ArticleCellular and molecular life sciences : CMLS2019
A novel leptin receptor antagonist uncouples leptin's metabolic and immune functions.
Article in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- The neuroimmune network in Alzheimer's and Parkinson's diseases: from mechanistic insights to biomarker-guided immunotherapies and clinical translation.Inflammopharmacology · 2026Review
- Sympathetic regulation of bone homeostasis and remodeling: molecular mechanisms, pathophysiological roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Molecular mechanisms and therapeutic implications of the sympathetic nervous system in bone-related disorders: a brain-bone axis perspective.Bone research · 2025Review
- Pre-existing adipose tissue signaling profile related to obesity determines disease outcome of COVID-19: addressing obesity should be a priority for future pandemic preparedness.Frontiers in endocrinology · 2025Article
- Evidence That Peripheral Leptin Resistance in Omental Adipose Tissue and Liver Correlates with MASLD in Humans.International journal of molecular sciences · 2024Article
- Obesity and leptin in breast cancer angiogenesis.Frontiers in endocrinology · 2024Review
- Leptin: A Heavyweight Player in Obesity-Related Cancers.Biomolecules · 2023Review
- Mechanism of receptor assembly via the pleiotropic adipokine Leptin.Nature structural & molecular biology · 2023Article
- Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies.Cancer biology & medicine · 2023Review
- Malnutrition and Erythropoietin Resistance among Patients with End-Stage Kidney Disease: Where Is the Perpetrator of Disaster?Nutrients · 2022Article
- Article
- Association of Serum Adipokines and Resting Energy Expenditure in Patients With Chronic Kidney Disease.Frontiers in nutrition · 2022Article
- Leptin-Activity Modulators and Their Potential Pharmaceutical Applications.Biomolecules · 2021Review
- Effect of Leptin on Chronic Inflammatory Disorders: Insights to Therapeutic Target to Prevent Further Cardiovascular Complication.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Leptin: an unappreciated key player in SLE.Clinical rheumatology · 2020Review
- Emerging Role of Adipocyte Dysfunction in Inducing Heart Failure Among Obese Patients With Prediabetes and Known Diabetes Mellitus.Frontiers in cardiovascular medicine · 2020Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Leptin links body energy stores to high energy demanding processes like reproduction and immunity. Based on leptin's role in autoimmune diseases and cancer, several leptin and leptin receptor (LR) antagonists have been developed, but these intrinsically lead to unwanted weight gain. Here, we report on the uncoupling of leptin's metabolic and immune functions based on the cross talk with the epidermal growth factor receptor (EGFR). We show that both receptors spontaneously interact and, remarkably, that this complex can partially overrule the lack of LR activation by a leptin antagonistic mutein. Moreover, this leptin mutant induces EGFR phosphorylation comparable to wild-type leptin. Exploiting this non-canonical leptin signalling pathway, we identified a camelid single-domain antibody that selectively inhibits this LR-EGFR cross talk without interfering with homotypic LR signalling. Administration in vivo showed that this single-domain antibody did not interfere with leptin's metabolic functions, but could reverse the leptin-driven protection against starvation-induced thymic and splenic atrophy. These findings offer new opportunities for the design and clinical application of selective leptin and LR antagonists that avoid unwanted metabolic side effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.