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Cited by 80Adipokines, Inflammation, and Metabolic DiseasesBone Metabolism and DiseasesAdipose Tissue and Metabolism

Carboxylated and uncarboxylated forms of osteocalcin directly modulate the glucose transport system and inflammation in adipocytes

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Hill, H., Grams, J., Walton, R., Liu, J., Moellering, D., Garvey, W.·2014·Hormone and Metabolic Research
DOI 10.1055/s-0034-1368709PMC PMC5349189
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Abstract

Osteocalcin is secreted by osteoblasts and improves insulin sensitivity in vivo, although mechanisms remain unclear. We tested the hypothesis that osteocalcin directly modulates cell biology in insulin-targeted peripheral tissues. In L-6 myocytes, osteocalcin stimulated glucose transport both in the absence (basal) and presence of insulin. Similarly, in primary cultured adipocytes, both carboxylated and uncarboxylated osteocalcin increased basal and insulin-stimulated glucose transport as well as insulin sensitivity. Osteocalcin also increased basal and insulin-stimulated glucose oxidation, though there was no effect on fatty acid synthesis or lipolysis. In primary-cultured adipocytes, both forms of osteocalcin suppressed secretion of tumor necrosis factor alpha into the media; however, only carboxylated osteocalcin suppressed interleukin 6 release, and neither form of osteocalcin modulated monocyte chemoattractant protein-1 secretion. Both carboxylated and uncarboxylated osteocalcin increased secretion of adiponectin and the anti-inflammatory cytokine interleukin 10. In conclusion, both carboxylated and uncarboxylated osteocalcin directly increase glucose transport in adipocytes and muscle cells, while suppressing proinflammatory cytokine secretion and stimulating interleukin 10 and adiponectin release. Thus, these results provide a mechanism for the insulin-sensitizing effects of osteocalcin and help elucidate the role that bone plays in regulating systemic metabolism.

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  • OCN may mediate its beneficial effects by stimulating the synthesis of adiponectin and IL-10, by decreasing TNF-α in adipocytes, and by upregulating thermogenic genes in AT and mitochondrial biogenesis in SkM.

    “OCN may also mediate its beneficial effects by stimulating the synthesis of adiponectin [201,211] and IL-10, by decreasing TNF-α in adipocytes [211] and by upregulating thermogenic genes in AT [212] and mitochondrial biogenesis in SkM [213].”

    From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [211]

    The Results section ('Osteocalcin directly modulates adipocytokine production'; page not available) reports increased adiponectin secretion, increased IL-10 secretion from whole adipose tissue, and decreased TNF-α secretion from isolated adipocytes. It measures secretion rather than synthesis and reports no increase in IL-10 secretion from isolated adipocytes. The thermogenic-gene and skeletal-muscle mitochondrial claims are assigned to other citations, not this paper. (LLM, conf=0.85)

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  • IL-6 upregulates the secretion of OCN by bone, which reduces the expression of TNF-α and increases that of IL-10 and adiponectin in adipocytes.

    “Additionally, it has been found to upregulate the secretion of OCN by bone [71] (2b), which reduces the expression of TNF-α and increases that of IL-10 (3a) and adiponectin in adipocytes [211] (3b).”

    From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [211]

    The Results (‘Osteocalcin directly modulates adipocytokine production’) show that osteocalcin decreased TNFα secretion and increased adiponectin secretion in isolated rat adipocytes. IL-10 secretion increased in whole adipose tissue, but not in isolated adipocytes. The study reports secretion rather than expression; the IL-6–bone claim is attached to a different citation ([71]). (LLM, conf=0.88)

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Authors
Hill, H., Grams, J., Walton, R., Liu, J., Moellering, D., & Garvey, W.
Affiliations
University of Alabama at Birmingham (US)
ORCID
Venue
Hormone and Metabolic Research
Publisher
Georg Thieme Verlag KG
Published
2014-02-19
Volume
46
Issue
05
Pages
341-347
ISSN
  • 0018-5043 (ISSN-L)
  • 1439-4286
DOI
10.1055/s-0034-1368709
PMC
PMC5349189
OpenAlex
W2000839792
Cited by
80
References
23
Citations by year
2026: 1 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 14 · 2020: 10 · 2019: 6 · 2018: 5 · 2017: 9 · 2016: 6 · 2015: 7 · 2014: 5
FWCI
6.80
Type
journal article
Language
en
Open access
Locations
  • Hormone and Metabolic Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01CX000432)
  • Society of University Surgeons
  • National Institutes of Health (5p60dk079626-05)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK-079626, R01DK038765, DK038765, DK-083562, R01DK083562, P30DK079626)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
osteocalcin, carboxylated osteocalcin, uncarboxylated osteocalcin, glucose transport, insulin sensitivity, adipocytes, skeletal muscle, glucose oxidation, inflammation, TNF-α, interleukin-6, IL-10, adiponectin
MeSH terms
Animals, Biological Transport, Cells, Cultured, Glucose, Insulin, Lipolysis, Male, Mice, Inbred C57BL, Protein Processing, Post-Translational, Osteocalcin, Interleukin-6, Interleukin-10, Rats, Wistar, Adipocytes, Lipogenesis, Mice, Rats

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