scholarly journals Genistein Modulated Lipid Metabolism, Hepatic PPARγ, and Adiponectin Expression in Bilateral Ovariectomized Rats with Nonalcoholic Steatohepatitis (NASH)

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 24
Author(s):  
Sudaporn Pummoung ◽  
Duangporn Werawatganon ◽  
Maneerat Chayanupatkul ◽  
Naruemon Klaikeaw ◽  
Prasong Siriviriyakul

The aim of this study was to evaluate the protective effects of genistein on lipid accumulation and apoptosis in estrogen deficient rats with NASH. Female Sprague–Dawley rats (n = 48) were divided into ovariectomized (OVX) and non-OVX groups. Each group was then sub-divided into 3 subgroups; control, NASH (rats fed with a high-fat, high-fructose (HFHF) diet), and NASH+Gen (rats fed with HFHF diet plus daily genistein at 16 mg/kg BW). Results showed that HFHF diet induced liver fat accumulation in both non-OVX and OVX rats, which was evidenced by hepatic steatosis on liver pathology and increased hepatic free fatty acid (FFA) and triglyceride levels. Hepatic fat accumulation was significantly more severe in NASH rats with OVX than non-OVX. Hepatocyte apoptosis was more severe in NASH groups compared with that in control groups. Genistein administration significantly improved histopathology of NASH in both non-OVX and OVX rats and attenuated hepatic lipid accumulation, oxidative stress, and hepatocyte apoptosis. Genistein also down-regulated PPARγ and up-regulated adiponectin expression. In summary, NASH could be worsened by estrogen deficiency, indicating the protective action of estrogen on NASH. Genistein administration alleviated hepatic steatosis and apoptosis through the down-regulation of PPARγ and up-regulation of adiponectin expression.

2011 ◽  
Vol 212 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Aiying Liu ◽  
Liping Gao ◽  
Shoulei Kang ◽  
Ying Liu ◽  
Chuanying Xu ◽  
...  

After menopause, the development of cardiovascular disease (CVD) is due not only to estrogen decline but also to androgen decline. This study examined the effects of either estradiol (E2) or testosterone replacement alone or E2–testosterone combination on isolated myocytes in ovariectomized (Ovx) rats subjected to ischemia/reperfusion (I/R). Furthermore, we determined whether the effects are associated with β2-adrenoceptor (β2-AR). Five groups of adult female Sprague–Dawley rats were used: Sham operation (Sham) rats, bilateral Ovx rats, Ovx rats with E2 40 μg/kg per day (Ovx+E), Ovx rats with testosterone 150 μg/kg per day (Ovx+T), and Ovx rats with E2 40 μg/kg per day+testosterone 150 μg/kg per day (Ovx+E/T). We determined the lactate dehydrogenase (LDH) release, percentage of rod-shaped cells and apoptosis of ventricular myocytes from rats of all groups subjected to I/R. Then, we determined the above indices and contractile function with or without a selective β2-AR antagonist ICI 118 551. We also determined the expression of β2-AR. Our data show that either E2 or testosterone replacement alone or E2 and testosterone in combination decreased the LDH release, increased the percentage of rod-shaped cells, reduced apoptotic cells (%), and combination treatment appeared to be more effective than either E2 or testosterone replacement alone. ICI 118 551 abolished the effects of the three. Combination supplementation also enhanced the expression of β2-AR. We concluded that in Ovx rats, testosterone enhances E2's cardioprotection, while E2 and testosterone in combination was more effective and the protective effects may be associated with β2-AR. The study highlights the potential therapeutic application for CVD in postmenopausal women.


Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2943
Author(s):  
Hui-Hui Xiao ◽  
Xueli Yu ◽  
Chen Yang ◽  
Chi-On Chan ◽  
Lu Lu ◽  
...  

Flavonoids, found in a wide variety of foods and plants, are considered to play an important role in the prevention and treatment of osteoporosis. Our previous studies demonstrated that Erythrina cortex extract (EC) rich in prenylated isoflavonoids exerted bone protective effects in ovariectomized (OVX) rats. The present study aimed to investigate the interactions of gut microbiota with the EC extract to explore the underlying mechanisms involved in its beneficial effects on bone. Sprague-Dawley female rats of 3-months-old were ovariectomized and treated with EC extract for 12 weeks. EC extract reversed ovariectomy-induced deterioration of bone mineral density and bone microarchitecture as well as downregulated cathepsin K (Ctsk) and upregulated runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) in the tibia of OVX rats. Its protective effects on bone were correlated with changes in microbial richness and the restorations of several genera. EC increased the serum circulating levels of acetate and propionate in OVX rats. We conclude that the bone protective effects of EC extract were associated with the changes in microbial compositions and serum short chain fatty acids (SCFAs) in OVX rats.


2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jean-Marc Lavoie ◽  
Abdolnaser Pighon

One segment of the population that is particularly inclined to liver fat accumulation is postmenopausal women. Although nonalcoholic hepatic steatosis is more common in men than in women, after menopause there is a reversal in gender distribution. At the present time, weight loss and exercise are regarded as first line treatments for NAFLD in postmenopausal women, as it is the case for the management of metabolic syndrome. In recent years, there has been substantial evidence coming mostly from the use of the animal model, that indeed estrogens withdrawal is associated with modifications of molecular markers favouring the activity of metabolic pathways ultimately leading to liver fat accumulation. In addition, the use of the animal model has provided physiological and molecular evidence that exercise training provides estrogens-like protective effects on liver fat accumulation and its consequences. The purpose of the present paper is to present information relative to the development of a state of NAFLD resulting from the absence of estrogens and the role of exercise training, emphasizing on the contribution of the animal model on these issues.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Liming Xue ◽  
Yin Wang ◽  
Yiping Jiang ◽  
Ting Han ◽  
Yan Nie ◽  
...  

Er-Xian Decoction (EXD),Epimediumherbs (herbs ofEpimedium brevicornumMaxim, EBH), and icariin (ICA) have been proven to have estrogen-like and antiosteoporotic activity and are used for the treatment of osteoporosis, menopausal syndrome, and age-associated diseases. The present study found that EXD, EBH, and ICA treatments, emulating estrogen, significantly contributed to bone density and architecture in OVX rats and that EXD is similar to estrogen and exerts a concomitant effect on bone formation and bone resorption at the tissue level, while EBH and ICA produced bone-protective effects mainly by inhibiting bone resorption. Nevertheless, EXD, EBH, and ICA treatments manifested a fewer adverse effects on the uterus, mammary gland, and vagina compared to estrogen administrations. Among the EXD, EBH, and ICA, EXD was found to have superior efficacy and safety profile.


2012 ◽  
Vol 213 (3) ◽  
pp. 251-261 ◽  
Author(s):  
Paramita M Ghosh ◽  
Zhen-Ju Shu ◽  
Bing Zhu ◽  
Zhongding Lu ◽  
Yuji Ikeno ◽  
...  

Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic functional and structural impairment and overall metabolic risk. Previous studies noted an association between hepatic steatosis and age in humans and rodents. However, the mechanisms leading to age-associated hepatic fat accumulation remain unknown. Earlier work from our group showed that β-adrenergic receptor (β-AR) levels and β-AR-stimulated adenylyl cyclase activity increase in rat liver during aging. Here we investigated whether age-associated increases in β-AR signaling play a role in augmenting hepatic lipid accumulation. We demonstrate an increase in hepatic lipid content during senescence and a significant correlation between hepatic fat content and stimulation of adenylyl cyclase activity by the β-AR agonist isoproterenol in rat liver. Isoproterenol administration to young and old rodents in vivo increased hepatic lipid accumulation. Furthermore, in vitro overexpression of β1- and β2-AR subtypes in hepatocytes from young rodents increased cellular lipid content, whereas inhibition of β-ARs by receptor subtype-specific inhibitors reduced lipid levels in hepatocytes from senescent animals. Isoproterenol-induced hepatic lipid accumulation in vivo was prevented by the β-AR nonselective blocker propranolol, suggesting a novel therapeutic effect of this class of drugs in hepatic steatosis. Acipimox, which inhibits adipose tissue lipolysis, did not alter isoproterenol-mediated hepatic fat accumulation; thus β-AR responsive hepatic lipid accumulation does not appear to be related primarily to altered lipolysis. These findings suggest that augmented hepatic β-AR signaling during aging may increase lipid accumulation in liver and advocate a possible role for β-adrenergic blockers in preventing or retarding the development of hepatic steatosis.


2021 ◽  
Vol 11 (4) ◽  
pp. 1392
Author(s):  
Sanghee Lee ◽  
Gwang Ju Jang ◽  
Miyoung Yoo ◽  
Haeng Jeon Hur ◽  
Mi Jeong Sung

Saururus chinensis (SC), a traditional medicine, has been used for the treatment of edema, jaundice, gonorrhea, and several inflammatory diseases in China and Korea. Our previous studies reported the anti-osteoporotic activity of SC extract (SCE) in ovariectomized (OVX) rats but the mechanism of this effect was unclear. The aim of this study was to explore the anti-osteoporotic effect of SCE and elucidate the underlying mechanisms in ovariectomized rats using a metabolomics approach based on ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF MS) to analyze metabolic changes. Female Sprague-Dawley (SD) rats were divided into sham, OVX, and SCE treatment groups. Partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) score plots separated OVX and sham groups fairly well. Further, 22 potential biomarkers were identified in the rat models of estrogen deficiency-induced osteoporosis, and SCE showed regulatory effects on three vital metabolic pathways associated with these biomarkers, namely, glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, and linoleic acid metabolism. The metabolomics approach reliably confirmed that SCE exerted its anti-osteoporotic effect by intervening with lipid metabolism, thus preventing osteoporosis. This study also showed the promising potential of this approach in an evaluation of natural medicine efficacy.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2022
Author(s):  
Jhih-Han Yeh ◽  
Yu-Tang Tung ◽  
Yu-Sheng Yeh ◽  
Yi-Wen Chien

Background: Obesity is a state of excess energy storage resulting in body fat accumulation, and postmenopausal obesity is a rising issue. In this study using ovariectomized (OVX) rats, we mimicked low estrogen levels in a postmenopausal state in order to investigate the effects of different amounts and types of dietary fatty acids on body fat accumulation and body lipid metabolism. Methods: At 9 weeks of age, rats (n = 40) were given an ovariectomy, eight of which were sham-operated to serve as a control group (S). We then divided OVX rats into four different intervention groups: diet with 5% soybean oil (C), and diet with 5% (L), 15% (M), and 20% (H) (w/w) experimental oil, containing 60% monounsaturated fatty acids (MUFAs) and with a polyunsaturated/saturated fatty acid (P/S) ratio of 5. Results: After OVX, compared to the S group, the C group showed significantly higher body weight, and insulin and leptin levels. Compared to the C group, the H group had lower hepatic triglyceride level and FAS enzyme activity, and higher hepatic ACO and CPT-1 gene expressions and enzyme activities. Conclusions: An OVX leads to severe weight gain and lipid metabolism abnormalities, while according to previous studies, high fat diet may worsen the situation. However, during our experiment, we discovered that the experimental oil mixture with 60% MUFAs and P/S = 5 may ameliorate these imbalances.


2021 ◽  
Vol 30 (2) ◽  
pp. 205-212
Author(s):  
Erling Guo ◽  
Jin-Hwan Yoon ◽  
Wooyeon Jo ◽  
Jaeho Jin ◽  
Sang Ki Lee

PURPOSE: Perivascular adipose tissue (PVAT) is a type of adipose tissue that surrounds vessels to provide anti-contractile effects. This study aimed to investigate the effect of resistance training on NADPH oxidase, adiponectin, and endothelial NOS (eNOS) expression in the abdominal aorta and PVAT of ovariectomized rats.METHODS: Sprague-Dawley rats at 20 weeks of age were divided into three groups: sham control (Sham, n=10), OVX-control (OVX_ Con, n=10), and OVX-resistance exercise (OVX_Rex, n=10). Resistance training was performed by climbing a ladder for 12 weeks. Western blotting was used to analyze target protein expression in the rat abdominal aorta and PVAT.RESULTS: NADPH oxidase (p67phox) expression was significantly higher in the OVX_Con group than in the sham group, but it was significantly decreased in the OVX_Rex group. The expression of adiponectin, AKT, and eNOS in both abdominal aorta and PVAT was significantly reduced in the OVX_Con group than in the Sham group, but it was improved in the OVX_Rex group.CONCLUSIONS:The results suggest that regular resistance training inhibits p67phox and increases adiponectin expression and phosphorylation of AKT and eNOS in abdominal aortic PVAT of ovariectomized rats.


Author(s):  
Bani Adlina Shabrina ◽  
Nita Kristiani ◽  
Khairunisa Irnanda ◽  
Fajar Aji Lumakso ◽  
Riris Istighfari Jenie

Osteoporosis has become a major public health concern, due to its rising incidence every year. Osteoporosis mostly occurs in women at menopause, especially in Asia. Secang (Caesalpinia sappan L.) heartwood contains brazilin and brazilein which are known to suppress expression of NF-ĸB, an osteoclastogenesis protein playing an important role in osteoporosis.  Thus, the aim of this research is to investigate the inhibition of osteoporosis by ethanolic extract of secang (Caesalpinia sappan L.) (EES) in ovariectomized (OVX) rats. Thirty female Sprague Dawley rats were divided into five groups treated for 20 days:  group I were OVX and treated with 1000 mg/kgBW EES; group II were OVX and treated with 500 mg/kgBW EES; group III were OVX and treated with CMC-Na; group IV were shame OVX baseline; and group V were non-OVX-baseline. Bone density was examined by using X-Ray rontgen and was strengthen by qualitative data of Giemsa staining. Moreover, total number of osteoclasts in bone slide was observed by TRAP expression using double staining immunohistochemistry with hematoxylin eosin (HE) – TRAP. Treatment of 500 mg/kgBW EES in ovariectomized rats showed the highest bone density of 0.60 gr/cm3 and the lowest number of osteoclasts was 4.66 osteoclasts per field of view. These results showed that EES is potent to be developed as an antiosteoporosis agent. Further study on its dose adjustment and molecular mechanism needs to be conducted.Keywords: Caesalpinia sappan L., osteoporosis, RANK, bone density


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1114
Author(s):  
Chung-Hwan Chen ◽  
Tsung-Lin Cheng ◽  
Chi-Fen Chang ◽  
Hsuan-Ti Huang ◽  
Sung-Yen Lin ◽  
...  

Osteoarthritis (OA) and osteoporosis (OP) are common among older women, especially postmenopausal women. Glucosamine (GlcN) is a common medication for OA, but it may induce insulin resistance and β-cell dysfunction, especially if ovarian hormones are lacking. Raloxifene (RLX) is a selective estrogen receptor modulator and also an OP drug. Previously, we found that estrogen could improve GlcN-induced insulin resistance in ovariectomized (OVX) rats. Here, we further hypothesized that RLX, similarly to estrogen, can ameliorate GlcN-induced insulin resistance in OVX rats. We used GlcN to induce insulin resistance in OVX rats as a model for evaluating the protective effects of RLX in vivo. We used a pancreatic β-cell line, MIN-6, to study the mechanisms underlying the effect of RLX in GlcN-induced β-cell dysfunction in vitro. Increases in fasting plasma glucose, insulin, and homeostasis model assessments of insulin resistance in OVX Sprague Dawley rats treated with GlcN were reversed by RLX treatment (n = 8 in each group). Skeletal muscle GLUT-4 increased, liver PEPCK decreased, pancreatic islet hypertrophy, and β-cell apoptosis in OVX rats treated with GlcN was ameliorated by RLX. The negative effects of GlcN on insulin secretion and cell viability in MIN-6 cells were related to the upregulation of reticulum (ER) stress-associated proteins (C/EBP homologous protein, phospho-extracellular signal-regulated kinase, phospho-c-JunN-terminal kinase), the expression of which was reduced by RLX. Pretreatment with estrogen receptor antagonists reversed the protective effects of RLX. GlcN can induce insulin resistance, β-cell dysfunction, and apoptosis in OVX rats and increase ER stress-related proteins in β-cells, whereas RLX can reverse these adverse effects. The effects of RLX act mainly through estrogen receptor α; therefore, RLX may be a candidate drug for postmenopausal women with OA and OP.


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