Trypanosoma cruzi: Does the intake of nanoencapsulated benznidazole control acute infections?

Chagas Disease (CD) affects around eight million people worldwide. It is considered a neglected disease that presents few treatment options with efficacy only in the acute phase. Nanoparticles have many positive qualities for treating parasite infections and may be effectively and widely employed in clinical medicine. This research aimed to evaluate the nanoencapsulated benznidazole treatment in animals experimentally infected with Trypanosoma cruzi. To analyze the treatment efficacy, we evaluated survival during thirty days, parasitemia, genotoxicity, and heart and liver histopathology. Thirty-five female Swiss mice were organized into seven groups characterizing a dose curve: A - Negative control (uninfected animals), B - Positive control (infected animals), C - Benznidazole (BNZ) 100 mg/kg (infected animals), D - 5 mg/kg Benznidazole nanocapsules (NBNZ) (infected animals), E - 10 mg/kg Benznidazole nanocapsules (infected animals), F - 15 mg/kg Benznidazole nanocapsules (infected animals), G - 20 mg/kg Benznidazole nanocapsules (infected animals). The animals were infected with the Y strain of T. cruzi intraperitoneally. The treatment was administered for eight days by oral gavage. It was possible to observe that the treatment with the highest NBNZ dose presented efficacy similar to the standard benznidazole drug. The 20 mg/kg NBNZ dose was able to reduce parasitemia, increase survival, and drastically reduce heart and liver tissue damage compared to the 100 mg/kg BNZ dose. Moreover, it showed a lower DNA damage index than the BNZ treatment. In conclusion, the nanoencapsulation of BNZ promotes an improvement in parasite proliferation control with a five times smaller dose relative to the standard dose of free BNZ, thus demonstrating to be a potential innovative therapy for CD.

(Pro)Renin Receptor Antagonism Attenuates High-Fat-Diet-Induced Hepatic Steatosis.

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage directly related to diabetes, obesity, and metabolic syndrome. The (pro)renin receptor (PRR) has recently been demonstrated to play a role in glucose and lipid metabolism. Here, we test the hypothesis that the PRR regulates the development of diet-induced hepatic steatosis and fibrosis. C57Bl/6J mice were fed a high-fat diet (HFD) or normal-fat diet (NFD) with matching calories for 6 weeks. An 8-week methionine choline-deficient (MCD) diet was used to induce fibrosis. Two weeks following diet treatment, mice were implanted with a subcutaneous osmotic pump delivering either the peptide PRR antagonist, PRO20, or scrambled peptide for 4 or 6 weeks. Mice fed a 6-week HFD exhibited increased liver lipid accumulation and liver triglyceride content compared with NFD-fed mice. Importantly, PRO20 treatment reduced hepatic lipid accumulation in HFD-fed mice without affecting body weight or blood glucose. Furthermore, PRR antagonism attenuated HFD-induced steatosis, particularly microvesicular steatosis. In the MCD diet model, the percentage of collagen area was reduced in PRO20-treated compared with control mice. PRO20 treatment also significantly decreased levels of liver alanine aminotransferase, an indicator of liver damage, in MCD-fed mice compared with controls. Mechanistically, we found that PRR antagonism prevented HFD-induced increases in PPARγ and glycerol-3-phosphate acyltransferase 3 expression in the liver. Taken together, our findings establish the involvement of the PRR in liver triglyceride synthesis and suggest the therapeutic potential of PRR antagonism for the treatment of liver steatosis and fibrosis in NAFLD.

Renin-a in the Subfornical Organ Plays a Critical Role in the Maintenance of Salt-Sensitive Hypertension.

The brain renin-angiotensin system plays important roles in blood pressure and cardiovascular regulation. There are two isoforms of prorenin in the brain: the classic secreted form (prorenin/sREN) encoded by renin-a, and an intracellular form (icREN) encoded by renin-b. Emerging evidence indicates the importance of renin-b in cardiovascular and metabolic regulation. However, the role of endogenous brain prorenin in the development of salt-sensitive hypertension remains undefined. In this study, we test the hypothesis that renin-a produced locally in the brain contributes to the pathogenesis of hypertension. Using RNAscope, we report for the first time that renin mRNA is expressed in several regions of the brain, including the subfornical organ (SFO), the paraventricular nucleus of the hypothalamus (PVN), and the brainstem, where it is found in glutamatergic, GABAergic, cholinergic, and tyrosine hydroxylase-positive neurons. Notably, we found that renin mRNA was significantly elevated in the SFO and PVN in a mouse model of DOCA-salt-induced hypertension. To examine the functional importance of renin-a in the SFO, we selectively ablated renin-a in the SFO in renin-a-floxed mice using a Cre-lox strategy. Importantly, renin-a ablation in the SFO attenuated the maintenance of DOCA-salt-induced hypertension and improved autonomic function without affecting fluid or sodium intake. Molecularly, ablation of renin-a prevented the DOCA-salt-induced elevation in NADPH oxidase 2 (NOX2) in the SFO without affecting NOX4 or angiotensin II type 1 and 2 receptors. Collectively, our findings demonstrate that endogenous renin-a within the SFO is important for the pathogenesis of salt-sensitive hypertension.

(Pro)renin Receptor and Blood Pressure Regulation: A Focus on the Central Nervous System.

The renin-angiotensin system (RAS) is classically described as a hormonal system in which angiotensin II (Ang II) is one of the main active peptides. The action of circulating Ang II on its cognate Ang II type-1 receptor (AT1R) in circumventricular organs has important roles in regulating the autonomic nervous system, blood pressure (BP) and body fluid homeostasis, and has more recently been implicated in cardiovascular metabolism. The presence of a local or tissue RAS in various tissues, including the central nervous system (CNS), is well established. However, because the level of renin, the rate-limiting enzyme in the systemic RAS, is very low in the brain, how endogenous angiotensin peptides are generated in the CNS-the focus of this review-has been the subject of considerable debate. Notable in this context is the identification of the (pro)renin receptor (PRR) as a key component of the brain RAS in the production of Ang II in the CNS. In this review, we highlight cellular and anatomical locations of the PRR in the CNS. We also summarize studies using gain- and loss-of function approaches to elucidate the functional importance of brain PRR-mediated Ang II formation and brain RAS activation, as well as PRR-mediated Ang II-independent signaling pathways, in regulating BP. We further discuss recent developments in PRR involvement in cardiovascular and metabolic diseases and present perspectives for future directions.

Feasibility trial of the dialectical behavior therapy skills training group as add-on treatment for adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: Our aim was to explore the feasibility, and efficacy of a Dialectical Behavior Therapy Skill Training Group (DBT-ST) as an add-on treatment for adult attention-deficit/hyperactivity disorder (ADHD) in Latin America. METHOD: Adults with ADHD (n = 31) with stable medication treatment for ADHD and residual symptoms (ASRS > 20) were randomly assigned to DBT-ST (n = 16) or treatment as usual (TaU; n = 15) for 12 weeks. Feasibility was accessed by attendance and completion rates at 12 weeks. Efficacy outcomes were measured with the ASRS, and performed at 0, 6, 12, and 16 weeks. RESULTS: The DBT-ST protocol had 81.25% completion rate, with a mean attendance of 87.25% of the sessions. No significant interactions between group and time were detected for outcome measures. DISCUSSION: The DBT-ST was feasible as add-on treatment for adult patients with ADHD in Latin America. Replicating previous findings, DBT-ST has shown no significantly higher improvement in ADHD symptoms in comparison with TaU. Registered at the Clinical Trials database (NCT03326427).

Increased (Pro)renin Receptor Expression in the Hypertensive Human Brain.

Overactivation of the renin-angiotensin system (RAS) - a central physiological pathway involved in controlling blood pressure (BP) - leads to hypertension. It is now well-recognized that the central nervous system (CNS) has its own local RAS, and the majority of its components are known to be expressed in the brain. In physiological and pathological states, the (pro)renin receptor (PRR), a novel component of the brain RAS, plays a key role in the formation of angiotensin II (Ang II) and also mediates Ang II-independent PRR signaling. A recent study reported that neuronal PRR activation is a novel mechanism for cardiovascular and metabolic regulation in obesity and diabetes. Expression of the PRR is increased in cardiovascular regulatory nuclei in hypertensive (HTN) animal models and plays an important role in BP regulation in the CNS. To determine the clinical significance of the brain PRR in human hypertension, we investigated whether the PRR is expressed and regulated in the paraventricular nucleus of the hypothalamus (PVN) and rostral ventrolateral medulla (RVLM) - two key cardiovascular regulatory nuclei - in postmortem brain samples of normotensive (NTN) and HTN humans. Here, we report that the PRR is expressed in neurons, but not astrocytes, of the human PVN and RVLM. Notably, PRR immunoreactivity was significantly increased in both the PVN and RVLM of HTN subjects. In addition, PVN-PRR immunoreactivity was positively correlated with systolic BP (sBP) and showed a tendency toward correlation with age but not body mass index (BMI). Collectively, our data provide clinical evidence that the PRR in the PVN and RVLM may be a key molecular player in the neural regulation of BP and cardiovascular and metabolic function in humans.

Small RNA modifications in Alzheimer's disease.

Background While significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications are important regulators of complex physiological and pathological processes, including aging, stress responses, and epigenetic inheritance. However, whether small RNAs and their modifications are altered in dementia is not known. Methods We performed LC-MS/MS-based, high-throughput assays of small RNA modifications in post-mortem samples of the prefrontal lobe cortices of Alzheimer's disease (AD) and control individuals. We noted that some of the AD patients has co-occurring vascular cognitive impairment-related pathology (VaD). Findings We report altered small RNA modifications in AD samples compared with normal controls. The 15-25-nucleotide (nt) RNA fraction of these samples was enriched for microRNAs, whereas the 30-40-nt RNA fraction was enriched for tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). Interestingly, most of these altered RNA modifications were detected both in the AD and AD with co-occurring vascular dementia subjects. In addition, sequencing of small RNA in the 30-40-nt fraction from AD cortices revealed reductions in rsRNA-5S, tsRNA-Tyr, and tsRNA-Arg. Interpretation These data suggest that sncRNAs and their associated modifications are novel signals that may be linked to the pathogenesis and development of Alzheimer's disease. Fund NIH grants (R01HL122770, R01HL091905, 1P20GM130459, R01HD092431, P50HD098593, GM103440), AHA grant (17IRG33370128), Sigmund Gestetner Foundation Fellowship to P Kehoe.

The neuronal (pro)renin receptor and astrocyte inflammation in the central regulation of blood pressure and blood glucose in mice fed a high-fat diet.

We report here that the neuronal (pro)renin receptor (PRR), a key component of the brain renin-angiotensin system (RAS), plays a critical role in the central regulation of high-fat-diet (HFD)-induced metabolic pathophysiology. The neuronal PRR is known to mediate formation of the majority of angiotensin (ANG) II, a key bioactive peptide of the RAS, in the central nervous system and to regulate blood pressure and cardiovascular function. However, little is known about neuronal PRR function in overnutrition-related metabolic physiology. Here, we show that PRR deletion in neurons reduces blood pressure, neurogenic pressor activity, and fasting blood glucose and improves glucose tolerance without affecting food intake or body weight following a 16-wk HFD. Mechanistically, we found that a HFD increases levels of the PRR ligand (pro)renin in the circulation and hypothalamus and of ANG II in the hypothalamus, indicating activation of the brain RAS. Importantly, PRR deletion in neurons reduced astrogliosis and activation of the astrocytic NF-κB p65 (RelA) in the arcuate nucleus and the ventromedial nucleus of the hypothalamus. Collectively, our findings indicate that the neuronal PRR plays essential roles in overnutrition-related metabolic pathophysiology.

Zinc toxicity in seedlings of three trees from the Fabaceae associated with arbuscular mycorrhizal fungi.

Due to diverse human activities zinc (Zn) may reach phytotoxic levels in the soil. Here, we evaluated the differential sensibility of three Brazilian tree species from the Fabaceae to increasing soil Zn concentrations and its physiological response to cope with excess Zn. A greenhouse experiment was conducted with the species: Mimosa caesalpiniaefolia, Erythrina speciosa and Schizolobium parahyba, and the addition of 0, 200, 400 and 600 mg Zn kg-1 to the soil. Plants were harvested after three months of cultivation, and growth, root symbiosis, biochemical markers and elemental composition were analyzed. Soil Zn addition reduced seedling growth, irrespective of the species, with a strong reduction in M. caesalpiniaefolia. Regarding root symbiosis, in N2-fixing species, nitrogenase activity was reduced by the highest Zn concentrations. Zn addition caused plants nutritional imbalances, mainly in roots. The content of photosynthetic pigments in leaves decreased up to 40%, suggesting that high Zn contents interfered with its biosynthesis, and altered the content of foliar polyamines and free amino acids, depending on the species and the soil Zn concentration. Zn toxicity in M. caesalpiniaefolia plants was observed at available soil Zn concentrations greater than 100 mg kg-1 (DTPA-extractable), being the most sensitive species and E. speciosa was moderately sensitive. S. parahyba was a moderately tolerant species, which seems to be related to polyamines accumulation and to mycorrhizal association. This last species has the potential for revegetation of areas with moderately high soil Zn concentration and for phytostabilization purposes. Future research evaluating the tolerance to multiple metal stress under field conditions should confirm S. parayba suitability in Zn contaminated areas of tropical regions.

Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer's disease.

High salt (sodium) intake leads to the development of hypertension despite the fact that plasma sodium concentration ([Na+]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) sodium contributes to elevated sympathetic activity and high blood pressure (BP) in rodent models of hypertension. However, whether there is an increased accumulation of sodium in the CSF of humans with chronic hypertension is not well defined. Here, we investigated CSF [Na+] from hypertensive and normotensive human subjects with family histories of Alzheimer's disease in samples collected in a clinical trial, as spinal tap is not a routine clinical procedure for hypertensive patients. The [Na+] and osmolality in plasma and CSF were measured by flame photometry. Daytime ambulatory BP was monitored while individuals were awake. Participants were deidentified and data were analyzed in conjunction with a retrospective analysis of patient history and diagnosis. We found that CSF [Na+] was significantly higher in participants with high BP compared with normotensive participants; there was no difference in plasma [Na+], or plasma and CSF osmolality between groups. Subsequent multiple linear regression analyses controlling for age, sex, race, and body mass index revealed a significant positive correlation between CSF [Na+] and BP but showed no correlation between plasma [Na+] and BP. In sum, CSF [Na+] was higher in chronic hypertensive individuals and may play a key role in the pathogenesis of human hypertension. Collectively, our findings provide evidence for the clinical significance of CSF [Na+] in chronic hypertension in humans.

Alamandine enhances cardiomyocyte contractility in hypertensive rats through a nitric oxide-dependent activation of CaMKII.

Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the TGR (mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca2+ dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca2+ spark rate and enhanced Ca2+ reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca2+ transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating CaMKII as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the CaMKII site, thereby indicating that NO acts upstream of CaMKII in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of CaMKII.

(Pro)renin receptor knockdown in the paraventricular nucleus of the hypothalamus attenuates hypertension development and AT1 receptor-mediated calcium events.

Activation of the brain renin-angiotensin system (RAS) is a pivotal step in the pathogenesis of hypertension. The paraventricular nucleus (PVN) of the hypothalamus is a critical part of the angiotensinergic sympatho-excitatory neuronal network involved in neural control of blood pressure and hypertension. However, the importance of the PVN (pro)renin receptor (PVN-PRR)-a key component of the brain RAS-in hypertension development has not been examined. In this study, we investigated the involvement and mechanisms of the PVN-PRR in DOCA-salt-induced hypertension, a mouse model of hypertension. Using nanoinjection of adeno-associated virus-mediated Cre recombinase expression to knock down the PRR specifically in the PVN, we report here that PVN-PRR knockdown attenuated the enhanced blood pressure and sympathetic tone associated with hypertension. Mechanistically, we found that PVN-PRR knockdown was associated with reduced activation of ERK (extracellular signal-regulated kinase)-1/2 in the PVN and rostral ventrolateral medulla during hypertension. In addition, using the genetically encoded Ca2+ biosensor GCaMP6 to monitor Ca2+-signaling events in the neurons of PVN brain slices, we identified a reduction in angiotensin II type 1 receptor-mediated Ca2+ activity as part of the mechanism by which PVN-PRR knockdown attenuates hypertension. Our study demonstrates an essential role of the PRR in PVN neurons in hypertension through regulation of ERK1/2 activation and angiotensin II type 1 receptor-mediated Ca2+ activity. NEW & NOTEWORTHY PRR knockdown in PVN neurons attenuates the development of DOCA-salt hypertension and autonomic dysfunction through a decrease in ERK1/2 activation in the PVN and RVLM during hypertension. In addition, PRR knockdown reduced AT1aR expression and AT1R-mediated calcium activity during hypertension. Furthermore, we characterized the neuronal targeting specificity of AAV serotype 2 in the mouse PVN and validated the advantages of the genetically encoded calcium biosensor GCaMP6 in visualizing neuronal calcium activity in the PVN.

Chrysobalanus icaco L. Leaves Normalizes Insulin Sensitivity and Blood Glucose and Inhibits Weight Gain in High-Fat Diet-Induced Obese Mice.

Chrysobalanus icaco L. is a medicinal plant present in the Brazilian coastline and known for its hypoglicemic and antioxidant properties. Here, we assessed the beneficial metabolic effects of the aqueous extract of C. icaco (AECI) leaves in diet-induced obese mice. Swiss mice were fed standard chow (SC used as controls) or high-fat diet (HFD) to induce obesity. After 10 weeks, mice on each diet were divided into two groups with one group used as control while the other group treated with AECI for 4 weeks resulting in four groups of mice: SC; SC treated with AECI (SC + AECI); HFD; and HFD treated with AECI (HFD + AECI). AECI was administered drinking water at about 200 mg/kg. AECI was able to normalize insulin (13,682 ± 1090 vs. 9828 ± 485 AU, P < .05) and fasting blood glucose (192.8 ± 14.2 vs. 132.3 ± 6.4 mg/dL, P < .05) and inhibit weight gain (39 ± 5.7%) and fat storage in liver (72.60 ± 3.83%, P < .0001), despite the high-fat intake. These findings reinforce the use of AECI in hyperglycemia and highlight the potential extract's effect in preventing weight gain and fat accumulation in liver of diet-induced obese mice.

Assessment of muscular strength with the modified sphygmomanometer test: what is the best method and source of outcome values?

BACKGROUND: Tests that are usually employed for the clinical assessment of muscular strength have notable disadvantages. The Modified Sphygmomanometer Test (MST) is a promising method because it is low-cost and provides objective measures. OBJECTIVES: To investigate the most adequate method and sources of outcome values for the assessment of strength with the MST. METHOD: Methodological study with 40 healthy adults (22.98 ± 2.26 years), who did not practice physical activity regularly. The strength of the flexors and extensors of the elbow and knee, the handgrip of the dominant side and anterior trunk flexors were randomly assessed with portable dynamometers and the MST (bag and cuff adaptations, and sphygmomanometer without adaptation) by a single examiner. An independent examiner read and recorded the values. The sources of the investigated outcome values were the first trial and the means of two and three trials. One-way ANOVAs and Pearson Correlation Coefficients were used for the analyses (α=0.05). RESULTS: For the MST methods applied to assess all muscular groups, similar values were found for all sources of outcome values (0.01

Assessment of muscular strength with the modified sphygmomanometer test: what is the best method and source of outcome values? / Avaliação da força muscular com o teste do esfigmomanômetro modificado: qual o melhor método e forma de operacionalização?

BACKGROUND: Tests that are usually employed for the clinical assessment of muscular strength have notable disadvantages. The Modified Sphygmomanometer Test (MST) is a promising method because it is low-cost and provides objective measures. OBJECTIVES: To investigate the most adequate method and sources of outcome values for the assessment of strength with the MST. METHOD: Methodological study with 40 healthy adults (22.98±2.26 years), who did not practice physical activity regularly. The strength of the flexors and extensors of the elbow and knee, the handgrip of the dominant side and anterior trunk flexors were randomly assessed with portable dynamometers and the MST (bag and cuff adaptations, and sphygmomanometer without adaptation) by a single examiner. An independent examiner read and recorded the values. The sources of the investigated outcome values were the first trial and the means of two and three trials. One-way ANOVAs and Pearson Correlation Coefficients were used for the analyses (α=0.05). RESULTS: For the MST methods applied to assess all muscular groups, similar values were found for all sources of outcome values (0.01<F<0.26; 0.77<p<1.00) with significant and positive correlations between the measures obtained with the dynamometers (0.51<r<0.94; p<0.003). CONCLUSIONS: All MST methods showed adequate results for the assessment of strength in healthy individuals, and after familiarization, only one trial was sufficient to provide reliable measures. The sphygmomanometer without adaptation is not time consuming, compared to the other adaptations, and showed the capability of measuring higher values of strength. The bag method was easily trained to be used and stabilized. .

CONTEXTUALIZAÇÃO: Testes comumente utilizados para a avaliação clínica da força muscular apresentam importantes desvantagens. O Teste do Esfigmomanômetro Modificado (TEM) é promissor para esse fim, por ser barato e fornecer medidas objetivas. OBJETIVOS: Investigar o método e a forma de operacionalização mais adequados para avaliação da força muscular com o TEM. MÉTODO: Estudo metodológico, com 40 adultos saudáveis (22,98±2,26 anos), não praticantes de atividade física regular. A força dos músculos flexores/extensores de cotovelo e joelho e preensores palmares do lado dominante e flexores anteriores de tronco foi avaliada com os dinamômetros portáteis e diferentes métodos do TEM (adaptações da bolsa, da braçadeira e não adaptado) por um único examinador, em ordem aleatória, com leitura e registro dos valores por outro examinador. As operacionalizações investigadas foram: primeira repetição e médias de duas e três repetições. One-way ANOVA e Coeficientes de Correlação de Pearson foram utilizados para análises (α=0,05). RESULTADOS: Para todo os métodos do TEM, utilizados para avaliar os grupos musculares, foram encontrados valores similares para todas as formas de operacionalização(0,01<F<0,26;0,77<p<1,00) e correlações significativas e positivas com as medidas dos dinamômetros(0,51<r<0,94; p<0,003). CONCLUSÕES: Estatisticamente, os diferentes métodos do TEM se mostraram igualmente adequados para avaliação da força muscular de adultos saudáveis, e apenas uma repetição, após familiarização, foi suficiente para obtenção de resultados adequados. Nenhuma demanda de tempo para realizar a adaptação ...

[Model of high-fat diet-induced obesity associated to insulin resistance and glucose intolerance]. / Modelo de obesidade induzida por dieta hiperlipídica e associada à resistência à ação da insulina e intolerância à glicose.

OBJECTIVE: Validate a model of high-fat diet-induced obesity, of low cost, easy reproducibility, that could express characteristics observed in human, and would enable subsequent therapy proposals. MATERIALS AND METHODS: Sixteen Swiss mice received a standard diet (DP) or high-fat diet (DH) for 10 weeks. RESULTS: Although the DP group had greater water (p < 0.01) and feed (p < 0.001) consumption, the DH group had greater body weight (p < 0.5) and adipose tissue gain (p < 0.001), favoring higher adiposity index (p < 0.001), glucose (p < 0.01), and area under the curve in the insulin (p < 0.001) and glucose (p < 0.01) tolerance tests. CONCLUSION: A high-fat diet-induced obesity model has been validated, which was also associated with insulin resistance and glucose intolerance after a period of 10 weeks.

Modelo de obesidade induzida por dieta hiperlipídica e associada à resistência à ação da insulina e intolerância à glicose / Model of high-fat diet-induced obesity associated to insulin resistance and glucose intolerance

OBJETIVO: Validar um modelo de obesidade induzida por dieta hiperlipídica, de baixo custo, fácil reprodutibilidade, que mimetizasse características observadas no humano e viabilizasse posteriores proposições terapêuticas. MATERIAIS E MÉTODOS: Dezesseis camundongos Swiss receberam dieta padrão (DP) ou dieta hiperlipídica (DH), durante 10 semanas. RESULTADOS: Embora o grupo DP tenha apresentado maior consumo de água (p < 0,01) e ração (p < 0,001), o grupo DH apresentou maior ganho de peso corpóreo (p < 0,5) e aumento de coxins adiposos (p < 0,001), favorecendo maior índice de adiposidade (p < 0,001), glicemia (p < 0,01) e área sob a curva nos testes de tolerância à insulina (p < 0,001) e à glicose (p < 0,01). CONCLUSÃO: Validou-se um modelo de obesidade induzida por dieta hiperlipídica associada à resistência à ação da insulina e à intolerância à glicose, em um período de 10 semanas.

OBJECTIVE: Validate a model of high-fat diet-induced obesity, of low cost, easy reproducibility, that could express characteristics observed in human, and would enable subsequent therapy proposals. MATERIALS AND METHODS: Sixteen Swiss mice received a standard diet (DP) or high-fat diet (DH) for 10 weeks. RESULTS: Although the DP group had greater water (p < 0.01) and feed (p < 0.001) consumption, the DH group had greater body weight (p < 0.5) and adipose tissue gain (p < 0.001), favoring higher adiposity index (p < 0.001), glucose (p < 0.01), and area under the curve in the insulin (p < 0.001) and glucose (p < 0.01) tolerance tests. CONCLUSION: A high-fat diet-induced obesity model has been validated, which was also associated with insulin resistance and glucose intolerance after a period of 10 weeks.