-
Current Opinion in Clinical Nutrition... Jul 2011Recent findings suggest that the bone is an active regulator of energy and glucose metabolism. The purpose of this review is to summarize current evidence in humans. (Review)
Review
PURPOSE OF REVIEW
Recent findings suggest that the bone is an active regulator of energy and glucose metabolism. The purpose of this review is to summarize current evidence in humans.
RECENT FINDINGS
Both cross-sectional and longitudinal studies support osteocalcin as an active regulator of carbohydrate metabolism in humans, being the muscular load of physical activity one of the possible links between the osteoblast and the insulin axis. This axis could also have been involved in the modulation of nonalcoholic steatohepatitis. The osteoblast-to-insulin axis seems to act paradoxically in patients with increased growth hormone (acromegaly) and during bone repair. Some possible evolutionary implications are suggested.
SUMMARY
Osteocalcin may have a role in the regulation of systemic energy metabolism, given the common origin of the osteoblast with the two other cells implicated (adipocytes and muscle cells). Bioactivity of circulating human carboxylated and uncarboxylated osteocalcin should be characterized in depth, especially in those patients with increased concentrations (renal failure). Osteocalcin is one of the clues in the interaction between calcium and glucose metabolism, and the discovery of the osteocalcin receptor will aid in the study of these relationships.
Topics: Adipose Tissue; Animals; Biological Evolution; Bone and Bones; Carbohydrate Metabolism; Energy Metabolism; Humans; Insulin; Insulin Resistance; Kidney Diseases; Leptin; Liver; Motor Activity; Osteoblasts; Osteocalcin
PubMed: 21519236
DOI: 10.1097/MCO.0b013e328346df4e -
Annals of Clinical Biochemistry Jul 2000
Review
Topics: Bone and Bones; Chemistry, Clinical; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hyperthyroidism; Hypothyroidism; Menopause; Osteitis Deformans; Osteocalcin; Osteomalacia; Osteoporosis; Reference Values; Reproducibility of Results
PubMed: 10902858
DOI: 10.1177/000456320003700402 -
Endocrine Oct 2017Osteocalcin is considered as a bone-derived hormone affecting on the body fat distribution and body mass index. Several cross-sectional studies have investigated the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Osteocalcin is considered as a bone-derived hormone affecting on the body fat distribution and body mass index. Several cross-sectional studies have investigated the association between serum osteocalcin and body mass index. The aim of this study was to summarize the evidence on the relationship between serum osteocalcin and body mass index.
METHODS
We conducted a complete search up to November 2016 in PubMed and SCOPUS and reviewed reference list of all relevant articles and reviews. The DerSimonian-Laird method were used to pool effect sizes of eligible studies. The potential sources of heterogeneity were assessed using the standard χ test.To find possible the sources of between-study heterogeneity, we carried out subgroup analyses based on sex, and type of study population.
RESULTS
There was a significant inverse association in the overall result of this study between serum osteocalcin levels and BMI(r = -0.161; 95% CI: -0.197, -0.124, p < 0.000). In the subgroup analysis to find the sources of significant heterogeneity between-study, we observed that the type of the study population may be the source of between-study heterogeneity and the most correlation was seen in metabolic syndrome studies (r = -0.265; p = 0.000).
CONCLUSION
Findings from the available data indicated an overall significant inverse association between serum osteocalcin and body mass index. Further studies based on the type of study population are needed to better clarify these associations.
Topics: Animals; Body Mass Index; Humans; Metabolic Syndrome; Obesity; Osteocalcin
PubMed: 28822067
DOI: 10.1007/s12020-017-1384-4 -
EMBO Reports Feb 2024Many physiological osteocalcin-regulated functions are affected in adult offspring of mothers experiencing unhealthy pregnancy. Furthermore, osteocalcin signaling during...
Many physiological osteocalcin-regulated functions are affected in adult offspring of mothers experiencing unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin may broadly function during pregnancy to determine organismal homeostasis in adult mammals. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin-deficient, newborn and adult mice of various genotypes and origin maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are Osteocalcin-deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that osteocalcin exerts dominant functions in most organs it influences. Furthermore, through their synergistic regulation of multiple physiological functions, osteocalcin of maternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.
Topics: Animals; Female; Humans; Mice; Pregnancy; Blood Glucose; Homeostasis; Insulin; Insulin Secretion; Mammals; Osteocalcin; Prenatal Exposure Delayed Effects
PubMed: 38228788
DOI: 10.1038/s44319-023-00031-3 -
Nephrology, Dialysis, Transplantation :... Jan 2011
Review
Topics: Chronic Disease; Energy Metabolism; Glucose; Humans; Insulin Resistance; Kidney Diseases; Osteocalcin
PubMed: 21131432
DOI: 10.1093/ndt/gfq721 -
The Journal of Experimental Medicine Oct 2017That osteocalcin (OCN) is necessary for hippocampal-dependent memory and to prevent anxiety-like behaviors raises novel questions. One question is to determine whether...
That osteocalcin (OCN) is necessary for hippocampal-dependent memory and to prevent anxiety-like behaviors raises novel questions. One question is to determine whether OCN is also sufficient to improve these behaviors in wild-type mice, when circulating levels of OCN decline as they do with age. Here we show that the presence of OCN is necessary for the beneficial influence of plasma from young mice when injected into older mice on memory and that peripheral delivery of OCN is sufficient to improve memory and decrease anxiety-like behaviors in 16-mo-old mice. A second question is to identify a receptor transducing OCN signal in neurons. Genetic, electrophysiological, molecular, and behavioral assays identify , an orphan G protein-coupled receptor expressed in neurons of the CA3 region of the hippocampus, as transducing OCN's regulation of hippocampal-dependent memory in part through inositol 1,4,5-trisphosphate and brain-derived neurotrophic factor. These results indicate that exogenous OCN can improve hippocampal-dependent memory in mice and identify molecular tools to harness this pathway for therapeutic purposes.
Topics: Aging; Animals; CA3 Region, Hippocampal; Cognition; Electrophysiology; Female; Male; Maze Learning; Memory; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteocalcin; Receptors, G-Protein-Coupled
PubMed: 28851741
DOI: 10.1084/jem.20171320 -
Clinical Calcium Nov 2007Osteocalcin (OC) is a product of osteoblasts and accumulated in the extracellular matrix of bone. It has been recognized that serum OC is a marker of osteoblast... (Review)
Review
Osteocalcin (OC) is a product of osteoblasts and accumulated in the extracellular matrix of bone. It has been recognized that serum OC is a marker of osteoblast activity, and the levels reflect the rate of bone formation. The present assay system was developed to assess the major circulating forms of intact and the large N-terminal fragments. OC binds to the crystal of hydroxyapatite, at least partly, through gamma-carboxylation of three residues. Increased rate of immature undercarboxylated osteocalcin, therefore, might display risks for osteoporotic fractures in clinical studies. However, at present, measurement of OC does not substitute for bone mass measurement and only provide limited values to evaluate the conditions of patients with primary osteoporosis.
Topics: 1-Carboxyglutamic Acid; Animals; Biomarkers; Durapatite; Humans; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Protein Binding; Risk
PubMed: 17982186
DOI: No ID Found -
Oncotarget Aug 2015
Topics: 1-Carboxyglutamic Acid; Animals; Humans; Mice; Osteocalcin
PubMed: 26343369
DOI: 10.18632/oncotarget.5126 -
Nature Reviews. Endocrinology Jan 2013Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines and... (Review)
Review
Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bone matrix protein that regulates hydroxyapatite size and shape through its vitamin-K-dependent, γ-carboxylated form. The concentration of osteocalcin in the circulation is a measure of bone formation. The undercarboxylated form of osteocalcin is active in glucose metabolism in mice. Total serum osteocalcin concentrations in humans are inversely associated with measures of glucose metabolism; however, human data are inconclusive with regard to the role of uncarboxylated osteocalcin in glucose metabolism because most studies do not account for the influence of vitamin K on the proportion of undercarboxylated osteocalcin or differentiate between the total and uncarboxylated forms of osteocalcin. Furthermore, most human studies do not concomitantly measure other bone turnover markers to isolate the role of osteocalcin as a measure of bone formation from its effect on glucose metabolism. Carefully designed studies are required to define the role of osteocalcin and its carboxylated or undercarboxylated forms in the regulation of glucose metabolism in humans.
Topics: Animals; Energy Metabolism; Glucose; Humans; Osteocalcin
PubMed: 23147574
DOI: 10.1038/nrendo.2012.201 -
Nihon Rinsho. Japanese Journal of... Feb 2004
Review
Topics: Animals; Bone Matrix; Bone Remodeling; Cholecalciferol; Gene Expression Regulation; Humans; Neoplasm Proteins; Osteocalcin; Osteogenesis; Promoter Regions, Genetic; Transcription Factors
PubMed: 15035112
DOI: No ID Found