Perfluorooctanoic acid-induced lipid metabolism disorder in SD rat liver and its effect on the expression of fatty acid metabolism-related proteins / 中南大学学报(医学版)

OBJECTIVES@#Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR.@*METHODS@#A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH2O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting.@*RESULTS@#After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05).@*CONCLUSIONS@#PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.

Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Sensação subjetiva do zumbido pré e pós intervenção nutricional em alterações metabólicas / Tinnitus sensation pre and post nutritional intervention in metabolic disorders

BACKGROUND: different etiologies are related to tinnitus including metabolic disorders (blood glucose and lipids). AIM: the aim of this study was compare tinnitus severity by self-report measures pre and post nutritional intervention, using the Tinnitus Handicap Inventory. METHOD: participants of this study were twenty one male and female subjects, with ages ranging from 40 to 82 years. Inclusion criteria involved the presence of tinnitus and metabolic disorder diagnosed by laboratory exams. All subjects were submitted to a nutritional intervention program. Audiological evaluation and the Tinnitus Handicap Inventory were applied pre and post intervention. RESULTS: when comparing the presence of tinnitus pre and post intervention, data analysis indicates statistical difference concerning tinnitus sensation - 71.5 percent of the individuals referred less impact of tinnitus in daily activities. CONCLUSION: an important difference was observed concerning tinnitus influence in subject's life by self-report measures. A direct relation between tinnitus and metabolic disorders in cases related with this symptom was verified.

TEMA: diferentes etiologias estão relacionadas com a presença de zumbido, incluindo doenças metabólicas (glicêmicas e lipídicas). OBJETIVO: comparar o grau de severidade do zumbido por meio de medidas de auto-análise em sujeitos com alterações metabólicas pré e pós-intervenção nutricional, utilizando o Questionário de Gravidade do Zumbido. MÉTODO: vinte e um sujeitos, homens e mulheres, com idade entre 40 e 82 anos, participaram deste estudo. Critérios de inclusão abrangeram a presença de zumbido e de alteração metabólica diagnosticada por meio de exames laboratoriais. Todos os sujeitos foram submetidos a um programa de intervenção nutricional. A avaliação audiológia e o questionário de gravidade de zumbido foram aplicados pré e pós-intervenção. RESULTADOS: comparando os resultados pré e pós-intervenção os dados mostram uma diferença estatisticamente significante com relação à sensação do zumbido em 71,5 por cento dos sujeitos, os quais referiram menor impacto do zumbido nas atividades diárias. CONCLUSÃO: uma importante diferença foi observada com relação à influência do zumbido na vida do sujeito quando utilizadas as medidas de auto-análise. Verificou-se uma relação direta entre zumbido e alterações metabólicas em casos relacionados a estes sintomas.