CYNTHIA RODRIGUES MULLER
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
15 resultados
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Agora exibindo 1 - 10 de 15
- Aerobic exercise training prevents kidney lipid deposition in mice fed a cafeteria diet(2018) MULLER, C. R.; V, A. L. Americo; FIORINO, P.; EVANGELISTA, F. S.Aim: The objective of this study was to investigate the potential of aerobic exercise training (AET) to prevent kidney lipid accumulation and the contribution of renal metabolism to mediate this response. Main methods: Male C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n = 13), CHOW-TR (chow diet, trained; n = 13), CAF-SED (cafeteria diet, sedentary; n = 13) and CAF-TR (cafeteria diet, trained; n = 13). AET consisted in running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks. Key findings: AET prevented weight gain in both trained groups. Food intake was not different among groups, however water intake, urine output, urine potassium and osmolarity were reduced in CAF-SED and CAF-TR groups. Kidney lipid deposition increased in CAF-SED (4.12 +/- 0.5%/area) compared with CHOW-SED (1.7 +/- 0.54%/area), and the AET prevented this increase in the CAF-TR group (2.1 +/- 0.5%/area). The Bowman's capsule area decreased in CAF-SED and CAF-TR groups while the Bowman' space reduced in CAF-SED compared to CHOW-SED group, which was prevented by AET in the CAF-TF group. We observed a 27% increase in the p-AMPK expression in CAF-TR compared to CHOW-SED group without differences in the SIRT-1, PGC1-alpha, ACC and p-ACC. beta-HAD activity increased in CAF-SED (43.9 +/- 4.57 nmol.min(-1).ug(-1)) and CAF-TR (44.7 +/- 2.6 nmol.min(-1).ug(-1)) groups compared to CHOW-SED (35.1 +/- 2.9 nmol.min(-1).ug(-1)) e CHOW-TR (36.6 +/- 2.7 nmol.min(-1).ug(-)1). Significance: AET prevented kidney lipid accumulation induced by cafeteria diet and this response was not associated with changes in the renal metabolic activity that favors lipid oxidation.
- Effects of Aerobic Exercise Protocol on Genes Related to Insulin Resistance and Inflammation in the Pancreas of ob/ob Mice with NAFLD(2020) SILVA, Lucas Lucena Simoes e; FERNANDES, Matheus Santos de Sousa; KUBRUSLY, Marcia Saldanha; MULLER, Cynthia Rodrigues; AMERICO, Anna Laura Viacava; STEFANO, Jose Tadeu; EVANGELISTA, Fabiana Sant'Anna; OLIVEIRA, Claudia Pinto; JUKEMURA, JosePurpose: To evaluate the effect of 8 weeks of aerobic training on insulin resistance and inflammatory response in obese mice (ob/ob) with NAFLD. Materials and Methods: Male ob/ob mice were randomly divided into sedentary (n=7) and trained (n=7) groups. Aerobic training consisted of 5 weekly sessions, 60 min per session at 60% of the maximum speed of the running test. Hepatic and pancreatic samples were collected to evaluate histological features and gene expression associated with insulin resistance and inflammatory response after 8-week experiment protocol. RNA was performed by TRIzol (R). PCR experiments were performed using the Rotor-Gene RG-3000. Parametric data were assessed by t-test, one-way ANOVA and Bonferroni test for multiple comparisons. Non-parametric data were assessed by the Mann-Whitney tests with Dunn's post-test of multiple comparisons. Histological analysis was assessed by chi-square test with Fisher's exact test. Significant variables were considered when p<0.05. All the analyses were performed by GraphPad Prism V6.0 software (GraphPad Software Inc.). Results: Reductions in bodyweight (p = 0.008), weight evolution (p = 0.03), food intake (p <0.0001) and fat content were observed in trained group. Moreover, the trained group showed better results in peak velocity (p=0.03) physical effort tolerance (p=0.006) and distance (p=0.01). Gene expression showed differences in IL-10 (p=0.03) and GLUT-2 (p=0.03) in hepatic analysis, between groups. Pancreatic gene expression showed difference between groups in IRS-2 (p=0.004), GLUT-2 (p=0.03) and IL-10 (p=0.008) analysis. Also, the trained group showed lower values for interlobular fat and inflammatory infiltrate in histological analysis when compared to sedentary animals. Conclusion: An 8-week physical training protocol was able to attenuate bodyweight gain, food intake and generate positive effects on gene expression related to insulin resistance and inflammation in both liver and pancreas of ob/ob mice.
conferenceObject Differentiated contribution of fat pads to the prevention of insulin resistance through aerobic exercise training(2017) AMERICO, Anna Laura Viacava; MULLER, Cynthia Rodrigues; FONSECA-ALANIZ, Miriam Helena; EVANGELISTA, Fabiana Sant'AnnaconferenceObject Exercise training prevents hypertension, dyslipidemia and renal lipid deposition in young rats fed a high-fat diet(2015) MULLER, Cynthia; AMERICO, Anna Laura; NETO, Giuseppe; EVANGELISTA, Fabiana; FARAH, Vera; FIORINO, Patricia- Potential of Aerobic Physical Training to Minimize the Effects of Leptin Deficiency in Female Mice(2020) AZEVEDO-MARTINS, Anna; BOSCHETTI, Daniela; MULLER, Cynthia; AMERICO, Anna; VECCHIATTO, Bruno; MARTUCCI, Luiz; PEREIRA, Renata; OLIVEIRA, Claudia; EVANGELISTA, Fabiana
article 13 Citação(ões) na Scopus Physical training improves body weight and energy balance but does not protect against hepatic steatosis in obese mice(2015) EVANGELISTA, Fabiana S.; MULLER, Cynthia R.; STEFANO, Jose T.; TORRES, Mariana M.; MUNTANELLI, Bruna R.; SIMON, Daniel; ALVARES-DA-SILVA, Mario R.; PEREIRA, Isabel V.; COGLIATI, Bruno; CARRILHO, Flair J.; OLIVEIRA, Claudia P.This study sought to determine the role of physical training (PT) on body weight (BW), energy balance, histological markers of nonalcoholic fatty liver disease (NAFLD) and metabolic gene expression in the liver of ob/ob mice. Adult male ob/ob mice were assigned into groups sedentary (S; n = 8) and trained (T; n = 9). PT consisted in running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks. BW of S group was higher from the 4th to 8th week of PT compared to their own BW at the beginning of the experiment. PT decreased daily food intake and increased resting oxygen consumption and energy expenditure in T group. No difference was observed in respiratory exchange ratio, but the rates of carbohydrate and lipids oxidation, and maximal running capacity were greater in T than S group. Both groups showed liver steatosis but not inflammation. PT increased CPT1a and SREBP1c mRNA expression in T group, but did not change MTP, PPAR-alpha, PPAR-gamma, and NFKB mRNA expression. In conclusion, PT prevented body weight gain in ob/ob mice by inducing negative energy balance and increased physical exercise tolerance. However, PT did not change inflammatory gene expression and failed to prevent liver steatosis possible due to an upregulation in the expression of SREBP1c transcription factor. These findings reveal that PT has positive effect on body weight control but not in the liver steatosis in a leptin deficiency condition.conferenceObject Aerobic exercise training prevents renal damage in insulin resistance mice(2017) MULLER, Cynthia Rodrigues; AMERICO, Anna Laura Viacava; FIORINO, Patricia; EVANGELISTA, Fabiana Sant'Anna- Exposure to high-fat diet since post-weaning induces cardiometabolic damage in adult rats(2016) FIORINO, P.; AMERICO, A. L. V.; MULLER, C. R.; EVANGELISTA, F. S.; SANTOS, F.; LEITE, A. P. O.; FARAH, V.Aims: This study sought to investigate the metabolic, hemodynamic and autonomic responses in adult rats exposed to high-fat diet since post-weaning. Main methods: Young male Wistar rats were assigned into groups fed with standard normal diet (3% lipids; ND, n=8) or high-fat diet (30% lipids; HD, n=8) during 8 weeks. Body composition, food intake, serum triglycerides, total cholesterol, insulin, leptin and adiponectin concentrations were determined. Hemodynamic and autonomic evaluations were performed. Renin angiotensin system and nitric oxide were also studied by pharmacological blockades. Key findings: HD group showed no difference in body weight, total cholesterol, food intake in calories and insulin concentration, but visceral fat pads weight, triglycerides and leptin were higher in HD group. Moreover, HD group decreased adiponectin level, increased 12% of mean arterial pressure (MAP) and 6% of heart rate compared with ND group. Spectral analyses showed an increase in cardiovascular sympathetic modulation in HD compared with ND group. Depressor responses after losartan were higher in HD compared with ND group: -9 +/- 0.7 vs.-3 +/- 1.6 mmHg. Pressor responses after L-NAME were higher in HD compared with ND: 45 +/- 8 vs. 32 +/- 5 mmHg. Significance: High-fat diet consumption during early period of life can increase WAT mass and MAP. These alterations may be mediated by an augment in sympathetic activity associated with higher leptin and lower adiponectin levels. These cardiometabolic damages can lead to the development of hypertension and increase cardiovascular risk in adulthood.
- Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse(2016) PREITE, Nailliw Z.; NASCIMENTO, Bruna P. P. do; MULLER, Cynthia R.; AMERICO, Anna Laura V.; HIGA, Talita S.; EVANGELISTA, Fabiana S.; LANCELLOTTI, Carmen L.; HENRIQUES, Felipe dos Santos; BATISTA JR., Miguel Luiz; BIANCO, Antonio C.; RIBEIRO, Miriam O.The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through beta-adrenergic receptors (AR). Here, we wished to define the role played by the AR beta(3) isoform in this process. This study focused on the AR beta(3) knockout mice (AR beta 3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). AR beta 3KO mice defend core temperature during cold exposure (4 degrees C for 5h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, AR beta 3KO mice kept on a high-fat diet (HFD; 40% fat) for 8 weeks exhibited greater susceptibility to diet-induced obesity, markedly increased epididymal adipocyte area with clear signs of inflammation. The HFD-induced glucose intolerance was similar in both groups but serum hypertriglyceridemia and hypercholesterolemia were less intense in AR beta 3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in AR beta 3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, AR beta(3) inactivation does not affect BAT thermogenesis but increases susceptibility to diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation.
- Post-weaning Exposure to High-Fat Diet Induces Kidney Lipid Accumulation and Function Impairment in Adult Rats(2019) MULLER, Cynthia R.; LEITE, Ana Paula O.; YOKOTA, Rodrigo; PEREIRA, Renata O.; V, Anna Laura Americo; NASCIMENTO, Nilberto R. F.; EVANGELISTA, Fabiana S.; FARAH, Vera; FONTELES, Manasses C.; FIORINO, PatriciaAim: We investigated the kidney morphofunctional consequences of high-fat diet intake since post-weaning in adult rats. Main Methods: Male Wistar rats were divided into two groups: ND (normal diet; n = 10) and HD (high-fat diet; n = 10). The high-fat diet was introduced post-weaned and animals were followed for 8 weeks. Key Findings: HD group did not change body weight gain even though food consumption has decreased with no changes in caloric consumption. The HD group showed glucose intolerance and insulin resistance. The glomerular filtration rate (GFR) was decreased in vivo (ND: 2.8 +/- 1.01; HD: 1.1 +/- 0.14 ml/min) and in the isolated perfusion method (34% of decrease). Renal histological analysis showed a retraction in glomeruli and an increase in kidney lipid deposition (ND: 1.5 +/- 0.17 HD: 5.9 +/- 0.06%). Furthermore, the high-fat diet consumption increased the pro-inflammatory cytokines IL-6 (ND: 1,276 +/- 203; HD: 1,982 +/- 47 pg/mUmg) and IL-lb (ND: 97 +/- 12 HD: 133 +/- 5 pg/mUmg) without changing anti-inflammatory cytokine IL-10. Significance: Our study provides evidence that high-fat diet consumption leads to renal lipid accumulation, increases inflammatory cytokines, induces glomeruli retraction, and renal dysfunction. These damages observed in the kidney could be associated with an increased risk to advanced CKD in adulthood suggesting that reduction of high-fat ingestion during an early period of life can prevent metabolic disturbances and renal lipotoxicity.