scholarly journals The PCSK9 Involves in the Dyslipidemia of Ovariectomized Mice and Its Mechanism

Author(s):  
Dan Zhao ◽  
Xue-qin Zhang ◽  
Wen-jing Guo ◽  
Zhi-hui Cui ◽  
Yi-cheng Wang ◽  
...  

Abstract Ovarian failure in postmenopausal female leads E2 to dramatic decrease which is an important reason of menopausal dyslipidemia. PCSK9 as a secretory lipid metabolic regulator plays a critical role in the cholesterol metabolism by negatively regulating LDLR in hepatocytes. Clinical data showed PCSK9 was elevated and positively correlated with LDL-C in the blood of postmenopausal women. However, the relationship between E2 and PCSK9 and the role of PCSK9 in postmenopausal dyslipidemia are still unclear. In this research, 10-week-old ovariectomized mice were fed for 4 weeks with normal diet or high-fat diet, then tested the lipid metabolism profiles and PCSK9 in the blood and the expression of LDLR and PCSK9 in the liver. On this basis, PCSK9-/- ovariectomized mice were used to further verify the effect of PCSK9 in dyslipidemia of ovariectomized mice. Finally, the ovariectomized mice with high-fat diet were subcutaneous injected respectively with E2 or PCSK9 inhibitor alone or both together for 2 weeks and were tested as previous experiment. The results showed PCSK9, TC and LDL-c all increased in the blood of in WT ovariectomized mice and their PCSK9 is positively correlated with LDL-c, while there were on obvious lipid metabolism disorder in the PCSK9−/− ovariectomized mice. PCSK9 inhibitor increased the LDLR on the liver and ameliorated the dyslipidemia in WT ovariectomized mice. It suggests that PCSK9 plays an important role in the dyslipidemia of ovariectomized mice, which provides a new strategy for clinical diagnosis and treatment of the dyslipidemia in post-menopause.

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Lanlan Fan ◽  
Xiaosheng Qu ◽  
Tao Yi ◽  
Yong Peng ◽  
Manjing Jiang ◽  
...  

The flavonoid dihydromyricetin (DMY) is the main component of Ampelopsis grossedentata (Hand-Mazz) W. T. Wang (AG), a daily beverage and folk medicine used in Southern China to treat jaundice hepatitis, cold fever, and sore throat. Recently, DMY and AG were shown to have a beneficial effect on lipid metabolism disorder. However, the mechanisms of how DMY and AG protect the liver during lipid metabolism disorder remain unclear. In this study, we first analyzed the chemical compounds of AG by HPLC-DAD-ESI-IT-TOF-MSn. Of the 31 compounds detected, 29 were identified based on previous results. Then, the effects of DMY and AG on high-fat diet hamster livers were studied and the metabolite levels and metabolic pathway activity of the liver were explored by 1H NMR metabolomics. Compared to the high-fat diet group, supplementation of AG and DMY attenuated the high-fat-induced increase in body weight, liver lipid deposition, serum triglycerides and total cholesterol levels, and normalized endogenous metabolite concentrations. PCA and PLS-DA score plots demonstrated that while the metabolic profiles of hamsters fed a high-fat diet supplemented with DMY or AG were both far from those of hamsters fed a normal diet or a high-fat diet alone, they were similar to each other. Our data suggest that the underlying mechanism of the protective effect of DMY and AG might be related to an attenuation of the deleterious effect of high-fat diet-induced hyperlipidemia on multiple metabolic pathways including amino acid metabolism, ketone body metabolism, energy metabolism, tricarboxylic acid cycle, and enhanced fatty acid oxidation.


2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Lin-Lin Xie ◽  
Yu-Li Zhao ◽  
Jian Yang ◽  
Hui Cheng ◽  
Zhen-Dong Zhong ◽  
...  

The effects of acupuncture on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models. However, the potential for acupuncture to mediate protective effects on obese-induced OA has not been examined. Here, we investigated the effects of different acupuncture patterns on OA pathogenesis in high-fat diet- (HFD-) induced obese rats. After 12-week diet-induced obesity, obese rats were treated with three acupuncture protocols for 2 weeks, including ST36, GB34, and ST36+GB34. The results showed that the three acupuncture protocols both prevented obesity-induced cartilage matrix degradation and MMP expression and mitigated obesity-induced systemic and local inflammation but had different regulatory effects on lipid metabolism and gut microbiota disorder of obese-induced OA rats. Furthermore, the three acupuncture protocols increased the microbial diversity and altered the structure of community of feces in obese rats. We found that ST36 and GB34 could inhibit proinflammatory shift in the gut microbiome with an increase in the ratio of Bacteroidetes/Firmicutes and promote the recovery of relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus. Although both ST36 and GB34 had an anti-inflammatory effect on serum inflammatory mediators, only the acupuncture protocol with both ST36 and GB34 could effectively inhibit LPS-mediated joint inflammation in obesity rats. Therefore, relieving obesity-related chronic inflammation, lipid metabolism disorder, and gut microbiota disorder may be an important mechanism for acupuncture with ST36 and GB34 to promote OA recovery.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zhang ◽  
Pan Ren ◽  
Qunfu Kang ◽  
Weihong Liu ◽  
Sinai Li ◽  
...  

Lipid metabolism dysregulation plays a crucial role in the occurrence of atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM) for treating angina pectoris, has antiatherosclerotic effects and ameliorates blood lipids disturbance. However, its precise mechanism remains unclear. This study investigated the mechanism of TMP in ameliorating As in mice model. After six weeks of high-fat diet, 30 ApoE−/−mice were randomized (n=10) and treated with Lipitor, TMP, or distilled water for six weeks. The serum blood lipids and insulin levels were measured. The expressions of PAQR3, Insig-1, SCAP, SREBP-1c, IRS-1, PI3K, Akt, and mTORC-1 in the adipose tissues were determined. The results showed that TMP could significantly decrease blood lipids levels, insulin, and corrected plaque area of the ApoE−/−mice as compared to the untreated mice (P<0.05,P<0.01). Moreover, TMP could significantly downregulate the expressions of SCAP, SREBP-1c, PAQR3, IRS-1, PI3K, Akt, and mTORC1 (P<0.01). Thus, TMP may ameliorate lipid metabolism disorder and As by downregulating PAQR3 and inhibiting SCAP/SREBP-1c signaling pathway. In addition, PI3K/Akt/mTORC1 signaling pathway may be involved in this process.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Shanshan Ding ◽  
Jie Kang ◽  
Ling Tong ◽  
Yuchen Lin ◽  
Linghong Liao ◽  
...  

Lipid metabolism disorder is a common metabolic disorder characterized by abnormal lipid levels in blood. Erchen decoction (ECD) is a traditional Chinese medicine prescription, which is used for the treatment of diseases caused by retention of phlegm dampness. It has been reported to ameliorate the disorder of lipid metabolism. The aim of the present study was to investigate the effects and underlying mechanisms of ECD in lipid metabolism disorder induced by a high-fat diet (HFD) in rats. ECD (4.35g/kg/d) and atorvastatin (10mg/kg/d, positive control) were orally administered to HFD-fed rats for four weeks. The parameters, food, water consumption, body weight, body length, liver, and visceral fat weight and the content of serum lipids and lipid transporters were assessed. The effects of ECD on the mRNA and protein expression levels of lipid transport factors were measured by real-time PCR and western blotting. The present study demonstrated that ECD improved the disorders of serum lipid and lipid transporters in HFD-fed rats, TG (0.70±0.08 mmol/L, p<0.01), LDL-C (1.50±0.19 mmol/L, p<0.01), LDL (1.38±0.21 mmol/L, p<0.05), and oxLDL (1.77±0.39 ng/mL, p<0.05) were downregulated, while HDL-C (0.87±0.13 mmol/L, p<0.01), FFA (0.62±0.13 mmol/L, p<0.05), HDL (38.8±4.0 mg/dL, p<0.05), and CETP (903.6±120.0 ng/mL, p<0.05) were upregulated. But ECD obviously had no effects on the indices food/water/energy intake, body/tissue (liver and fat) weight, and BMI (p>0.05). Concomitantly, ECD reversed the abnormal expressions of those lipid transport factors in the liver and visceral fat.


2020 ◽  
Author(s):  
Man-jing Jiang ◽  
Shuai Huang ◽  
Li Li ◽  
Wan-fang Huang ◽  
Xiao-Sheng Qu ◽  
...  

Abstract Background: Rubus suavissimus S. Lee (RS), a sweet plant distributed in southwest of China and used as beverage and folk medicine, has been reported to improve the obesity phenotype and hyperlipidemia. However, the exact molecular mechanism remains unknown.Aim of the study: In this study, we aimed to investigate the preventive effects of RS in lipid metabolism disorder golden hamsters caused by high-fat diet and elucidate the potential molecular mechanisms.Method: Five groups of male LVG Syrian golden hamsters were compared: normal diet group (ND), high-fat diet group (HFD), Xuezhikang Cap group (140 mg/kg; HFD+XZK), low dose of RS group (3.6 g/kg; HFD+RSL), high dose of RS group (7.2 g/kg; HFD+RSH). After eight weeks, biochemical and pathological analyses were conducted to evaluate the preventive effect of RS on lipid metabolism. RT-qPCR, and western blotting analysis were used to explore the potential mechanism underlying.Results: Supplementation of a high-fat diet with RS prevented the symptoms of lipid metabolism disorder of golden hamsters and alleviated liver injury. RS upregulated the expression of the PPAR pathway mediators PPARγ and PPARα as well as its downstream targets CCAAT/enhancer binding protein α (C/EBPα), glucose transporter 4 (Glut4), lipoprotein lipase (LPL), and fatty acid binding protein 4 (aP2). Also, RS downregulated the expression of sterol regulatory element binding protein 1 (SREBP1) and its downstream targets acetyl-CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase-1 (SCD1), and fatty acid synthase (FAS).Conclusions: Our data suggest that RS prevents lipid metabolism disorder golden hamsters in high-fat diet and alleviates liver injury through the regulation of the SREBP/PPAR signaling pathway.


2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Jing Xiao

Objective C57 mice were fed with high-fat diet. After the pathological features were detected, a group of C57 high-fat diet mice were randomly selected for eight weeks aerobic and anti-resistance exercise. To observe the effect of exercise on liver glucose and lipid metabolism in mice fed with high fat. To explore the effect of exercise on liver glucose and lipid metabolism disorder caused by high fat feeding, to provide the direction and evidence for the treatment and rehabilitation of fatty liver and other diseases caused by high fat diet. C57 mice were fed with high-fat diet. After the pathological features were detected, a group of C57 high-fat diet mice were randomly selected for eight weeks aerobic and anti-resistance exercise. To observe the effect of exercise on liver glucose and lipid metabolism in mice fed with high fat. To explore the effect of exercise on liver glucose and lipid metabolism disorder caused by high fat feeding, to provide the direction and evidence for the treatment and rehabilitation of fatty liver and other diseases caused by high fat diet. Methods 30 male C57 mice were 8 weeks old, with an average weight of 20.02 ±0.06 g. The purchased mice were randomly divided into C57 diet group (n = 10) and high-fat diet group (n = 20). A pathological model of hepatic glycolipid metabolism disorder was established by high-fat feed feeding. The success of the model was measured by calculating the area under the blood glucose curve. After modeling, the C57 mice were randomly divided into high fat group and high fat exercise group, with 10 mice in each group. The mice in high fat exercise group were trained 6 days a week for 8 weeks. At the end of the exercise, the three groups were uniformly selected. Results 1. Compared with the normal diet quiet group, there was a significant difference in the area under the blood glucose curve in the high-fat diet quiet group (p < 0. 01). Compared with the quiet high-fat diet group, there was a significant difference in the area under the blood glucose curve after intraperitoneal injection of glucose in the high-fat diet exercise group (p < 0. 05). After two weeks of high fat diet feeding, the body weight of the quiet group was significantly higher than that of the quiet group fed with normal diet (p < 0.05). After two weeks exercise training of high-fat mice, the body weight of high-fat exercise group was significantly lower than that of quiet high-fat mice (p < 0.05). Compared with the normal diet group, the liver weight and liver weight of the high-fat quiet group increased (p < 0 01), while the liver weight and liver / body weight of the high-fat exercise group were lower than those of the high-fat quiet group (p < 0 05). The liver AST (aspartate amino transferase) and ALT(Alanine transferase) in the High-fat diet quiet group were significantly higher than those in the normal diet quiet group (p < 0. 01). The ALT (alanine transferase) in high-fat diet exercise group was lower than that in quiet high-fat diet group (p < 0.05). Conclusions 16-week high-fat diet can establish a pathological model of hepatic glycolipid metabolism disorder. Hyper-insulinemia, hyper-lipidemia and other pathological phenomena will occur in mice. 8 weeks aerobic combined with anti-exercise intervention can improve hepatic glycolipid metabolism disorder and liver function.


2011 ◽  
Vol 10 (1) ◽  
pp. 153 ◽  
Author(s):  
Lin Manting ◽  
Zhou Haihong ◽  
Li Jing ◽  
Chen Shaodong ◽  
Liu Yihua

2019 ◽  
Author(s):  
Caiqing Yao ◽  
Wenjing Tian ◽  
Jiaojiao Song ◽  
Junguo Wang

Abstract Background: Previous studies have shown that Lactobacillus plantarum LIP-1 has obvious hypolipidemic effect, and microencapsulated probiotics can ensure the strains live through the gastrointestinal tract, although there has been much research on both preparation and assessment methods for probiotics microcapsules, most assessments are made in vitro and few are validated in vivo. In this study, the protective effect of microencapsulation and the possible hypolipidaemic mechanisms of probiotic Lactobacillus plantarum LIP-1 (hereafter LIP-1) were evaluated in rats. Methods: Treatments included rats fed on: normal diet, high-fat diet, high-fat diet with an intragastric supplement of either non-microencapsulated LIP-1 cells (NME LIP-1) or microencapsulated LIP-1 (ME LIP-1). Lipid metabolism indicators were measured during the experiment and following euthanasia. Results: Microencapsulation increased survival and colonization of LIP-1 in the colon. ME LIP-1 was superior to NME LIP-1 in reducing cholesterol. The mechanisms behind the hypolipidemic effect exerted by LIP-1 are possibly due to: promoting the excretion of cholesterol, improving antioxygenic potentials, enhancing recovery from the injury in the liver and intestinal mucosa, promoting the generation of SCFAs, and improving lipid metabolism. Conclusions: This study confirms the role of ME LIP-1 in the prevention and cure of hyperlipidemia and provides theoretical support for the probiotics to enter clinical use. Keywords: Microencapsulated LIP-1; non-microencapsulated LIP-1 cells; hypolipidaemic effect; lipid metabolism; antioxidative activity


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