Dual regulation of TxNIP by ChREBP and FoxO1 in liver
Benedicte Noblet,
Fadila Benhamed,
InSug O-Sullivan,
Wenwei Zhang,
Gaëlle Filhoulaud,
Alexandra Montagner,
Arnaud Polizzi,
Solenne Marmier,
Anne-Françoise Burnol,
Sandra Guilmeau,
Tarik Issad,
Hervé Guillou,
Catherine Bernard,
Terry Unterman,
Catherine Postic
Affiliations
Benedicte Noblet
Université de Paris, Institut Cochin, CNRS, INSERM, 75014 Paris, France
Fadila Benhamed
Université de Paris, Institut Cochin, CNRS, INSERM, 75014 Paris, France
InSug O-Sullivan
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612; Medical Research Service, Jesse Brown VA Medical Center, Chicago, IL 60612, USA
Wenwei Zhang
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612; Medical Research Service, Jesse Brown VA Medical Center, Chicago, IL 60612, USA
Gaëlle Filhoulaud
Université de Paris, Institut Cochin, CNRS, INSERM, 75014 Paris, France
Alexandra Montagner
Toxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, France
Arnaud Polizzi
Toxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, France
Solenne Marmier
Université de Paris, Institut Cochin, CNRS, INSERM, 75014 Paris, France
Anne-Françoise Burnol
Université de Paris, Institut Cochin, CNRS, INSERM, 75014 Paris, France
Sandra Guilmeau
Université de Paris, Institut Cochin, CNRS, INSERM, 75014 Paris, France
Tarik Issad
Université de Paris, Institut Cochin, CNRS, INSERM, 75014 Paris, France
Hervé Guillou
Toxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, France
Catherine Bernard
Institut de Recherches Servier, Noisy-le-Roi, Île-de-France, France
Terry Unterman
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612; Medical Research Service, Jesse Brown VA Medical Center, Chicago, IL 60612, USA; Corresponding author
Summary: TxNIP (Thioredoxin-interacting protein) is considered as a potential drug target for type 2 diabetes. Although TxNIP expression is correlated with hyperglycemia and glucotoxicity in pancreatic β cells, its regulation in liver cells has been less investigated. In the current study, we aim at providing a better understanding of Txnip regulation in hepatocytes in response to physiological stimuli and in the context of hyperglycemia in db/db mice. We focused on regulatory pathways governed by ChREBP (Carbohydrate Responsive Element Binding Protein) and FoxO1 (Forkhead box protein O1), transcription factors that play central roles in mediating the effects of glucose and fasting on gene expression, respectively. Studies using genetically modified mice reveal that hepatic TxNIP is up-regulated by both ChREBP and FoxO1 in liver cells and that its expression strongly correlates with fasting, suggesting a major role for this protein in the physiological adaptation to nutrient restriction.
