TY - JOUR
T1 - Hepatic transforming growth factor-beta 1 stimulated clone-22 D1 controls systemic cholesterol metabolism
AU - Jäger, Julia
AU - Greiner, Vera
AU - Strzoda, Daniela
AU - Seibert, Oksana
AU - Niopek, Katharina
AU - Sijmonsma, Tjeerd P.
AU - Schäfer, Michaela
AU - Jones, Allan
AU - de Guia, Roldan
AU - Martignoni, Marc
AU - Dallinga-Thie, Geesje M.
AU - Diaz, Mauricio B.
AU - Hofmann, Thomas G.
AU - Herzig, Stephan
PY - 2014
Y1 - 2014
N2 - Disturbances in lipid homeostasis are hallmarks of severe metabolic disorders and their long-term complications, including obesity, diabetes, and atherosclerosis. Whereas elevation of triglyceride (TG)-rich very-low-density lipoproteins (VLDL) has been identified as a risk factor for cardiovascular complications, high-density lipoprotein (HDL)-associated cholesterol confers atheroprotection under obese and/or diabetic conditions. Here we show that hepatocyte-specific deficiency of transcription factor transforming growth factor (31-stimulated clone (TSC) 22 D1 led to a substantial reduction in HDL levels in both wild-type and obese mice, mediated through the transcriptional down-regulation of the HDL formation pathway in liver. Indeed, overexpression of TSC22D1 promoted high levels of HDL cholesterol in healthy animals, and hepatic expression of TSC22D1 was found to be aberrantly regulated in disease models of opposing energy availability. The hepatic TSC22D1 transcription factor complex may thus represent an attractive target in HDL raising strategies in obesity/diabetes-related dyslipidemia and atheroprotection. (C) 2014 The Authors. Published by Elsevier GmbH
AB - Disturbances in lipid homeostasis are hallmarks of severe metabolic disorders and their long-term complications, including obesity, diabetes, and atherosclerosis. Whereas elevation of triglyceride (TG)-rich very-low-density lipoproteins (VLDL) has been identified as a risk factor for cardiovascular complications, high-density lipoprotein (HDL)-associated cholesterol confers atheroprotection under obese and/or diabetic conditions. Here we show that hepatocyte-specific deficiency of transcription factor transforming growth factor (31-stimulated clone (TSC) 22 D1 led to a substantial reduction in HDL levels in both wild-type and obese mice, mediated through the transcriptional down-regulation of the HDL formation pathway in liver. Indeed, overexpression of TSC22D1 promoted high levels of HDL cholesterol in healthy animals, and hepatic expression of TSC22D1 was found to be aberrantly regulated in disease models of opposing energy availability. The hepatic TSC22D1 transcription factor complex may thus represent an attractive target in HDL raising strategies in obesity/diabetes-related dyslipidemia and atheroprotection. (C) 2014 The Authors. Published by Elsevier GmbH
U2 - https://doi.org/10.1016/j.molmet.2013,12.007
DO - https://doi.org/10.1016/j.molmet.2013,12.007
M3 - Article
C2 - 24634828
SN - 2212-8778
VL - 3
SP - 155
EP - 166
JO - Molecular metabolism
JF - Molecular metabolism
IS - 2
ER -