title: The Role of Hepatic Transforming Growth Factor-Beta1 Stimulated Clone-22 D4 (TSC22D4) in Acute Metabolic Dyslipidemia
creator: Jones, Allan
subject: 570
subject: 570 Life sciences
description: Metabolism is defined as the sum of all biochemical reactions taking place in any given system at a specific point in time. Deregulation of metabolic balance in the human body can thereby have severe consequences in regard to health and well-being. In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. Abnormally high levels of triglycerides (TG) in the blood (“hypertriglyceridemia”) represent a hallmark of disorders such as the Metabolic Syndrome, type 2 diabetes and atherosclerosis. Indeed, hypertriglyceridemia has been identified as an important risk factor for long-term diabetic complications, whilst hypotriglyceridemia occurs in patients suffering from a tumour-associated wasting condition known as cachexia. In this study, we identify the hepatic transforming growth factor-beta 1 stimulated clone (TSC)-22 D4 as a critical molecular determinant of systemic lipid homeostasis and lipoprotein metabolism. Using a large-scale luminescence based mammalian interactome (LUMIER) screen, TSC22D4 was identified as an as-yet unknown interaction partner of the TBL1/TBLR1 transcriptional co-factor complex. TSC22D4 was found to be down-regulated under conditions of diet-induced obesity and induced in cancer cachexia. Liver-specific ablation of TSC22D4 in mice triggered serum hyperlipidemia through the induction of lipogenic gene expression in the liver and an associated increase in the release of TG-rich very-low-density-lipoprotein (VLDL) particles. Conversely, restoration of TSC22D4 in obese mice led to reduced VLDL release and TG accumulation in the liver. TSC22D4 expression levels were found to inversely correlate with the degree of weight loss in a mouse model of cancer cachexia. In future, it will be interesting to investigate if the induction of hepatic TSC22D4 activity represents a cause or protective consequence in the onset of tumour-associated cachexia. In this regard, TSC22D4 may serve as a molecular marker for disease progression and prognosis in patients.
date: 2011
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/12930/1/Thesis_Allan_Jones.pdf
identifier: DOI:10.11588/heidok.00012930
identifier: urn:nbn:de:bsz:16-opus-129307
identifier:   Jones, Allan  (2011) The Role of Hepatic Transforming Growth Factor-Beta1 Stimulated Clone-22 D4 (TSC22D4) in Acute Metabolic Dyslipidemia.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/12930/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng