Quantitative proteomics study of carnosine effect in an animal model of Western diet-induced nonalcoholic fatty liver disease.

The nonalcoholic fatty liver disease (NAFLD), which is closely related to westernized dietary (WD) patterns, displays a rising epidemiological and economic burden. Since there is no pharmacological therapy approved for this disease, mechanistic studies are warranted. In this work, we investigated the action of carnosine (CAR), a natural dipeptide with several protection roles against oxidative stress in the liver of NAFLD rats. NAFLD was induced by WD-rich sugars and fat, verifying the histological evidence of steatosis. As intraperitoneal administration of CAR reversed liver steatosis, the protein profiles of NAFLD liver and CAR NAFLD liver were evaluated by label-free proteomics approach. A total of 2531 proteins were identified and the 230 and 276 were significantly up- and downregulated, respectively, by CAR treatment of NAFLD rats and involved in fundamental pathways such as oxidative stress and lipid metabolism. Perilipin 2 and apolipoprotein E, components of the plasma membrane of vesicle, resulted in highly downregulated in the CAR-treated NAFLD liver. The advanced bioanalytical approach demonstrated the efficacy of CAR in overcoming the main symptoms of NAFLD, ameliorating the steatosis in the liver.

Carnosine supplementation and retinal oxidative parameters in a high-calorie diet rat model.

BACKGROUND: To assess oxidative effects induced by a high-calorie diet on the retina of Wistar rats and test the antioxidative effects of carnosine supplementation. METHODS: Wistar rats were randomly divided into the following groups: standard diet (SD), high-calorie diet (HcD), standard diet + carnosine (SD + Car), and high-calorie diet + carnosine (HcD + Car). The body weight, adiposity index, plasma glucose, total lipids, high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid, creatinine, and triglycerides of the animals were evaluated. The retinas were analyzed for markers of oxidative stress. Hydrogen peroxide production was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCF) oxidation. The total glutathione (tGSH), total antioxidant capacity (TAC), protein carbonyl, and sulfhydryl groups of the antioxidant system were analyzed. RESULTS: TAC levels increased in the retinas of the SD + Car group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the HcD group (p < 0.05). The levels of GSH and the GSSH:GSSG ratio were increased in the HcD + Car group compared to the SD + Car group (p < 0.05). An increase in the retinal carbonyl content was observed in the HcD group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the SD + Car group (p < 0.05). A high-calorie diet (HcD) was also associated with a decrease in retinal sulfhydryl-type levels compared to the SD group (p < 0.05). CONCLUSION: The results suggest that feeding a high-calorie diet to rats can promote an increase in carbonyl content and a reduction in sulfhydryl groups in their retinas. The administration of carnosine was not effective in attenuating these oxidative markers. TRIAL REGISTRATION: Animal Ethics Committee of Botucatu Medical School - Certificate number 1292/2019.

Rice (Oryza sativa L.) bran preserves cardiac function by modulating pro-inflammatory cytokines and redox state in the myocardium from obese rats.

PURPOSE: This study aimed to evaluate the effect of rice bran (RB) supplementation to a high-sugar fat (HSF) diet on cardiac dysfunction in an experimental obesity model. METHODS: Male Wistar rats were distributed into three groups: control, high-sugar fat, and high-sugar fat supplemented with 11% RB for 20 weeks. RESULTS: HSF diet promoted obesity and metabolic complications. Obese rats showed cardiac structural and functional impairment associated with high levels of interleukin-6, tumoral necrosis factor alpha, and malondialdehyde, and decreased activity of superoxide dismutase and catalase in the myocardium. RB supplementation was able to mitigate obesity and its metabolic alterations in HSF diet-fed animals. Moreover, the RB also prevented structural and functional damage, inflammation, and redox imbalance in the heart of these animals. CONCLUSION: This study suggests that RB supplementation prevents cardiac dysfunction in rats fed on HSF by modulating systemic metabolic complications and inflammation and oxidative stress in the myocardium, representing potential alternative therapy.

Differentially expressed proteins obtained by label-free quantitative proteomic analysis reveal affected biological processes and functions in Western diet-induced steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a pathological manifestation with a progressive incidence in response to the epidemic of hepatic steatosis caused primarily by excessive energy intake. The present study unravels affected biological processes and functions by the presence of NASH in rats using a label-free quantitative proteomic strategy. NASH was induced by a Western high-sugar and high-fat diet for 20 weeks. The liver tissue was collected for histology and for a mass spectrometry-based proteomic protocol. The NASH group showed severe lipidosis, hepatocyte ballooning, and the presence of collagen deposition. Among upregulated proteins in NASH perilipin-2 (Plin-2; F6QBA3; difference [diff]: 2.29), ferritin heavy (Fth1; Q66HI5; diff: 2.19) and light (Ftl1; P02793; diff: 1.75) chains, macrophage migration inhibitory factor 1 (Mif; P30904; diff: 1.69), and fibronectin (Fn1; F1LST1; diff: 0.35) were observed, whereas among downregulated proteins, plectin (Q6S399; diff: -3.34), some Cyp2 family proteins of the cytochrome P450 complex, glutathione S-transferases, flavin-containing monooxygenase 1 (Fmo1; P36365; diff: -2.08), acetyl-CoA acetyltransferase 2 (Acat2; Q5XI22; diff: -2.25), acyl-CoA oxidase 2 (Acox2; F1LNW3; diff: -1.59), and acyl-CoA oxidase 3 (Acox3; F1M9A7; diff: -2.41) were observed. Also, biological processes and functions such as LPS/IL-1 inhibition of RXR, fatty acid metabolism, Nrf2-mediated oxidative stress response, xenobiotic metabolism, and PXR/RXR and CAR/RXR activations were predicted to be affected. In conclusion, the liver of rats with NASH induced by Western diet shows a decreased capacity of metabolizing lipids, fatty acids, and xenobiotic compounds that predispose fibrosis development.

Tomato-Oleoresin Anti-Inflammatory Effect Recovers Obesity-Induced Cardiac Dysfunction by Modulating Myocardial Calcium Handling.

BACKGROUND/AIMS: Considering the importance of inflammation on obesity-related disorders pathogenesis, including cardiac dysfunction, the interest in natural anti-inflammatory therapeutic strategies has emerged. The lycopene is a carotenoid presents in tomato and red fruits that displays anti-inflammatory properties. In this sense, we will evaluate the anti-inflamma-tory effect of tomato-oleoresin supplementation on obesity- related cardiac dysfunction by modulating myocardial calcium kinetic. METHODS: Male Wistar rats were initially randomized into 2 experimental groups: (Control, n= 20) or high sugar- fat diet (HSF, n=20) for 20 weeks. At week 20th, once detected the cardiac dysfunction (cardiac remodeling, systolic and diastolic dysfunction) by echocardiography in HSF group, animals were randomly divided to begin the treatment with tomato-oleoresin, performing 4 groups: Control (n= 10); Control + tomato tomato-oleoresin supplementation (Control + Ly, n= 10); HSF (n= 10) or HSF + tomato tomato-oleoresin supplementation (HSF + Ly, n= 10). Tomato oleoresin was mixed with maize oil equivalent to 10mg lycopene/kg body weight (BW) per day and given orally, by gavage, every morning for a 10-week period. It was analyzed cardiac inflammatory parameters by the enzyme-linked immunosorbent assay (ELISA) and in vivo (echocardiography) and in vitro (studying isolated papillary muscles from the left ventricle) cardiac function. The groups were compared by Two-Way analysis of variance (ANOVA). RESULTS: The HSF diet induced cardiac dysfunction (FS(%) C: 60.4±1.3; C+Ly: 60.9±1.3; HSF: 51.7±1.3; HSF+Ly: 59.4±1.4) and inflammation (TNF-α: C:1.88±0.41; C+Ly: 1.93±1.01; HSF: 4.58±1.99; HSF+Ly: 2.03±0.55; IL-6: C:0.58±0.16; C+Ly: 0.40±0.16; HSF: 2.00±0.45; HSF+Ly: 0.53±0.26; MCP-1: C:0.31±0.08; C+Ly: 0.43±0.22; HSF: 1.54±0.32; HSF+Ly: 0.50±0.16). Tomato-oleoresin supplementation improved cardiac remodeling and dysfunction, cardiac inflammation and myocardial calcium kinetic. CONCLUSION: the anti-inflammatory effect of tomato-oleoresin supplementation treated the obesity-induced cardiac dysfunction by modulating myocardial calcium handling.

Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases.

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

Comparative effects of acute-methionine loading on the plasma sulfur-amino acids in NAC-supplemented HIV+ patients and healthy controls.

In this study, an acute overloading of methionine (MetLo) was used to investigate the trassulfuration pathway response comparing healthy controls and HIV+ patients under their usual diet and dietary N-acetyl-L-cysteine (NAC) supplementation. MetLo (0.1 g Met/kg mass weight) was given after overnight fasting to 20 non-HIV+ control subjects (Co) and 12 HIV+ HAART-treated patients. Blood samples were taken before and after the MetLo in two different 7-day dietary situations, with NAC (1 g/day) or with their usual diet (UD). The amino acids (Met, Hcy, Cys, Tau, Ser, Glu and Gln) and GSH were determined by HPLC and their inflow rate into circulation (plasma) was estimated by the area under the curve (AUC). Under UD, the HIV+ had lower plasma GSH and amino acids (excepting Hcy) and higher oxidative stress (GSSG/GSH ratio), similar remethylation (RM: Me/Hcy + Ser ratio), transmethylation (TM; Hcy/Met ratio) and glutaminogenesis (Glu/Gln ratio), lower transsulfuration (TS: Cys/Hcy + Ser ratio) and Cys/Met ratio and, higher synthetic rates of glutathione (GG: GSH/Cys ratio) and Tau (TG: Tau/Cys ratio). NAC supplementation changed the HIV pattern by increasing RM above control, normalizing plasma Met and TS and, increasing plasma GSH and GG above controls. However, plasma Cys was kept always below controls probably, associatively to its higher consumption in GG (more GSSG than GSH) and TG. The failure of restoring normal Cys by MetLo, in addition to NAC, in HIV+ patients seems to be related to increased flux of Cys into GSH and Tau pathways, probably strengthening the cell-antioxidant capacity against the HIV progression (registered at http://www.clinicaltrials.gov , NCT00910442).

Effects of carnosine supplementation on markers for the pathophysiological development of metabolic dysfunction-associated steatotic liver disease in a diet-induced model.

Consumption of diets high in sugar and fat is related to the development of Metabolic dysfunction-associated steatotic liver disease (MASLD). Carnosine (CAR) is a dipeptide with antioxidant and anti-inflammatory action and has been studied for treating diseases. This work aimed to evaluate the effects of CAR on diet-induced MASLD in rats. Male Wistar rats were distributed into 2 groups (17 weeks): normocaloric (Co, n = 12), and hypercaloric diet rich in lipids and simple carbohydrates (MASLD, n = 12). After, the animals were redistributed to begin the treatment with CAR (4 weeks): Co (n = 6), Co + CAR (n = 6), MASLD (n = 6), and MASLD + CAR (n = 6), administered intraperitoneally (250 mg/kg). Evaluations included nutritional, hormonal and metabolic parameters; hepatic steatosis, inflammatory and oxidative markers. MASLD group had a higher adiposity index, systolic blood pressure, glucose, plasma and liver triglycerides and cholesterol, insulin, hepatic steatosis, oxidative markers, and lower PPAR-α (Peroxisome Proliferator-activated receptor α), compared to the Co. CAR attenuated plasma and hepatic triglyceride and cholesterol levels, hepatic steatosis, CD68+ macrophages, and hepatic oxidative markers, in addition to increasing HDL cholesterol levels and PPAR-α, compared to the untreated MASLD group. CAR acts in importants pathophysiological processes of MASLD and may be a therapeutic compound to control the disease.

Proteomic study of gamma-oryzanol preventive effect on a diet-induced non-alcoholic fatty liver disease model.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease associated with obesity and diabetes prevalence. The use of natural compounds has become an attractive approach to prevent NAFLD and its progression. Gamma-oryzanol (Orz) is a natural compound whose beneficial effects on chronic metabolic diseases have been reported. Therefore, we aimed to investigate the preventive effect of Orz on the hepatic proteome in a diet induced NAFLD model. Wistar rats were randomly distributed into three experimental groups (n=6/group) according to the diet received for 30 weeks: Control group, high sugar-fat (HSF) group, and HSF+Orz group. The isolated Orz was added to the chow at the dose of 0.5% (w/w). We evaluated the nutritional profile, characterized the presence of steatosis through histological analysis, triglyceride content in liver tissue and hepatic inflammation. Next, we performed label-free quantitative proteomics of hepatic tissue. Network analysis was performed to describe involved protein pathways. NAFLD induction was characterized by the presence of hepatic steatosis. Orz prevented lipid accumulation. The compound prevented alterations of the hepatic proteome, highlighted by the modulation of lipid metabolism, inflammation, oxidative stress, xenobiotic metabolism, and the sirtuin signaling pathway. It was possible to identify key altered pathways of NAFLD pathophysiology modulated by Orz which may provide insights into NAFLD treatment targets.

Dietary, anthropometric, and biochemical determinants of uric acid in free-living adults.

BACKGROUND: High plasma uric acid (UA) is a prerequisite for gout and is also associated with the metabolic syndrome and its components and consequently risk factors for cardiovascular diseases. Hence, the management of UA serum concentrations would be essential for the treatment and/or prevention of human diseases and, to that end, it is necessary to know what the main factors that control the uricemia increase. The aim of this study was to evaluate the main factors associated with higher uricemia values analyzing diet, body composition and biochemical markers. METHODS: 415 both gender individuals aged 21 to 82 years who participated in a lifestyle modification project were studied. Anthropometric evaluation consisted of weight and height measurements with later BMI estimation. Waist circumference was also measured. The muscle mass (Muscle Mass Index - MMI) and fat percentage were measured by bioimpedance. Dietary intake was estimated by 24-hour recalls with later quantification of the servings on the Brazilian food pyramid and the Healthy Eating Index. Uric acid, glucose, triglycerides (TG), total cholesterol, urea, creatinine, gamma-GT, albumin and calcium and HDL-c were quantified in serum by the dry-chemistry method. LDL-c was estimated by the Friedewald equation and ultrasensitive C-reactive protein (CRP) by the immunochemiluminiscence method. Statistical analysis was performed by the SAS software package, version 9.1. Linear regression (odds ratio) was performed with a 95% confidence interval (CI) in order to observe the odds ratio for presenting UA above the last quartile (♂UA > 6.5 mg/dL and ♀ UA > 5 mg/dL). The level of significance adopted was lower than 5%. RESULTS: Individuals with BMI ≥ 25 kg/m2 OR = 2.28(1.13-4.6) and lower MMI OR = 13.4 (5.21-34.56) showed greater chances of high UA levels even after all adjustments (gender, age, CRP, gamma-gt, LDL, creatinine, urea, albumin, HDL-c, TG, arterial hypertension and glucose). As regards biochemical markers, higher triglycerides OR = 2.76 (1.55-4.90), US-CRP OR = 2.77 (1.07-7.21) and urea OR = 2.53 (1.19-5.41) were associated with greater chances of high UA (adjusted for gender, age, BMI, waist circumference, MMI, glomerular filtration rate, and MS). No association was found between diet and UA. CONCLUSIONS: The main factors associated with UA increase were altered BMI (overweight and obesity), muscle hypotrophy (MMI), higher levels of urea, triglycerides, and CRP. No dietary components were found among uricemia predictors.

Fructose Consumption Alters Biogenic Amines Associated with Cardiovascular Disease Risk Factors. / Consumo de Frutose Altera Aminas Biogênicas Associadas a Fatores de Risco Cardiovasculares.

BACKGROUND: Cardiovascular diseases (CVD) are the major cause of mortality worldwide, whose most prominent risk factor is unhealthy eating habits, such as high fructose intake. Biogenic amines (BAs) perform important functions in the human body. However, the effect of fructose consumption on BA levels is still unclear, as is the association between these and CVD risk factors. OBJECTIVE: This study aimed to establish the association between BA levels and CVD risk factors in animals that consumed fructose. METHODS: Male Wistar rats received standard chow (n=8) or standard chow + fructose in drinking water (30%) (n=8) over a 24-week period. At the end of this period, the nutritional and metabolic syndrome (MS) parameters and plasmatic BA levels were analyzed. A 5% level of significance was adopted. RESULTS: Fructose consumption led to MS, reduced the levels of tryptophan and 5-hydroxitryptophan, and increased histamine. Tryptophan, histamine, and dopamine showed a correlation with metabolic syndrome parameters. CONCLUSION: Fructose consumption alters BAs associated with CVD risk factors.

FUNDAMENTO: As doenças cardiovasculares (DCV) são a principal causa de mortalidade do mundo, e um de seus fatores de risco são os hábitos alimentares não saudáveis, tais como, o alto consumo de frutose. As aminas biogênicas (ABs) realizam funções importantes no corpo humano. Entretanto, o efeito do consumo de frutose nos níveis das ABs ainda não está claro, bem como a associação entre estes e os fatores de risco da DCV. OBJETIVO: Este estudo teve o objetivo de estabelecer a associação entre os níveis de ABs e os fatores de risco de DCV em animais que consumiram frutose. MÉTODOS: Ratos Wistar machos receberam ração convencional (n=8) ou ração convencional + frutose na água de beber (30%) (n=8) durante 24 semanas. Ao final, foram analisados os parâmetros nutricionais e da síndrome metabólica (SM) e os níveis plasmáticos das ABs. Foi adotado um nível de significância de 5%. RESULTADOS: O consumo de frutose levou à SM, reduziu os níveis de triptofano e 5-hidroxitriptofano e aumentou a histamina. Os níveis de triptofano, histamina e dopamina apresentaram correlação com parâmetros de síndrome metabólica. CONCLUSÃO: O consumo de frutose altera as ABs associadas a fatores de risco de doenças cardiovasculares.

Gamma-oryzanol reduces renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to high sugar-fat diet.

INTRODUCTION: The receptor for AGEs (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface receptors expressed in many organs, among them, the kidneys. When activated, RAGE leads to a sequence of signaling that results in inflammation and oxidative stress, both involved in kidney disease pathogenesis. Gamma-oryzanol (γOz) comprises a mixture of ferulic acid (FA) esters and phytosterols (sterols and triterpene alcohols) mainly found in rice, with antioxidant and anti-inflammatory activities. AIM: To evaluate the effect of γOz to reduce renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to a high sugar-fat diet. METHODS: Male Wistar rats (±187g) were randomly divided into two experimental groups: control (n = 7 animals) and high sugar-fat diet (HSF, n = 14 animals) for 20 weeks. After this period, when the presence of renal disease risk factors was detected in the HSF group (insulin resistance, dyslipidemia, increased systolic blood pressure and obesity), the HSF animals were divided to begin the treatment with γOz or continue receiving only HSF for 10 more weeks. RESULTS: No effect of γOz on obesity and metabolic parameters was observed. However, kidney inflammation and oxidative stress decreased as soon as RAGE levels were reduced in HSF + γOz. CONCLUSION: It is possible to conclude that the gamma- oryzanol was effective in reducing inflammation and oxidative stress in the kidney by modulating the AGEs/RAGE axis.

Relationship between Innate Immune Response Toll-Like Receptor 4 (TLR-4) and the Pathophysiological Process of Obesity Cardiomyopathy. / Relação entre Resposta Imune Inata do Receptor Toll-Like-4 (TLR-4) e o Processo Fisiopatológico da Cardiomiopatia da Obesidade.

BACKGROUND: Obesity is a chronic low-grade inflammation condition related to cardiac disorders. However, the mechanism responsible for obesity-related cardiac inflammation is unclear. The toll-like receptor 4 (TLR-4) belongs to a receptor of the transmembrane family responsible for the immune response whose activation stimulates the production of proinflammatory cytokines. OBJECTIVE: To test whether the activation of the TLR-4 receptor participates in the obesity cardiomyopathy process, due to cytokine production through NF-ĸB activation. METHODS: Male Wistar rats were randomized into two groups: the control group (C, n= 8 animals) that received standard diet/water and the obese group (OB, n= 8 animals) that were fed a high sugar-fat diet and water plus 25% of sucrose for 30 weeks. Nutritional analysis: body weight, adiposity index, food, water, and caloric intake. Obesity-related disorders analysis: plasma glucose, uric acid and triglycerides, HOMA-IR, systolic blood pressure, TNF-α in adipose tissue. Cardiac analysis included: TLR-4 and NF-ĸB protein expression, TNF-α and IL-6 levels. Comparison by unpaired Student's t-test or Mann- Whitney test with a p-value < 0.05 as statistically significant. RESULTS: The OB group showed obesity, high glucose, triglycerides, uric acid, HOMA, systolic blood pressure, and TNF-α in adipose tissue. OB group presented cardiac remodeling and diastolic dysfunction. TLR-4 and NF-ĸB expression and cytokine levels were higher in OB. CONCLUSION: Our findings conclude that, in an obesogenic condition, the inflammation derived from cardiac TLR-4 activation can be a mechanism able to lead to remodeling and cardiac dysfunction.

FUNDAMENTO: A obesidade é uma condição inflamatória crônica de baixo grau relacionada a distúrbios cardíacos. No entanto, o mecanismo responsável pela inflamação cardíaca relacionada à obesidade não é claro. O receptor do tipo toll 4 (TLR-4) pertence a um receptor da família das transmembranas, responsável pela resposta imune, cuja ativação estimula a produção de citocinas pró-inflamatórias. OBJETIVO: Testar se a ativação do receptor TLR-4 participa do processo de cardiomiopatia da obesidade, devido à produção de citocinas por meio da ativação do NF-ĸB. MÉTODOS: Ratos Wistar machos foram randomizados em dois grupos: o grupo controle (C, n = 8 animais) que recebeu dieta padrão/água e o grupo obeso (OB, n = 8 animais) que foi alimentado com dieta rica em açúcar e gordura e água mais 25% de sacarose por 30 semanas. Análise nutricional: peso corporal, índice de adiposidade, alimentos, água e ingestão calórica. Análise de distúrbios relacionados à obesidade: glicose plasmática, ácido úrico e triglicerídeos, HOMA-IR, pressão arterial sistólica, TNF-α no tecido adiposo. A análise cardíaca incluiu: expressão das proteínas TLR-4 e NF-ĸB, níveis de TNF-α e IL-6. Comparação pelo teste t de Student não pareado ou teste de Mann-Whitney com um valor de p <0,05 como estatisticamente significativo. RESULTADOS: O grupo OB apresentou obesidade, glicose elevada, triglicerídeos, ácido úrico, HOMA, pressão arterial sistólica e TNF-α no tecido adiposo. O grupo OB apresentou remodelação cardíaca e disfunção diastólica. A expressão de TLR-4 e NF-ĸB e os níveis de citocinas foram maiores em OB. CONCLUSÃO: Nossos achados concluem que, em uma condição obesogênica, a inflamação derivada da ativação do TLR-4 cardíaco pode ser um mecanismo capaz de levar à remodelação e disfunção cardíaca.

Rice bran modulates renal disease risk factors in animals submitted to high sugar-fat diet.

INTRODUCTION: Obesity, diabetes, and hypertension are common risk factors for chronic kidney disease (CKD). CKD arises due to many pathological insults, including inflammation and oxidative stress, which affect renal function and destroy nephrons. Rice bran (RB) is rich in vitamins and minerals, and contains significant amount of antioxidants. The aim of this study was to evaluate the preventive effect of RB on renal disease risk factors. METHODS: Male Wistar rats (±325 g) were divided into two experimental groups to received a high sugar-fat diet (HSF, n = 8) or high sugar-fat diet with rice bran (HSF + RB, n = 8) for 20 weeks. At the end, renal function, body composition, metabolic parameters, renal inflammatory and oxidative stress markers were analyzed. RESULTS: RB prevented obesity [AI (HSF= 9.92 ± 1.19 vs HSF + RB= 6.62 ± 0.78)], insulin resistance [HOMA (HSF= 83 ± 8 vs. HSF + RB= 42 ± 11)], dyslipidemia [TG (HSF= 167 ± 41 vs. HSF + RB=92 ± 40)], inflammation [TNF-α (HSF= 80 ± 12 vs. HSF + RB=57 ± 14), IL-6 (903 ± 274 vs. HSF + RB=535 ± 277)], oxidative stress [protein carbonylation (HSF= 3.38 ± 0.18 vs. HSF + RB=2.68 ± 0.29), RAGE (HSF=702 ± 36 vs. RSF + RB=570 ± 190)], and renal disease [protein/creatinine ratio (HSF=1.10 ± 0.38 vs. HSF + RB=0.49 ± 0.16)]. CONCLUSION: In conclusion, rice bran prevented renal disease by modulating risk factors.

Antioxidant and anti-inflammatory properties of gamma- oryzanol attenuates insulin resistance by increasing GLUT- 4 expression in skeletal muscle of obese animals.

BACKGROUND: Skeletal muscle is the most important organ for whole-body glucose homeostasis. However, it has been suggested that obesity-related inflammation could be involved in insulin resistance and diabetes mellitus type 2 (DM2) development due several mechanisms, among them, the reduced expression of the glucose transporter type 4 (GLUT-4). Gamma-oryzanol (γOz) is a compound present in the whole grain of rice that presents anti-inflammatory and antioxidant activities. The aim of this study was to verify if the effect antioxidant and anti-inflammatory of yOz attenuate insulin resistance in skeletal muscle of obese rats by increasing GLUT- 4 expression. METHODS: Male Wistar rats (±187 g) were initially randomly distributed into 2 experimental groups (control, n = 6, and high sugar-fat diet (HSF), n = 12) for 20 weeks. At week 20th of this study, once obesity and insulin resistance were detected in the HSF group, animals were divided to begin the treatment with γOz or continue receiving HSF for 10 more weeks. At the end it was analyzed nutritional, metabolic, inflammatory and oxidative stress parameters and GLUT-4 protein expression. RESULTS: The treatment improved insulin resistance, reduced inflammation, increased antioxidant response and GLUT-4 expression. CONCLUSION: It is possible to conclude that the antioxidant and anti-inflammatory activity of yOz attenuates insulin resistance by increasing GLUT-4 expression in skeletal muscle of obese animals.

Gamma-oryzanol as a potential modulator of oxidative stress and inflammation via PPAR-y in adipose tissue: a hypothetical therapeutic for cytokine storm in COVID-19?

The literature has reported a higher prevalence of negative clinical outcomes due to Coronavirus disease 19 (COVID-19) in obese individuals. This can be explained by the cytokine storm, result from the cytokine production from both obesity and viral infection. Gamma-oryzanol (γOz) is a compound with anti-inflammatory and antioxidant activities. However, little is known about the γOz action as a possible agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of this study was to test the hypothesis that γOz attenuates the cytokine storm by stimulating PPAR-γ in the adipose tissue. METHODS: Male Wistar rats were randomly divided into three experimental groups and fed ad libitum for 30 weeks with control diet (C, n = 6), high sugar-fat diet (HSF, n = 6) or high sugar-fat diet + Î³Oz (HSF + Î³Oz, n = 6). HSF groups also received water + sucrose (25%). The γOz dose was 0.5% in the chow. Evaluation in animals included caloric intake, body weight, adiposity index, plasma triglycerides, and HOMA-IR. In adipose tissue was evaluated: PPAR-γ gene and protein expression, inflammatory and oxidative stress parameters, and histological analysis. RESULTS: Adipose tissue dysfunction was observed in HSF group, which presented remarkable PPAR-γ underexpression and increased levels of cytokines, other inflammatory markers and oxidative stress. The γOz treatment prevented adipose tissue dysfunction and promoted PPAR-γ overexpression. CONCLUSION: Natural compounds as γOz can be considered a coadjutant therapy to prevent the cytokine storm in COVID-19 patients with obesity conditions.

Association of dyslipidemia with intakes of fruit and vegetables and the body fat content of adults clinically selected for a lifestyle modification program.

To investigate the relationship of dyslipidemia with demographic distribution and patterns of body fat and dietary intakes. From a universe of adults clinically selected for a lifestyle modification program 979 subjects (409 males and 570 females, 52.2 +/- 9.6 years) fulfilled the inclusion criteria. Overnight-fasting plasma was assayed (dry chemistry) for triglycerides (TG), total (TC) and HDL fraction of cholesterol given the non-HDL (n-HDL) fraction by the difference. Anthropometric assessment included body weight (kg), height (m), fat (bioelectrical impedance) and waist circumference (WC). Food intake was assessed by the 24-hour recall questionnaire and the food groups evaluated through recommendations from an adapted food pyramid. The chances of dyslipidemia from other variable changes were determined by logistic regression with p < 0.05. Normal values of BMI and WC were protective against all dyslipidemia markers whereas only hypercholesterolemia was influenced by diet (meat intake >2 servings). Dietary intakes have protective effects against hypertriglyceridemia with whole grains, odds ratio (OR) 0.342 (CI 95%, 0.154-0.760), fruits > or =3 servings (OR 0.523, 0.290-0.941) and vegetables > or =4 servings (OR 0.360, 0.176-0.735). In general total body and abdominal adiposity influenced all dyslipidemia markers while dietary intake of fruits and vegetables protected against triglyceridemia.

Lycopene Modulates Pathophysiological Processes of Non-Alcoholic Fatty Liver Disease in Obese Rats.

Background: The higher consumption of fat and sugar are associated with obesity development and its related diseases such as non-alcoholic fatty liver disease (NAFLD). Lycopene is an antioxidant whose protective potential on fatty liver degeneration has been investigated. The aim of this study was to present the therapeutic effects of lycopene on NAFLD related to the obesity induced by a hypercaloric diet. Methods: Wistar rats were distributed in two groups: Control (Co, n = 12) and hypercaloric (Ob, n = 12). After 20 weeks, the animals were redistributed into the control group (Co, n = 6), control group supplemented with lycopene (Co+Ly, n = 6), obese group (Ob, n = 6), and obese group supplemented with lycopene (Ob+Ly, n = 6). Ob groups also received water + sucrose (25%). Animals received lycopene solution (10 mg/kg/day) or vehicle (corn oil) via gavage for 10 weeks. Results: Animals which consumed the hypercaloric diet had higher adiposity index, increased fasting blood glucose, hepatic and blood triglycerides, and also presented in the liver macro and microvesicular steatosis, besides elevated levels of tumor necrosis factor-α (TNF-α). Lycopene has shown therapeutic effects on blood and hepatic lipids, increased high-density lipoprotein cholesterol (HDL), mitigated TNF-α, and malondialdehyde (MDA) and further improved the hepatic antioxidant capacity. Conclusion: Lycopene shows therapeutic potential to NAFLD.

Protective Effect of Tomato-Oleoresin Supplementation on Oxidative Injury Recoveries Cardiac Function by Improving ß-Adrenergic Response in a Diet-Obesity Induced Model.

The system redox imbalance is one of the pathways related to obesity-related cardiac dysfunction. Lycopene is considered one of the best antioxidants. The aim of this study was to test if the tomato-oleoresin would be able to recovery cardiac function by improving ß-adrenergic response due its antioxidant effect. A total of 40 animals were randomly divided into two experimental groups to receive either the control diet (Control, n = 20) or a high sugar-fat diet (HSF, n = 20) for 20 weeks. Once cardiac dysfunction was detected by echocardiogram in the HSF group, animals were re- divided to begin the treatment with Tomato-oleoresin or vehicle, performing four groups: Control (n = 6); (Control + Ly, n = 6); HSF (n = 6) and (HSF + Ly, n = 6). Tomato oleoresin (10 mg lycopene/kg body weight (BW) per day) was given orally every morning for a 10-week period. The analysis included nutritional and plasma biochemical parameters, systolic blood pressure, oxidative parameters in plasma, heart, and cardiac analyses in vivo and in vitro. A comparison among the groups was performed by two-way analysis of variance (ANOVA). Results: The HSF diet was able to induce obesity, insulin-resistance, cardiac dysfunction, and oxidative damage. However, the tomato-oleoresin supplementation improved insulin-resistance, cardiac remodeling, and dysfunction by improving the ß-adrenergic response. It is possible to conclude that tomato-oleoresin is able to reduce the oxidative damage by improving the system's ß-adrenergic response, thus recovering cardiac function.

Association between Cardiac Remodeling and Metabolic Alteration in an Experimental Model of Obesity Induced by Western Diet.

The high consumption of fat and sugar contributes to the development of obesity and co-morbidities, such as dyslipidemia, hypertension, and cardiovascular disease. The aim of this study was to evaluate the association between dyslipidemia and cardiac dysfunction induced by western diet consumption. Wistar rats were randomly divided into two experimental groups and fed ad libitum for 20 weeks with a control diet (Control, n = 12) or a high-sugar and high-fat diet (HSF, n = 12). The HSF group also received water + sucrose (25%). Evaluations included feed and caloric intake; body weight; plasma glucose; insulin; uric acid; HOMA-IR; lipid profile: [total cholesterol (T-chol), high-density lipoprotein (HDL), non-HDL Chol, triglycerides (TG)]; systolic blood pressure, and Doppler echocardiographic. Compared to the control group, animals that consumed the HSF diet presented higher weight gain, caloric intake, feed efficiency, insulin, HOMA-IR, and glucose levels, and lipid profile impairment (higher TG, T-chol, non-HDL chol and lower HDL). HSF diet was also associated with atrial-ventricular structural impairment and systolic-diastolic dysfunction. Positive correlation was also found among the following parameters: insulin versus estimated LV mass (r = 0.90, p = 0.001); non-HDL versus deceleration time (r = 0.46, p = 0.02); TG versus deceleration time (r = 0.50, p = 0.01). In summary, our results suggest cardiac remodeling lead by western diet is associated with metabolic parameters.