ArticleCell metabolism2025
The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice.
Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Trajectory of the body weight after drug discontinuation in the treatment of anti-obesity medications.BMC medicine · 2025Pooled it
- GLP-1 Receptor Agonist and GIP/GLP-1 Receptor Dual Agonist Therapeutics at the Intersection of Alcohol Use Disorder, Obesity, and Cardiometabolic Dysfunction.Biological psychiatry global open science · 2026Review
- Lipid sensing and brain hormone receptors in food intake and glucose regulation.Nature reviews. Endocrinology · 2026Review
- Review
- Glycemic and bodyweight effects ofScience advances · 2026Article
- Clinical Potential of GIP in Type 2 Diabetes and Obesity.Diabetes care · 2026Review
- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
- Junctophilin-2-orchestrated calcium signalosome regulates brown adipocyte thermogenesis and energy metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Design and therapeutic rationale of antibody-peptide conjugates: insights from maridebart cafraglutide (AMG133) and emerging applications.Antibody therapeutics · 2026Review
- Tirzepatide as a multi-organ integrator in metabolic diseases: a review of molecular mechanisms and clinical translation.Endocrine · 2026Review
- Adipose Tissue Plasticity, Lipoprotein Metabolism, and Cardiovascular Risk: The Emerging Role of the GLP-1 Axis.Circulation research · 2026Review
- Tirzepatide retention in iWAT with mesoporous polydopamine encapsulation enhances weight loss through leptin receptor signaling.Journal of advanced research · 2026Article
- Article
- Lipolysis in Health and Disease: Pathways, Regulation, and Metabolic Consequences.Current diabetes reports · 2026Review
- Multi-omic profiling reveals Retatrutide alleviates adipose tissue fibrosis via metabolic reprogramming and tissue repair.Diabetology & metabolic syndrome · 2026Article
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- Endogenous GIP signaling is indispensable for DPP-4 inhibitor-mediated metabolic control in mice.Journal of diabetes investigation · 2026Article
- Interaction between fatty pancreas disease and genetically predicted glucose-dependent insulinotropic polypeptide on incident type 2 diabetes: evidence from the UK Biobank.Frontiers in endocrinology · 2026Article
- Interpretable bioimpedance-based modeling of body composition and metabolic indices related to physical function in maintenance hemodialysis patients.Frontiers in nutrition · 2026Article
- Comparative Efficacy of Semaglutide and Tirzepatide in Chinese Adults with Obesity without Diabetes: A Real-World Observational Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Obesity is a chronic disease that contributes to the development of insulin resistance, type 2 diabetes (T2D), and cardiovascular risk. Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) co-agonism provide an improved therapeutic profile in individuals with T2D and obesity when compared with selective GLP-1R agonism. Although the metabolic benefits of GLP-1R agonism are established, whether GIPR activation impacts weight loss through peripheral mechanisms is yet to be fully defined. Here, we generated a mouse model of GIPR induction exclusively in the adipocyte. We show that GIPR induction in the fat cell protects mice from diet-induced obesity and triggers profound weight loss (∼35%) in an obese setting. Adipose GIPR further increases lipid oxidation, thermogenesis, and energy expenditure. Mechanistically, we demonstrate that GIPR induction activates SERCA-mediated futile calcium cycling in the adipocyte. GIPR activation further triggers a metabolic memory effect, which maintains weight loss after the transgene has been switched off, highlighting a unique aspect in adipocyte biology. Collectively, we present a mechanism of peripheral GIPR action in adipose tissue, which exerts beneficial metabolic effects on body weight and energy balance.
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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.