scholarly journals Blackcurrant (Ribes nigrum) Extract Prevents Dyslipidemia and Hepatic Steatosis in Ovariectomized Rats

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1541
Author(s):  
Naoki Nanashima ◽  
Kayo Horie ◽  
Kanako Yamanouchi ◽  
Toshiko Tomisawa ◽  
Maiko Kitajima ◽  
...  

Estrogen is involved in lipid metabolism. Menopausal women with low estrogen secretion usually gain weight and develop steatosis associated with abnormal lipid metabolism. A previous study showed that blackcurrant (Ribes nigrum L.) extract (BCE) had phytoestrogen activity. In this study, we examined whether BCE improved lipid metabolism abnormalities and reduced liver steatosis in ovariectomized rats, as a menopausal animal model. Twelve-week-old ovariectomized (OVX) rats were fed a regular diet (Ctrl) or a 3% BCE supplemented diet while sham rats were fed a regular diet for three months. Body weight, visceral fat weight, levels of serum triglycerides, total cholesterol, and LDL cholesterol decreased in the BCE-treated OVX and sham rats, but not in OVX Ctrl rats. The results of hematoxylin and eosin staining revealed that BCE decreased the diameters of adipocytes and the nonalcoholic fatty liver disease activity score. Furthermore, quantitative RT-PCR indicated a decreased expression of hepatitis-related genes, such as tumor necrosis factor-α, IL-6, and IL-1β in OVX rats after BCE treatment. This is the first study that reported improvement of lipid metabolism abnormalities in OVX rats by BCE administration. These results suggest that the intake of BCE alleviated dyslipidemia and prevented nonalcoholic steatohepatitis during menopause in this animal model.

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 560
Author(s):  
Kayo Horie ◽  
Naoki Nanashima ◽  
Hayato Maeda ◽  
Toshiko Tomisawa ◽  
Indrawati Oey

Estrogen exerts cardioprotective effects in menopausal women. Phytoestrogens are plant-derived substances exhibiting estrogenic activity that could beneficially affect vascular health. We previously demonstrated that blackcurrant (Ribes nigrum L.) extract (BCE) treatment exerted beneficial effects on vascular health via phytoestrogenic activity in ovariectomized (OVX) rats, which are widely used as menopausal animal models. Here, we examined whether BCE treatment reduced elastin degradation and prevented pathological vascular remodeling in OVX rats fed a regular diet (OVX Control) or a 3% BCE-supplemented diet (OVX BCE), compared with sham surgery rats fed a regular diet (Sham) for 3 months. The results indicated a lower staining intensity of elastic fibers, greater elastin fragmentation, and higher α-smooth muscle actin protein expression in OVX Control rats than in OVX BCE and Sham rats. Pathological vascular remodeling was only observed in OVX Control rats. Additionally, we investigated matrix metalloproteinase (MMP)-12 mRNA expression levels to elucidate the mechanism underlying elastin degradation, revealing significantly upregulated MMP-12 mRNA expression in OVX Control rats compared with that in Sham and OVX BCE rats. Together, we identify BCE as exerting a vascular protective effect through reduced MMP-12 expression and vascular smooth muscle cell proliferation. To our knowledge, this is the first report indicating that BCE might protect against elastin degradation and pathological vascular remodeling during menopause.


2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Franciele Neves Moreno ◽  
Lilian Brites Campos-Shimada ◽  
Silvio Claudio da Costa ◽  
Rosângela Fernandes Garcia ◽  
Alessandra Lourenço Cecchini ◽  
...  

Vitex agnus-castus(VAC) is a plant that has recently been used to treat the symptoms of menopause, by its actions on the central nervous system. However, little is known about its actions on disturbances in lipid metabolism and nonalcoholic fat liver disease (NAFLD), frequently associated with menopause. Ovariectomized (OVX) rats exhibit increased adiposity and NAFLD 13 weeks after ovary removal and were used as animal models of estrogen deficiency. The rats were treated with crude extract (CE) and a butanolic fraction of VAC (ButF) and displayed the beneficial effects of a reduction in the adiposity index and a complete reversion of NAFLD. NAFLD reversion was accompanied by a general improvement in the liver redox status. The activities of some antioxidant enzymes were restored and the mitochondrial hydrogen peroxide production was significantly reduced in animals treated with CE and the ButF. It can be concluded that the CE and ButF fromVitex agnus-castuswere effective in preventing NAFLD and oxidative stress, which are frequent causes of abnormal liver functions in the postmenopausal period.


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.


2004 ◽  
Vol 279 (51) ◽  
pp. 52961-52969 ◽  
Author(s):  
Kazuhiko Namekata ◽  
Yasushi Enokido ◽  
Isao Ishii ◽  
Yasuo Nagai ◽  
Takayuki Harada ◽  
...  

Author(s):  
Hijrawati Ayu Wardani ◽  
Mahardian Rahmadi ◽  
Chrismawan Ardianto ◽  
Santhra Segaran Balan ◽  
Norshafarina Shari Kamaruddin ◽  
...  

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is indicated by liver steatosis without excessive alcohol use or other liver disease. Several studies have reported that metabolic syndromes such as obesity, type 2 diabetes mellitus, and dyslipidemia have a linear correlation associated with NAFLD pathophysiology. One of the characteristics of dyslipidemia in NAFLD is increase in serum triglycerides. This study aimed to develop a model of NAFLD characterized by an increase in serum triglyceride levels and histological profile of liver steatosis by high-fat diet in rats. Methods Twelve Wistar rats were fed with pellets enriched with 60% fat. They were housed individually, and the remaining pellets were weighted every day for intake evaluation. Blood samples were collected at day 0 and at the end of each trial period at days 7, 14, 21, and 28 for the measurement of triglyceride levels. Every animal from each group was also sacrificed for liver histopathological examination. Results This study has established developing the NAFLD animal model by induction of a high-fat diet. The levels of serum triglycerides were increased from baseline 80.41 ± 12.82 to 1152.00 ± 73.62, 493.66 ± 159.98, 556.00 ± 120.79, and 489.00 ± 156.75 mg/dL at days 7, 14, 21, and 28, respectively. Liver histology also showed liver steatosis development, inflammation, and hepatocellular ballooning, which were associated with the NAFLD state. Conclusions High-fat diet in rats induced hypertriglyceridemia along with NAFLD-like liver histopathology.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Blanca Martínez Soriano ◽  
Antonio Güemes ◽  
Guillermo Pola ◽  
Azucena Gonzalo ◽  
Pilar Palacios Gasós ◽  
...  

Introduction. The hepatic steatosis of the nonalcoholic origin or NAFLD is increasing at present, particularly in Western countries, parallel to the increase in obesity, constituting one of the most prevalent hepatic processes in the Western society. Melatonin has been successfully tested in experimental models in mice as a drug capable of reversing steatosis. The effect of melatonin on fat metabolism can be summarized as a decrease in lipid peroxidation and a decrease in oxidative stress, biochemical phenomena intimately related to fat deposition in the hepatocyte. There are hardly any studies in large animals. Objective. In this study, we investigate the effects of melatonin administered orally at a dose of 10 mg/kg/day to reverse established hepatic steatosis induced by a special diet in a porcine animal model. Materials and Methods. We analyze the parameters of oxidative stress: malondialdehyde (MDA), 4-hydroxyalkenals (4-HDA), and carbonyls, degree of fat infiltration (analyzed by direct vision by a pathologist and by means of a computer program of image treatment), and serological parameters of lipid metabolism and hepatic damage. These parameters were analyzed in animals to which hepatic steatosis was induced by means of dietary modifications. Results. We have not been able to demonstrate globally a beneficial effect of melatonin in the improvement or reversal of liver steatosis once established, induced by diet in a porcine animal model. However, we have found several signs of improvement at the histological level, at the level of lipid metabolism, and at the level of oxidative stress parameters. We have verified in our study that, in the histological analysis of the liver sample by means of the program image treatment (free of subjectivity) of the animals that continue with the diet, those that consume melatonin do not increase steatosis as much as those that do not consume it significantly (p=0.002). Regarding the parameters of oxidative stress, MDA modifies in a significant manner within the group of animals that continue with the diet and take melatonin (p=0.004). As for lipid metabolism, animals that maintain the steatotic diet and take melatonin lower total and LDL cholesterol levels and increase HDL levels, although these results do not acquire statistical significance. Conclusions. In this study, it has not been possible to demonstrate a beneficial effect of melatonin in the improvement or reversal of liver steatosis once established and induced by diet in the porcine model. It is true that signs of improvement have been found at the histological level, at the level of lipid metabolism, and at the level of oxidative stress phenomena, when comparing animals with established steatosis that are treated with melatonin with those who do not take it. This work is the first study conducted in a large animal model in which the effect of melatonin is studied as a treatment in the reversal of established hepatic steatosis.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Bin Cheng ◽  
Ai-Zhen Zhou ◽  
Wen Ge ◽  
Xiao-Min Yao ◽  
Juan Wang

Huo-Xue-Qu-Yu formula (HXQYF) is a prescription consisting of Ginkgo biloba leaf and Paeonia lactiflora Pall. for treating hyperlipidemia and NAFLD in China. Here, we investigated the hepatic and renal function, oxidative stress and lipid metabolism, and potential mechanisms of HXQYF on nonalcoholic fatty liver disease (NAFLD) rat models. NAFLD rat models were induced with high-fat diet (HFD) and 10% fructose water for 18 weeks and orally administered with or without HXQYF simultaneously. The results showed that HXQYF (22.5, 45, 90 mg/kg) significantly improved blood lipid levels via reducing serum TC, TG, LDL-C, and APOB values and elevating HDL-C and APOA1 levels in NAFLD rats. The higher levels of ALT, AST, CR, and BUN in serum induced by HFD were reduced by HXQYF. HE staining showed that HXQYF (90 mg/kg) reduced the accumulation of fat droplets and alleviated inflammatory response in liver cells. Three doses of HXQYF exhibited notable antioxidant effects by elevating SOD, GSH, and CAT activities and decreasing MDA and OH-1 levels in the liver. Furthermore, abnormal lipid metabolism caused by HFD was alleviated by HXQYF, which was associated with the upregulation of PPAR-α, AdipoR2, and CPT1 mRNAs as well as the downregulation of CYP2E1 and SREBP-1c mRNAs in liver tissue. In conclusion, our work verified that HXQYF could reduce the degree of hepatic steatosis, suppress oxidative stress, and attenuate lipid metabolism, thus preventing NAFLD.


2020 ◽  
Vol 245 (3) ◽  
pp. 411-423 ◽  
Author(s):  
Ya Liu ◽  
Xiaoqing Zhou ◽  
Ye Xiao ◽  
Changjun Li ◽  
Yan Huang ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disease worldwide, is characterized by liver steatosis and is often accompanied with other pathological features such as insulin resistance. However, the underlying mechanisms are not fully understood, and specific pharmacological agents need to be developed. Here, we investigated the role of microRNA-188 (miR-188) as a negative regulator in hepatic glucose and lipid metabolism. miR-188 was upregulated in the liver of obese mice. Loss of miR-188 alleviated diet-induced hepatosteatosis and insulin resistance. In contrast, liver-specific overexpression of miR-188 aggravated hepatic steatosis and insulin resistance during high-fat diet feeding. Mechanistically, we found that the negative effects of miR-188 on lipid and glucose metabolism were mediated by the autophagy pathway via targeting autophagy-related gene 12 (Atg12). Furthermore, suppressing miR-188 in the liver of obese mice improved liver steatosis and insulin resistance. Taken together, our findings reveal a new regulatory role of miR-188 in glucose and lipid metabolism through the autophagy pathway, and provide a therapeutic insight for NAFLD.


2021 ◽  
pp. 1-8
Author(s):  
Elke Roeb

<b><i>Background:</i></b> Nonalcoholic fatty liver disease (NAFLD) describes a continuum of liver abnormalities from simple nonalcoholic fatty liver (NAFL) to nonalcoholic fatty liver hepatitis or steatohepatitis (NASH) to NASH fibrosis. It has a variable course, but just like alcoholic fatty liver disease, it can lead to liver cirrhosis and cancer (hepatocellular carcinoma). <b><i>Summary:</i></b> NAFLD is a clinical entity characterized by the presence of liver steatosis, which affects at least 5% of hepatocytes. Affected are people who consume little or no alcohol and who have no secondary cause of liver steatosis such as viral hepatitis, drug intake (e.g., tamoxifen, amiodarone, methotrexate, etc.), or lipodystrophy. NAFLD is, nowadays, the most common liver disease in Europe, with an estimated prevalence of 25%. The currently widely recognized recommendation for the therapy of NAFLD is a lifestyle modification with the goal of weight loss. Although no drugs are currently approved for the treatment of NAFLD, several candidates are in clinical trials. Besides weight loss and physical activity, corresponding single active ingredients or combination therapies are intended to stop the progression of the disease and, in the best case, reverse it. The newly propagated name MAFLD (metabolic-associated fatty liver disease) should indicate that the disease is associated with metabolic disorders. The term MAFLD also implies multiple overlapping causes and drivers of this soaring disease. <b><i>Key Messages:</i></b> The prevalence of NAFLD continues to rise worldwide. NAFLD, NASH, and fibrosis in NAFLD occur predominantly in patients with obesity and type 2 diabetes (T2DM) or else precede these conditions. The progression of NAFLD is highly dependent on changes in glucose, lipid metabolism, and fibrogenesis. A new definition and nomenclature of fatty liver disease, “metabolic associated fatty liver disease” (MAFLD), should be discussed carefully, since around 40% of the global population with NAFLD are classified as non-obese and almost 1/5 as lean. Since the pathogenesis of fatty liver disease, obesity, and glucose and lipid metabolism diseases are very closely related, it is important to continue to look for mechanisms that these diseases have in common and develop new therapeutic approaches.


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