ArticleAmerican journal of physiology. Endocrinology and metabolism2010
Obese carboxypeptidase E knockout mice exhibit multiple defects in peptide hormone processing contributing to low bone mineral density.
Article in American journal of physiology. Endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Ai-Assisted Discovery of a Direct Physical Interaction Between a Venom Serpin from the Parasitoid WaspToxins · 2025Article
- Navigating the Strengths and Constraints of Mouse Models in Obesity Research.Endocrinology · 2025Review
- Sex differences in the genetic regulation of the human plasma proteome.Nature communications · 2025Article
- Osteoprotegerin mediates adipogenesis in obesity.Journal of advanced research · 2024Article
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- Proteome-wide Mendelian randomization provides novel insights into the pathogenesis and druggable targets of osteoporosis.Frontiers in medicine · 2024Article
- Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases.Nature genetics · 2023Article
- Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma.PeerJ · 2023Article
- Mice heterozygous for a null mutation of CPE show reduced expression of carboxypeptidase e mRNA and enzyme activity but normal physiology, behavior, and levels of neuropeptides.Brain research · 2022Article
- Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.Endocrinology · 2021Review
- Using "-omics" Data to Inform Genome-wide Association Studies (GWASs) in the Osteoporosis Field.Current osteoporosis reports · 2021Review
- Neuropeptidomic Analysis of a Genetically Defined Cell Type in Mouse Brain and Pituitary.Cell chemical biology · 2021Article
- Neurotrophic factor-α1, a novel tropin is critical for the prevention of stress-induced hippocampal CA3 cell death and cognitive dysfunction in mice: comparison to BDNF.Translational psychiatry · 2021Article
- Nonenzymatic and Trophic Activities of Carboxypeptidase E Regulate Bone Mass and Bioenergetics of Skeletal Stem Cells in Mice.JBMR plus · 2020Article
- Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts.Genome biology · 2020Article
- A systematic review on different models of inducing obesity in animals: Advantages and limitations.Journal of advanced veterinary and animal research · 2020Review
- Neuroanatomy of melanocortin-4 receptor pathway in the mouse brain.Open life sciences · 2020Article
- POMC: The Physiological Power of Hormone Processing.Physiological reviews · 2018Review
- Dissecting carboxypeptidase E: properties, functions and pathophysiological roles in disease.Endocrine connections · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Carboxypeptidase E (CPE) is a prohormone/proneuropeptide processing enzyme, and mice bearing CPE mutations exhibit an obese and diabetic phenotype. Studies on CPE knockout (KO) mice revealed poor prohormone processing, resulting in deficiencies in peptide hormones/neuropeptides such as insulin, gonadotropin-releasing hormone, and cocaine- and amphetamine-regulated transcript (CART). Here, we show that CPE KO mice, an obese animal model, have low bone mineral density (BMD) accompanied by elevated plasma CTX-1 (carboxy-terminal collagen crosslinks), and osteocalcin, indicators of increased bone turnover. Receptor activator for NF-kappaB ligand (RANKL) expression was elevated approximately 2-fold relative to osteoprotegerin in the femur of KO animals, suggesting increased osteoclastic activity in the KO mice. In the hypothalamus, mature CART, a peptide involved in eating behavior and implicated in bone metabolism, was undetectable. The melanocortin and neuropeptide Y (NPY) systems in the hypothalamus have also been implicated in bone remodeling, since MC4R KO and NPY KO mice have increased BMD. However, reduction of alpha-MSH, the primary ligand of MC4R by up to 94% and the lack of detectable NPY in the hypothalamus of CPE KO do not recapitulate the single-gene KO phenotypes. This study highlights the complex physiological interplay between peptides involved in energy metabolism and bone formation and furthermore suggests the possibility that patients, bearing CPE and CART mutations leading to inactive forms of these molecules, may be at a higher risk of developing osteoporosis.
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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.