addition, we conclude that chemerin does not protect against NAFLD. Therefore, this thesis raises the question whether medications directed against inflammation or chemerin will be effective against these diseases.

M3 - Thesis fully internal (DIV)

SN - 978-90-367-7762-9

PB - University of Groningen

CY - [Groningen]

ER -

Revisiting the roles of hepatic inflammation and adipokines in metabolic disease

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