Project description:This study considers the physiological modulation of liver proteins due to the supplementation with fish oils under two different dietary backgrounds: low- or high- fat and sucrose diets, and the effect of their combination with an antioxidant agent (grape polyphenols) which provides reducing power. For this scope, a quantitative proteomics approach based on the Isobaric Tag for relative and Absolute Quantitation methodology (iTRAQ)-coupled to nano-LC-MS/MS and complemented with 2D-DIGE analysis were used for determining the regulation of liver proteins exerted by the supplementation with fish oils, polyphenols or their combination of Wistar Kyoto rats in the two chosen dietary backgrounds. This experimental design was useful to investigate if the behavior of fish oils changes when the dietary background is modified and the possible synergy between fish oils and polyphenols. Results show that the capacity of fish oils, polyphenols or their combination for down or up-regulating liver proteins depends on the dietary context. In the background of low-fat low-sucrose healthy diets, 10 different proteins were altered by the sum of three supplements, in opposite to the 45 altered proteins found in the high-fat high-sucrose unhealthy diets. In both situations, fish oils seemed to be the main force for regulating liver proteins, although the addition of polyphenols was able to modulate some fish oils effects. Moreover, we provide evidence of the effect of fish oils and their combination with grape polyphenols for improving biochemical parameters and for reducing enzymes of hepatic lipogenesis and glycolysis, for enhancing fatty acid beta oxidation and insulin signaling and for the amelioration of endoplasmic reticule stress and protein oxidation when are included in an unhealthy diet.
Project description:This study considers the physiological modulation of liver proteins due to the supplementation with fish oils under two different dietary backgrounds: low- or high- fat and sucrose diets, and the effect of their combination with an antioxidant agent (grape polyphenols) which provides reducing power. For this scope, a quantitative proteomics approach based on the Isobaric Tag for relative and Absolute Quantitation methodology (iTRAQ)-coupled to nano-LC-MS/MS and complemented with 2D-DIGE analysis were used for determining the regulation of liver proteins exerted by the supplementation with fish oils, polyphenols or their combination of Wistar Kyoto rats in the two chosen dietary backgrounds. This experimental design was useful to investigate if the behavior of fish oils changes when the dietary background is modified and the possible synergy between fish oils and polyphenols. Results show that the capacity of fish oils, polyphenols or their combination for down or up-regulating liver proteins depends on the dietary context. In the background of low-fat low-sucrose healthy diets, 10 different proteins were altered by the sum of three supplements, in opposite to the 45 altered proteins found in the high-fat high-sucrose unhealthy diets. In both situations, fish oils seemed to be the main force for regulating liver proteins, although the addition of polyphenols was able to modulate some fish oils effects. Moreover, we provide evidence of the effect of fish oils and their combination with grape polyphenols for improving biochemical parameters and for reducing enzymes of hepatic lipogenesis and glycolysis, for enhancing fatty acid beta oxidation and insulin signaling and for the amelioration of endoplasmic reticule stress and protein oxidation when are included in an unhealthy diet.
Project description:Investigation of gene expression level changes in pancreatic and liver tissues of diabetic db/db mice supplemented with selenate, compared to the diabetic db/db mice administered placebo. Fasting blood glucose levels increased continuously in diabetic db/db mice administered placebo (DMCtrl) but decreased gradually in selenate-supplemented diabetic db/db mice (DMSe) and approached normal values when the experiment ended. The size of pancreatic islets increased, causing the plasma insulin concentration to double in DMSe mice compared with that in DMCtrl mice. Two six chip studies using total RNA respectively isolated from pancreatic and liver tissues of three selenate-supplemented diabetic db/db mice, and three diabetic db/db mice administered placebo.
Project description:Investigation of gene expression level changes in pancreatic and liver tissues of diabetic db/db mice supplemented with selenate, compared to the diabetic db/db mice administered placebo. Fasting blood glucose levels increased continuously in diabetic db/db mice administered placebo (DMCtrl) but decreased gradually in selenate-supplemented diabetic db/db mice (DMSe) and approached normal values when the experiment ended. The size of pancreatic islets increased, causing the plasma insulin concentration to double in DMSe mice compared with that in DMCtrl mice.
Project description:The type 2 diabetes medication, rosiglitazone, has come under scrutiny for possibly increasing the risk of cardiac disease and death. To investigate the effects of rosiglitazone on the diabetic heart, we performed cardiac transcriptional profiling of a murine model of type 2 diabetes, the C57BL/KLS-leprdb/leprdb (db/db) mouse. We compared cardiac gene expression profiles from three groups: untreated db/db mice (db-c), db/db mice after rosiglitazone treatment (db-t), and non-diabetic db/+ mice. Mice were divided into three groups: Non-diabetic controls (db/+), untreated diabetic controls (db-c), and rosiglitazone-treated diabetic mice (db-t). Whole-heart RNA from five mice from each of the three groups after four months with or without treatment was used for microarray analysis.Universal Reference RNAs for mouse (Stratagene, La Jolla, CA) were purchased as microarray reference controls.
Project description:Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report that SMPDL3b excess, as observed in podocytes in diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival insulin signaling by interfering with insulin receptor isoforms binding to caveolin-1 in PM. SMPDL3b excess affects the production of active sphingolipids resulting in decreased ceramide-1-phosphate (C1P) content as observed in human podocytes in vitro and in kidney cortexes of diabetic db/db mice in vivo. Podocyte-specific Smpdl3b deficiency in db/db mice is sufficient to restore kidney cortex C1P content and to protect from DKD. Exogenous administration of C1P restores IR signaling in vitro and prevents established DKD progression in vivo. Taken together, we identified SMPDL3b as a modulator of insulin signaling and demonstrated that supplementation with exogenous C1P may represent a lipid therapeutic strategy to treat diabetic complications such as DKD.
Project description:The microarray analysis is to investigate the different expression profile of microRNAs in bone marrow-derived progenitor cells from type 2 diabetic mice and healthy control mice. microRNA expression profiles were compared between bone marrow-derived progenitor cells from either type 2 diabetic db/db mice or their in-colony control litter db/+ mice.
Project description:The microarray analysis is to investigate the different expression profile of microRNAs in bone marrow-derived progenitor cells from type 2 diabetic mice and healthy control mice. microRNA expression profiles were compared between bone marrow-derived progenitor cells from either type 2 diabetic db/db mice or their in-colony control litter db/+ mice. Total RNA was extracted from bone marrow-derived progenitor cells from either type 2 diabetic db/db mice (Jackson lab, # 000642) or their in-colony control litter db/+ mice. N=3 per group.