Serum Osteocalcin Is Associated With Measures of Insulin Resistance, Adipokine Levels, and the Presence of Metabolic Syndrome

Saleem, Umer; Mosley, Thomas H.; Kullo, Iftikhar J.

doi:10.1161/atvbaha.110.204859

Cited by 180 publications

(170 citation statements)

References 27 publications

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“…A total of 1,284 Afro-Americans and 1,209 non-Hispanic whites individuals were evaluated and, in both populations, osteocalcin was inversely related to leptin and metabolic markers, such as body mass index, waist circumference, blood glucose, insulin and triglycerides, and directly related to adiponectin. In this study, the worse the severity of the metabolic syndrome the lower levels of osteocalcin were found, independently of the glycemic changes (33). More recently, Bao and cols.…”

Section: Osteocalcin Levels and Metabolic Parameters In Humanssupporting

confidence: 64%

“…A large observational study correlated osteocalcin levels with adipokines (leptin and adiponectin) and markers of metabolic syndrome, body fat and physical activity (33). A total of 1,284 Afro-Americans and 1,209 non-Hispanic whites individuals were evaluated and, in both populations, osteocalcin was inversely related to leptin and metabolic markers, such as body mass index, waist circumference, blood glucose, insulin and triglycerides, and directly related to adiponectin.…”

Section: Osteocalcin Levels and Metabolic Parameters In Humansmentioning

confidence: 99%

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Osteocalcin, energy and glucose metabolism

Zanatta

Boguszewski

Borba

et al. 2014

Arq Bras Endocrinol Metab

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Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Undercarboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome. Arq Bras Endocrinol Metab. 2014;58(5):444-51 Keywords Osteocalcin; undercarboxylated osteocalcin; metabolic syndrome; glucose; energy metabolism; diabetes; obesity; leptin; insulin; adiponectin RESUMO A osteocalcina é uma proteína da matriz óssea que tem sido implicada com várias ações hormonais relacionadas à homeostase de glicose e ao metabolismo energéti-co. Modelos animais e experimentais têm demonstrado que a osteocalcina é liberada do osso para a circulação sanguínea e age nas células betapancreáticas e no tecido adiposo. A osteocalcina decarboxilada é a isoforma hormonalmente ativa e estimula a secreção e sensibilidade à insulina no tecido adiposo e muscular. A insulina e a leptina, por sua vez, atuam no tecido ósseo modulando a secreção da osteocalcina, formando uma alça de retroalimentação tradicional em que o esqueleto torna-se um órgão endócrino. Novos estudos ainda são necessários para elucidar o papel da osteocalcina na regulação glicêmica e no metabolismo energético em humanos, com potenciais implicações terapêuticas no tratamento de diabetes, obesidade e síndrome metabólica. Arq Bras Endocrinol Metab. 2014;58(5):444-51 Descritores

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Section: Osteocalcin Levels and Metabolic Parameters In Humanssupporting

confidence: 64%

Section: Osteocalcin Levels and Metabolic Parameters In Humansmentioning

confidence: 99%

Osteocalcin, energy and glucose metabolism

Zanatta

Boguszewski

Borba

et al. 2014

Arq Bras Endocrinol Metab

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“…Higher levels of osteocalcin were also associated with a lower odds ratio of developing metabolic syndrome in black and in white nonHispanic individuals [29,38]. A case-control study actually identified coding variants in the fourth exon of human OCN that appeared to correlate with type 2 diabetes in AfricanAmerican patients [39].…”

Section: Clinical Relevance Of the Osteocalcin-mediated Regulation Ofmentioning

confidence: 99%

“…A fast growing number of studies, however, have now established that multiple aspects of osteocalcin biology are similar in rodents and humans. Indeed, levels of circulating osteocalcin have been inversely correlated with BMI, fat mass and plasma glucose levels in adult or elderly men and women of diverse ethnicities [26][27][28][29]. Additional studies have linked low osteocalcin to impaired levels of HbA 1c , fasting insulin and insulin resistance (estimated by the HOMA of insulin resistance HOMA-IR) in adult men and women, irrespective of whether they have diabetes [28,[30][31][32][33].…”

Section: Clinical Relevance Of the Osteocalcin-mediated Regulation Ofmentioning

confidence: 99%

The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism

2011

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Bone remodelling, which maintains bone mass constant during adulthood, is an energy-demanding process. This, together with the observation that the adipocyte-derived hormone leptin is a major inhibitor of bone remodelling, led to the hypothesis that bone cells regulate energy metabolism through an endocrine mechanism. Studies to test this hypothesis identified osteocalcin, a hormone secreted by osteoblasts, as a positive regulator of insulin secretion, insulin resistance and energy expenditure. Remarkably, insulin signalling in osteoblasts is a positive regulator of osteocalcin production and activation via its ability to indirectly enhance bone resorption by osteoclasts. In contrast, leptin is a potent inhibitor of osteocalcin function through its effect on the sympathetic tone. Hence, osteocalcin is part of a complex signalling network between bone and the organs more classically associated with the regulation of energy homeostasis, such as the pancreas and adipose tissue. This review summarises the molecular and cellular bases of the present knowledge on osteocalcin biology and discusses the potential relevance of osteocalcin to human metabolism and pathology.

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“…After the observation of reduced insulin secretion and increased insulin resistance in Osteocalcin-deficient mice, serum osteocalcin level was found to be associated with HbA1c and type II diabetes in humans (13). On this basis, the implication of osteocalcin in humans was then extended to MetS (14,15). Most of the available studies have reported an association between osteocalcin and the absence/presence of MetS.…”

Section: Introductionmentioning

confidence: 99%

Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort

Confavreux¹,

Szulc²,

Casey³

et al. 2014

European Journal of Endocrinology

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Background: Bone has emerged as an endocrine organ regulating energy metabolism through secretion of osteocalcin. In epidemiological studies, presence of metabolic syndrome (MetS) was associated with lower osteocalcin level. Objectives: We evaluated whether osteocalcin level was associated with MetS severity in men and whether it was more strongly associated with MetS compared with N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP), and C-terminal telopeptide of type I collagen (bCTX). Methods: We included 798 men aged 51-85 years for total osteocalcin measurement. Number of MetS criteria was used to define severity. We used polytomous logistic regression to assess the relationship between MetS severity and osteocalcin level. Results: Thirty percent of men had MetS. In patients with MetS, the higher the number of MetS traits were present, the lower was the average osteocalcin level (0-2 criteria: 551 men: 19.5G6.7 ng/ml, three criteria: 155 men: 19.3G7.4 ng/ml, four criteria: 72 men: 17.3G5.7 ng/ml, and five criteria: 20 men: 15.0G5.1 ng/ml; P for trendZ0.002). In the polytomous logistic regression model, an increase in osteocalcin level of 10 ng/ml was associated with lower prevalence of severe MetS: three criteria (odds ratio (OR)Z0.93 (0.70-1.24)), four criteria (ORZ0.54 (0.34-0.84)), and five criteria (ORZ0.28 (0.10-0.82)) in comparison with no MetS (P for trendZ0.008). After adjustment, using stepwise analysis of the polytomous logistic regression model, we observed that osteocalcin, age, and apparent free testosterone entered in the model but not other bone markers (PINP, bCTX, and BAP). Conclusion: In older Caucasian men, total osteocalcin level was associated with MetS severity. Osteocalcin was more strongly associated with MetS severity than other bone turnover markers.

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Serum Osteocalcin Is Associated With Measures of Insulin Resistance, Adipokine Levels, and the Presence of Metabolic Syndrome

Cited by 180 publications

References 27 publications

Osteocalcin, energy and glucose metabolism

Osteocalcin, energy and glucose metabolism

The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism

Lower serum osteocalcin is associated with more severe metabolic syndrome in elderly men from the MINOS cohort

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