The model of rat lipid metabolism disorder induced by chronic stress accompanying high-fat-diet

<p>Abstract Objective</p> <p>To develop an animal model of Lipid Metabolism Disorder, which conforms to human clinical characteristic. Methods: There were 24 male Wistar rats that were randomly divided into 3 groups with 8 rats in each. They were group A (normal diet), group B (high-fat-diet), group C (chronic stress+ high-fat-diet). Group A was fed with normal diet, while group B and C were fed with high-fat-diet, going on for 55 days. From the 35th day, group B and C received one time of daily chronic stress, going on for 21 days. After that, the activities of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the levels of the serum triglyceride (TG), Cholesterol (Ch), high-density lipoprotein-Cholesterol (HDL-C) and liver TG were evaluated. Results: Compared with group A, the activities of the serum ALT and AST, and the levels of the serum CH, TG, HDL-C and liver TG were found to be markedly increased, when the level of HDL-C was markedly decreased in group B and C, and the results of group C was more obviously. Conclusion: Chronic stress and high-fat-diet have the synergistic action in rat's Lipid Metabolism Disorder. They lead to a model of Lipid Metabolism Disorder, which conforms to human clinical characteristic much better.</p

Research of influence and mechanism of combining exercise with diet control on a model of lipid metabolism rat induced by high fat diet

OBJECTIVE: To investigate the influence and mechanism of combining exercise with diet control on a model of lipid metabolism rat induced by high fat diet. METHODS: Twenty-four male Wistar rats were randomly divided into 3 groups of 8: normal, model and intervention. The model group and intervention group were fed with high fat diet, while the normal group received basal feed. From day 1, the intervention group was randomly given interventions such as swimming exercise and dietary restriction. The interventions duration were 28 days. At the end of the experiment, the levels of rats’ body weight and liver weight were detected, the serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and hepatic triglyceride content (TG) were detected by using biochemical assay, serum level of gastrin (GAS), motilin (MTL) were assayed by the enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the level of body weight and liver weight in the normal rats, body weight and liver weight in the rat of the model group were significantly increase (P<0.05 or P<0.01). Plasma concentrations of TC, LDL-C and hepatic TG in the model group were significantly increased compared with those in the normal group (P<0.05 or P<0.01). The contents of GAS, MTL, HDL-C in the model rats’plasma were significantly reduced compared with those of the normal group (P<0.05 or P<0.01). Compared with those in the model group, rats’ body weight, liver weight, serum TC, LDL-C, and TG content of liver in the intervention group decreased significantly (P<0.05 or P<0.01). Meanwhile, serum content of GAS, MTL, HDL-C were significantly improved in the intervention rats compared to the model group. CONCLUSION: The action of combining exercise with diet control for lipid metabolism disorder might be related to regulation of GAS, MTL and other gastrointestinal hormones

Global acetylome profiling indicates EPA impedes but OA promotes prostate cancer motility through altered acetylation of PFN1 and FLNA.

Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in men. Metastasis is the main cause of PCa-associated death. Recent evidence indicated a significant reduction in PCa mortality associated with higher ω-3 polyunsaturated fatty acids (PUFAs) consumption. However, the underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study the effect of fatty acids treatment. Results indicated that oleic acid (OA, monounsaturated fatty acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic acid, 100 µM) reduces the acetyl-CoA level, which alters the global acetylome. After treatment, two crucial cell motility regulators, PFN1 and FLNA, were found with altered acetylation levels. OA increased the acetylation of PFN1 and FLNA, whereas EPA decreased PFN1 acetylation level. Furthermore, OA promotes while EPA inhibits PCa migration and invasion. Immunofluorescence assay indicated that EPA impedes the formation of lamellipodia or filopodia through reduced localization of PFN1 and FLNA to the leading edge of cells. Therefore, perturbed acetylome may be one critical step in fatty acid-affected cancer cell motility. This study provides some new insights into the response of ω-3 PUFAs treatment and a better understanding of cancer cell migration and invasion modulation

Sarcopenia-related Traits, Body Mass Index and Ovarian Cancer Risk: Investigation of Causal Relationships Through Multivariable Mendelian Randomization Analyses

Objective: This study was aimed at exploring the causal relationships of four sarcopenia-related traits (appendicular lean mass, usual walking pace, right hand grip strength, and levels of moderate to vigorous physical activity) with body mass index (BMI) and ovarian cancer risk, by using univariable and multivariable Mendelian randomization (MR) methods. Materials and Methods: Univariable and multivariable MR was performed to estimate causal relationships among sarcopenia-related traits, BMI, and ovarian cancer risk, in aggregated genome-wide association study (GWAS) data from the UK Biobank. Genetic variants associated with each variable (P < 5 × 10−8) were identified as instrumental variables. Three methods—inverse variance weighted (IVW) analysis, weighted median analysis, and MR-Egger regression—were used. Results: Univariable MR analyses revealed positive causal effects of high appendicular lean mass (P = 0.02) and high BMI (P = 0.001) on ovarian cancer occurrence. In contrast, a genetically predicted faster usual walking pace was associated with lower risk of ovarian cancer (P = 0.03). No evidence was found supporting roles of right hand grip strength and levels of moderate to vigorous physical activity in ovarian cancer development (P = 0.56 and P = 0.22, respectively). In multivariable MR analyses, the association between a genetically predicted faster usual walking pace and lower ovarian cancer risk remained significant (P = 0.047). Conclusions: Our study highlights a role of slower usual walking pace in the development of ovarian cancer. Further studies are required to validate our findings and understand the underlying mechanisms

A comprehensive analysis of filamentous phage display vectors for cytoplasmic proteins: an analysis with different fluorescent proteins

Filamentous phage display has been extensively used to select proteins with binding properties of specific interest. Although many different display platforms using filamentous phage have been described, no comprehensive comparison of their abilities to display similar proteins has been conducted. This is particularly important for the display of cytoplasmic proteins, which are often poorly displayed with standard filamentous phage vectors. In this article, we have analyzed the ability of filamentous phage to display a stable form of green fluorescent protein and modified variants in nine different display vectors, a number of which have been previously proposed as being suitable for cytoplasmic protein display. Correct folding and display were assessed by phagemid particle fluorescence, and with anti-GFP antibodies. The poor correlation between phagemid particle fluorescence and recognition of GFP by antibodies, indicates that proteins may fold correctly without being accessible for display. The best vector used a twin arginine transporter leader to transport the displayed protein to the periplasm, and a coil-coil arrangement to link the displayed protein to g3p. This vector was able to display less robust forms of GFP, including ones with inserted epitopes, as well as fluorescent proteins of the Azami green series. It was also functional in mock selection experiments

SecA, a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data

Targeting and translocation of the two lipoproteins in Escherichia coli via the SRP/Sec/YidC pathway.

In Escherichia coli, two main protein targeting pathways to the inner membrane exist: the SecB pathway for the essentially posttranslational targeting of secretory proteins and the SRP pathway for cotranslational targeting of inner membrane proteins (IMPs). At the inner membrane both pathways converge at the Sec translocase, which is capable of both linear transport into the periplasm and lateral transport into the lipid bilayer. The Sec-associated YidC appears to assist the lateral transport of IMPs from the Sec translocase into the lipid bilayer. It should be noted that targeting and translocation of only a handful of secretory proteins and IMPs have been studied. These model proteins do not include lipoproteins. Here, we have studied the targeting and translocation of two secretory lipoproteins, the murein lipoprotein and the bacteriocin release protein, using a combined in vivo and in vitro approach. The data indicate that both murein lipoprotein and bacteriocin release protein require the SRP pathway for efficient targeting to the Sec translocase. Furthermore, we show that YidC plays an important role in the targeting/translocation of both lipoproteins