<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The role of hepatic Growth Arrest and DNA Damage-inducible 45 beta (GADD45β) in adaptive metabolic control"^^ . "In mammals, the balance of energy storage and breakdown is essential for the maintenance of whole body energy homeostasis. An imbalance between energy intake and expenditure as well as an impaired adaption of the central metabolic organs to changes in nutrient availability (so-called metabolic inflexibility) is tightly associated with the onset and progression of obesity and type II diabetes (T2D) and represents a hallmark of the metabolic syndrome. The metabolic syndrome is associated with a spectrum of liver abnormalities described as non-alcoholic fatty liver disease (NAFLD). Thereby, intracellular fat accumulation leads to hepatic lipotoxicity, cellular stress and dysfunction. While the liver is recognized as a key organ contributing to systemic metabolic control, the molecular mechanisms of liver metabolism in coordinating metabolic flexibility remain still puzzling. \r\n\r\nIn order to determine the molecular mechanisms involved in metabolic flexibility and to find genes which display certain ‘inflexibility’ in conditions of metabolic dysfunction, a liver transcriptome analysis was performed on obese-diabetic db/db and wild type mice under fasting and fed conditions. Array results have uncovered one ‘inflexibility’ gene in the liver: GADD45β, a member of the “growth arrest and DNA damage-inducible 45” (GADD45) gene family. In particular, we have observed a strong upregulation of liver Gadd45b expression upon food deprivation in healthy animals, which was markedly less pronounced in db/db mice. While GADD45β is reported to be involved in hyperplasia of hepatocytes and in liver regeneration, there are no studies examining the role of GADD45β in metabolic function.\r\n\r\nIn this work, we have characterised GADD45β as a nutrient starvation-induced gene, which is differentially expressed in disease and ageing. Congruently, liver Gadd45b mRNA levels were lower in fasted men with T2D than in healthy individuals. Gadd45b induction was liver specific and not compensated by an induction of the other GADD45 family members. Furthermore, we could show that the Gadd45b induction is reversible after re-feeding and intrinsic to hepatocytes.\r\n\r\nIn the present work we describe for the first time a novel role for hepatic GADD45β in adaptive metabolism under the stress of food deprivation and nutrient overload. A whole-body deletion of the gene caused an accumulation of triglycerides and cholesterol in the liver under fasting conditions and in a mouse model for steatosis. Also, GADD45β KO mice were more insulin resistant after 4 months on high fat diet. Inversely, a liver-restricted GADD45β overexpression in systemic GADD45β KO mice could partially reverse their dysregulated fasting lipid metabolism, and GADD45β overexpression in db/db mice could partially reverse their diabetic phenotype.\r\n\r\nWhile the exact mechanism(s) by which GADD45β mediates its effects remain unclear we conclude that GADD45β may be a missing link between lipid and glucose homeostasis under conditions of nutrient stress, thereby protecting from metabolic dysfunction."^^ . "2016" . . . . . . . "Jessica"^^ . "Fuhrmeister"^^ . "Jessica Fuhrmeister"^^ . . . . . . "The role of hepatic Growth Arrest and DNA Damage-inducible 45 beta (GADD45β) in adaptive metabolic control (PDF)"^^ . . . "Jessica Fuhrmeister_Dissertation 2015.pdf"^^ . . . "The role of hepatic Growth Arrest and DNA Damage-inducible 45 beta (GADD45β) in adaptive metabolic control (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The role of hepatic Growth Arrest and DNA Damage-inducible 45 beta (GADD45β) in adaptive metabolic control (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The role of hepatic Growth Arrest and DNA Damage-inducible 45 beta (GADD45β) in adaptive metabolic control (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The role of hepatic Growth Arrest and DNA Damage-inducible 45 beta (GADD45β) in adaptive metabolic control (Other)"^^ . . . . . . "small.jpg"^^ . . . "The role of hepatic Growth Arrest and DNA Damage-inducible 45 beta (GADD45β) in adaptive metabolic control (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #18705 \n\nThe role of hepatic Growth Arrest and DNA Damage-inducible 45 beta (GADD45β) in adaptive metabolic control\n\n" . "text/html" . . . "000 Allgemeines, Wissenschaft, Informatik"@de . "000 Generalities, Science"@en . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . . . "600 Technik, Medizin, angewandte Wissenschaften"@de . "600 Technology (Applied sciences)"@en . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .