Control of cellular TH metabolism in human and mouse NASH
Prof. Dr. Henriette Kirchner & Prof. Dr. Jens Mittag
Hepatic TRβ signalling is impaired in human and murine NASH, and vice versa, elevating hepatic TH action improves non-alcoholic hepatosteatosis (NASH). Using human liver biopsies, NASH mouse models and iPSC-derived hepatocytes, we aim to identify the mechanisms that cause reduced TRβ expression in NASH, testing the hypothesis that this is mediated by epigenetic mechanisms involving miRNA and DNA methylation. Finally, we hypothesise that improving hepatic TRβ signalling in NASH will improve current treatment strategies.
Project Team Members
| Name | Position | Phone | |
|---|---|---|---|
| Alison Naujack | PhD candidate (Team Kirchner) | ||
| Nuria López Alcántara | PhD candidate (Team Mittag) | +49 451 3101 7830 |
Further Information
Selected Publicatons
Thyroid wars: the rise of central actions.
Capelli V, Diéguez C, Mittag J, López M.
2021. Trends Endocrinol Metab. doi: 10.1016/2021.05.006
GOAT links dietary lipids with the endocrine control of energy balance.
Kirchner H, Gutierrez JA, Solenberg PJ, Pfluger PT, Czyzyk TA, Willency JA, Schürmann A, Joost HG, Jandacek RJ, Hale JE, Heiman ML, Tschöp MH.
2009. Nat Med 15(7):741-5. doi: 10.1038/nm.1997
Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor.
Barnett BP, Hwang Y, Taylor MS, Kirchner H, Pfluger PT, Bernard V, Lin YY, Bowers EM, Mukherjee C, Song WJ, Longo PA, Leahy DJ, Hussain MA, Tschöp MH, Boeke JD, Cole PA.
2010. Science 330(6011):1689-92. doi: 10.1126/science.1196154
Critical Evaluation of the DNA-methylation Markers ABCG1 and SREBF1 for Type 2 Diabetes Stratification.
Krause C, Sievert H, Geißler C, Grohs M, El Gammal AT, Wolter S, Ohlei O, Kilpert F, Krämer UM, Kasten M, Klein C, Brabant GE, Mann O, Lehnert H, Kirchner H.
2019. Epigenomics 11(8):885-897. doi: 10.2217/epi-2018-0159
Mouse-human experimental epigenetic analysis unmasks dietary targets and genetic liability for diabetic phenotypes.
Multhaup ML, Seldin MM, Jaffe AE, Lei X , Kirchner H, Mondal P, Li Y, Rodriguez V, Drong A, Hussain M, Lindgren C, McCarthy M, Näslund E, Zierath JR, Wong GW, Feinberg AP.
2015. Cell Metab 21(1):138-49. doi: 10.1016/j.cmet.2014.12.014
Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients.
Kirchner H, Sinha I, Gao H, Ruby MA, Schönke M, Lindvall JM, Barrès R, Krook A, Näslund E, Dahlman-Wright K, Zierath JR.
2016. Mol Metab 5(3):171-83. Doi: 10.1016/j.molmet.2015.12.004
Interference of a Mutant Thyroid Hormone Receptor a1 With Hepatic Glucose Metabolism.
Vujovic M, Nordström K, Gauthier K, Flamant F, Visser TJ, Vennström B, Mittag J.
2009. Endocrinology 150(6):2940-7. doi: 10.1210/en.2008-1085
Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor α1.
Warner A, Rahman A, Solsjö P, Gottschling K, Davis B, Vennström B, Arner A, Mittag J.
2013. Proc Natl Acad Sci U S A 110(40):16241-16246. doi: 10.1073/pnas.1310300110
Hypothalamic AMPK ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.
Martínez-Sánchez N, Seoane-Collazo P, Contreras C, Varela L, Villarroya J, Rial-Pensado E, Buqué X, Aurrekoetxea I, Delgado TC, Vázquez-Martínez R, González-García I, Roa J, J Whittle AJ, Gomez-Santos B, Velagapudi V, Tung YCL, Morgan DA, Voshol PJ, Martínez de Morentin PB, López-González T, Liñares-Pose L, Gonzalez F, Chatterjee K, Sobrino T, Medina-Gómez G, Davis RJ, Casals N, Orešič M, Coll AP, Vidal-Puig A, Mittag J, Tena-Sempere M, Malagón MM, Diéguez C, Martínez-Chantar ML, Aspichueta P, Rahmouni K, Nogueiras R, Sabio G, Villarroya F, López M.
2017. Cell Metab 26(1):212-229.e12. doi: 10.1016/j.cmet.2017.06.014
Dwarfism and insulin resistance in male offspring caused by α1-adrenergic antagonism during pregnancy.
Oelkrug R, Herrmann B, Geissler C, Harder L, Koch C, Lehnert H, Oster H, Kirchner H, Mittag J.
2017. Mol Metab 6(10): 1126-36. doi: 10.1016/j.molmet.2017.06.016
Reduced expression of thyroid hormone receptor b in human nonalcoholic steatohepatitis.
Krause C, Grohs M, Gammal AT, Wolter S, Lehnert H, Mann O, Mittag J, Kirchner H.
2018. Endocr Connect (12):1448-1456. doi: 10.1530/EC-18-0499
