Tilapia nilotica Head Lipids Improved Bone Loss by Regulating Inflammation and Serum Metabolism Through Gut Microbiota in Ovariectomized Rats

Osteoporosis is a global health problem, and it is of great significance to replace the drugs with natural functional factors. In this study, we investigated the antiosteoporotic activity of lipids prepared from Tilapia nilotica fish head lipids (THLs) in the ovariectomized osteoporosis rats. THLs are composed of neutral lipids (NL, 77.84%), phospholipids (PL, 11.86%), and glycolipids (GL, 6.47%). There were apparent differences in the fatty acid composition of disparate components, and PL contains the most abundant Ω-3 polyunsaturated fatty acids. The results proved that THLs could improve bone microstructure, increase bone mineral density, and decrease bone resorption. To illustrate the antiosteoporotic mechanism, we analyzed the changes in gut microbial communities, proinflammation factors, serum metabolites, and metabolic pathways. Further study on gut microbiota showed that THLs significantly decreased the content of Alistipes in the gut and dramatically increased the beneficial bacteria such as Oscillospira, Roseburia, and Dubosiella. Meanwhile, proinflammation factors of serum in OVX rats decreased significantly, and metabolites were changed. Therefore, we speculated that THLs improved bone loss through reducing inflammation and changing the metabolites and metabolic pathways such as arachidonic acid metabolism and primary bile acid metabolism, etc., by altering gut microbiota. The results indicated that THLs could be a functional factor with antiosteoporotic activity.

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Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats

Journal of Endocrinology ◽

10.1530/joe-11-0356 ◽

2011 ◽

Vol 212 (2) ◽

pp. 179-186 ◽

Cited By ~ 11

Author(s):

Rana Samadfam ◽

Malaika Awori ◽

Agnes Bénardeau ◽

Frieder Bauss ◽

Elena Sebokova ◽

...

Keyword(s):

Bone Loss ◽

Bone Mass ◽

Trabecular Bone ◽

Bone Mineral ◽

Combination Treatment ◽

Mass Gain ◽

Ovariectomized Rats ◽

Concomitant Treatment ◽

Mineral Density ◽

Ovx Rats

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.

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Effects of the Peroxisome Proliferator-Activated Receptor (PPAR)-δ Agonist GW501516 on Bone and Muscle in Ovariectomized Rats

Endocrinology ◽

10.1210/en.2013-1166 ◽

2014 ◽

Vol 155 (6) ◽

pp. 2178-2189 ◽

Cited By ~ 7

Author(s):

M. P. Mosti ◽

A. K. Stunes ◽

M. Ericsson ◽

H. Pullisaar ◽

J. E. Reseland ◽

...

Keyword(s):

Skeletal Muscle ◽

Bone Loss ◽

Ovariectomized Rats ◽

Whole Body ◽

Control Group ◽

High Dose ◽

Peroxisome Proliferator ◽

Mineral Density ◽

Muscle Morphology ◽

Ovx Rats

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.

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The Preventive Effect of Biochanin A on Bone Loss in Ovariectomized Rats: Involvement in Regulation of Growth and Activity of Osteoblasts and Osteoclasts

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/594857 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Shu-Jem Su ◽

Yao-Tsung Yeh ◽

Huey-Wen Shyu

Keyword(s):

Bone Loss ◽

Mrna Expression ◽

Biological Effects ◽

Biochanin A ◽

Ovariectomized Rats ◽

Tartrate Resistant Acid Phosphatase ◽

Type I ◽

Mineral Density ◽

Ovx Rats

Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX) animal model has never been clarified. The objective of this study was to investigate the biological effects of BCA on bone loss in OVX ratsin vivoand on the development of osteoblasts and osteoclastsin vitro. Ovariectomy resulted in a marked increase in body weight and a decrease in femoral bone mineral density and trabecular bone volume that was prevented by BCA or 17β-estradiol (E2) treatment. However, an increase in uterine weight was observed in E2-treated OVX rats, but not in response to BCA treatment. Treatment with BCA increased the mRNA expression of osterix, collagen type I, alkaline phosphatase (ALP), and osteocalcin and decreased the mRNA expression of tartrate-resistant acid phosphatase (TRAP) and the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in the femur of OVX rats. Treatment with BCA or E2 prevented the OVX-induced increase in urinary deoxypyridinoline (DPD) and serum tumor necrosis factorα(TNF-α) and interleukin-1β(IL-1β).In vitro, BCA induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. BCA inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast bone resorption. These findings suggest that BCA treatment can effectively prevent the OVX-induced increase in bone loss and bone turnover possibly by increasing osteoblastic activities and decreasing osteoclastic activities.

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Short- and long-term effects of calcium and exercise on bone mineral density in ovariectomized rats

British Journal Of Nutrition ◽

10.1079/bjn2001428 ◽

2001 ◽

Vol 86 (4) ◽

pp. 521-527 ◽

Cited By ~ 18

Author(s):

Joseé Gala ◽

Manuel Di´az-curiel ◽

Concepcioó de la Piedra ◽

Jesu´s Calero

Keyword(s):

Bone Mineral Density ◽

Bone Loss ◽

Bone Mineral ◽

Exercise Programme ◽

Female Rats ◽

Ovariectomized Rats ◽

Standard Diet ◽

Mineral Density ◽

Left Femur ◽

Ovx Rats

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX–EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX–Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX–EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0·05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgroups of animals, showing a decrease of AP and TRAP levels in the younger animals with no significant variations in markers of bone remodelling in the older female rats compared with their respective OVX group.

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New Bone Formation with Teriparatide [Human Parathyroid Hormone-(1–34)] Is Not Retarded by Long-Term Pretreatment with Alendronate, Estrogen, or Raloxifene in Ovariectomized Rats

Endocrinology ◽

10.1210/en.2002-221061 ◽

2003 ◽

Vol 144 (5) ◽

pp. 2008-2015 ◽

Cited By ~ 76

Author(s):

Yanfei L. Ma ◽

Henry U. Bryant ◽

Qingqiang Zeng ◽

Allen Schmidt ◽

Jennifer Hoover ◽

...

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Formation Rate ◽

Prior Exposure ◽

Ovariectomized Rats ◽

Mineral Density ◽

Bone Formation Rate ◽

Teriparatide Treatment ◽

Antiresorptive Agents ◽

Ovx Rats

With the ready availability of several osteoporosis therapies, teriparatide [human PTH-(1–34)] is likely to be prescribed to postmenopausal women with prior exposure to agents that prevent bone loss, such as bisphosphonates, estrogen, or selective estrogen receptor modulators. Therefore, we evaluated the ability of once daily teriparatide to induce bone formation in ovariectomized (Ovx) rats with extended prior exposure to various antiresorptive agents, such as alendronate (ABP), 17α-ethinyl estradiol (EE), or raloxifene (Ral). Sprague Dawley rats were Ovx and treated with ABP (28 μg/kg, twice weekly), EE (0.1 mg/kg·d), or Ral (1 mg/kg·d) for 10 months before switching to teriparatide 30 μg/kg·d for another 2 months. Analysis of the proximal tibial metaphysis showed that all three antiresorptive agents prevented ovariectomy-induced bone loss after 10 months, but were mechanistically distinct, as shown by histomorphometry. Before teriparatide treatment, ABP strongly suppressed activation frequency and bone formation rate to below levels in other treatment groups, whereas these parameters were not different from sham values for EE or Ral. Trabecular area for ABP, EE, and Ral were greater than that in Ovx controls. However, the trabecular bone effects of ABP were attributed not only to effects on the secondary spongiosa, but also to the preservation of primary spongiosa, which was prevented from remodeling. After 2 months of teriparatide treatment, lumbar vertebra showed relative bone mineral density increases of 18%, 7%, 11%, and 10% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Histomorphometry showed that trabecular area was increased by 105%, 113%, 36%, and 48% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Teriparatide enhanced mineralizing surface, mineral apposition rate, and bone formation rate in all groups. Compression testing of vertebra showed that teriparatide improved strength (peak load) and toughness in all groups to a proportionately similar extent compared with 10 month levels. These data showed a surprising ability of the rat skeleton to respond to teriparatide despite extensive pretreatment with ABP, EE, or Ral. Therefore, the mature skeleton of Ovx rats remains highly responsive to the appositional effects of teriparatide regardless of pretreatment status in terms of cancellous bone area or rate of bone turnover.

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Red wine polyphenols modulate bone loss in the ovariectomized rat model of postmenopausal osteoporosis

Journal of the Hellenic Veterinary Medical Society ◽

10.12681/jhvms.20860 ◽

2019 ◽

Vol 70 (2) ◽

pp. 1541

Author(s):

C. PASSALI ◽

A. PATSAKI ◽

P. LELOVAS ◽

N. ALIGIANNIS ◽

M. MAKROPOULOU ◽

...

Keyword(s):

Bone Loss ◽

Rat Model ◽

Red Wine ◽

Bending Test ◽

Ovariectomized Rats ◽

Mineral Density ◽

Ovx Rats ◽

Trabecular Bone Loss ◽

Wine Polyphenols ◽

Red Wine Polyphenols

The aim of this study was to examine the effect of Red Wine Polyphenols (RWPs) extract on bone mineral density (BMD) in the ovariectomized (OVX) rat model. Thirty-five 10-month-old Wistar rats were separated into controls (CTRL), OVX and OVX plus RWPs in their drinking water (dose, 50 mg/kg body weight per day), starting immediately after OVX for 6 months. Βody and uterine weight, BMD of the tibia at baseline, 3 and 6 months post-OVX, and 3-pointing bending of the femur, were examined. Statistical comparison of the total tibia BMD within groups during the study period showed a significant reduction in the OVX and OVX+RWPs groups both from baseline to 3 and 6 months and from 3 to 6 months, whereas in the CTRL group, there was no significant change. For the proximal tibial metaphysis, comparison of BMD percentage changes from baseline to 3 months and 6 months and from 3 to 6 months revealed highly statistical differences between OVX and OVX+RWPs groups (P = 0.000). OVX induced a significant reduction of biomechanical parameters as expected; the 3-point bending test showed that the maximum force before fracture, energy absorption and fracture stress significantly increased in the OVX group treated with RWPs compared with the nontreated OVX rats (P = 0.048, P = 0.002 and P = 0.003, respectively). Dietary intake of RWPs for 6 months significantly prevented trabecular bone loss and improved bone strength in estrogen-deficient ovariectomized rats.

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Chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-β1 levels in ovariectomized rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-097 ◽

2009 ◽

Vol 87 (1) ◽

pp. 51-55 ◽

Cited By ~ 11

Author(s):

Yong-Qi Li ◽

Hui Ji ◽

Yang Shen ◽

Li-Ju Ding ◽

Pei Zhuang ◽

...

Keyword(s):

Bone Loss ◽

Postmenopausal Osteoporosis ◽

Chronic Treatment ◽

Transforming Growth Factor ◽

Ovariectomized Rats ◽

Tartrate Resistant Acid Phosphatase ◽

Mineral Density ◽

Receptor Antagonists ◽

Ovx Rats ◽

At1 Receptor Antagonists

Approximately 50% of hypertensive patients are postmenopausal women; therefore, any antihypertensive therapy must not adversely affect bone loss in this population. Recently, however, concern has been raised that use of angiotensin AT1 receptor antagonists may increase the tendency to develop postmenopausal osteoporosis by decreasing transforming growth factor-β1 (TGF-β1), which has been implicated in bone mass maintenance. In the present study, we selected telmisartan and valsartan as representatives of angiotensin AT1 receptor antagonists and used ovariectomized (OVX) rats as a model of human postmenopausal osteoporosis. After 3 months treatment with telmisartan (5 mg/kg daily) or valsartan (10 mg/kg daily), OVX rats showed no signs of adverse effects on bone mineral density of the lumbar vertebrae (L1–L5) or the total femur, nor did treatment affect serum levels of osteocalcin and osteoclast-derived tartrate-resistant acid phosphatase (TRACP-5b). Bone TGF-β1 content remained unchanged, although treatment with telmisartan and valsartan significantly reduced serum TGF-β1 levels (p < 0.05). In conclusion, chronic treatment with angiotensin AT1 receptor antagonists reduced serum but not bone TGF-β1 levels and did not accelerate ovariectomy-induced bone loss in rats.

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Lactobacillus intestinalis YT2 restores the gut microbiota and improves menopausal symptoms in ovariectomized rats

Beneficial Microbes ◽

10.3920/bm2020.0217 ◽

2021 ◽

pp. 1-14

Author(s):

E.Y. Lim ◽

E.-J. Song ◽

J.G. Kim ◽

S.Y. Jung ◽

S.-Y. Lee ◽

...

Keyword(s):

Gut Microbiota ◽

Menopausal Symptoms ◽

Ovariectomized Rats ◽

Mrna Levels ◽

Mineral Density ◽

Microbial Composition ◽

Ovx Rats ◽

Menopausal Women ◽

Gut Microorganisms

There are many studies focusing on the alleviation of menopausal symptoms; however, little is known about the role of gut microorganisms in menopausal symptoms. Ovariectomized (OVX) rats were administered a novel strain (YT2) of Lactobacillus intestinalis (a species with significantly reduced abundance in OVX rats) and the potential probiotic effect on the improvement of menopausal symptoms was evaluated. Of note, the gut microbial composition completely shifted after ovariectomy in rats. Treatment with L. intestinalis YT2 significantly alleviated menopausal symptoms, such as increased fat mass, decreased bone mineral density, increased pain sensitivity, depression-like behaviour, and cognitive impairment. Additionally, the administration of L. intestinalis YT2 restored the intestinal microbial composition, including an increased Firmicutes/Bacteroides ratio. L. intestinalis YT2 also promoted gut barrier integrity by increasing the mRNA levels of tight junction-related markers. In conclusion, L. intestinalis YT2 treatment alleviated menopausal symptoms via the modulation of the gut microbiota. Importantly, these results suggest that L. intestinalis YT2 should be considered as a therapeutic probiotic agent for menopausal women.

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Effects of Kalsis, A Dietary Supplement, on Bone Metabolism in the Ovariectomized Rats

Journal of Osteoporosis ◽

10.1155/2012/639427 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Mercedes Montero ◽

Manuel Díaz-Curiel ◽

David Guede ◽

Jose Ramón Caeiro ◽

Marta Martín-Fernández ◽

...

Keyword(s):

Bone Loss ◽

Group Treatment ◽

Food Supplement ◽

Female Rats ◽

Ovariectomized Rats ◽

Tartrate Resistant Acid Phosphatase ◽

Mineral Density ◽

Ovx Rats ◽

Carboxyterminal Telopeptide ◽

Trabecular Number

We studied the ability of Kalsis, a food supplement that contains selenium, citric acid, and vitamin E, to prevent the effects of ovariectomy on bone loss. Six-month-old, Wistar female rats were studied. Groups (n=12): SHAM: sham-operated rats; OVX: ovariectomized rats, treated with vehicle; OVX + Kalsis: ovariectomized rats treated with Kalsis (25 mg/kg/day) for 3 months. Bone mineral density (BMD) was determined by DXA in lumbar spine and femur. Computerized microtomography (μCT) in femur and serum osteocalcin (BGP), aminoterminal propeptide of procollagen I (PINP),β-isomer of carboxyterminal telopeptide of collagen I (CTX), and 5b isoenzyme of tartrate-resistant acid phosphatase (TRAP) were performed. Treatment with Kalsis prevented BMD loss in OVX group.μCT showed a decrease in BV/TV, and trabecular number, and an increase in trabecular separation in OVX rats. Kalsis administration attenuated partially bone loss observed byμCT due to ovariectomy. BGP, PINP, and the resorption index (CTX/TRAP) were increased in OVX group. Treatment with Kalsis maintained this increase. The mechanism of action of this supplement is not through a decrease in bone remodelling rate. The antioxidant action of this food supplement, due to the synergism of all its components, as a cause of its beneficial effect is suggested.

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Combined use of epigallocatechin-3-gallate (EGCG) and caffeine in low doses exhibits marked anti-obesity synergy through regulation of gut microbiota and bile acid metabolism

Food & Function ◽

10.1039/d0fo01768j ◽

2021 ◽

Author(s):

Ming-zhi Zhu ◽

Fang Zhou ◽

Jian Ouyang ◽

Qi-ye Wang ◽

Yi-long Li ◽

...

Keyword(s):

Bile Acid ◽

Synergistic Effect ◽

Gut Microbiota ◽

Acid Metabolism ◽

Bile Acid Metabolism ◽

Low Doses ◽

Combined Use

Combined use of epigallocatechin-3-gallate (EGCG) and caffeine in low doses exhibits marked anti-obesity synergy. The synergistic effect may be attributed to regulation of gut microbiota and BA metabolism.

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