Multifaceted interaction of bone, muscle, lifestyle interventions and metabolic and cardiovascular disease: role of osteocalcin

Levinger, Itamar; Brennan‐Speranza, Tara C.; Zulli, Anthony; Parker, Lewan; Lin, Xuzhu; Lewis, Joshua R.; Yeap, Bu B.

doi:10.1007/s00198-017-3994-3

Cited by 43 publications

(36 citation statements)

References 100 publications

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“…Our results showed an association between serum levels of ucOC and sex, being these levels higher in women than men, in consistency with the previously reported 45 . However, the cause of this sex-based difference has not been explored yet.…”

Section: Discussionsupporting

confidence: 93%

Circulating Undercarboxylated Osteocalcin as Estimator of Cardiovascular and Type 2 Diabetes Risk in Metabolic Syndrome Patients

Riquelme-Gallego

García-Molina

Cano-Ibáñez

et al. 2020

Sci Rep

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Undercarboxylated osteocalcin (ucoc) could be a biomarker of glucose disturbances and cardiovascular risk. our study aimed to determine the association between serum levels of ucoc and cardiovascular risk in metabolic syndrome (MetS) patients and to analyse its potential role as estimator of type 2 diabetes (T2D) risk in this population. This cross-sectional study included 235 patients with MetS, 53.2% women, aged 55-75 years. Circulating ucOC levels were measured by ELISA. Cardiovascular risk was determined as Z-score of the diagnostic criteria for MetS (CV-ZS). Linear regression model was performed to analyse the association between circulating ucoc and cV-ZS. A receiver operating curve (ROC) was performed to analyse the usefulness of ucOC as T2D risk estimator. Patients above the CV-ZS median showed significant lower ucOC levels. We found an inverse association between ucOC levels and CV-ZS in MetS patients without T2D. Patients with ucOC levels below the 25 th percentile showed worse cardiometabolic profile and higher cardiovascular and T2D risk. The area under the curve performed better when ucOC levels were included along with the classic T2D risk factors. The measurement of circulating ucOC could be a useful tool to identify increased cardiovascular and T2D risk in MetS patients without T2D. Current lifestyle is causing a remarkable increase in overweight up to epidemic numbers globally 1. In Spain, over 60% of the adult population is overweight or obese 2. According to this trend, an increase of 16% in the number of cases is estimated by 2030 associated with a 58% increase in direct healthcare costs 3. A large body of evidence has shown that all-cause mortality, and especially cardiovascular-related mortality, is associated with an increased central adiposity and overweight 4. Visceral obesity in conjunction with other disorders, such as dyslipidaemia, hypertension and fasting hyperglycaemia lead to the metabolic syndrome (MetS), conferring thus a larger risk of developing cardiovascular disease (CVD) 5. An association between osteoporosis, CVD and cardiovascular-related mortality has been reported 6,7. The common risk factors involved in bone fragility and CVD could partially explain this association. Therefore, the

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Section: Discussionsupporting

confidence: 93%

Circulating Undercarboxylated Osteocalcin as Estimator of Cardiovascular and Type 2 Diabetes Risk in Metabolic Syndrome Patients

Riquelme-Gallego

García-Molina

Cano-Ibáñez

et al. 2020

Sci Rep

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“…5 ). The interaction between OC and other proteins, particularly during glucose metabolism, has been studied ( Garbossa and Folli, 2017 ; Kanazawa, 2015 , 2017 ; Levinger et al., 2017 ; Liu et al., 2015 ; Takeno et al., 2018 ; Thomas et al., 2017 ), whereas the interaction between OC and FBXW2 has not been previously studied. To the author's knowledge, this is the first study to reveal an interaction between OC and FBXW2.…”

Section: Discussionmentioning

confidence: 99%

FBXW2 localizes with osteocalcin in bovine periosteum on culture dishes as visualized by double immunostaining

Akiyama

2018

Heliyon

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Osteocalcin (OC) is a well-known protein related to bone, however, the role of F-box and WD-40 domain-containing protein 2 (FBXW2) in bone remains unclear. In 2016, the presence of FBXW2 in bovine periosteum was reported. In this study, double immunostaining was used to investigate the relationship between OC and FBXW2. FBXW2 showed tubular structures, and OC showed a similar localization pattern as FBXW2. Double immunostaining findings suggested that FBXW2 tubes were coated with OC. To the author's knowledge, this is the first study to reveal the interaction between OC and FBXW2.

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“…The skeleton is an endocrine organ that has been shown, at least in mice, to modulate glucose metabolism ( 1 – 3 ). One bone-specific hormone that plays a role in this energy regulation is osteocalcin (OC) ( 4 , 5 ). Undercarboxylated osteocalcin (ucOC), the biologically active form of OC, regulates glucose metabolism by targeting the pancreas and perhaps several insulin-sensitive organs, including skeletal muscle ( 6 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles

et al. 2017

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Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT)-AKT substrate of 160 kDa (AS160) signaling cascade. Extensor digitorum longus (EDL) and soleus muscles from male C57BL/6 mice were isolated, divided into halves, and then incubated with ucOC with or without the pretreatment of ERK inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It also enhanced phosphorylation of ERK2 (Thr202/Tyr204) and AS160 (Thr642) in both muscle types and increased mTOR phosphorylation (Ser2481) in EDL only. ucOC had no significant effect on the phosphorylation of AMPKα (Thr172). The inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC-stimulated glucose uptake and AS160 phosphorylation in both muscle types, but appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken together, ucOC at the physiological range directly increased glucose uptake in both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC effect on muscle glucose uptake seem to be muscle type-specific, involving enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation. Our study suggests that, since ucOC increases muscle glucose uptake without insulin, it could be considered as a potential agent to improve muscle glucose uptake in insulin resistant conditions.

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Multifaceted interaction of bone, muscle, lifestyle interventions and metabolic and cardiovascular disease: role of osteocalcin

Cited by 43 publications

References 100 publications

Circulating Undercarboxylated Osteocalcin as Estimator of Cardiovascular and Type 2 Diabetes Risk in Metabolic Syndrome Patients

Circulating Undercarboxylated Osteocalcin as Estimator of Cardiovascular and Type 2 Diabetes Risk in Metabolic Syndrome Patients

FBXW2 localizes with osteocalcin in bovine periosteum on culture dishes as visualized by double immunostaining

Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles

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