ArticleNature2017
MC4R-dependent suppression of appetite by bone-derived lipocalin 2.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 261 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
261 citing papers in PubMed, 1 synthesis or guideline pooled it, 446 citations in OpenAlex.
- A systematic review of the implications of lipocalin-2 expression in periodontal disease.Evidence-based dentistry · 2025Pooled it
- The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study.Scientific reports · 2025Trial
- DuodenalGut · 2022Trial
- Biomaterials at the interface of bone-derived factors and inter-organ communication: Current evidence and future perspectives.Bioactive materials · 2026Review
- Osteoporosis and Alzheimer's Disease: The Role of Sclerostin.Current osteoporosis reports · 2026Review
- The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026Review
- Tibial bone compression promotes recovery after brain injury through osteocyte PIEZO1.Nature neuroscience · 2026Article
- Spatiotemporal immunomodulation with programmable biomaterials to promote musculoskeletal tissue regeneration.Bioactive materials · 2026Review
- Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior.Brain, behavior, and immunity · 2026Article
- Multifunctional scaffold inspired by hepatocyte exosomes promotes bone regeneration by regulating osteogenic differentiation via PI3K/AKT pathway.Materials today. Bio · 2026Article
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Bone‑origin repair in diabetic foot ulcers: Mechanisms of callus formation and endocrine effects in healing (Review).International journal of molecular medicine · 2026Review
- Creatinine-normalized urinary lipocalin-2 in children with obesity: association with insulin resistance in a cross-sectional study.Scientific reports · 2026Article
- Bone as an endocrine regulator of lipid and energy metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- The crossroads between osteosarcopenia and intrinsic capacity-a narrative review.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Review
- Hippocampal Lipocalin-2 in T2DM Associated Neurodegeneration: A Therapeutic Perspective.Neurochemical research · 2026Review
- Endoplasmic Reticulum Stress in the Keratinocytes Contributes to Chronic Itch by Activation of Lipocalin 2/MC4R/TRPV1 Pathway.Neuroscience bulletin · 2026Article
- LCN2/SLC22A17 mediates the phagocytosis of GABAergic synapses by oligodendrocyte progenitor cells and contributes to cancer-induced pain and comorbid anxiety-like behaviors in mice.Acta neuropathologica communications · 2026Article
- The differential expression of lipocalin-2 in pig tissues and its molecular mechanism of regulating cell viability, differentiation, adipogenesis, and glycometabolism in porcine intramuscular preadipocytes.In vitro cellular & developmental biology. Animal · 2026Article
- Panx3 deficiency in mice impairs bone fracture healing and causes transient hypoglycemia in neonatal animals.Molecular medicine (Cambridge, Mass.) · 2026Article
201 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity. In addition, osteoblast-derived LCN2 inhibits food intake. LCN2 crosses the blood-brain barrier, binds to the melanocortin 4 receptor (MC4R) in the paraventricular and ventromedial neurons of the hypothalamus and activates an MC4R-dependent anorexigenic (appetite-suppressing) pathway. These results identify LCN2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone.
Indexed as
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What OpenQuestion holds
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.