Serum osteocalcin is associated with improved metabolic state via adiponectin in females versus testosterone in males. Gender specific nature of the bone–energy homeostasis axis

Buday, Barbara; Pach, Ferenc Péter; Literáti-Nagy, Botond; Vitai, Márta; Vecsei, Zsuzsa; Korányi, László

doi:10.1016/j.bone.2013.07.018

Cited by 44 publications

(32 citation statements)

References 32 publications

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“…However, results from other studies indicate no association between lower circulating uncarboxylated OC levels and higher HOMA-IR (Shea et al 2009). Results from one recent study have indicated that there is a sex-specific action of the bone-energy homoeostasis axis with OC being associated with improved metabolic state via adiponectin in females, and via testosterone in males (Buday et al 2013). Direct clinical evidence has been reported for the role of OC in energy metabolism, via the removal of an OC-producing osteoid osteoma, which resulted in elevated serum glucose, potentially associated with decreased levels of undercarboxylated OC (Confavreux et al 2012).…”

Section: Clinical Evidence: Oc and Metabolism/fertilitymentioning

confidence: 97%

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Oldknow

MacRae

Farquharson

2015

Journal of Endocrinology

102

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Recent developments in endocrinology, made possible by the combination of mouse genetics, integrative physiology and clinical observations have resulted in rapid and unanticipated advances in the field of skeletal biology. Indeed, the skeleton, classically viewed as a structural scaffold necessary for mobility, and regulator of calcium-phosphorus homoeostasis and maintenance of the haematopoietic niche has now been identified as an important regulator of male fertility and whole-body glucose metabolism, in addition to the classical insulin target tissues. These seminal findings confirm bone to be a true endocrine organ. This review is intended to detail the key events commencing from the elucidation of osteocalcin (OC) in bone metabolism to identification of new and emerging candidates that may regulate energy metabolism independently of OC.Key WordsJournal of Endocrinology (2015) 225, R1-R19

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Section: Clinical Evidence: Oc and Metabolism/fertilitymentioning

confidence: 97%

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Oldknow

MacRae

Farquharson

2015

Journal of Endocrinology

102

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“…The expression of adiponectin appears to be stimulated by GluOC to a greater extent in females than in males (4,24,45). The plasma adiponectin level is lower in men than in women regardless of menopausal status (5, 36, 56).…”

Section: E668 Sex Difference In Osteocalcin Actionmentioning

confidence: 99%

“…Most such studies have found that the serum concentration of osteocalcin is inversely correlated with markers of metabolic syndrome such as glucose intolerance and insulin resistance (11,24,25,36). However, the effects of osteocalcin on glucose metabolism in humans appear to be dependent on sex difference (4,24,45). The serum concentration of osteocalcin is thus correlated with that of adiponectin in women, but not in men, for example (4).…”

mentioning

confidence: 99%

Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet

Yasutake

Mizokami

Kawakubo‐Yasukochi

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, highsucrose diet. Am J Physiol Endocrinol Metab 310: E662-E675, 2016. First published February 16, 2016 doi:10.1152/ajpendo.00334.2015.-Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion, pancreatic ␤-cell proliferation, and adiponectin expression in adipocytes. Previously, we showed that long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level, improved glucose tolerance, and increased the fasting serum insulin concentration as well as pancreatic ␤-cell area in female mice fed a normal or high-fat, high-sucrose diet. We have now performed similar experiments with male mice and found that such GluOC administration induced glucose intolerance, insulin resistance, and adipocyte hypertrophy in those fed a high-fat, high-sucrose diet. In addition, GluOC increased the circulating concentration of testosterone and reduced that of adiponectin in such mice. These phenotypes were not observed in male mice fed a high-fat, high-sucrose diet after orchidectomy, but they were apparent in orchidectomized male mice or intact female mice that were fed such a diet and subjected to continuous testosterone supplementation. Our results thus reveal a sex difference in the effects of GluOC on glucose homeostasis. Given that oral administration of GluOC has been considered a potentially safe and convenient option for the treatment or prevention of metabolic disorders, this sex difference will need to be taken into account in further investigations. adiponectin; insulin resistance; osteocalcin; sex difference; testosterone OSTEOCALCIN IS A BONE MATRIX PROTEIN synthesized by osteoblasts that also functions as a hormone in the uncarboxylated state to regulate various aspects of physiology, including glucose metabolism, brain function, and male fertility (14,17,30,39,40). Uncarboxylated osteocalcin (GluOC) constitutes ϳ10% of total circulating osteocalcin in adult mice under normal physiological conditions (2, 10). However, the serum concentration of GluOC is increased in pathological conditions such as vitamin K deficiency and osteoporosis (2,26,31). Animal studies have shown that an increase in the circulating concentration of GluOC prevents obesity and glucose intolerance (10,13,28,30). Mice genetically deficient in Esp (a protein tyrosine phosphatase expressed in osteoblasts), a gainof-function model for osteocalcin, were thus protected from obesity, glucose intolerance, and insulin resistance induced by a high-fat diet (14, 30). Continuous administration of GluOC via a subcutaneous osmotic pump lowered blood glucose levels and increased pancreatic ␤-cell mass, insulin secretion, and insulin sensitivity in mice with high-fat diet-or gold thioglucose-induced obesity, with this latter effect being achieved via upregulation of expression of the gene for the insulin-sensitizing adipokine adiponectin in adipocytes (10). Moreove...

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“…For a more detailed discussion of relevance and the Boruta algorithm see Kohavi and John (1997) and Rudnicki et al (2015). This algorithm has been used in different fields, including bioinformatics, remote sensing, bacteriology and medicine (Aagaard et al, 2012;Ackerman et al, 2013;Buday et al, 2013;Duro et al, 2012;Herrera and Bazaga, 2013;Leutner et al, 2012;Ma et al, 2014;Menikarachchi et al, 2012;Saulnier et al, 2011;Strempel et al, 2013).…”

Section: Methodsmentioning

confidence: 99%

Application of all-relevant feature selection for the failure analysis of parameter-induced simulation crashes in climate models

et al. 2016

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Abstract. Climate models are extremely complex pieces of software. They reflect the best knowledge on the physical components of the climate; nevertheless, they contain several parameters, which are too weakly constrained by observations, and can potentially lead to a simulation crashing. Recently a study by Lucas et al. (2013) has shown that machine learning methods can be used for predicting which combinations of parameters can lead to the simulation crashing and hence which processes described by these parameters need refined analyses. In the current study we reanalyse the data set used in this research using different methodology. We confirm the main conclusion of the original study concerning the suitability of machine learning for the prediction of crashes. We show that only three of the eight parameters indicated in the original study as relevant for prediction of the crash are indeed strongly relevant, three others are relevant but redundant and two are not relevant at all. We also show that the variance due to the split of data between training and validation sets has a large influence both on the accuracy of predictions and on the relative importance of variables; hence only a cross-validated approach can deliver a robust prediction of performance and relevance of variables.

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Serum osteocalcin is associated with improved metabolic state via adiponectin in females versus testosterone in males. Gender specific nature of the bone–energy homeostasis axis

Cited by 44 publications

References 32 publications

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet

Application of all-relevant feature selection for the failure analysis of parameter-induced simulation crashes in climate models

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