ArticleCell cycle (Georgetown, Tex.)2013
Intermittent injections of osteocalcin reverse autophagic dysfunction and endoplasmic reticulum stress resulting from diet-induced obesity in the vascular tissue via the NFκB-p65-dependent mechanism.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The effect of exercise training on osteocalcin, adipocytokines, and insulin resistance: a systematic review and meta-analysis of randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- Bone as an endocrine regulator of lipid and energy metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- Osteocalcin improves testicular morphology but does not ameliorate testosterone synthesis signaling in azoospermic mice.Clinical and experimental reproductive medicine · 2024Article
- Bone Mineral Density, C-Terminal Telopeptide of Type I Collagen, and Osteocalcin as Monitoring Parameters of Bone Remodeling in CML Patients Undergoing Imatinib Therapy: A Basic Science and Clinical Review.Diseases (Basel, Switzerland) · 2024Review
- Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Undercarboxylated, But Not Carboxylated, Osteocalcin Suppresses TNF-α-Induced Inflammatory Signaling Pathway in Myoblasts.Journal of the Endocrine Society · 2022Article
- Osteocalcin association with vascular function in chronic kidney disease.Journal of clinical hypertension (Greenwich, Conn.) · 2022Article
- Osteocalcin and the physiology of danger.FEBS letters · 2022Review
- Sex Differences in Metabolic and Behavioral Responses to Exercise but Not Exogenous Osteocalcin Treatment in Mice Fed a High Fat Diet.Frontiers in physiology · 2022Article
- Explaining Divergent Observations Regarding Osteocalcin/GPRC6A Endocrine Signaling.Endocrinology · 2021Review
- Roles of bone-derived hormones in type 2 diabetes and cardiovascular pathophysiology.Molecular metabolism · 2020Review
- In vitro treatment of 3 T3-L1 adipocytes with recombinant Calcium/calmodulin-dependent Protein Kinase IV (CaMKIV) limits ER stress and improves insulin sensitivity through inhibition of autophagy via the mTOR/CREB signaling pathway.BMC endocrine disorders · 2020Article
- The facts of the matter: What is a hormone?PLoS genetics · 2020Article
- Osteokines and the vasculature: a review of thePeerJ · 2019Article
- Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease.Nutrients · 2018Review
- Undercarboxylated Osteocalcin: Experimental and Human Evidence for a Role in Glucose Homeostasis and Muscle Regulation of Insulin Sensitivity.Nutrients · 2018Review
- Regulation of Energy Metabolism by Bone-Derived Hormones.Cold Spring Harbor perspectives in medicine · 2018Review
- Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells.Scientific reports · 2017Article
- Progranulin causes adipose insulin resistance via increased autophagy resulting from activated oxidative stress and endoplasmic reticulum stress.Lipids in health and disease · 2017Article
- Endoplasmic Reticulum Stress in Arterial Smooth Muscle Cells: A Novel Regulator of Vascular Disease.Current cardiology reviews · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The osteoblast-specific secreted molecule osteocalcin behaves as a hormone-regulating glucose and lipid metabolism, but the role of osteocalcin in cardiovascular disease (CVD) is not fully understood. In the present study, we investigated the effect of osteocalcin on autophagy and endoplasmic reticulum (ER) stress secondary to diet-induced obesity in the vascular tissue of mice and in vascular cell models and clarified the intracellular events responsible for osteocalcin-mediated effects. The evidences showed that intermittent injections of osteocalcin in mice fed the high-fat diet were associated with a reduced body weight gain, decreased blood glucose and improved insulin sensitivity compared with mice fed the high-fat diet receiving vehicle. Simultaneously, the administration of osteocalcin not only attenuated autophagy and ER stress but also rescued impaired insulin signaling in vascular tissues of mice fed a high-fat diet. Consistent with these results in vivo, the addition of osteocalcin reversed autophagy and ER stress and restored defective insulin sensitivity in vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) in the presence of tunicamycin or in knockout XBP-1 (a transcription factor which mediates ER stress response) cells or in Atg7(-/-) cells. The protective effects of osteocalcin were nullified by suppression of Akt, mammalian target of rapamycin (mTOR) or nuclear factor kappa B (NFκB), suggesting that osteocalcin inhibits autophagy, ER stress and improves insulin signaling in the vascular tissue and cells under insulin resistance in a NFκB-dependent manner, which may be a promising therapeutic strategies of cardiovascular dysfunction secondary to obesity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.