Changes in the local control of TH action during NASH (blue) in human (A) and mouse (B).

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 Email
Alison Naujack PhD candidate (Team Kirchner)   Mail
Nuria López Alcántara PhD candidate (Team Mittag) +49 451 3101 7830 Mail

 

Further Information

Homepage Team Kirchner

Homepage Team Mittag

 

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