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Reproductive Sciences (Thousand Oaks,... Jun 2024We explore the interaction between estrogen and PCSK9 and their collective impact on lipid metabolism, especially concerning the regulation of low-density lipoprotein...
We explore the interaction between estrogen and PCSK9 and their collective impact on lipid metabolism, especially concerning the regulation of low-density lipoprotein receptor levels. Utilizing both animal and cellular models, including ovariectomized mice and HepG2 cell lines, we demonstrate that estrogen deficiency leads to a disruption in lipid metabolism, characterized by elevated levels of total cholesterol and LDL-C. The study commences with mice undergoing ovariectomy, followed by a diet regimen comprising either high-fat diet or normal feed for a four-week duration. Key assessments include analyzing lipid metabolism, measuring PCSK9 levels in the bloodstream, and evaluating hepatic low-density lipoprotein receptor expression. We will also conduct correlation analyses to understand the relationship between PCSK9 and various lipid profiles. Further, a subset of ovariectomized mice on high-fat diet will undergo treatment with either estrogen or PCSK9 inhibitor for two weeks, with a subsequent re-evaluation of the earlier mentioned parameters. Our findings reveal that estrogen inhibits PCSK9-mediated degradation of low-density lipoprotein receptor, a process crucial for maintaining lipid homeostasis. Through a series of experiments, including immunohistochemistry and western blot analysis, we establish that PCSK9 is involved in lipid metabolism disorders caused by estrogen deficiency and that estrogen regulates PCSK9 and low-density lipoprotein receptor at post-transcriptional level. The study provides a mechanism for the involvement of PCSK9 in elucidating the disorders of lipid metabolism caused by estrogen deficiency due to perimenopause and ovarian decline.
PubMed: 38871967
DOI: 10.1007/s43032-024-01614-8 -
Applied Biochemistry and Biotechnology Jun 2024
Correction to: Dietary Effects of Nanopowder Eggshells on Mineral Contents, Bone Turnover Biomarkers, and Regulators of Bone Resorption in Healthy Rats and Ovariectomy‑Induced Osteoporosis Rat Model.
PubMed: 38869815
DOI: 10.1007/s12010-024-04968-6 -
Aging Jun 2024The global prevalence of osteoporosis is being exacerbated by the increasing number of aging societies and longer life expectancies. In response, numerous drugs have...
The global prevalence of osteoporosis is being exacerbated by the increasing number of aging societies and longer life expectancies. In response, numerous drugs have been developed in recent years to mitigate bone resorption and enhance bone density. Nonetheless, the efficacy and safety of these pharmaceutical interventions remain constrained. Corylin (CL), a naturally occurring compound derived from the anti-osteoporosis plant L., has exhibited promising potential in impeding osteoclast differentiation. This study aims to evaluate the effect and molecular mechanisms of CL regulating osteoclast differentiation and its potential as a therapeutic agent for osteoporosis treatment . Our investigation revealed that CL effectively inhibits osteoclast formation and their bone resorption capacity by downregulating the transcription factors NFATc1 and c-fos, consequently resulting in the downregulation of genes associated with bone resorption. Furthermore, it has been observed that CL can effectively mitigate the migration and fusion of pre-osteoclast, while also attenuating the activation of mitochondrial mass and function. The results obtained from an study have demonstrated that CL is capable of attenuating the bone loss induced by ovariectomy (OVX). Based on these significant findings, it is proposed that CL exhibits considerable potential as a novel drug strategy for inhibiting osteoclast differentiation, thereby offering a promising approach for the treatment of osteoporosis.
Topics: Animals; Osteoclasts; Osteoporosis; Cell Differentiation; Mice; Bone Resorption; Female; Ovariectomy; NFATC Transcription Factors; RAW 264.7 Cells; Osteogenesis; Flavonoids
PubMed: 38862240
DOI: 10.18632/aging.205885 -
Nutrition Research and Practice Jun 2024This study evaluated the beneficial effects of an ethanol extract of gum resin (FJH-UBS) in osteoporosis.
BACKGROUND/OBJECTIVES
This study evaluated the beneficial effects of an ethanol extract of gum resin (FJH-UBS) in osteoporosis.
MATERIALS/METHODS
MC3T3-E1 osteoblastic cells and RAW 264.7 osteoclastic cells were treated with FJH-UBS. The alkaline phosphatase (ALP) activity, mineralization, collagen synthesis, osteocalcin content, and Runt-related transcription factor 2 (RUNX2) and Osterix expression were measured in MC3T3-E1 cells. The actin ring structures, tartrate-resistant acid phosphatase (TRAP) activity, and the nuclear factor of activator T-cells, cytoplasm 1 (NFATc1) expression were evaluated in RAW 264.7 cells. Ovariectomized ICR mice were orally administered FJH-UBS for eight weeks. The bone mineral density (BMD) and the serum levels of osteocalcin, procollagen 1 N-terminal propeptide (P1NP), osteoprotegerin, and TRAP 5b were analyzed.
RESULTS
FJH-UBS increased the ALP activity, collagen, osteocalcin, mineralization, and RUNX2 and osterix expression in MC3T3-E1 osteoblastic cells, whereas it decreased the TRAP activity, actin ring structures, and NFATc1 expression in RAW 264.7 osteoclastic cells. In ovariectomy-induced osteoporosis mice, FJH-UBS positively restored all of the changes in the bone metabolism biomarkers (BMD, osteocalcin, P1NP, osteoprotegerin, and TRAP 5b) caused by the ovariectomy.
CONCLUSION
FJH-UBS has anti-osteoporotic activity by promoting osteoblast activity and inhibiting osteoclast activity and , suggesting that FJH-UBS is a potential functional food ingredient for osteoporosis.
PubMed: 38854466
DOI: 10.4162/nrp.2024.18.3.309 -
Microbial Biotechnology Jun 2024Proanthocyanidin-rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current...
Proanthocyanidin-rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current study aims to explore GSE's preventive and therapeutic impact on bone loss induced by oestrogen deficiency and the underlying mechanism through the gut microbiota (GM) and metabolomic responses. In oestrogen-deficient ovariectomized (OVX) mice, GSE ameliorated bone loss by inhibiting the expansion of bone marrow adipose tissue (BMAT), restoring BMAT lipolysis and promoting bone formation. GSE regulated OVX-induced GM dysbiosis by reducing the abundance of opportunistic pathogenic bacteria, such as Alistipes, Turicibacter and Romboutsia, while elevating the abundance of beneficial bacteria, such as Bifidobacterium. The modified GM primarily impacted lipid and amino acid metabolism. Furthermore, the serum metabolites of GSE exhibited a significant enrichment in lipid metabolism. In summary, GSE shows potential as a functional food for preventing oestrogen deficiency-induced bone loss by modulating GM and metabolite-mediated lipid metabolism.
Topics: Gastrointestinal Microbiome; Animals; Grape Seed Extract; Mice; Female; Estrogens; Lipid Metabolism; Dysbiosis; Mice, Inbred C57BL; Bacteria; Osteoporosis; Disease Models, Animal; Adipose Tissue; Ovariectomy
PubMed: 38850270
DOI: 10.1111/1751-7915.14485 -
FASEB Journal : Official Publication of... Jun 2024Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause...
Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female mdx mice and the potential of estrogen replacement therapy (using estradiol) to protect against functional and metabolic perturbations. We also investigated the effect of estrogen depletion, and replacement, on the skeletal muscle proteome through an untargeted proteomic approach with TMT-labelling. Our study confirms that loss of estrogen in female mdx mice reduces exercise capacity, tricarboxylic acid cycle intermediates, and citrate synthase activity but that these deficits are offset through estrogen replacement therapy. Furthermore, ovariectomy downregulated protein expression of RNA-binding motif factor 20 (Rbm20), a critical regulator of sarcomeric and muscle homeostasis gene splicing, which impacted pathways involving ribosomal and mitochondrial translation. Estrogen replacement modulated Rbm20 protein expression and promoted metabolic processes and the upregulation of proteins involved in mitochondrial dynamics and metabolism. Our data suggest that estrogen mitigates dystrophinopathic features in female mdx mice and that estrogen replacement may be a potential therapy for post-menopausal DMD carriers.
Topics: Animals; Female; Mice, Inbred mdx; Mice; Estrogens; RNA-Binding Proteins; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Mice, Inbred C57BL; Ovariectomy; Mitochondria; Mitochondria, Muscle
PubMed: 38847487
DOI: 10.1096/fj.202400329R -
Endocrine, Metabolic & Immune Disorders... 2024Nitrate, as nitric oxide (NO) donor, has been suggested as a nutrition-based treatment for decreasing the risk of menopause-related obesity. This study aimed to specify...
BACKGROUND AND OBJECTIVE
Nitrate, as nitric oxide (NO) donor, has been suggested as a nutrition-based treatment for decreasing the risk of menopause-related obesity. This study aimed to specify the effects of chronic inorganic nitrate administration on uncoupling protein-1 (UCP-1), peroxisome proliferator-activated-receptor-947; (PPAR-947;) coactivator-1945; (PGC-1945;), and PPAR-947; expression in gonadal adipose tissue (GAT) of ovariectomized (OVX) rats.
METHODS
Female rats were assigned to 3 groups: Control, OVX, and OVX+nitrate (n=7/group), which consumed water containing inorganic nitrate (100 mg/L) for 9 months. At month 9, GAT was used for the measurement of NO metabolites (NOx), mRNA levels of NO synthases (endothelial (eNOS), inducible (iNOS), neuronal (nNOS)), and mRNA and protein levels of UCP-1, PGC-1945;, and PPAR-947;.
RESULTS
OVX rats had lower NOx concentration (45%) and eNOS (38%) and nNOS (30%) expression in GAT that was restored to normal values following nitrate administration. OVX rats had significantly lower mRNA and protein levels of UCP-1 (83% and 30%), PGC-1945; (65% and 39%), and PPAR-947; (66% and 34.5%) in GAT. Chronic inorganic nitrate administration in OVXrats increased mRNA and protein levels of UCP-1 (128% and 34%), PGC-1945; (115% and 43%), and PPAR-947; (236% and 38%), respectively.
CONCLUSION
In OVX rats, chronic nitrate administration increased gene and protein levels of UCP-1, PGC-1945;, and PPAR-947; in GAT, indicating the anti-obesity effects of nitrate are partially mediated by the white adipose tissue (WAT) browning. Moreover, the stimulatory effect of inorganic nitrate on the WAT browning in OVX rats was associated with blunting the OVXinduced NO deficiency in GAT.
Topics: Animals; Female; Ovariectomy; Nitrates; Rats; Uncoupling Protein 1; Rats, Wistar; Adipose Tissue, Brown; Nitric Oxide; Gene Expression Regulation; Transcription Factors; Adipose Tissue; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
PubMed: 38847150
DOI: 10.2174/0118715303239481231030043730 -
Journal of Obstetrics and Gynaecology :... Dec 2024This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy.
BACKGROUND
This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy.
METHODS
Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period.
RESULTS
Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I.
CONCLUSION
The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.
Topics: Animals; Female; Ovary; Rats; Transplantation, Heterotopic; Estrous Cycle; Ovariectomy; Anti-Mullerian Hormone; Follicle Stimulating Hormone; Estradiol; Rats, Sprague-Dawley; Organ Size; Ovarian Follicle; Reproduction
PubMed: 38847083
DOI: 10.1080/01443615.2024.2362416 -
Scientific Reports Jun 2024Woodsmoke (WS) exposure is associated with significant health-related sequelae. Different populations can potentially exhibit varying susceptibility, based on endocrine...
Woodsmoke (WS) exposure is associated with significant health-related sequelae. Different populations can potentially exhibit varying susceptibility, based on endocrine phenotypes, to WS and investigating neurological impacts following inhaled WS is a growing area of research. In this study, a whole-body inhalation chamber was used to expose both male and female C57BL/6 mice (n = 8 per group) to either control filtered air (FA) or acute WS (0.861 ± 0.210 mg/m) for 4 h/d for 2 days. Neuroinflammatory and lipid-based biological markers were then assessed. In a second set of studies, female mice were divided into two groups: one group was ovariectomized (OVX) to simulate an ovarian hormone-deficient state (surgical menopause), and the other underwent Sham surgery as controls, to mechanistically assess the impact of ovarian hormone presence on neuroinflammation following FA and acute WS exposure to simulate an acute wildfire episode. There was a statistically significant impact of sex (P ≤ 0.05) and statistically significant interactions between sex and treatment in IL-1β, CXCL-1, TGF-β, and IL-6 brain relative gene expression. Hippocampal and cortex genes also exhibited significant changes in acute WS-exposed Sham and OVX mice, particularly in TGF-β (hippocampus) and CCL-2 and CXCL-1 (cortex). Cortex GFAP optical density (OD) showed a notable elevation in male mice exposed to acute WS, compared to the control FA. Sham and OVX females demonstrated differential GFAP expression, depending on brain region. Overall, targeted lipidomics in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) serum and brain lipids demonstrated more significant changes between control FA and acute WS exposure in female mice, compared to males. In summary, male and female mice show distinct neuroinflammatory markers in response to acute WS exposure. Furthermore, ovarian hormone deficiency may impact the neuroinflammatory response following an acute WS event.
Topics: Animals; Female; Male; Mice; Neuroinflammatory Diseases; Mice, Inbred C57BL; Sex Factors; Ovariectomy; Brain; Ovary
PubMed: 38844478
DOI: 10.1038/s41598-024-63562-2 -
Behavioural Brain Research Jul 2024Estrogen receptor (ER) activation by 17-ß estradiol (E2) can attenuate neuronal injury and behavioral impairments following global cerebral ischemia (GCI) in rodents....
Selective estrogen receptor activation prior to global cerebral ischemia in female rats impacts microglial activation and anxiety-like behaviors without effects on CA1 neuronal injury.
Estrogen receptor (ER) activation by 17-ß estradiol (E2) can attenuate neuronal injury and behavioral impairments following global cerebral ischemia (GCI) in rodents. This study sought to further examine the discrete roles of ERs through characterization of the effects of selective ER activation on post-ischemic pro-inflammatory microglial activation, hippocampal neuronal injury, and anxiety-like behaviors. Forty-six ovariectomized (OVX) adult female Wistar rats received daily s.c injections (100 μg/kg/day) of propylpyrazole triol (PPT; ERα agonist), diarylpropionitrile (DPN; ERβ agonist), G-1 (G-protein coupled ER agonist; GPER), E2 (activating all receptors), or vehicle solution (VEH) for 21 days. After final injection, rats underwent GCI via 4-vessel occlusion (n=8 per group) or sham surgery (n=6, vehicle injections). The Open Field Test (OFT), Elevated Plus Maze (EPM), and Hole Board Test (HBT) assessed anxiety-like behaviors. Microglial activation (Iba1, CD68, CD86) in the basolateral amygdala (BLA), CA1 of the hippocampus, and paraventricular nucleus of the hypothalamus (PVN) was determined 8 days post-ischemia. Compared to sham rats, Iba1 activation and CA1 neuronal injury were increased in all ischemic groups except DPN-treated rats, with PPT-treated ischemic rats also showing increased PVN Iba1-ir expression. Behaviorally, VEH ischemic rats showed slightly elevated anxiety in the EPM compared to sham counterparts, with no significant effects of agonists. While no changes were observed in the OFT, emotion regulation via grooming in the HBT was increased in G-1 rats compared to E2 rats. Our findings support selective ER activation to regulate post-ischemic microglial activation and coping strategies in the HBT, despite minimal impact on hippocampal injury.
Topics: Animals; Female; Microglia; Rats; Anxiety; Rats, Wistar; CA1 Region, Hippocampal; Brain Ischemia; Pyrazoles; Phenols; Ovariectomy; Neurons; Propionates; Behavior, Animal; Estradiol; Disease Models, Animal; Receptors, Estrogen; Nitriles
PubMed: 38844057
DOI: 10.1016/j.bbr.2024.115094