scholarly journals Flaxseed oil ameliorated high-fat-diet-induced bone loss in rats by promoting osteoblastic function in rat primary osteoblasts

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Fulian Chen ◽  
Yan Wang ◽  
Hongwei Wang ◽  
Zhenhua Dong ◽  
Yan Wang ◽  
...  

Abstract Background α-Linolenic acid (ALA) is a plant-derived omega-3 unsaturated fatty acid that is rich in flaxseed oil (FO). The effect of FO on bone health is controversial. This study aims to evaluate the effect of FO on bone damage induced by a high-fat diet (HFD) and to explore the possible mechanism. Methods Male Sprague-Dawley rats were fed a normal control diet (NC, 10% fat), FO diet (NY, 10% fat), HFD (60% fat), or HFD containing 10% FO (HY, 60% fat) for 22 weeks. Micro CT and three-point bending tests were conducted to evaluate bone microstructure and biomechanics. Serum was collected for the detection of ALP, P1NP, and CTX-1. Rat primary osteoblasts (OBs) were treated with different concentrations of ALA with or without palmitic acid (PA) treatment. The ALP activity, osteogenic-related gene and protein expression were measured. Results Rats in the HFD group displayed decreased biomechanical properties, such as maximum load, maximum fracture load, ultimate tensile strength, stiffness, energy absorption, and elastic modulus, compared with the NC group (p < 0.05). However, HY attenuated the HFD-induced decreases in bone biomechanical properties, including maximum load, maximum fracture load, and ultimate tensile strength (p < 0.05). Trabecular bone markers such as trabecular volume bone mineral density (Tb. vBMD), trabecular bone volume/total volume (Tb. BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) were decreased, trabecular separation (Tb. Sp) and the structure model index (SMI) were increased in the HFD group compared with the NC group, and all parameters were remarkably improved in the HY group compared to the HFD group (p < 0.05). However, cortical bone markers such as cortical volume bone mineral density (Ct. vBMD), cortical bone volume/total volume (Ct. BV/TV) and cortical bone thickness (Ct. Th) were not significantly different among all groups. Moreover, the serum bone formation markers ALP and P1NP were higher and the bone resorption marker CTX-1 was lower in the HY group compared with levels in the HFD group. Compared with the NC group, the NY group had no difference in the above indicators. In rat primary OBs, PA treatment significantly decreased ALP activity and osteogenic gene and protein (β-catenin, RUNX2, and osterix) expression, and ALA dose-dependently restored the inhibition induced by PA. Conclusions FO might be a potential therapeutic agent for HFD-induced bone loss, most likely by promoting osteogenesis.

2020 ◽  
Author(s):  
Yan Wang ◽  
Fulian Chen ◽  
Hongwei Wang ◽  
Yan Wang ◽  
Mengqi Zhang ◽  
...  

Abstract Background Obesity has a negative impact on bone health; thus far, no specific pharmacotherapy has been approved. Berberine has shown improvements in osteoporosis in some animal models. However, it remains unknown whether berberine ameliorates obesity-induced bone damage. This study aims to evaluate the effect of berberine on bone damage in high-fat diet (HFD)-induced obese rats. Methods Male Sprague-Dawley rats were randomly assigned to a normal control diet (ND) group or HFD group. After the HFD induced obesity, the models were successfully established. Then, these rats were randomly divided into the HFD + berberine (HB) group or HFD group and were intraperitoneally administered berberine or an equivalent volume of DMSO, respectively, once a day for another 10 weeks. Micro-CT and three-point bending tests were conducted to evaluate bone microstructure and biomechanics. Serum was collected for the detection of P1NP, CTX-1, calcium (Ca) and phosphorus (P), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). HE staining was performed to observe the number of trabecular and bone marrow adipocytes. Results HFD-induced obese rats displayed decreased biomechanical properties, such as maximum load, maximum fracture load, ultimate tensile strength, stiffness, and energy absorption, compared with the ND rats (p<0.05). However, berberine attenuated bone damage, including maximum load, maximum fracture load, and stiffness, in the HB group compared with the HFD group (p<0.05). Trabecular bone markers were decreased in the HFD group compared with the ND group (p<0.05). All parameters were improved, as shown by micro-CT and HE staining, in the HB group compared to the HFD group. Cortical bone markers were not significantly different among all groups. Moreover, CTX-1, TNF-α, IL-1β and the number of adipocytes in bone marrow were significantly increased in HFD-induced obese rats. After treatment with berberine, TNF-α, IL-1β and the number of adipocytes in bone marrow were significantly decreased, and P1NP levels were higher in the HB group than in the HFD group. Conclusions Berberine might be a potential therapeutic agent for treating bone damage in HFD-induced obese rats by inhibiting inflammatory factors, reducing bone marrow adiposity and improving bone formation.


2014 ◽  
Vol 111 (10) ◽  
pp. 1811-1821 ◽  
Author(s):  
Jyoti Gautam ◽  
Dharmendra Choudhary ◽  
Vikram Khedgikar ◽  
Priyanka Kushwaha ◽  
Ravi Shankar Singh ◽  
...  

The relationship between fat and bone mass at distinct trabecular and cortical skeletal compartments in a high-fat diet (HFD) model was studied. For this, C57BL/6 mice were assigned to four groups of eight animals each. Two groups, each of males and females, received a standard chow diet while the remaining other two groups received the HFD for a period of 10 weeks. Male mice on the HFD were heavier and gained more weight (15·8 %; P<  0·05) v. those on the control diet or when compared with the female rats fed the HFD. We observed an increased lipid profile in both males and females, with significantly higher lipid levels (about 20–25 %; P< 0·01) in males. However, glucose intolerance was more pronounced in females than males on the HFD (about 30 %; P< 0·05). The micro-architectural assessment of bones showed that compared with female mice on the HFD, male mice on the HFD showed more deterioration at the trabecular region. This was corroborated by plasma osteocalcin and carboxy-terminal collagen crosslinks (CTx) levels confirming greater loss in males (about 20 %; P< 0·01). In both sexes cortical bone parameters and strength remained unchanged after 10 weeks of HFD treatment. The direct effect of the HFD on bone at the messenger RNA level in progenitor cells isolated from femoral bone marrow was a significantly increased expression of adipogenic marker genes v. osteogenic genes. Overall, the present data indicate that obesity induced by a HFD aggravates bone loss in the cancellous bone compartment, with a greater loss in males than females, although 10 weeks of HFD treatment did not alter cortical bone mass and strength in both males and females.


2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1666
Author(s):  
Dean S. Ross ◽  
Tzu-Hsuan Yeh ◽  
Shalinie King ◽  
Julia Mathers ◽  
Mark S. Rybchyn ◽  
...  

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene/protein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance/pre-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 570
Author(s):  
Masayoshi Yamada ◽  
Chongxiao Chen ◽  
Toshie Sugiyama ◽  
Woo Kyun Kim

Changes in medullary and cortical bone structure with age remain unclear. Twenty Hy-Line W36 hens, 25 or 52 weeks of age, were euthanized, and both tibiae were collected when an egg was present in the magnum. Serial cross sections of the tibiae were stained with Alcian blue. The bones were scanned using micro-computed tomography. Trabecular width (Tb.Wi) was significantly higher (p < 0.05) in 25-week-old hens, whereas medullary bone tissue volume (TV) was significantly higher (p < 0.01) in 52-week-old hens. 25-week-old hens had significantly higher (p < 0.01) bone volume fraction (BVF = calcified tissue / TV). Moreover, the cortical bone parameters were significantly higher (TV and bone mineral content (BMC) at p < 0.05, and bone volume (BV) and BVF at p < 0.01) in younger hens. Open porosity and total porosity, which indicate less density, were significantly higher (p < 0.01) in older hens. Older hens showed significantly higher (p < 0.01) tibial diaphysis TV than younger hens. Younger hens had significantly higher (p < 0.01) BV, BVF and bone mineral density (BMD) of the tibial diaphysis. These findings reveal that reductions in medullary bone quality might be associated with age-related low estrogen levels and stimulation of osteoclastic bone resorption by parathyroid hormone. Cortical bone quality decreased with enlargement of the Haversian canals and loss of volume, with a longer egg-laying period leading to osteoporosis.


2018 ◽  
Vol 119 (10) ◽  
pp. 1111-1118 ◽  
Author(s):  
Monika Sobol ◽  
Stanisława Raj ◽  
Grzegorz Skiba

AbstractConsumption of a high-fat diet, rich in SFA, causes deterioration of bone properties. Some studies suggest that feeding inulin to animals may increase mineral absorption and positively affect bone quality; however, these studies have been carried out only on rodents fed a standard diet. The primary objective of this study was to determine the effect of inulin on bone health of pigs (using it as an animal model for humans) fed a high-fat diet rich in SFA, having an unbalanced ratio of lysine:metabolisable energy. It was hypothesised that inulin reduces the negative effects of such a diet on bone health. At 50 d of age, twenty-one pigs were randomly allotted to three groups: the control (C) group fed a standard diet, and two experimental (T and TI) groups fed a high-fat diet rich in SFA. Moreover, TI pigs consumed an extra inulin supply (7 % of daily feed intake). After 10 weeks, whole-body bone mineral content (P=0·0054) and bone mineral density (P=0·0322) were higher in pigs of groups TI and C compared with those of group T. Femur bone mineral density was highest in pigs in group C, lower in group TI and lowest in group T (P=0·001). Femurs of pigs in groups TI and C had similar, but higher, maximum strength compared with femurs of pigs in group T (P=0·0082). In conclusion, consumption of a high-fat diet rich in SFA adversely affected bone health, but inulin supplementation in such a diet diminishes this negative effect.


2020 ◽  
Vol 48 (9) ◽  
pp. 2151-2160
Author(s):  
Jakob E. Schanda ◽  
Claudia Keibl ◽  
Patrick Heimel ◽  
Xavier Monforte ◽  
Stefan Tangl ◽  
...  

Background: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. Hypothesis: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. Study Design: Controlled laboratory study. Methods: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro–computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. Results: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head ( P = .005) and the medial humeral head ( P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head ( P = .004) and the medial humeral head ( P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group ( P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group ( r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. Conclusion: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. Clinical Relevance: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1795-1795
Author(s):  
Chen Du ◽  
Gina Tran ◽  
Victorine Imrhan ◽  
Chandan Prasad ◽  
Parakat Vijayagopal ◽  
...  

Abstract Objectives The purpose of this study was to compare the effects of alpha tocopherol, gamma tocopherol, and the combination of alpha and gamma tocopherols on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism in C57BL/6 J mice fed a high-fat diet. Methods A total of 75 male C57BL/6 mice were randomized to either a low fat diet (LFD) with 6% fat, a high fat diet (HFD) with 20% fat, HFD supplemented with alpha tocopherol (AT), gamma tocopherol (GT), or the combination of AT and GT. LFD and HFD were provided to corresponding groups of mice without vitamin E isoform supplements for 15 weeks to induce bone loss. At the end of the 15 weeks, AT, GT, and a combination of AT and GT were added to 3 of the HFD groups and fed for 10 weeks. LFD group and one of the HFD groups were continued on the same diet for another 10 weeks without additional supplements. All mice were euthanized at the end of the 25 weeks period. Left and right fibula bones were excised, cleaned, and scanned using the Lunar PIXImus dual-energy x-ray absorptiometry (DEXA) densitometer to assess BMD, BMC, lean tissue, and fat tissue content. Serum biomarkers of bone metabolism were evaluated post euthanization. Results HFD resulted in significantly lower fibular BMD and higher tibial bone fat content in comparison to LFD. Animals in the HFD supplemented with GT, but not AT, showed significantly reduced effect of HFD in lowering BMD. Additionally, in the group fed HFD supplemented with GT, a significantly higher concentration of alkaline phosphatase (ALP) and N-terminal propeptide of type I procollagen (PINP) were noted, compared to LFD. This may be indicative of increased bone formation resulting from GT incorporated into the HFD diet. Conclusions The findings of the study suggest that different isoforms of vitamin E affect bone density and bone metabolism differently. Within the different isoforms of vitamin E, gamma tocopherol may have protective effects in bone, especially in the situation of high fat diet induced bone loss. Further examination of the mechanistic action of vitamin E isoforms on skeletal health is warranted. Funding Sources Texas Woman's University.


2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0040
Author(s):  
Chris Stauch ◽  
Jesse King ◽  
Morgan Kim ◽  
David Waning ◽  
John Elfar ◽  
...  

Category: Diabetes, Hindfoot, Midfoot/Forefoot, obesity Introduction/Purpose: In recent decades, the prevalence of obesity in the United States has increased dramatically. This can be attributed in-part to the high-fat “Western Diet”. Consequentially, the economic burden of obesity to the healthcare system has rapidly increased, accounting for more than 10 percent of all medical spending in America. Furthermore, with regards to orthopedics, obesity has been shown to be a strong risk factor for musculoskeletal pain, injury, and post-operative complications. The purpose of this study was to determine the effects of high intensity cardiovascular training and controlled dietary intake on body weight, body fat percentage (BFP), and bone mineral density (BMD) in obese and non-obese mice. These results will provide a better understanding of how to optimally facilitate weight loss in obese patients. Methods: Following IAUCUC approval, 8 diet-induced obesity (DIO) C57BL/6 mice were obtained along with 6 non-obese C57BL/6 control mice. DIO mice were fed a high-fat diet (60% fat by kcal) ad libitum starting at the age of 6 weeks. Control mice were fed a standard low-fat diet (10% fat by kcal) ad libitum from birth. Starting at the age of 14 weeks, all mice underwent a controlled high intensity cardiovascular training protocol using a treadmill four times per week at 30 minute intervals. This was carried out for seven weeks including a one-week acclimation period. Speed, distance, and time spent running were all constant between groups. Mouse body weights were recorded several times per week throughout the study. Additionally, BFP and BMD were obtained bi-weekly using dual energy X-ray absorptiometry (DEXA) to assess morphophysiological changes longitudinally. Results: Preliminary investigations with a controlled exercise regimen reveal that obese mice, when fed a high-fat diet, continue to gain weight rapidly despite high intensity cardiovascular training whereas control mice maintain their weight. Following the seven-week training period, control mice gained an average of 1.25 g (p=0.41), while DIO mice gained an average of 8.55 g (p<0.001). DIO mice also showed an 8.74% increase in body fat percentage (p=0.002) while control mice showed a 0.51% decrease in body fat percentage (p=0.75). Lastly, BMD was significantly lower in DIO mice compared to controls following the exercise protocol (p<0.05). Conclusion: The results of this study support the hypothesis that a controlled exercise regimen alone is ineffective for facilitating weight loss. In fact, obese mice administered a high-fat diet actually gain weight despite undergoing a rigorous exercise program. Additionally, simple differences in dietary intake have significant effects on body weight, body fat percentage, and bone mineral density. This suggests that while exercise may play a small role in maintaining a normal weight, obesity is irreversible with exercise alone. Obese orthopedic patients should be counseled on dietary modifications before engaging in an exercise program.


Sign in / Sign up

Export Citation Format

Share Document