Gender Dimorphism and Lack of Day/Night Variation or Effects of Energy Deprivation on Undercarboxylated Osteocalcin Levels in Humans

Authors

  • Joo-Pin Foo,

    1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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  • Konstantinos N. Aronis,

    1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    2. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, Massachusetts, USA
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  • John P. Chamberland,

    1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    2. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, Massachusetts, USA
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  • Bindiya Thakkar,

    1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    2. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, Massachusetts, USA
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  • Ole-Petter Hamnvik,

    1. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, Massachusetts, USA
    2. Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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  • Mary Brinkoetter,

    1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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  • Lesya Zaichenko,

    1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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  • Christos S. Mantzoros

    Corresponding author
    1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    2. Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, Massachusetts, USA
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  • Disclosure: All authors state that they have no conflicts of interest and have nothing to disclose.

  • Funding agencies: The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929 and 81913. The Mantzoros Laboratory is also supported by Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. Amylin Pharmaceuticals, Inc. supplied metreleptin for this study and approved the design of the study but had no role in the study design; conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. The project described was also supported by Grant Number UL1 RR025758- Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Abstract

Objective

Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short-term and/or chronic energy deprivation alters ucOC levels, and whether leptin may mediate these changes in humans.

Design and Methods

Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels.

Results

Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short-term and chronic energy deprivation or leptin administrations do not alter ucOC levels.

Conclusions

The hypothesis that ucOC plays a role in energy homeostasis or of leptin in regulating ucOC in humans is not supported.

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