Thirty days of combined consumption of a high-fat diet and fructose-rich beverages promotes insulin resistance and modulates inflammatory response and histomorphometry parameters of liver, pancreas, and adipose tissue in Wistar rats.

OBJECTIVE: The aim of this study was to verify the effects of consumption of a high-fat diet (HFD) combined with fructose-rich beverages (FRT) in promoting metabolic and physiologic changes associated with insulin resistance. METHODS: Thirty-two male Wistar rats (250 ± 10 g) were randomly allocated into four groups (n = 8) that received either a standard diet (CON), HFD, FRT, or HFD + FRT for 30 d. Insulin sensitivity and glucose tolerance were evaluated using the insulin tolerance test (ITT) and oral glucose tolerance test (OGTT). Serum samples were used to analyze the metabolic parameters and hormone levels. Interleukin (IL)-6, IL-10, IL-1ß, and tumor necrosis factor-α assays were performed in the liver, pancreas, gastrocnemius muscle, and epididymal adipose tissue by enzyme-linked immunosorbent assay. Histologic and morphometric analyses were performed on the liver, pancreas, and adipose tissues. RESULTS: Consumption of HFD + FRT promoted a significant increase (P < 0.05) in body weight, index adiposity, and in the area under the curve of ITT (P < 0.001) and OGTT (P < 0.001) when compared with the CON group. Consumption of FRT alone increased fasting glucose (P = 0.015), insulin (P = 0.035), and homeostasis model assessment index (P = 0.018), and these changes were of greater magnitude when FRT was combined with HFD. Moreover, the rats fed an HFD + FRT demonstrated a significant increase in lipid droplets in the liver (P < 0.001), an increase in adipocyte area, and an increase in inflammatory cytokines in the liver, pancreas, skeletal muscle, and adipose tissue. CONCLUSION: Consumption of an HFD + FRT promotes insulin resistance, increases inflammatory cytokines, and modulates histomorphometric parameters of the liver, pancreas, and adipose tissue, typical of insulin resistance in humans.

Antioxidant Effects of Oral Ang-(1-7) Restore Insulin Pathway and RAS Components Ameliorating Cardiometabolic Disturbances in Rats.

In prevention studies of metabolic syndrome (MetS), Ang-(1-7) has shown to improve the insulin signaling. We evaluated the HPßCD/Ang-(1-7) treatment on lipid metabolism, renin-angiotensin system (RAS) components, oxidative stress, and insulin pathway in the liver and gastrocnemius muscle and hepatic steatosis in rats with established MetS. After 7 weeks of high-fat (FAT) or control (CT) diets, rats were treated with cyclodextrin (HPßCD) or HPßCD/Ang-(1-7) in the last 6 weeks. FAT-HPßCD/empty rats showed increased adiposity index and body mass, gene expression of ACE/ANG II/AT1R axis, and oxidative stress. These results were accompanied by imbalances in the insulin pathway, worsening of liver function, hyperglycemia, and dyslipidemia. Oral HPßCD/Ang-(1-7) treatment decreased ACE and AT1R, increased ACE2 gene expression in the liver, and restored thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), insulin receptor substrate (Irs-1), glucose transporter type 4 (GLUT4), and serine/threonine kinase 2 (AKT-2) gene expression in the liver and gastrocnemius muscle improving hepatic function, cholesterol levels, and hyperglycemia in MetS rats. Overall, HPßCD/Ang-(1-7) treatment restored the RAS components, oxidative stress, and insulin signaling in the liver and gastrocnemius muscle contributing to the establishment of blood glucose and lipid homeostasis in MetS rats.

Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet.

Oxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats.