GILSON MASAHIRO MURATA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
10 resultados
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- Endoplasmic Reticulum Stress and Autophagy Markers in Soleus Muscle Disuse-Induced Atrophy of Rats Treated with Fish Oil(2021) MARZUCA-NASSR, Gabriel Nasri; KUWABARA, Wilson Mitsuo Tatagiba; VITZEL, Kaio Fernando; MURATA, Gilson Masahiro; TORRES, Rosangela Pavan; MANCINI-FILHO, Jorge; ALBA-LOUREIRO, Tatiana Carolina; CURI, RuiEndoplasmic reticulum stress (ERS) and autophagy pathways are implicated in disuse muscle atrophy. The effects of high eicosapentaenoic (EPA) or high docosahexaenoic (DHA) fish oils on soleus muscle ERS and autophagy markers were investigated in a rat hindlimb suspension (HS) atrophy model. Adult Wistar male rats received daily by gavage supplementation (0.3 mL per 100 g b.w.) of mineral oil or high EPA or high DHA fish oils (FOs) for two weeks. Afterward, the rats were subjected to HS and the respective treatments concomitantly for an additional two-week period. After four weeks, we evaluated ERS and autophagy markers in the soleus muscle. Results were analyzed using two-way analysis of variance (ANOVA) and Bonferroni post hoc test. Gastrocnemius muscle omega-6/omega-3 fatty acids (FAs) ratio was decreased by both FOs indicating the tissue incorporation of omega-3 fatty acids. HS altered (p < 0.05) the protein content (decreasing total p38 and BiP and increasing p-JNK2/total JNK2 ratio, and caspase 3) and gene expressions (decreasing BiP and increasing IRE1 and PERK) of ERS and autophagy (decreasing Beclin and increasing LC3 and ATG14) markers in soleus. Both FOs attenuated (p < 0.05) the increase in PERK and ATG14 expressions induced by HS. Thus, both FOs could potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy.
- Dexamethasone programs lower fatty acid absorption and reduced PPAR-gamma and fat/CD36 expression in the jejunum of the adult rat offspring(2021) SOUZA, Dailson Nogueira de; TEIXEIRA, Caio Jordao; VERONESI, Vanessa Barbosa; MURATA, Gilson Masahiro; SANTOS-SILVA, Junia Carolina; HECHT, Fernanda Ballerini; VICENTE, Julia Modesto; BORDIN, Silvana; ANHE, Gabriel ForatoThe progeny of rats born and breastfed by mothers receiving dexamethasone (DEX) during pregnancy exhibits permanent reduction in body weight and adiposity but the precise mechanisms related to this programming are not fully understood. In order to clarify this issue, the present study investigated key aspects of lipoprotein production and lipid metabolism by the liver and the intestine that would explain the reduced adiposity seen in the adult offspring exposed to DEX in utero. Female Wistar rats were treated with DEX (0.1 mg/kg/day) between the 15th and the 21st days of pregnancy, while control mothers were treated with vehicle. Male offspring born to control mothers were nursed by either adoptive control mothers (CTL/CTL) or DEX-treated mothers (CTL/DEX). Male offspring born to DEX-treated mothers were nursed by either control mothers (DEX/CTL) or adoptive DEX-treated mothers (DEX/DEX). We found that only the male DEX/DEX offspring had reduced adiposity. Additionally, male DEX/DEX progeny had lower circulating triacylglycerol (TAG) levels only in fed-state. The four groups of offspring presented similar energy expenditure, respiratory quotient and very low-density lipoprotein (VLDL) production. On the other hand, DEX/DEX rats displayed reduced TAG levels after gavage with olive oil and reduced expression of fatty acid translocase Cd36 (Fat/Cd36) and peroxisome proliferator-activated receptor gamma (Pparg) in the jejunum. Altogether, our study supports the notion that reduced fat absorption by the jejunum may contribute to the lower adiposity of the adult offspring born and breastfed by mothers treated with DEX during pregnancy.
- Recreational Dance Practice Modulates Lymphocyte Profile and Function in Diabetic Women(2021) PASSOS, Maria Elizabeth Pereira; BORGES, Leandro; SANTOS-OLIVEIRA, Laiane Cristina dos; ALECRIM-ZEZA, Amanda Lins; LOBATO, Tiago Bertola; OLIVEIRA, Heloisa Helena de; SANTOS, Cesar Miguel Momesso; DINIZ, Vinicius Leonardo Sousa; ISER-BEM, Patricia Nancy; MANOEL, Richelieau; MURATA, Gilson Masahiro; HIRABARA, Sandro Massao; CURI, Rui; PITHON-CURI, Tania Cristina; HATANAKA, Elaine; GORJAO, RenataThis study aimed to investigate the impact of a 16-week dance-based aerobic exercise program on lymphocyte function in healthy and type 2 diabetes mellitus (T2DM) women. We enrolled 23 women: 11 with T2DM and 12 non-diabetic controls. Initially, we performed anthropometry and body composition measurements, afterwards, plasma levels of C-reactive protein, lipids, and glucose were determined. We used flow cytometry to measure the CD25 and CD28 expression in circulating lymphocytes, T-regulatory (Treg) cell percentage, lymphocyte proliferation, and cytokines released by cultured lymphocytes. The T2DM group had a lower proportion of CD28+ cells and a higher percentage of Treg lymphocytes and proliferative capacity at the baseline compared with the control group. After 16 weeks of the program, differences in lymphocytes between the T2DM and the control groups disappeared. The dance program promoted IL-10 increase in both groups. We found decreased IL-4, IL-2, and IL-6 secretion in lymphocytes from the control group and increased IL-17 secretion and IL-10/IL-17 ratio in the T2DM group after the program. The program promoted marked changes in lymphocytes in diabetic women, leading to a balance between the different profiles.
- A novel supplement with yeast 6-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice(2021) NEHMI, Victor Abou; MURATA, Gilson Masahiro; MORAES, Ruan Carlos Macedo de; LIMA, Gabriely Cristina Alves; MIRANDA, Danielle Araujo De; RADLOFF, Katrin; COSTA, Raquel Galvao Figueredo; JESUS, Joyce de Cassia Rosa de; FREITAS, Jessica Alves De; VIANA, Nayara Izabel; PIMENTA, Ruan; LEITE, Katia Ramos Moreira; OTOCH, Jose Pinhata; PESSOA, Ana Flavia MarcalObjective: To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast beta-glucans, minerals and silymarin (Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice. Methods: After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice. Results: After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-alpha, AMP-activated protein kinase-1 alpha, peroxisome proliferator-activated receptor c co-activator-1 alpha, and mitochondrial transcription factor A expression levels were augmented; however, levels of inhibitor of nuclear factor-kappa B kinase subunit a and p65 nuclear factor-kappa B expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic-pituitary-adrenal axis immune interface status, was found to be modulated by the supplement. Conclusion: We discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.
- Small intestine remodeling in male Goto-Kakizaki rats(2021) PEREIRA, Joice Naiara Bertaglia; MURATA, Gilson Masahiro; SATO, Fabio Takeo; MAROSTI, Aline Rosa; CARVALHO, Carla Roberta de Oliveira; CURI, RuiBackground: Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The Goto-Kakizaki (GK) rat is an experimental model of spontaneous and non-obese T2DM. There is evidence that the intestine contributes to IR development in GK animals. This information prompted us to investigate small intestine remodeling in this animal model. Methods: Four-month-old male Wistar (control) and GK rats were utilized for the present study. After removing the small intestine, the duodenum, proximal jejunum, and distal ileum were separated. We then measured villi and muscular and mucosa layer histomorphometry, goblet cells abundance, total myenteric and submucosal neuron populations, and inflammatory marker expression in the small intestinal segments and intestinal transit of both groups of animals. Key Results: We found that the GK rats exhibited decreased intestinal area (p < 0.0001), decreased crypt depth in the duodenum (p = 0.01) and ileum (p < 0.0001), increased crypt depth in the jejunum (p < 0.0001), longer villi in the jejunum and ileum (p < 0.0001), thicker villi in the duodenum (p < 0.01) and ileum (p < 0.0001), thicker muscular layers in the duodenum, jejunum, and ileum (p < 0.0001), increased IL-1 beta concentrations in the duodenum and jejunum (p < 0.05), and increased concentrations of NF-kappa B p65 in the duodenum (p < 0.01), jejunum and ileum (p < 0.05). We observed high IL-1 beta reactivity in the muscle layer, myenteric neurons, and glial cells of the experimental group. GK rats also exhibited a significant reduction in submucosal neuron density in the jejunum and ileum, ganglionic hypertrophy in all intestinal segments studied (p < 0.0001), and a slower intestinal transit (about 25%) compared to controls. Conclusions: The development of IR and T2DM in GK rats is associated with small intestine remodeling that includes marked alterations in small intestine morphology, local inflammation, and reduced intestinal transit.
- Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice(2021) SOUSA, Marciana V.; AMARAL, Andressa G.; FREITAS, Jessica A.; MURATA, Gilson M.; WATANABE, Elieser H.; BALBO, Bruno E.; TAVARES, Marcelo D.; HORTEGAL, Renato A.; ROCON, Camila; SOUZA, Leandro E.; IRIGOYEN, Maria C.; SALEMI, Vera M.; ONUCHIC, Luiz F.Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13-18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals. Smoking increased serum urea nitrogen in cystic and noncystic mice and independently enhanced tubular cell proliferation and apoptosis. Smoking also increased renal fibrosis, however this effect was much higher in cystic than in noncystic animals. Pkd1 deficiency and smoking showed independent and additive effects on reducing renal levels of glutathione. Systolic function and several cardiac structural parameters were also negatively affected by smoking and the Pkd1-deficient status, following independent and additive patterns. Smoking did not increase, however, cardiac apoptosis or fibrosis in cystic and noncystic mice. Notably, smoking promoted a much higher reduction in body weight in Pkd1-deficient than in noncystic animals. Our findings show that smoking aggravated the renal and cardiac phenotypes of Pkd1-deficient cystic mice, suggesting that similar effects may occur in human ADPKD.
- A probiotic has differential effects on allergic airway inflammation in A/J and C57BL/6 mice and is correlated with the gut microbiome (vol 9, 134, 2021)(2021) CASARO, Mateus B.; THOMAS, Andrew M.; MENDES, Eduardo; FUKUMORI, Claudio; RIBEIRO, Willian R.; OLIVEIRA, Fernando A.; CRISMA, Amanda R.; MURATA, Gilson M.; BIZZARRO, Bruna; SA-NUNES, Anderson; SETUBAL, Joao C.; MAYER, Marcia P. A.; MARTINS, Flaviano S.; VIEIRA, Angelica T.; ANTIORIO, Ana T. F. B.; TAVARES-DE-LIMA, Wothan; CAMARA, Niels O. S.; CURI, Rui; DIAS-NETO, Emmanuel; FERREIRA, Caroline M.
- Agomelatine reduces circulating triacylglycerides and hepatic steatosis in fructose-treated rats(2021) VERONESI, Vanessa Barbosa; PIOLI, Mariana Rodrigues; SOUZA, Dailson Nogueira de; TEIXEIRA, Caio Jordao; MURATA, Gilson Masahiro; SANTOS-SILVA, Junia Carolina; HECHT, Fernanda Ballerini; VICENTE, Julia Modesto; BORDIN, Silvana; ANHE, Gabriel ForatoAgomelatine (AGO) is an antidepressant drug with agonistic activity at melatonin receptor 1 (MT1) and MT2 and with neutral antagonistic activity at serotonin receptor 5-HT2(c). Although experimental studies show that melatonin reduces hypertriglyceridemia and hepatic steatosis induced by excessive fructose intake, no studies have tested if AGO exerts similar actions. To address this issue we have treated male Wistar rats with fructose (15% in the drinking water) and/or AGO (40 mg/kg/day) for two weeks. AGO reduced body weight gain, feeding efficiency and hepatic lipid levels without affecting caloric intake in fructose-treated rats. AGO has also decreased very low-density lipoprotein (VLDL) production and circulating TAG levels after an oral load with olive oil. Accordingly, treatment with AGO reduced the hepatic expression of fatty acid synthase (Fasn), a limiting step for hepatic de novo lipogenesis (DNLG). The expression of apolipoprotein B (Apob) and microsomal triglyceride transfer protein (Mttp) in the ileum, two crucial proteins for intestinal lipoprotein production, were also downregulated by treatment with AGO. Altogether, the present data show that AGO mimics the metabolic benefits of melatonin when used in fructose-treated rats. This study also suggests that it is relevant to evaluate the potential of AGO to treat metabolic disorders in future clinical trials.
- A probiotic has differential effects on allergic airway inflammation in A/J and C57BL/6 mice and is correlated with the gut microbiome(2021) CASARO, Mateus B.; THOMAS, Andrew M.; MENDES, Eduardo; FUKUMORI, Claudio; RIBEIRO, Willian R.; OLIVEIRA, Fernando A.; CRISMA, Amanda R.; MURATA, Gilson M.; BIZZARRO, Bruna; SA-NUNES, Anderson; SETUBAL, Joao C.; MAYER, Marcia P. A.; MARTINS, Flaviano S.; VIEIRA, Angelica T.; ANTIORIO, Ana T. F. B.; TAVARES-DE-LIMA, Wothan; CAMARA, Niels O. S.; CURI, Rui; DIAS-NETO, Emmanuel; FERREIRA, Caroline M.The phenotypes of allergic airway diseases are influenced by the interplay between host genetics and the gut microbiota, which may be modulated by probiotics. We investigated the probiotic effects on allergic inflammation in NJ and C57BU6 mice. C57BU6 mice had increased gut microbiota diversity compared to NJ mice at baseline. Acetate producer probiotics differentially modulated and altered the genus abundance of specific bacteria, such as Akkermansia and Allistipes, in mouse strains. We induced airway inflammation followed by probiotic treatment and found that only A/J mice exhibited decreased inflammation, and the beneficial effects of probiotics in NJ mice were partially due to acetate production. To understand the relevance of microbial composition colonization in the development of allergic diseases, we implanted female C57BU6 mice with NJ embryos to naturally modulate the microbial composition of NJ mice, which increased gut microbiota diversity and reduced eosinophilic inflammation in A/J. These data demonstrate the central importance of microbiota to allergic phenotype severity.
- Intramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mice(2021) RODRIGUES, Alice C.; SPAGNOL, Alexandre R.; FRIAS, Flavia de Toledo; MENDONCA, Mariana de; ARAUJO, Hygor N.; GUIMARAES, Dimitrius; SILVA, William J.; BOLIN, Anaysa Paola; MURATA, Gilson Masahiro; SILVEIRA, LeonardoThe role of microRNAs in metabolic diseases has been recognized and modulation of them could be a promising strategy to treat obesity and obesity-related diseases. The major purpose of this study was to test the hypothesis that intramuscular miR-1 precursor replacement therapy could improve metabolic parameters of mice fed a high-fat diet. To this end, we first injected miR-1 precursor intramuscularly in high-fat diet-fed mice and evaluated glucose tolerance, insulin sensitivity, and adiposity. miR-1-treated mice did not lose weight but had improved insulin sensitivity measured by insulin tolerance test. Next, using an in vitro model of insulin resistance by treating C2C12 cells with palmitic acid (PA), we overexpressed miR-1 and measured p-Akt content and the transcription levels of a protein related to fatty acid oxidation. We found that miR-1 could not restore insulin sensitivity in C2C12 cells, as indicated by p-Akt levels and that miR-1 increased expression of Pgc1a and Cpt1b in PA-treated cells, suggesting a possible role of miR-1 in mitochondrial respiration. Finally, we analyzed mitochondrial oxygen consumption in primary skeletal muscle cells treated with PA and transfected with or without miR-1 mimic. PA-treated cells showed reduced basal respiration, oxygen consumption rate-linked ATP production, maximal and spare capacity, and miR-1 overexpression could prevent impairments in mitochondrial respiration. Our data suggest a role of miR-1 in systemic insulin sensitivity and a new function of miR-1 in regulating mitochondrial respiration in skeletal muscle.