C/EBPβ isoforms and the regulation of metabolism: A fine balance between health and disease

Tobias Ackermann

C/EBPβ isoforms and the regulation of metabolism: A fine balance between health and disease

Tobias Ackermann

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Calorie inname en dieet samenstellingen reguleren de eiwit productie en functionaliteit in de cel en oefenen hierdoor een directe invloed uit op de gezondheid en het metabolisme van organismen. Afwijkingen in het metabolisme en verhoogde calorie-inname kunnen leiden tot het ontstaan van metabole ziekten zoals type 2 diabetes en obesitas. Voorheen zijn verschillende factoren geïdentificeerd welke reageren op dieet samenstellingen en calorie-inname en hierdoor een cellulaire respons in gang zetten.
In dit proefschrift beschrijven we dat C/EBPβ-LIP een belangrijke factor is die aangestuurd wordt door diëten. C/EBPβ-LIP is een DNA-binding eiwit en vermindert de productie van DNA gecodeerde RNAs en eiwitten om de cellulaire functies te reguleren. Muizen met verminderde hoeveelheden LIP zijn metabool gezonder dan muizen met normale LIP hoeveelheden onder dezelfde diëtaire omstandigheden. Verder beschrijven we hoe verhoogde hoeveelheden LIP resulteert in een metabolisme die vergelijkbaar is met het metabolisme van kanker cellen.
We hebben in dit proefschrift LIP geïdentificeerd als factor die gereguleerd wordt door het dieet en de verwerking van voedingsstoffen in de cel veranderd. Om deze reden dragen we LIP voor als belangrijke regulator van lichaamsfuncties, en speculeren we dat een vermindering van LIP door farmacologische inhibitie wellicht kan bijdragen aan de behandeling van metabole ziekten en kanker.

Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Calkhoven, Cor, Supervisor Hartleben, Götz, Co-supervisor de Haan, Gerald, Beoordelingscommissie van de Sluis, Bart, Beoordelingscommissie Coffer, Paul J., Beoordelingscommissie, Externe Persoon
Datum van toekenning	29-okt.-2018
Plaats van publicatie	[Groningen]
Uitgever	University of Groningen
Gedrukte ISBN's	978-94-034-1117-0
Elektronische ISBN's	978-94-034-1116-3
Status	Published - 2018

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Title and contentsFinal publisher's version, 501 KB
Chapter IFinal publisher's version, 341 KB
Chapter IIFinal publisher's version, 1,2 MB
Chapter IIIFinal publisher's version, 1,73 MB
Chapter IVFinal publisher's version, 2,51 MB
Chapter VFinal publisher's version, 1,01 MB
Chapter VIFinal publisher's version, 1,17 MB
Scientific summaryFinal publisher's version, 332 KB
Wetenschappelijke samenvattingFinal publisher's version, 334 KB
lay summariesFinal publisher's version, 296 KB
AcknowledgementsFinal publisher's version, 344 KB
Complete thesisFinal publisher's version, 8,34 MB
PropositionsFinal publisher's version, 284 KB

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title = "C/EBPβ isoforms and the regulation of metabolism: A fine balance between health and disease",

abstract = "The caloric intake and the composition of the diet controls protein production and functionality in the cell and thereby have direct impact on the health and metabolism of the organism. Aberrant metabolism and increased caloric intake result in metabolic disorders like type II diabetes or obesity. In the past, several factors were identified which respond to and mediate the cellular response to the diet composition and caloric intake in organisms. In this thesis, we describe C/EBPβ-LIP as an important factor which activity and function is controlled by the diet. C/EBPβ LIP is a DNA-binding protein and reduces the production of DNA encoded RNAs and proteins to alter cellular functions. Mice with reduced levels of C/EBPβ-LIP show a healthier metabolism compared to mice with normal levels of C/EBPβ-LIP; although they eat the same diet. Furthermore, this thesis shows that high levels of C/EBPβ-LIP lead to an activated metabolism in cells which resembles the metabolism of cancer cells. Taken together, we identified C/EBPβ-LIP as a factor which is controlled by the diet and which alters the processing of the nutrients in the cell. Therefore, we hypothesise that C/EBPβ-LIP is an important mediator of the diet to regulate body functions and a reduction of C/EBPβ-LIP level by pharmaceuticals might help to treat metabolic disorders and cancer.",

author = "Tobias Ackermann",

year = "2018",

language = "English",

isbn = "978-94-034-1117-0",

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TY - BOOK

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T2 - A fine balance between health and disease

AU - Ackermann, Tobias

PY - 2018

Y1 - 2018

N2 - The caloric intake and the composition of the diet controls protein production and functionality in the cell and thereby have direct impact on the health and metabolism of the organism. Aberrant metabolism and increased caloric intake result in metabolic disorders like type II diabetes or obesity. In the past, several factors were identified which respond to and mediate the cellular response to the diet composition and caloric intake in organisms. In this thesis, we describe C/EBPβ-LIP as an important factor which activity and function is controlled by the diet. C/EBPβ LIP is a DNA-binding protein and reduces the production of DNA encoded RNAs and proteins to alter cellular functions. Mice with reduced levels of C/EBPβ-LIP show a healthier metabolism compared to mice with normal levels of C/EBPβ-LIP; although they eat the same diet. Furthermore, this thesis shows that high levels of C/EBPβ-LIP lead to an activated metabolism in cells which resembles the metabolism of cancer cells. Taken together, we identified C/EBPβ-LIP as a factor which is controlled by the diet and which alters the processing of the nutrients in the cell. Therefore, we hypothesise that C/EBPβ-LIP is an important mediator of the diet to regulate body functions and a reduction of C/EBPβ-LIP level by pharmaceuticals might help to treat metabolic disorders and cancer.

AB - The caloric intake and the composition of the diet controls protein production and functionality in the cell and thereby have direct impact on the health and metabolism of the organism. Aberrant metabolism and increased caloric intake result in metabolic disorders like type II diabetes or obesity. In the past, several factors were identified which respond to and mediate the cellular response to the diet composition and caloric intake in organisms. In this thesis, we describe C/EBPβ-LIP as an important factor which activity and function is controlled by the diet. C/EBPβ LIP is a DNA-binding protein and reduces the production of DNA encoded RNAs and proteins to alter cellular functions. Mice with reduced levels of C/EBPβ-LIP show a healthier metabolism compared to mice with normal levels of C/EBPβ-LIP; although they eat the same diet. Furthermore, this thesis shows that high levels of C/EBPβ-LIP lead to an activated metabolism in cells which resembles the metabolism of cancer cells. Taken together, we identified C/EBPβ-LIP as a factor which is controlled by the diet and which alters the processing of the nutrients in the cell. Therefore, we hypothesise that C/EBPβ-LIP is an important mediator of the diet to regulate body functions and a reduction of C/EBPβ-LIP level by pharmaceuticals might help to treat metabolic disorders and cancer.

M3 - Thesis fully internal (DIV)

SN - 978-94-034-1117-0

PB - University of Groningen

CY - [Groningen]

ER -

C/EBPβ isoforms and the regulation of metabolism: A fine balance between health and disease

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