CYNTHIA RODRIGUES MULLER
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- 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.
- Aerobic Exercise Training Exerts Beneficial Effects Upon Oxidative Metabolism and Non-Enzymatic Antioxidant Defense in the Liver of Leptin Deficiency Mice(2020) FERNANDES, Matheus Santos de Sousa; SILVA, Lucas de Lucena de Simoes e; KUBRUSLY, Marcia Saldanha; LIMA, Talitta Ricarlly Lopes de Arruda; MULLER, Cynthia Rodrigues; AMERICO, Anna Laura Viacava; FERNANDES, Mariana Pinheiro; COGLIATI, Bruno; STEFANO, Jose Tadeu; LAGRANHA, Claudia Jacques; EVANGELISTA, Fabiana S.; OLIVEIRA, Claudia P.Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of liver disease, which is associated with several etiological factors, including stress and dysfunction in oxidative metabolism. However, studies showed that aerobic exercise training (AET) can combat the oxidative stress (OS) and improves mitochondrial functionality in the NAFLD. To test the hypothesis that AET improves oxidative metabolism and antioxidant defense in the liver of ob/ob mice. Male ob/ob mice with eight weeks old were separated into two groups: the sedentary group (S), n=7, and the trained group (T), n=7. The T mice were submitted to an 8-week protocol of AET at 60% of the maximum velocity achieved in the running capacity test. Before AET, no difference was observed in running test between the groups (S=10.4 +/- 0.7 min vs. T= 13 +/- 0.47 min). However, after AET, the running capacity was increased in the T group (12.8 +/- 0.87 min) compared to the S group (7.2 +/- 0.63 min). In skeletal muscle, the T group (26.91 +/- 1.12 U/mg of protein) showed higher citrate synthase activity compared with the S group (19.28 +/- 0.88 U/mg of protein) (p =0.006). In the analysis of BW evolution, significant reductions were seen in the T group as of the fourth week when compared to the S group. In addition, food intake was not significant different between the groups. Significant increases were observed in the activity of enzymes citrate synthase (p=0.004) and beta-HAD (p=0.01) as well as in PGC-1 alpha gene expression (p=0.002) in the liver of T group. The levels of TBARs and carbonyls, as well as SOD, CAT and GST were not different between the groups. However, in the nonenzymatic antioxidant system, we found that the T group had higher sulfhydryl (p = 0.02), GSH (p=0.001) and GSH/GSSG (p=0.02) activity. In conclusion, the AET improved body weight evolution and the aerobic capacity, increased the response of oxidative metabolism markers in the liver such as PGC-1 alpha gene expression and citrate synthase and beta-HAD enzyme activities in ob/ob mice. In addition, AET improved the non-enzymatic antioxidant defense and did not change the enzymatic defense.