Epigenetic regulation of hepatic gene expression in the pathogenesis of insulin resistance

• Applicant: Professorin Dr. Henriette Kirchner
• Subject Area: Endocrinology, Diabetology, Metabolism ; Gastroenterology
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 279373746

• Final Report Year: 2023

Final Report Abstract

We identified altered DNA methylation in visceral adipose tissue of humans with impaired glucose tolerance and associated dysregulation of gene expression and metabolic parameters. Moreover, we identified microRNA 182-5p as important regulator of hepatic insulin sensitivity and contributor to the development of fatty liver diseases. Therefore, future studies should focus on antagonizing hepatic microRNA 182-5p in order to improve insulin resistance and fatty liver. Overall, we demonstrated the epigenetic alterations in metabolically active tissue of humans with type 2 diabetes exist and that these alterations likely contribute to the development and manifestation of metabolic diseases. In mice, epigenetic dysregulation is dynamically induced by high-fat feeding, causal for the development of insulin resistance and can be reversed by weight loss.

Publications

• Epigenetic Downregulation of FASN in Visceral Adipose Tissue of Insulin Resistant Subjects. Experimental and Clinical Endocrinology & Diabetes, 129(09), 674-682.
  Sievert, Helen; Krause, Christin; Geißler, Cathleen; Grohs, Martina; El-Gammal, Alexander T.; Wolter, Stefan; Mann, Oliver; Lehnert, Hendrik & Kirchner, Henriette
  
• Restructuring of the male mice peripheral circadian network after bariatric surgery. Journal of Endocrinology, 250(2), 67-79.
  Neumann, Anne-Marie; Geißler, Cathleen; Pilorz, Violetta; Olejniczak, Iwona; Lewis, Alfor G.; Seeley, Randy J.; Shomroni, Orr; Salinas-Riester, Gabriela; Kirchner, Henriette & Oster, Henrik
  
• Dietary induction of obesity and insulin resistance is associated with changes in Fgf21 DNA methylation in liver of mice. The Journal of Nutritional Biochemistry, 100, 108907.
  Geißler, Cathleen; Krause, Christin; Neumann, Anne-Marie; Britsemmer, Jan H.; Taege, Natalie; Grohs, Martina; Kaehler, Meike; Cascorbi, Ingolf; Lewis, Alfor G.; Seeley, Randy J.; Oster, Henrik & Kirchner, Henriette
  
• Transcriptional Alterations in X-Linked Dystonia–Parkinsonism Caused by the SVA Retrotransposon. International Journal of Molecular Sciences, 23(4), 2231.
  Pozojevic, Jelena; Algodon, Shela Marie; Cruz, Joseph Neos; Trinh, Joanne; Brüggemann, Norbert; Laß, Joshua; Grütz, Karen; Schaake, Susen; Tse, Ronnie; Yumiceba, Veronica; Kruse, Nathalie; Schulz, Kristin; Sreenivasan, Varun K. A.; Rosales, Raymond L.; Jamora, Roland Dominic G.; Diesta, Cid Czarina E.; Matschke, Jakob; Glatzel, Markus; Seibler, Philip ... & Westenberger, Ana
  
• Differences in DNA methylation of HAMP in blood cells predicts the development of type 2 diabetes. Molecular Metabolism, 75, 101774.
  Ouni, Meriem; Eichelmann, Fabian; Jähnert, Markus; Krause, Christin; Saussenthaler, Sophie; Ott, Christiane; Gottmann, Pascal; Speckmann, Thilo; Huypens, Peter; Wolter, Stefan; Mann, Oliver; De Angelis, Martin Hrabé; Beckers, Johannes; Kirchner, Henriette; Schulze, Matthias B. & Schürmann, Annette
  
• Fatty Acid Induced Hypermethylation in the Slc2a4 Gene in Visceral Adipose Tissue Is Associated to Insulin-Resistance and Obesity. International Journal of Molecular Sciences, 24(7), 6417.
  Britsemmer, Jan H.; Krause, Christin; Taege, Natalie; Geißler, Cathleen; Lopez-Alcantara, Nuria; Schmidtke, Linda; Naujack, Alison-Michelle; Wagner, Jonas; Wolter, Stefan; Mann, Oliver & Kirchner, Henriette
  
• Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity.
  Krause, Christin; Britsemmer, Jan H.; Bernecker, Miriam; Molenaar, Anna; Taege, Natalie; Geißler, Cathleen; Kaehler, Meike; Iben, Katharina; Judycka, Anna; Wagner, Jonas; Wolter, Stefan; Mann, Oliver; Pfluger, Paul T.; Cascorbi, Ingolf; Lehnert, Hendrik; Stemmer, Kerstin; Schriever, Sonja C. & Kirchner, Henriette
  
• Resistance to thyroid hormone induced tachycardia in RTHα syndrome. Nature Communications, 14(1).
  Dore, Riccardo; Watson, Laura; Hollidge, Stefanie; Krause, Christin; Sentis, Sarah Christine; Oelkrug, Rebecca; Geißler, Cathleen; Johann, Kornelia; Pedaran, Mehdi; Lyons, Greta; Lopez-Alcantara, Nuria; Resch, Julia; Sayk, Friedhelm; Iwen, Karl Alexander; Franke, Andre; Boysen, Teide Jens; Dalley, Jeffrey W.; Lorenz, Kristina; Moran, Carla ... & Mittag, Jens
  
• When should I run—the role of exercise timing in metabolic health. Acta Physiologica, 237(4).
  Kirchner, Henriette; Weisner, Leon & Wilms, Britta