The effects of tocotrienol in a rat model of bone loss due to metabolic syndrome

Abstract

Metabolic syndrome (MetS) is characterized by the simultaneous occurrence of at least three medical conditions including central obesity, high blood pressure, high fasting blood glucose, high triglyceride and low high-density lipoprotein (HDL) cholesterol. Recent studies investigating the relationship between MetS and osteoporosis showed heterogeneous findings. Further research needs to be conducted to better understand the impacts of MetS on bone. The first part of our study was aimed to investigate the impact of MetS on bone, using a rat model fed with high carbohydrate high-fat (HCHF) diet to induce MetS. This model mimics the MetS changes observed in human. Findings from the pilot study demonstrated the successful establishment of MetS using HCHF diet, with components of MetS partially developed after 8 weeks and fully developed after 12 weeks. A significant bone loss was detected at the trabecular region (p<0.05) but not in the cortical region of the femur in HCHF animals after 16 weeks (p>0.05). The biomechanical strength test showed that the femur of the HCHF rats endured significantly lower load, but significantly higher displacement and strain compared to the normal rats (p<0.05). Bone histomorphometric analysis showed that HCHF rats had significantly lower osteoblast surface, osteoid surface, osteoid volume and significantly higher eroded surface; resulting in a reduction in trabecular bone volume (p<0.05). The HCHF diet also caused a significantly higher serum CTX-1 level (p<0.05). Therefore, HCHF diet induced MetS exerts negative effects on the bone, possibly by causing an imbalance in bone remodelling and resulting in deterioration of the trabecular bone structure. Currently, there is no treatment targeting both MetS and osteoporosis together. Tocotrienol, a type of vitamin E, has been reported for its effects in preventing individual medical conditions associated with MetS and bone loss. Therefore, it is important to repurpose tocotrienol, namely palm and annatto tocotrienol as an agent for the management of both diseases which is the second part of our study. Supplementation of palm or annatto tocotrienol (60 or 100 mg/kg) improved the medical complications associated with MetS. Tocotrienol prevented hyperglycaemia, hypertension and dyslipidaemia in the animals fed with HCHF diet. Supplementation of palm and annatto tocotrienol improved trabecular bone microstructure and bone strength of femur in HCHF rats. Besides, palm and annatto tocotrienol significantly reduced pro-inflammatory cytokines (IL-1α and IL-6) and leptin level in the HCHF rats (p<0.05). However, palm tocotrienol were slightly better in improving glucose tolerance and increasing HDL cholesterol in the HCHF rats as compared to annatto tocotrienol. In conclusion, tocotrienol is a potential agent to prevent MetS and osteoporosis concurrently, which may be due to its ability to reduce the inflammatory response and leptin levels associated with HCHF diet.