title: Multifaceted interaction of bone, muscle, lifestyle interventions and metabolic and cardiovascular disease: role of osteocalcin.
abstract: Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional evidence associating osteocalcin (OC) and ucOC with metabolic risk and cardiovascular disease. The complexity in assessing such correlations, due to the observational nature of human studies, is discussed. Several studies have reported that higher levels of ucOC and OC are correlated with lower fat mass and HbA1c. In addition, improved measures of glycaemic control via pharmacological and non-pharmacological (e.g. exercise or diet) interventions are often associated with increased circulating levels of OC and/or ucOC. There is also a relationship between lower circulating OC and ucOC and increased measures of vascular calcification and cardiovascular disease. However, not all studies have reported such relationship, some with contradictory findings. Equivocal findings may arise because of the observational nature of the studies and the inability to directly assess the relationship between OC and ucOC on glycaemic control and cardiovascular health in humans. Studying OC and ucOC in humans is further complicated due to numerous confounding factors such as sex differences, menopausal status, vitamin K status, physical activity level, body mass index, insulin sensitivity (normal/insulin resistance/T2DM), tissue-specific effects and renal function among others. Current observational and indirect interventional evidence appears to support a relationship between ucOC with metabolic and cardiovascular disease. There is also emerging evidence to suggest a direct role of ucOC in human metabolism. Further mechanistic studies are required to (a) clarify causality, (b) explore mechanisms involved and
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia. itamar.levinger@vu.edu.au.
authors.forename: I
authors.initials: I
authors.lastname: Levinger
authors.affiliation: Department of Physiology and Bosch Institute for Medical Research, University of Sydney, Sydney, Australia.
authors.forename: T C
authors.initials: TC
authors.lastname: Brennan-Speranza
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Zulli
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Parker
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia.
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.affiliation: Centre for Kidney Research, Children's Hospital at Westmead School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.|School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Lewis
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.|Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.
authors.forename: B B
authors.initials: BB
authors.lastname: Yeap
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D015444:Exercise / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008019:Life Style; D024821:Metabolic Syndrome / Q000378:metabolism*; D015675:Osteocalcin / Q000187:drug effects / Q000502:physiology*; D014812:Vitamin K / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D015675:Osteocalcin; D014812:Vitamin K
keywords: Cardiovascular disease; Glucose uptake; Insulin sensitivity; Osteocalcin