Beneficial effects of empagliflozin and liraglutide on the cerebral microcirculation of diabetic rats.

OBJECTIVES: This study aimed to evaluate the effects of the antidiabetics liraglutide, a GLP-1 analog, and empagliflozin, an SGLT-2 inhibitor, on the brain microcirculation of diabetic rats. METHODS: Type 2 diabetes mellitus (DM) was experimentally induced in male Wistar rats by combining a high-fat diet and a low dose of streptozotocin (35 mg/kg). Liraglutide (100 µg/kg s.c.) and empagliflozin (10 mg/kg, oral) were administered for 5 weeks. Body weight was monitored periodically. Oral glucose tolerance, fasting glycemia, and blood triglycerides were evaluated after the treatments. Endothelial-leukocyte interactions in the brain microcirculation and structural capillary density were assessed. RESULTS: DM rats presented metabolic and cerebrovascular alterations. Liraglutide treatment decreased body weight and blood triglycerides of DM rats. Empagliflozin treatment improved glucose tolerance but only the combination therapy significantly reduced fasting blood glucose. Both treatments and their combination reduced leukocyte adhesion into the endothelium of brain venules. However, empagliflozin was more effective in preventing DM-induced microvascular rarefaction. CONCLUSION: These findings suggest that chronic treatment with SGLT2 inhibitors and GLP-1 receptor agonists may serve as potential therapeutic approaches to prevent microvascular complications associated with diabetes.

Body composition, but not insulin resistance, influences postprandial lipemia in patients with Turner's syndrome.

OBJECTIVE: The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. METHODS: Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. RESULTS: We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment-insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). CONCLUSION: We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

Atazanavir Is a Competitive Inhibitor of SARS-CoV-2 Mpro, Impairing Variants Replication In Vitro and In Vivo.

Atazanavir (ATV) has already been considered as a potential repurposing drug to 2019 coronavirus disease (COVID-19); however, there are controversial reports on its mechanism of action and effectiveness as anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through the pre-clinical chain of experiments: enzymatic, molecular docking, cell-based and in vivo assays, it is demonstrated here that both SARS-CoV-2 B.1 lineage and variant of concern gamma are susceptible to this antiretroviral. Enzymatic assays and molecular docking calculations showed that SARS-CoV-2 main protease (Mpro) was inhibited by ATV, with Morrison's inhibitory constant (Ki) 1.5-fold higher than GC376 (a positive control) dependent of the catalytic water (H2Ocat) content. ATV was a competitive inhibitor, increasing the Mpro's Michaelis-Menten (Km) more than sixfold. Cell-based assays indicated that different lineages of SARS-CoV-2 is susceptible to ATV. Using oral administration of ATV in mice to reach plasmatic exposure similar to humans, transgenic mice expression in human angiotensin converting enzyme 2 (K18-hACE2) were partially protected against lethal challenge with SARS-CoV-2 gamma. Moreover, less cell death and inflammation were observed in the lung from infected and treated mice. Our studies may contribute to a better comprehension of the Mpro/ATV interaction, which could pave the way to the development of specific inhibitors of this viral protease.

Estudo transversal da capacidade funcional e força muscular em setuagenários institucionalizados / Transversal study of functional capacity and muscle strength in institutionalized elderly

Introdução: As pessoas estão envelhecendo cada vez mais no Brasil e no mundo. Estudos apontam que o processo de envelhecimento populacional é acompanhado com o aumento de ocorrência de morbidade e incapacidade. Diferentes condições podem ser apresentadas pelo envelhecimento, como: diminuição da capacidade funcional, diminuição da força e da massa muscular, entre outros. Objetivo: Investigar a redução da capacidade funcional, secundária a redução de força muscular de membros inferiores em idosos institucionalizados em duas instituições de longa permanência (ILPI) no município de Nova Iguaçu (RJ/Brasil). Métodos: Trata-se de um estudo transversal, exploratório de caráter quantitativo em duas IAPI em Nova Iguaçu/RJ/ no período do mês de julho e agosto de 2017, em que foram selecionados 60 idosos de ambos os sexos (34 homens e 26 mulheres), com faixa etária ≥ 60 anos. Os voluntários foram avaliados quanto a capacidade funcional e a força muscular. Para a capacidade funcional, foi utilizado a escala de Barthel. Para o teste de força, o presente estudo usou para forma de avaliação a escala de Medical Research Council (MRC). Resultados: Os resultados mostraram que 61,7% dos idosos são classificados como independentes pelo índice de Barthel. Na escala de MRC, 95% dos idosos apresentaram fraqueza muscular. Conclusão: Concluímos que a maior proporção de idosos institucionalizados foram considerados independentes, porém, apresentaram quadro de fraqueza muscular. (AU)

Introduction: People are aging more and more in Brazil and worldwide. Studies show that the process of population aging is accompanied by increased occurrence of morbidity and disability. Different conditions can be presented by aging, such as: decreased functional capacity, decreased strength and muscle mass, among others. Objective: To investigate the reduction of functional capacity, secondary to the reduction of muscular strength of lower limbs in elderly institutionalized in two institutions in the municipality of Nova Iguaçu/RJ Brazil. Methods: This is a quantitative exploratory study in two elderly institutions at Nova Iguaçu during the period of July and August 2017, with 60 elderly men and women (34 males and 26 females), age range ≥ 60 years. The volunteers were assessed for functional capacity and muscle strength. For functional capacity, the Barthel scale was used. For strength testing, the present study used the Medical Research Council (MRC) scale for evaluation. Results: The results of the present study showed that 61.7% of the elderly are classified as independent by the Barthel index. In the MRC scale, 95% of the elderly presented muscular weakness. Conclusion: We concluded that the most proportion of institutionalized elderly was considered independent but presented a picture of muscular weakness. (AU)

Impact of a high-fat diet containing canola or soybean oil on body development and bone; parameters in adult male rats / Impacto de una dieta alta en grasa que contiene aceite de canola o aceite de soja en el desarrollo del cuerpo y los huesos; parámetros en ratas macho adultas

Introduction: The role of the fatty acid in the prevention or progression of chronic diseases has generated significant interest on the part of researchers. Thus, our objective was to evaluate the long-term effects of high-fat diet containing soybean or canola oil on body development and bone parameters of male rats. Methods: After weaning, rats were grouped and fed either a control diet (7S) or a high-fat diet containing soybean (19S) or canola oil (19C). Femur and lumbar vertebra (LV4) structure were determined at 180 days by dual-energy X-ray absorptiometry and computed tomography. Results: The groups showed similar food intake, body mass and length development. The bone parameters of the 19C were similar to the control group, while the 19S showed lower bone parameters when compared to the other groups. Conclusions: The high-fat diet containing soybean oil was unfavorable to bone structure, while the canola oil contributed bone health during the adult stage of life (AU)

Introducción: El papel del ácido graso en la prevención o la progresión de las enfermedades crónicas ha generado un interés significativo por parte de los investigadores. Por lo tanto, nuestro objetivo fue evaluar los efectos a largo plazo de la dieta alta en grasas que contienen soja o aceite de canola en los parámetros de desarrollo del cuerpo y los huesos de ratas macho. Métodos: Después del destete, las ratas se agruparon y se alimentaron con una dieta control (7S) o una dieta alta en grasa que contiene soja (19S) o aceite de canola (19C). Fémur y vértebras lumbares (LV4) estructura se determinaron a los 180 días por absorciometría dual de rayos X y tomografía computarizada. Resultados: Los grupos mostraron similares ingesta de alimentos, la masa corporal y el desarrollo de longitud. Los parámetros óseos de la 19C fueron similares al grupo control, mientras que los 19S mostró parámetros óseos inferiores en comparación con los otros grupos. Conclusiones: La dieta alta en grasas que contiene aceite de soja fue desfavorable a la estructura ósea, mientras que el aceite de canola contribuyó salud de los huesos en la etapa adulta de la vida (AU)

Adipocyte morphology and leptin signaling in rat offspring from mothers supplemented with flaxseed during lactation.

OBJECTIVE: We have recently shown that maternal flaxseed supplementation during lactation induces insulin resistance in adult offspring. Here, we studied the effects of maternal dietary flaxseed during lactation on adipocyte morphology and leptin signaling in the hypothalamic-pituitary-thyroid axis as well as on behavioral traits in the adult progeny. METHODS: Lactating rats were fed a control (C) diet or a diet with 25% flaxseed (F). After weaning, pups received a standard diet until postnatal day (PN) 180. Male offspring were killed at PN21 and 180. Data were considered significant at P < 0.05. RESULTS: Weaned F rats presented a lower total and subcutaneous fat mass and higher subcutaneous adipocyte area (+48%), but at adulthood they presented higher subcutaneous and visceral adipocyte areas (+40% and 1.9-fold increase, respectively), with no change in body fat mass. At PN21, F pups had hyperleptinemia (+69%), lower T(3) (-33%), higher TSH (2.1-fold increase), higher pituitary leptin receptor (Ob-R, +11%), signal transducer and activator of transcription 3 (STAT3, +21%), and phosphorylated-STAT3 (p-STAT3, +77%) protein content. Adult F offspring only showed lower T(4) (-28%) and higher thyroid Ob-R (+52%) expression. Maternal flaxseed intake during lactation did not result in behavioral changes in the adult offspring. CONCLUSIONS: Maternal flaxseed supplementation decreases offspring adiposity and increases pituitary leptin signaling at weaning, but it induces hypertrophic adipocytes and higher thyroid leptin receptor in adulthood. The present data suggest that extensive use of flaxseed during lactation is undesirable.

Diet containing low n-6/n-3 polyunsaturated fatty acids ratio, provided by canola oil, alters body composition and bone quality in young rats.

PURPOSE: Adipocytes and osteoblasts were derived from a common progenitor, and canola oil intake may have an adipogenic and osteogenic effect. Thus, our objective was to evaluate the effect on adipocyte, lipid profile, glucose homeostasis, and bone of canola oil as main lipid source on the diet during development. METHODS: After weaning, rats were divided into two groups (n = 10 per group): control (S) and experimental (C) diets containing 7 mL/100 g soybean or canola oil, respectively. At 60 days, body composition, liver and intra-abdominal fat mass, adipocyte morphology, serum analysis, femur and lumbar vertebras density by dual-energy X-ray absorptiometry and computed tomography were determined. Differences were considered significant with P < 0.05. RESULTS: C group showed the following: lower liver (-12%) and intra-abdominal fat mass (-19%) area of adipocyte (-60%), cholesterol (-33%), insulin (-22%), lower total body (-9%) and spine (-33%) bone mineral content and bone area (-7 and -24%, respectively), femur mass (-9%), width of the diaphysis (-6%), femur (-10%) and lumbar vertebrae bone mineral density (-9%), and radiodensity of femoral head (-8%). CONCLUSIONS: The lower intra-abdominal adiposity could have more beneficial effects in a short term, since it can be associated with a better insulin sensitivity and lipid profile, than the small reduction in femur and lumbar vertebra density. However, it has to be considered the incremental effect of this reduction along the aging process.

Abdominal adiposity, insulin and bone quality in young male rats fed a high-fat diet containing soybean or canola oil.

OBJECTIVES: A low ratio of omega-6/omega-3 polyunsaturated fatty acids is associated with healthy bone properties. However, fatty diets can induce obesity. Our objective was to evaluate intra-abdominal adiposity, insulin, and bone growth in rats fed a high-fat diet containing low ratios of omega-6/omega-3 provided in canola oil. METHODS: After weaning, rats were grouped and fed either a control diet (7S), a high-fat diet containing soybean oil (19S) or a high-fat diet of canola oil (19C) until they were 60 days old. Differences were considered to be significant if p<0.05. RESULTS: After 60 days, the 19S and 19C groups showed more energy intake, body density growth and intraabdominal fat mass. However, the 19S group had a higher area (200%) and a lower number (44%) of adipocytes, while the 7S and 19C groups did not differ. The serum concentrations of glucose and insulin and the insulin resistance index were significantly increased in the 19C group (15%, 56%, and 78%, respectively) compared to the 7S group. Bone measurements of the 19S and 19C groups showed a higher femur mass (25%) and a higher lumbar vertebrae mass (11%) and length (5%). Computed tomography analysis revealed more radiodensity in the proximal femoral epiphysis and lumbar vertebrae of 19C group compared to the 7S and 19S groups. CONCLUSIONS: Our results suggest that the amount and source of fat used in the diet after weaning increase body growth and fat depots and affect insulin resistance and, consequently, bone health.

Abdominal adiposity, insulin and bone quality in young male rats fed a high-fat diet containing soybean or canola oil

OBJECTIVES: A low ratio of omega-6/omega-3 polyunsaturated fatty acids is associated with healthy bone properties. However, fatty diets can induce obesity. Our objective was to evaluate intra-abdominal adiposity, insulin, and bone growth in rats fed a high-fat diet containing low ratios of omega-6/omega-3 provided in canola oil. METHODS: After weaning, rats were grouped and fed either a control diet (7S), a high-fat diet containing soybean oil (19S) or a high-fat diet of canola oil (19C) until they were 60 days old. Differences were considered to be significant if p<0.05. RESULTS: After 60 days, the 19S and 19C groups showed more energy intake, body density growth and intraabdominal fat mass. However, the 19S group had a higher area (200 percent) and a lower number (44 percent) of adipocytes, while the 7S and 19C groups did not differ. The serum concentrations of glucose and insulin and the insulin resistance index were significantly increased in the 19C group (15 percent, 56 percent, and 78 percent, respectively) compared to the 7S group. Bone measurements of the 19S and 19C groups showed a higher femur mass (25 percent) and a higher lumbar vertebrae mass (11 percent) and length (5 percent). Computed tomography analysis revealed more radiodensity in the proximal femoral epiphysis and lumbar vertebrae of 19C group compared to the 7S and 19S groups. CONCLUSIONS: Our results suggest that the amount and source of fat used in the diet after weaning increase body growth and fat depots and affect insulin resistance and, consequently, bone health.

Evaluation of body development, fat mass and lipid profile in rats fed with high-PUFA and -MUFA diets, after neonatal malnutrition.

Neonatal malnutrition is associated with several features of the metabolic syndrome, later in life. Although the recovery of malnutrition was studied with different high-fat diets, few studies compare the effects of enriched vegetable oil diets, containing PUFA and MUFA, after weaning. Our aim was to evaluate the recovery with soya oil- or rapeseed oil-enriched diet, after malnutrition in rats whose mothers were food restricted (FR) during lactation. Dams were 50 % FR and compared to standard diet-fed dams (control, C). At 21 d, FR offspring had a lower body mass and length. After weaning C and FR offspring were fed a diet containing 7 % soya oil (7 %sC and 7 %sFR), or supplemented with 19 % soya oil (19 %sC or 19 %sFR) or 19 % rapeseed oil (19 %cC or 19 %cFR). The normal animals fed enriched vegetable oil diets had more visceral fat mass, but lower serum TAG and higher HDL-cholesterol. The 19 %FR groups showed significantly less food intake and body development compared to the 7 %sFR, and the same pattern was observed when this group was compared to the C groups. Absolute and relative mass of vital organs and body were lower in the FR groups. Visceral fat depot was lower in 19 %FR than 7 %FR and C groups. Serum glucose, albumin, TAG, cholesterol, leptin and triiodothyronine did not show significant changes. However, 19 %FR groups showed higher HDL-cholesterol and the 19 %sFR group showed lower serum thyroxine. The data suggest that a higher vegetable oil diet in the recovery of neonatal malnutrition ameliorates some features of the metabolic syndrome later in life.