Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model.

BACKGROUND: Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity. METHODS: After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated. Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis. RESULTS/DISCUSSION: Characterization of CM by protein array showed the presence of different cytokines and growth factors, including chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I, adiponectin, transforming growth factor (TGF) ß, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis. CONCLUSION: Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due to obesity and corroborate to the paracrine action of MSCs in heart disease models.

Murinometric measurements and retroperitoneal adipose tissue in young rats exposed to the high-fat diet: Is there correlation?

AIM: This study aimed to verify the correlation between murine measurements and retroperitoneal adipose tissue in rats exposed to the high-fat diet. Material and methods: Wistar male adult rats, descendants of mothers who consumed a high-fat diet during pregnancy and lactation and fed the same diet after weaning were used. At 60 days of life, body weight, longitudinal axis and waist circumference (WC) were measured. The Body Mass Index (BMI) and the Lee Index were calculated for a posterior analysis of the correlation with the amount of retroperitoneal adipose tissue dissected on the same day. For analysis of the data, the Pearson correlation test was used, considering statistical significance for p <0.05. Results: Body weight had a weak correlation (r= 0.31; p= 0.38) with retroperitoneal adipose tissue. While the longitudinal correlated moderately and negative (r= -0.40; p= 0.25). Abdominal circumference (r= 0.62; p= 0.05), body mass index (r= 0.61; p= 0.03) and Lee (r= 0.69; p= 0.03) correlated moderately and positively with adipose tissue. Conclusion: Among the measured murine measurements, weight and longitudinal axis were not good indicators to represent accumulation of retroperitoneal adipose tissue in rats. However, Lee's index seems to be the best murine marker to diagnose the accumulation of retroperitoneal fat. BMI, CA and Lee index were murine parameters with higher correlation.

Effects of maternal high fat intake during pregnancy and lactation on total cholesterol and adipose tissue in neonatal rats.

AIM: Obesity during pregnancy is one of the most established risk factors for negative long-term programming. The aim of the present study was to investigate the effects of maternal consumption of a high-fat diet during pregnancy and lactation on the weight gain, visceral adipose tissue and cholesterolemia in neonatal rats. METHODS: Wistar rats were divided into two groups according to the mother's diet during pregnancy and lactation: Control group (CG, n = 12) were the offspring of rats fed a standard diet (4% lipid) and the Test group (TG, n = 12) were pups rats fed on a high fat diet (23% lipid). The weight of the animals was measured on alternate days until the 22nd day of life, when collected visceral adipose tissue and blood were collected for biochemical analysis. For statistical analysis the Student t test, Sidak´s teste and two way ANOVA was used, with p <0.05. RESULTS: the test group showed differences in weight gain, visceral adipose tissue and higher cholesterol. CONCLUSION: a maternal exposure to a high-fat diet during pregnancy and lactation can promote changes in weight gain, hypercholesterolemia and an increase in adipose tissue in neonatal rats.

Murinometric measurements and retroperitoneal adipose tissue in young rats exposed to the high-fat diet: Is there correlation? / Medidas murinométricas e tecido adiposo retroperitoneal em ratos jovens expostos à dieta hiperlipídica: existe correlação?

Aim: This study aimed to verify the correlation between murine measurements and retroperitoneal adipose tissue in rats exposed to the high-fat diet. Material and methods: Wistar male adult rats, descendants of mothers who consumed a high-fat diet during pregnancy and lactation and fed the same diet after weaning were used. At 60 days of life, body weight, longitudinal axis and waist circumference (WC) were measured. The Body Mass Index (BMI) and the Lee Index were calculated for a posterior analysis of the correlation with the amount of retroperitoneal adipose tissue dissected on the same day. For analysis of the data, the Pearson correlation test was used, considering statistical significance for p<0.05. Results: Body weight had a weak correlation (r= 0.31; p= 0.38) with retroperitoneal adipose tissue. While the longitudinal correlated moderately and negative (r= -0.40; p= 0.25). Abdominal circumference (r= 0.62; p= 0.05), body mass index (r= 0.61; p= 0.03) and Lee (r= 0.69; p= 0.03) correlated moderately and positively with adipose tissue. Conclusion: Among the measured murine measurements, weight and longitudinal axis were not good indicators to represent accumulation of retroperitoneal adipose tissue in rats. However, Lee's index seems to be the best murine marker to diagnose the accumulation of retroperitoneal fat. BMI, CA and Lee index were murine parameters with higher correlation.

Objetivo: Este estudo teve como objetivo verificar a correlação entre medidas murinométricas e tecido adiposo retroperitoneal em ratos expostos à dieta hiperlipídica. Material e métodos: Foram utilizados ratos Wistar machos adultos, descendentes de mães que consumiram dieta hiperlipídica durante a gestação e lactação e alimentados com a mesma dieta após o desmame. Aos 60 dias de vida, foram medidos o peso corporal, o eixo longitudinal e a circunferência da cintura (CC). O Índice de Massa Corporal (IMC) e o Índice de Lee foram calculados para posterior análise da correlação com a quantidade de tecido adiposo retroperitoneal dissecado no mesmo dia. Para análise dos dados, utilizou se o teste de correlação de Pearson, considerando significância estatística para p<0.05. Resultados: O peso corporal apresentou uma correlação fraca (r= 0,31; p= 0,38) com o tecido adiposo retroperitoneal. Enquanto o longitudinal correlacionou moderadamente e negativo (r= -0,40; p= 0,25). A circunferência abdominal (r = 0,62; p = 0,05), índice de massa corporal (r= 0,61; p= 0,03) e Lee (r= 0,69; p= 0,03) correlacionaram-se moderada e positivamente com o tecido adiposo. Conclusão: Entre as medidas murinométricas, o peso e o eixo longitudinal não foram bons indicadores para representar o acúmulo de tecido adiposo retroperitoneal em ratos. No entanto, o índice de Lee parece ser o melhor indicador murinométrico para diagnosticar o acúmulo de gordura retroperitoneal. O IMC, índice de Lee e CA foram parâmetros murinométricos com maior correlação.

Effects of maternal high fat intake during pregnancy and lactation on total cholesterol and adipose tissue in neonatal rats / Efeitos do consumo materno de dieta hiperlipídica durante a gestação e lactação no colesterol total e tecido adiposo de ratos neonatos

Abstract Aim Obesity during pregnancy is one of the most established risk factors for negative long-term programming. The aim of the present study was to investigate the effects of maternal consumption of a high-fat diet during pregnancy and lactation on the weight gain, visceral adipose tissue and cholesterolemia in neonatal rats. Methods Wistar rats were divided into two groups according to the mother's diet during pregnancy and lactation: Control group (CG, n = 12) were the offspring of rats fed a standard diet (4% lipid) and the Test group (TG, n = 12) were pups rats fed on a high fat diet (23% lipid). The weight of the animals was measured on alternate days until the 22nd day of life, when collected visceral adipose tissue and blood were collected for biochemical analysis. For statistical analysis the Student t test, Sidak´s teste and two way ANOVA was used, with p <0.05. Results the test group showed differences in weight gain, visceral adipose tissue and higher cholesterol. Conclusion a maternal exposure to a high-fat diet during pregnancy and lactation can promote changes in weight gain, hypercholesterolemia and an increase in adipose tissue in neonatal rats.

Resumo Objetivo A obesidade durante a gestação é um dos fatores de risco mais estabelecidos para uma programação negativa em longo prazo. O objetivo do presente estudo foi investigar os efeitos do consumo materno de uma dieta hiperlipídica durante a gestação e lactação no aumento do peso, do tecido adiposo visceral e colesterolemia em ratos neonatos. Métodos Ratos Wistar foram divididos em dois grupos de acordo com a dieta da mãe durante a gestação e lactação: grupo controle (GC, n=12) composto por filhotes de ratas alimentadas com uma dieta padrão (lipídios 4%) e o grupo teste (GT, n=12) composto de filhotes de ratas alimentadas com dieta hiperlipídica (lipídios 23%). O peso dos animais foi aferido em dias alternados até o 22° dia de vida, quando foi coletado sangue para análises bioquímicas. Para a análise estatística utilizou-se os seguintes testes: two way ANOVA, teste de Sidak e teste t de Student, com p< 0,05. Resultados O grupo teste mostrou diferença no ganho de peso, no tecido adiposo visceral e nos níveis de colesterol. Conclusão Uma exposição materna a uma dieta hiperlipídica durante a gestação e lactação pode promover maior ganho ponderal, hipercolesterolemia e um aumento do tecido adiposo em ratos neonatos.

Murinometric measurements and retroperitoneal adipose tissue in young rats exposed to the high-fat diet: Is there correlation?

Abstract Aim This study aimed to verify the correlation between murine measurements and retroperitoneal adipose tissue in rats exposed to the high-fat diet. Material and methods: Wistar male adult rats, descendants of mothers who consumed a high-fat diet during pregnancy and lactation and fed the same diet after weaning were used. At 60 days of life, body weight, longitudinal axis and waist circumference (WC) were measured. The Body Mass Index (BMI) and the Lee Index were calculated for a posterior analysis of the correlation with the amount of retroperitoneal adipose tissue dissected on the same day. For analysis of the data, the Pearson correlation test was used, considering statistical significance for p 0.05. Results: Body weight had a weak correlation (r= 0.31; p= 0.38) with retroperitoneal adipose tissue. While the longitudinal correlated moderately and negative (r= -0.40; p= 0.25). Abdominal circumference (r= 0.62; p= 0.05), body mass index (r= 0.61; p= 0.03) and Lee (r= 0.69; p= 0.03) correlated moderately and positively with adipose tissue. Conclusion: Among the measured murine measurements, weight and longitudinal axis were not good indicators to represent accumulation of retroperitoneal adipose tissue in rats. However, Lee's index seems to be the best murine marker to diagnose the accumulation of retroperitoneal fat. BMI, CA and Lee index were murine parameters with higher correlation.

Resumo Objetivo Este estudo teve como objetivo verificar a correlação entre medidas murinométricas e tecido adiposo retroperitoneal em ratos expostos à dieta hiperlipídica. Material e métodos: Foram utilizados ratos Wistar machos adultos, descendentes de mães que consumiram dieta hiperlipídica durante a gestação e lactação e alimentados com a mesma dieta após o desmame. Aos 60 dias de vida, foram medidos o peso corporal, o eixo longitudinal e a circunferência da cintura (CC). O Índice de Massa Corporal (IMC) e o Índice de Lee foram calculados para posterior análise da correlação com a quantidade de tecido adiposo retroperitoneal dissecado no mesmo dia. Para análise dos dados, utilizou-se o teste de correlação de Pearson, considerando significância estatística para p 0.05. Resultados: O peso corporal apresentou uma correlação fraca (r= 0,31; p= 0,38) com o tecido adiposo retroperitoneal. Enquanto o longitudinal correlacionou moderadamente e negativo (r= -0,40; p= 0,25). A circunferência abdominal (r = 0,62; p = 0,05), índice de massa corporal (r= 0,61; p= 0,03) e Lee (r=0,69; p= 0,03) correlacionaram-se moderada e positivamente com o tecido adiposo. Conclusão: Entre as medidas murinométricas, o peso e o eixo longitudinal não foram bons indicadores para representar o acúmulo de tecido adiposo retroperitoneal em ratos. No entanto, o índice de Lee parece ser o melhor indicador murinométrico para diagnosticar o acúmulo de gordura retroperitoneal. O IMC, índice de Lee e CA foram parâmetros murinométricos com maior correlação.

Maternal transference of passive humoral immunity to Haemonchus contortus in goats.

This study evaluated the transference of maternal-specific antibodies against Haemonchus contortus and the humoral immune response of 32 goat kids to natural infection by the parasite, from birth to 5 months of age. All serum samples collected immediately after birth and before colostrum ingestion were negative for H. contortus antibodies, as demonstrated by ELISA. However, 30 and 60 days after colostrum and milk ingestion, antibody detection was positive and faecal egg count (FEC) was negative, suggesting the transference of humoral immunity by colostrum. All animals were FEC-negative for Strongylodea until four months of age, consistent with the stage of animal development where nourishment comes only from breastfeeding. Animals also presented a high serum IgA concentration, associated with lower levels of total IgG. This work demonstrated that passive humoral immunity against H. contortus in goat kids occurs via the colostrum and not by transplacental transference of antibodies.

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits.

We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1% cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with 3H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 +/- 0.056 and 0.170 +/- 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 +/- 0.033 h-1) was considerably greater than CE-FCR (0.046 +/- 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 +/- 0.1475 and CE = 0.2135 +/- 0.1580%/g) but in cholesterol-fed animals FC uptake (0.0890 +/- 0.0319%/g) was greater than CE uptake (0.0595 +/- 0.0207%/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1 percent cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with ³H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 ± 0.056 and 0.170 ± 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 ± 0.033 h-1) was considerably greater than CE-FCR (0.046 ± 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 ± 0.1475 and CE = 0.2135 ± 0.1580 percent/g) but in cholesterol-fed animals FC uptake (0.0890 ± 0.0319 percent/g) was greater than CE uptake (0.0595 ± 0.0207 percent/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.