Hendrik Lehnert, Prof. Dr. med. Dr. h.c., FRCP, FACP
Publications
Journal Articles (Selection)
International Journal of Molecular Sciences, in press
Intrapancreatic Fat and Risk of Pancreatic Ductal Adenocarcinoma—Pathophysiology, Clinical Implications, and Future Directions
Svenja Meyhöfer, Paula Lünswilken, Jens U. Marquardt, Dimitris Grammatopoulos, Harpal Randeva, Hendrik Lehnert
Pancreatic adenocarcinoma (PDAC) remains one of the most lethal malignancies world wide, with limited improvements in long-term survival despite significant progress in systemic therapy. This review focuses predominantly on pancreatic ductal adenocarcinoma (PDAC), the most common and best-studied pancreatic malignancy, while referencing other pancreatic neoplasms only where directly relevant to intrapancreatic fat biology.
Obesity has emerged as a major modifiable risk factor for PDAC. In addition, increasing attention has focused on ectopic fat depots, particularly intrapancreatic fat, as potential mediators linking metabolic disease to pancreatic carcinogenesis. This narrative review summarizes the classification and epidemiology of PDAC, the relationship between obesity and pancreatic cancer risk, the biology of intrapancreatic fat, as well as putative mechanisms by which intrapancreatic fat may promote pancreatic carcinogenesis.
In addition, we will review current diagnostic approaches, therapeutic and preventive considerations, and key unanswered questions for future research on the relevance of intrapancreatic fat deposits. Collectively, available evidence supports intrapancreatic fat as a biologically plausible and potential mediator of pancreatic cancer risk, warranting further prospective investigation.
Trends in Endocrinology and Metabolism, doi: 10.1016/j.tem.2026.08.002. Online ahead of print
Decoding the CRH system from clinical failures to therapeutic translation
Maria Pinheiro Da Silva, Spenser Williams, George Mastorakos, Hendrik Lehnert, George Chrousos, and Dimitris Grammatopoulos
The corticotropin-releasing hormone (CRH) system is a central regulator of stress adaptation, integrating neuroendocrine, autonomic, immune, and behavioural responses to internal and external challenges.
For over two decades, CRH receptor type 1 (CRH-R1) has been pursued as a therapeutic target for stress-related and neuropsychiatric disorders. Despite a compelling biological rationale and extensive preclinical validation, the vast majority of CRH-R1 antagonist clinical programmes have failed across depression, anxiety, PTSD, and alcohol use disorder. In contrast, CRH-R1 antagonism has recently demonstrated clinical proof-of-concept as an adjunct treatment in congenital adrenal hyperplasia, while CRH-R2 agonism is attracting growing translational interest in cardiovascular and metabolic disease.
This review provides an updated reassessment of CRH-system therapeutics, extracting generalisable lessons from both failure and success and outlining a roadmap for future drug development.
Exp. Clin. Endocrinol Diabetes. 2025. DOI: 10.1055/a-2730-1689.
Acute Cold Exposure Improves Glucose Tolerance and Induces Beta-Cell Secretion Response Linked to Lipid Utilization in Young Male with Obesity
Rodrigo Chamorro, Beatrice Bertozzi, Jenny Backhaus, Karl A. Iwen, Leonie Rademacher, Svenja Meyhoefer, Hendrik Lehnert, Sebastian M. Meyhöfer, Britta Wilms
In this study we investigated the effects of acute cold-activated brown adipose tissue (BAT) on markers of metabolic health in men with obesity but no other chronic diseases and aimed to characterize potential underlying mechanisms linked to cold exposure (CE). We saw that CE decreased fasting glucose and improved glucose tolerance in parallel with increased β-cell response.
Moreover, CE led to increased plasma triglycerides as well as expression levels of selected genes involved in lipid metabolism. This points towards a cold-induced insulin feedback signal required to sustain BAT thermogenesis demands. Our study thus revealed acute metabolic effects of thermogenically activated BAT and potential mediating mechanisms in young men with obesity.
Eur. J. Cancer 225:115561, 2025
Regulation of epithelial-mesenchymal plasticity in pancreatic ductal adenocarcinoma: Role of key molecules in tumor differentiation and therapy
Qi Ling, Meiching Ong, Björn Konukiewitz, Rüdiger Braun, Jens-Uwe Marquardt, Hendrik Lehnert, Holger Kalthoff, Hendrik Ungefroren
Understanding tumor development and improving treatment strategies of pancreatic ductal adenocarcinoma (PDAC) is critical. Tumor cell plasticity enables differentiation, de-differentiation, and trans-differentiation, processes regulated by EMT and MET. The transitions are often controlled by structurally similar but functionally opposing protein pairs, including alternatively spliced isoforms (RAC1/RAC1B or TAp73α/TAp73β), phosphorylated vs. unphosphorylated forms of the same protein (SMAD3), or ligand source (paracrine vs. autocrine TGF-β1).
These proteins modulate canonical and non-canonical TGF-β signaling or function as its effectors. This review explores their roles in epithelial signaling and differentiation, aiming to contribute to novel targeted and personalized PDAC treatments.
Front. Endocrinol. 15511348,16,2025
Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review
Hendrik Ungefroren, Harpal Randeva, Hendrik Lehnert, Jörg Schrader, Jens-Uwe Marquardt, Björn Konukiewitz, Ralf Hass
Here we review the available evidence on signaling interactions between TGF-ß and somatostatin (receptors) which we believe are of potential relevance for cancer development / progression and therapeutic approaches.
Die Innere Medizin 65,1250,2024
30 Jahre Intensivkurs Innere Medizin – Eine gemeinsame Erfolgsgeschichte
Hendrik Lehnert
A look back on 30 years of comprehensive seminars on Internal Medicine launched and initiated by the author in 1994.
Cells. 13,2010-,2024. doi: 10.3390/cells13232010
Characterization of Epithelial-Mesenchymal and Neuroendocrine Differentiation States in Pancreatic and Small Cell Ovarian Tumor Cells and Their Modulation by TGF-β1 and BMP-7
Hendrik Ungefroren, Julian von der Ohe, Rüdiger Braun, Yola Gätje, Olha Lapshyna, Jörg Schrader, Hendrik Lehnert, Jens-Uwe Marquardt, Björn Konukiewitz, Ralf Hass
We have shown that in PDAC-derived tumor cells, neuroendocrine differentiation is closely linked to epithelial-mesenchymal transition and TGF-β signaling. This may have implications for the therapeutic use of TGF-β inhibitors in PDAC management.
Dtsch. Med. Wochenschr. 149,1492-1499,2024 doi: 10.1055/a-2339-0591
Endocrinology, diabetology and metabolism in the 150 years of the DMW - A long and sustainable relationship
Hendrik Lehnert, Klaus Mann
The Deutsche Medizinische Wochenschrift is celebrating its 150th anniversary – and this period is precisely when endocrinology and diabetology evolved from the first experiments to molecular biology, genetic, and bioinformatics research. We highlight this process through critical discussion of papers over this time period.
Elife 12,RP92075,2024. doi: 10.7554/eLife.92075
Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity
Christin Krause, Jan H Britsemmer, Miriam Bernecker, Anna Molenaar, Natalie Taege, Nuria Lopez-Alcantara, Cathleen Geißler, Meike Kaehler, Katharina Iben, Anna Judycka, Jonas Wagner, Stefan Wolter, Oliver Mann, Paul Pfluger, Ingolf Cascorbi, Hendrik Lehnert, Kerstin Stemmer, Sonja C Schriever, Henriette Kirchner
Here we revealed that the repression of LRP6 by miR-182-5 p, which promotes lipogenesis and impairs glucose homeostasis, provides a novel mechanistic link between T2D and non-alcoholic fatty liver disease, and demonstrate in vivo that miR-182-5 p can serve as a future drug target for the treatment of obesity-driven hepatic steatosis.
Biomedicines 12,199-,2024. doi: 10.3390/biomedicines12010199
RAC1b Collaborates with TAp73α-SMAD4 Signaling to Induce Biglycan Expression and Inhibit Basal and TGF-β-Driven Cell Motility in Human Pancreatic Cancer
Hendrik Ungefroren, Julissa Reimann, Björn Konukiewitz, Rüdiger Braun, Ulrich F Wellner, Hendrik Lehnert, Jens-Uwe Marquardt
In this study we showed that tumor-suppressive TAp73-Smad4-Bgn signaling also operates in human pancreatic cancer cells and that RAC1b likely acts as an upstream activator of this pathway.
You can find all publications on PubMed here.
I am happy to send you PDFs of the publications. Please email office@hendrik-lehnert.de to request them.
Bücher
(Redaktion für die Deutsche Gesellschaft für Endokrinologie): Rationelle Diagnostik und Therapie in Endokrinologie, Diabetologie und Stoffwechsel - 3. Auflage
Thieme Verlag 2009
Hendrik Lehnert
(Redaktion für die Deutsche Gesellschaft für Endokrinologie): Rationelle Diagnostik und Therapie in Endokrinologie, Diabetologie und Stoffwechsel - 2. Auflage
Thieme Verlag 2003
Hendrik Lehnert
essentials: Intensivkurs zur Weiterbildung
Innere Medizin - 2. Auflage
Enke Verlag 1999
Hendrik Lehnert & Hans-Peter Schuster
essentials: Intensivkurs zur Weiterbildung
Innere Medizin - 1. Auflage
Enke Verlag 1998
Hendrik Lehnert & Hans-Peter Schuster
Verhaltensmedizinische Aspekte der Hypertonie
SMVerlag 1992
Herausgegeben von Dirk Hellhammer, Hendrik Lehnert & Ulrike Ehlert