Prefrontal Cortex and Hippocampus Inflammation in Mice Fed High-Carbohydrate or High-Fat Diets.

We previously reported that a high-carbohydrate diet (HCD) induced systemic inflammation and higher gene expression of proinflammatory mediators in the liver, skeletal muscle, and brain than a high-fat diet (HFD). However, the differences between the groups were less pronounced in the brain. In this study, we extended the evaluation of inflammation to specific areas of the brain. In this study, we evaluated the gene expression of caspase 2, caspase 3, caspase 9, cyclooxygenase-2 (Cox 2), inducible nitric oxide synthase (iNOS), interleukin (IL), IL-6, IL-1ß, IL-10, IL-4, tumor necrosis factor-alpha (TNF-α), integrin subunit alpha m (Itgam), S100 protein (S100), allograft inflammatory factor 1 (Aif1), and glial fibrillary acidic protein (Gfap) in the prefrontal cortex and hippocampus of male Swiss mice that were fed with HCD or HFD for 8 weeks. The HCD group exhibited higher IL-1ß expression, whereas the HFD group showed higher TNF-α expression in the prefrontal cortex. In the hippocampus, TNF-α expression was higher in the HFD group. IL-1ß and TNF-α are proinflammatory cytokines that have been associated with impaired brain function and numerous brain disorders. Our results indicate that both HCD and HFD promote prefrontal cortex inflammation; however, the hippocampus seems more sensitive to a HFD than HCD.

The Myristic Acid:Docosahexaenoic Acid Ratio Versus the n-6 Polyunsaturated Fatty Acid:n-3 Polyunsaturated Fatty Acid Ratio as Nonalcoholic Fatty Liver Disease Biomarkers.

It is well established that diets containing an increased omega-6 polyunsaturated fatty acid (n-6 PUFA) to omega-3 polyunsaturated fatty acid (n-3 PUFA) ratios are linked to inflammation and chronic diseases such as nonalcoholic fatty liver disease (NAFLD). However, the influence of an elevated n-6 PUFA:n-3 PUFA ratio in the tissues requires clarification. Herein, we identified primary experimental and clinical studies where it is possible to compare the performance of the myristic acid (Myr):docosahexaenoic acid (DHA) and n-6 PUFA:n-3 PUFA ratios in the liver and/or serum as potential NAFLD biomarkers. Articles were included if quantitative values of n-6 PUFA, n-3 PUFA, Myr, DHA, and information about liver inflammation or liver disease progression parameters were provided. Overall, most experimental (91.6%) and clinical studies (87.5%) reported higher Myr:DHA ratios associated with inflammation and/or NAFLD progression than the n-6 PUFA:n-3 PUFA ratio. We conclude that the Myr:DHA ratio represents a better biomarker of NAFLD than the n-6 PUFA:n-3 PUFA ratio. Future studies are necessary for verifying this observation.

Glycerol Potentiates the Effects of Glucose in Promoting Glucose Recovery During Hypoglycemia: From Basic to Clinical Investigations and Their Therapeutic Application.

We compared the effect of oral glucose versus oral glucose combined with glycerol (glucose + glycerol) in promoting glucose recovery during hypoglycemia. These studies were carried out in two series of experiments. In the first series of experiments, 16 overnight fasted rats received an intraperitoneal injection of lispro insulin (1 IU/kg), and 25 min later, they received oral water (control), glucose (0.25 g/kg), glycerol (2.5 g/kg), or glucose (0.25 g/kg) + glycerol (2.5 g/kg). In the second series of experiments on 164 eligible type 1 diabetic (T1D) patients, 30 individuals with a history of hypoglycemia were recruited. Five volunteers did not meet the inclusion criteria and two subjects were excluded after starting the clinical investigation; 23 patients concluded the study. All patients with symptoms of hypoglycemia ingested oral glucose (15 g) or glucose (15 g) + glycerol (9.45 g). To treat hypoglycemia in T1D patients, preparations containing glucose alone or glucose + glycerol were used alternately (2 weeks/2 weeks) in a double-blind crossover scheme. Throughout the clinical research (4 weeks), glucose concentrations were assessed with a continuous glucose monitoring device and the results after the use of glucose alone or glucose + glycerol preparations were compared. Oral glucose combined with glycerol was more effective in promoting glucose recovery in comparison with glucose alone, not only in rats but also in T1D patients. Taken together, our experimental and clinical investigations reported the best performance of oral administration of glucose + glycerol in comparison with isolated glucose.

Decreased Docosahexaenoic Acid Levels in Serum of HIV Carrier Patients.

The study aimed to measure serum fatty acids (FAs) composition in HIV carrier patients and compare it with non-HIV carrier patients. The FAs composition was measured by gas chromatography as follows: four saturated FAs myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0), and docosanoic acid (22:0); four monounsaturated FAs 7-hexadecenoic acid (16:1 n-9), palmitoleic acid (16:1 n-7), oleic acid (18:1 n-9), and vaccenic acid (18:1 n-7); and three polyunsaturated FAs linoleic acid (18:2 n-6), dihomo-γ-linolenic acid (20:3 n-6), and docosahexaenoic acid (DHA, 22:6 n-3). We reported herein lower (P < .05) DHA concentration (by 40%) in the serum of HIV carrier patients than in non-HIV carrier patients. This FA has a pivotal role as a precursor of anti-inflammatory molecules with beneficial effects on metabolism, cardiovascular system, and immunological system. Even though most clinical studies reported beneficial effects of DHA supplementation in HIV carrier patients, this issue remains under debate. Further investigations then require to fully clarify the role of DHA in preventing or alleviating the comorbidities associated with HIV infection.

Akt activation by insulin treatment attenuates cachexia in Walker-256 tumor-bearing rats.

Cancer-bearing often exhibits hypoinsulinemia, insulin (INS) resistance and glutamine depletion associated with cachexia. However, INS and glutamine effects on cachexia metabolic abnormalities, particularly on tumor-affected proteins related to INS resistance, are poorly known. The main purpose of this study was to investigate the effects of INS and glutamine dipeptide (GDP) treatments on phospho-protein kinase B (p-Akt), and phospho-hormone sensitive lipase (p-HSL) in Walker-256 tumor-bearing rats. INS (NPH, 40 UI/kg, subcutaneous), GDP (1.5 g/kg, oral), INS+GDP or vehicle (control rats) were administered for 13 days, once a day, starting at the day of inoculation of tumor cells. The experiments were performed 4 hours after the last treatment to evaluate acute effects of INS and GDP, besides the chronic effects. INS and/or INS+GDP treatments, which markedly increased the insulinemia, increased the p-Akt: total Akt ratio and prevented the increased p-HSLSer552 : total HSL ratio in the retroperitoneal fat of tumor-bearing rats, without changing the INS resistance and increased expression of factor tumor necrosis-α (TNF-α) in this tissue. INS and INS+GDP also increased the p-Akt: total Akt ratio, whereas GDP and INS+GDP increased the GLUT4 glucose transporter gene expression, in the gastrocnemius muscle of the tumor-bearing rats. Accordingly, treatments with INS and INS+GDP markedly reduced glycemia, increased retroperitoneal fat and attenuated the body mass loss of tumor-bearing rats. In conclusion, hyperinsulinemia induced by high-dose INS treatments increased Akt phosphorylation and prevented increased p-HSLSer552 : total HSL ratio, overlapping INS resistance. These effects are consistent with increased fat mass gain and weight loss (cachexia) attenuation of tumor-bearing rats, evidencing that Akt activation is a potential strategy to prevent loss of fat mass in cancer cachexia.

Brain Fatty Acid Composition and Inflammation in Mice Fed with High-Carbohydrate Diet or High-Fat Diet.

Both high fat diet (HFD) and high carbohydrate diet (HCD) modulate brain fatty acids (FA) composition. Notwithstanding, there is a lack of information on time sequence of brain FA deposition either for HFD or HCD. The changes in brain FA composition in mice fed with HFD or HCD for 7, 14, 28, or 56 days were compared with results of 0 (before starting given the diets). mRNA expressions of allograft inflammatory factor 1 (Aif1), cyclooxygenase-2 (Cox 2), F4/80, inducible nitric oxide synthase (iNOS), integrin subunit alpha m (Itgam), interleukin IL-1ß (IL-1ß), IL-6, IL-10, and tumor necrosis factor alpha (TNF-α) were measured. The HFD group had higher speed of deposition of saturated FA (SFA), monounsaturated FA (MUFA), and polyunsaturated FA (PUFA) at the beginning of the experimental period. However, on day 56, the total amount of SFA, MUFA, and PUFA were similar. mRNA expressions of F4/80 and Itgam, markers of microglia infiltration, were increased (p < 0.05) in the brain of the HCD group whereas inflammatory marker index (IMI) was higher (46%) in HFD group. In conclusion, the proportion of fat and carbohydrates in the diet modulates the speed deposition of FA and expression of inflammatory gene markers.

The influence of Gymnema sylvestre on the elevation of blood levels of lipids after administration of animal fat in male wistar rats - DOI: 10.4025/actascibiolsci.v26i3.1602 / Efeito da Gymnema sylvestre na elevação da lipidemia após administração de gordura de origem animal em ratos wistar - DOI: 10.4025/actascibiolsci.v26i3.1602

The aim of the present experiment was to investigate the influence of Gymnema sylvestre (Gs) on the elevation of blood levels of lipids after administration of animal fat in male Wistar rats (230250g). The animals, which were fasted for 22h, were separated in five groups that received (8:00 a.m) intragastric administration of: 1) 2ml of pork fat Batavo® /kg of body weight (PFB); 2) PFB+500mg/kg of Gs body weight (Gs 500mg); 3) PFB + 1g/kg of Gs body weight (Gs 1 g); 4) Gs 500mg; 5) Gs 1g. The animals were sacrificed 30min after the administration of these substances. No significant differences were verified in the serum concentration of total lipids, triglycerides and cholesterol in the animals, which received PBF in the presence or absence of Gs 500mg or Gs 1g. Therefore, the results showed that Gs could not affect the intestinal absorption of lipids

Neste trabalho investigamos a influência da Gymnema sylvestre (Gs) na elevação da lipidemia após administração de gordura de origem animal em ratos machos Wistar (230g - 250g). Os animais, em jejum por 22 horas, foram divididos em 5 grupos que receberam via intragástrica às 8h os seguintes tratamentos: 1) 2mL de gordura suína Batavo®/kg de peso corpóreo (GSB); 2) GSB + 500mg/kg de peso corpóreo de Gs (Gs 500mg); 3) GSB + 1g/kg de peso corpóreo de Gs (Gs 1g); 4) Gs 500mg; 5) Gs 1g. Os animais foram sacrificados 30min após a administração destas substâncias. Não observamos diferenças significativas na concentração sérica de lipídeos totais, triglicerídeos e colesterol total nos ratos que receberam GSB na ausência ou presença de Gs 500mg ou Gs 1g. Portanto, nossos resultados sugerem que a Gs não afeta a absorção intestinal de lipídeos