Liver-restricted Repin1 Deficiency Improves Whole Body Insulin Sensitivity, Alters Lipid Metabolism and Causes Secondary Changes in Adipose Tissue in Mice
- Matthias Kern1,*,
- Joanna Kosacka1,*,
- Nico Hesselbarth1,
- Julia Brückner1,
- John T. Heiker1,
- Gesine Flehmig2,
- Ingrid Klöting3,
- Peter Kovacs2,
- Madlen Matz-Soja4,
- Rolf Gebhardt4,
- Knut Krohn5,
- Susanne Sales6,
- Kerstin Abshagen7,
- Andrej Shevchenko6,
- Michael Stumvoll1,2,
- Matthias Blüher1,2 and
- Nora Klöting1,2⇑
- 1Department of Medicine, University of Leipzig, 04103 Leipzig, Germany
- 2IFB AdiposityDiseases, University of Leipzig, 04103 Leipzig, Germany
- 3Department of Laboratory Animal Science, University of Greifswald, Karlsburg, Germany
- 4Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany
- 5Interdisciplinary Center for Clinical Research, Core-Unit DNA Technologies, University of Leipzig, Leipzig, Germany
- 6Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- 7Institute for Experimental Surgery, Rostock University Medical School, 18057 Rostock, Germany
- Corresponding author: Nora Klöting, Email:
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 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 triglyceride content in the liver. Repin1 deficiency causes significant changes in potential downstream target molecules including Cd36, Pparg, Glut2 protein, Akt phosphorylation, 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.
* shared authorship
- Received June 18, 2013.
- Accepted April 19, 2014.
- © 2014 by the American Diabetes Association.
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