Liver-Restricted Repin1 Deficiency Improves Whole-Body Insulin Sensitivity, Alters Lipid Metabolism, and Causes Secondary Changes in Adipose Tissue in Mice
| Autor: | Peter Kovacs, Knut Krohn, Julia Brückner, Gesine Flehmig, Rolf Gebhardt, Nico Hesselbarth, Michael Stumvoll, John T. Heiker, Nora Klöting, Ingrid Klöting, Matthias Blüher, Andrej Shevchenko, Susanne Sales, Madlen Matz-Soja, Kerstin Abshagen, Joanna Kosacka, Matthias Kern |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment CD36 Adipose tissue Mice Insulin resistance Internal medicine Internal Medicine medicine Animals Insulin Chemerin Phosphorylation Muscle Skeletal Mice Knockout biology RNA-Binding Proteins Lipid metabolism Glucose clamp technique Lipid Metabolism medicine.disease DNA-Binding Proteins Glucose Endocrinology Adipose Tissue Gene Expression Regulation Liver Glucose Clamp Technique biology.protein GLUT2 Insulin Resistance Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Diabetes. 63:3295-3309 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db13-0933 |
| Popis: | Replication initiator 1 (Repin1) is a zinc finger protein highly expressed in liver and adipose tissue and maps within a quantitative trait locus (QTL) for body weight and triglyceride (TG) levels in the rat. The QTL has further been supported as a susceptibility locus for dyslipidemia and related metabolic disorders in congenic and subcongenic rat strains. Here, we elucidated the role of Repin1 in lipid metabolism in vivo. We generated a liver-specific Repin1 knockout mouse (LRep1−/−) and systematically characterized the consequences of Repin1 deficiency in the liver on body weight, glucose and lipid metabolism, liver lipid patterns, and protein/mRNA expression. Hyperinsulinemic-euglycemic clamp studies revealed significantly improved whole-body insulin sensitivity in LRep1−/− mice, which may be due to significantly lower TG content in the liver. Repin1 deficiency causes significant changes in potential downstream target molecules including Cd36, Pparγ, Glut2 protein, Akt phosphorylation, and lipocalin2, Vamp4, and Snap23 mRNA expression. Mice with hepatic deletion of Repin1 display secondary changes in adipose tissue function, which may be mediated by altered hepatic expression of lipocalin2 or chemerin. Our findings indicate that Repin1 plays a role in insulin sensitivity and lipid metabolism by regulating key genes of glucose and lipid metabolism. |
| Databáze: | OpenAIRE |
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