Osteocalcin Improves Metabolic Profiles, Body Composition and Arterial Stiffening in an Induced Diabetic Rat Model

Abstract

Recent studies have demonstrated the benefits of osteocalcin (OCN) on glucose homeostasis and metabolic dysregulation. However, its role in body composition and vascular function remains unknown. This study was designed to examine changes in metabolic parameters and body composition as well as arterial stiffness after OCN treatment in type 2 diabetic rats. Adult male Sprague Dawley (SD) rats were fed chow or high fat diet (HFD) for 8 weeks, and then diabetes was induced with an injection of low-dose streptozotocin (STZ) and treated daily with intraperitoneal injections of OCN for 12 weeks. Our data showed that OCN treatment improved glucose homeostasis and lipid metabolism. Further analysis revealed that OCN treatment resulted in increased insulin sensitivity. In addition, untreated diabetic rats experienced significant weight loss, whereas OCN-treated rats better maintained body weight (300.75±38.14 g vs. 335.50±23.70, =0.005). OCN also changed body composition, as evidenced by reduced body fat mass, specifically abdominal fat mass. OCN-treated diabetic rats also demonstrated decreased pulse-wave velocity, indicating of improved arterial stiffness. Taken together, our findings in the current study revealed that OCN therapy prevents arteriosclerosis in an induced diabetic rat model by exerting beneficial effects on glucose levels, insulin sensitivity, lipid metabolites, and body composition changes.

Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease

“…In another study, the administration of total osteocalcin repaired the alteration to PWV, concurrently with improvements in fasting blood glucose and circulating lipids [ 56 ]. Specifically, PWV, which is a measure of arterial stiffness, was increased (by 6%) in a rat model fed a high-fat diet and induced with diabetes via streptozotocin injection.…”

“…Following 12 weeks of a high-fat diet, daily intraperitoneal injections of total osteocalcin (30 ng/g) reversed the alteration in PWV, albeit by a small magnitude. Blood pressure, heart rate, and mean arterial pressure were not altered by the high-fat diet or the osteocalcin injections [ 56 ]. This study suggests that a daily injection of total osteocalcin can repair abnormal cardiovascular function ( Table 1 ).…”

Vitamin K effects in human health: new insights beyond bone and cardiovascular health

“…In apolipoprotein E-deficient mice, daily injections of BGP for 12 weeks resulted in endothelium protection from atherosclerosis, but whether this was also mediated by the concomitant improvement in glucose metabolism is unknown [15]. Similarly, diabetic rats given daily injections of BGP had an improvement in arterial stiffness as assessed by pulse wave velocity [16].…”

A Calcium-Deficient Diet in Dams during Gestation Increases Insulin Resistance in Male Offspring

“…On the other hand, OC appears to directly promote the expression of adiponectin, a hormone that may favor peripheral insulin sensitivity in obese animals, in white adipocytes [ 39 ]. Intermittent injections of recombinant OC increase energy expenditure, reduce fat mass, and improve insulin sensitivity [ 16 , 40 , 41 ]; therefore, OC is associated with global energy expenditure and fat mass. The mechanisms by which OC promotes insulin sensitivity and energy expenditure in vivo are still not fully understood.…”