ArticleEndocrinology2014
LGR4 and its ligands, R-spondin 1 and R-spondin 3, regulate food intake in the hypothalamus of male rats.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties.Discover oncology · 2026Review
- Charting spatial ligand-target activity using Renoir.Nature communications · 2026Article
- Deficiency of Leucine-Rich Repeat Containing G Protein-Coupled Receptor 4 in Pancreas Reduces β Cell Mass.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring diversity: a review of animal models for investigating variations in sex characteristics.Frontiers in pediatrics · 2025Review
- Regulation of RSPO3-LGR4 Signaling: Emerging Role in Inflammation Revealed by Network Analysis.Archives of clinical and biomedical research · 2025Article
- Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- Alternative Polyadenylation Results in mRNA Transcript Instability in Gestational Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.Frontiers in endocrinology · 2022Review
- The Role of LGR4 (GPR48) in Normal and Cancer Processes.International journal of molecular sciences · 2021Review
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
- Rspo1/Rspo3-LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKα-SREBP2 pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Association between LGR4 polymorphisms and peak bone mineral density and body composition.Journal of bone and mineral metabolism · 2020Article
- Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance.Diabetes & metabolism journal · 2019Article
- Altered R-spondin 1/CART neurocircuit in the hypothalamus contributes to hyperphagia in diabetes.Journal of neurophysiology · 2019Article
- Notoginsenoside Fe suppresses diet induced obesity and activates paraventricular hypothalamic neurons.RSC advances · 2019Article
- LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- LGR4 and Its Role in Intestinal Protection and Energy Metabolism.Frontiers in endocrinology · 2015Review
- Silencing of R-Spondin1 increases radiosensitivity of glioma cells.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4-LGR6 and Rspos (1-4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis.
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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.