Canagliflozin combined with aerobic exercise protects against chronic heart failure in rats via regulating the retinol metabolism signaling pathway.
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE225149 | GEO | 2023/02/17
REPOSITORIES: GEO
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Project description:The processes of adaptation to environmental heat and aerobic exercise training improve efficiency in various body systems and bring about acclimatory homeostasis. In order to examine the global genomic responses of the soleus and heart following exposure of rats to these stressors, nylon cDNA Atlas Array was used. Male rats were exposed to one of the following stressors: heat acclimation, aerobic training (treadmill), and combined heat acclimation and aerobic training for short (2, 3 days) and long (1 mo) time period. The study comprised seven experimental groups: Controls-untreated. Heat acclimated groups (2dac, Acc)â exposure to environmental heat at 34C for 2 or 30 days. Exercise groups (3dex, Ex)â graduated training protocol under normothermic conditions for 3 and 30 days at 24C. Exercise training and heat acclimation â (3dexac, ExAc)- exposed to both environmental heat and aerobic exercise as above. The Series data tables appended below: 1) Heart - normalized log2 ratio of geomeans defined as treatment/control 2) Soleus - normalized log2 ratio of geomeans defined as treatment/control 21 samples, 3 pool each, of: 1)Â Control untreated rats 2)Â Long-term heat acclimated rats 3)Â Long-term aerobic-exercised trained rats. 4)Â Rats exposed to long-term heat acclimation and exercise training. 5)Â Short term heat acclimated rats. 6)Â Short term aerobic exercised trained rats 7)Â Rats exposed to short-term heat acclimation and exercise training.
2010-05-27 | E-GEOD-7799 | biostudies-arrayexpress
Project description:This study aimed to examine if early life exercise could normalize the reduced heart mass we have previously observed in the adult hearts from growth restricted rats. We investigated the molecular pathways using microarray analysis to explain how endurance exercise in early life might be regulating the sustained increase in heart mass we have observed in these rats in adulthood. At 5 weeks of age, male WKY rats were allocated to one of the following exercise treatments: remained sedentary with post mortem (PM) at 9 or 24 weeks, early exercise training (from 5-9 weeks of age) with PM at 9 or 24 weeks, or later exercise training (from 20-24 weeks of age) with PM at 24 weeks (n=8 males/group). Exercise training involved treadmill running 5 days/ week for 4 weeks. Running duration progressively increased from 20 up to 60 minutes per day, with the treadmill speed set at 15 m/min for the first week and 20 m/min thereafter. At 9 or 24 weeks of age rats were killed with an intraperitoneal injection of Ilium Xylazil-20 (30 mg/kg) and Ketamine (225 mg/kg). The rats in the 9 week old early exercise and 24 week old later exercise groups were killed 72 hours following the last bout of treadmill running. Total RNA was obtained from the whole-hearts for analysis
2015-12-09 | GSE75781 | GEO
Project description:Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality; yet some individuals are exercise resistant, and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease-risk, we used selective breeding for 15 generation to develop rat models of low- and high-aerobic response to training. Before exercise training, rats selected as low- and high-responders had similar exercise capacities. However, after 8-wks of treadmill training low-responders failed to improve their exercise capacity, while high-responders improved by 54%. Remarkably, low-responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise resistant phenotype segregates with disease risk. Low-responders had impaired exercise-induced angiogenes0is in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low-responders. Low-responders had increased stress/inflammatory signaling and altered TGFM-NM-2 signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease. Cardiac and skeletal muscle from 3 high and 3 low responder rats were examined for differential miRNA expression using Exiqon microarrays
2014-05-23 | E-GEOD-57880 | biostudies-arrayexpress
Project description:Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the main site of glucose uptake, effectiveness of T2D treatment depends in large on the improvement of insulin sensitivity and metabolic adaptability of the muscle. We have shown previously in mice fed an obesogenic high-fat diet that a combination treatment using n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinedione (TZD) anti-diabetic drugs preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether TZD rosiglitazone could elicit the additive beneficial effects on metabolic flexibility when combined with n-3 LC-PUFA. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various dietary treatments: (i) cHF+F, cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids; (ii) cHF+ROSI, cHF with 10 mg rosiglitazone/kg diet; and (iii) cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combination treatment. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the single treatments, with rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism, and n-3 LC PUFA supporting complete oxidation of fatty acids in mitochondria. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combination treatment using n-3 LC-PUFA and TZDs could improve the efficacy of the treatment of obese and diabetic patients. Male C57BL/6N mice had free access to water and Chow. Three-month-old mice were randomly assigned (8 animals per group) to cHF diet (lipid content ~35% wt/wt) or to the following 'treatments' by isocaloric cHF-based diets, namely (i) cHF+F, cHF diet supplemented with n-3 LC-PUFA concentrate (46% DHA, 14% EPA, wt/wt, as triglycerides; product EPAX 1050 TG), which replaced 15% wt/wt of dietary lipids; (ii) cHF+ROSI, cHF diet supplemented with 10 mg rosiglitazone/kg diet; and (iii) cHF+F+ROSI, cHF diet supplemented with both n-3 LC-PUFA concentrate and rosiglitazone. cHF+ROSI at a higher dose, namely 100 mg rosiglitazone/kg diet was also included in the study, but not in the final microarray analysis. The treatment lasted for 8 weeks, whereafter the animals were first fasted for 10 hours during the light phase of the day (between 8.00hr and 18.00hr), than re-fed Chow (starting at 18.00hr), and killed the following day by cervical dislocation under pentobarbital anesthesia (between 9.00hr and 11.00hr); the so-called 'diet-switch protocol'. Gastrocnemius muscle was isolated and used for total RNA isolation.
2012-09-07 | E-GEOD-36716 | biostudies-arrayexpress
Project description:Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality; yet some individuals are exercise resistant, and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease-risk, we used selective breeding for 15 generation to develop rat models of low- and high-aerobic response to training. Before exercise training, rats selected as low- and high-responders had similar exercise capacities. However, after 8-wks of treadmill training low-responders failed to improve their exercise capacity, while high-responders improved by 54%. Remarkably, low-responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise resistant phenotype segregates with disease risk. Low-responders had impaired exercise-induced angiogenes0is in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low-responders. Low-responders had increased stress/inflammatory signaling and altered TGFβ signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease.
2014-05-23 | GSE57880 | GEO
Project description:This study aimed to examine if early life exercise could normalize the reduced heart mass we have previously observed in the adult hearts from growth restricted rats. We investigated the molecular pathways using microarray analysis to explain how endurance exercise in early life might be regulating the sustained increase in heart mass we have observed in these rats in adulthood. At 5 weeks of age, male WKY rats were allocated to one of the following exercise treatments: remained sedentary with post mortem (PM) at 9 or 24 weeks, early exercise training (from 5-9 weeks of age) with PM at 9 or 24 weeks, or later exercise training (from 20-24 weeks of age) with PM at 24 weeks (n=8 males/group). Exercise training involved treadmill running 5 days/ week for 4 weeks. Running duration progressively increased from 20 up to 60 minutes per day, with the treadmill speed set at 15 m/min for the first week and 20 m/min thereafter. At 9 or 24 weeks of age rats were killed with an intraperitoneal injection of Ilium Xylazil-20 (30 mg/kg) and Ketamine (225 mg/kg). The rats in the 9 week old early exercise and 24 week old later exercise groups were killed 72 hours following the last bout of treadmill running. Total RNA was obtained from the whole-hearts for analysis Total RNA obtained from the hearts of WKY rats. Male offspring remained sedentary or underwent treadmill running from 5-9 weeks (early exercise) or 20-24 weeks of age (later exercise).
2015-12-09 | E-GEOD-75781 | biostudies-arrayexpress
Project description:The processes of adaptation to environmental heat and aerobic exercise training improve efficiency in various body systems and bring about acclimatory homeostasis. In order to examine the global genomic responses of the soleus and heart following exposure of rats to these stressors, nylon cDNA Atlas Array was used. Male rats were exposed to one of the following stressors: heat acclimation, aerobic training (treadmill), and combined heat acclimation and aerobic training for short (2, 3 days) and long (1 mo) time period. The study comprised seven experimental groups: Controls-untreated. Heat acclimated groups (2dac, Acc)– exposure to environmental heat at 34C for 2 or 30 days. Exercise groups (3dex, Ex)– graduated training protocol under normothermic conditions for 3 and 30 days at 24C. Exercise training and heat acclimation – (3dexac, ExAc)- exposed to both environmental heat and aerobic exercise as above. The Series data tables appended below: 1) Heart - normalized log2 ratio of geomeans defined as treatment/control 2) Soleus - normalized log2 ratio of geomeans defined as treatment/control Keywords: stress response
2007-12-31 | GSE7799 | GEO
Project description:Chronic heart failure (CHF), with whether reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), is the end-stage of various cardiovascular diseases and severely affects the patients’ lifespan. There has been no effective drugs to improve clinical outcomes for a long time. Sine the recent years, as a hypoglycemic drug, sodium-glucose cotransporter 2 inhibitor (SGLT2i) has aroused great attention due to it’s cardiovascular benefits. However, the underlying mechanisms remain unclear, particularly regarding ferroptosis, a newly defined mechanism of iron-dependent non-apoptotic cell death in heart failure (HF). Here, we discovered and demonstrated that ferroptosis was a key mechanism in rat model of high-salt diet-induced HF, characterized by iron overloading and lipid peroxidation, which was blocked by canagliflozin administration. These findings highlight that targeting ferroptosis serves as a cardioprotective strategy for HF prevention and canagliflozin might display cardiovascular benefits through ferroptosis mitigation.
2022-05-20 | PXD029031 | Pride
Project description:Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the main site of glucose uptake, effectiveness of T2D treatment depends in large on the improvement of insulin sensitivity and metabolic adaptability of the muscle. We have shown previously in mice fed an obesogenic high-fat diet that a combination treatment using n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinedione (TZD) anti-diabetic drugs preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether TZD rosiglitazone could elicit the additive beneficial effects on metabolic flexibility when combined with n-3 LC-PUFA. Adult male C57BL/6J mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various dietary treatments: (i) cHF+F, cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids; (ii) cHF+ROSI, cHF with 10 mg rosiglitazone/kg diet; and (iii) cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combination treatment. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the single treatments, with rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism, and n-3 LC PUFA supporting complete oxidation of fatty acids in mitochondria. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combination treatment using n-3 LC-PUFA and TZDs could improve the efficacy of the treatment of obese and diabetic patients. Male C57BL/6N mice had free access to water and Chow. Three-month-old mice were randomly assigned (8 animals per group) to cHF+ROSI diet (lipid content ~35% wt/wt) supplemented with 10 mg rosiglitazone/kg diet, or cHF+F+ROSI in which n-3 LC-PUFA concentrate (46% DHA, 14% EPA, wt/wt, as triglycerides; product EPAX 1050 TG) replaced 15% wt/wt of dietary lipids. The treatment lasted for 8 weeks, whereafter the animals were first fasted for 10 hours during the light phase of the day (between 8.00hr and 18.00hr), than re-fed Chow (starting at 18.00hr), and killed the following day by cervical dislocation under pentobarbital anesthesia (between 9.00hr and 11.00hr); the so-called 'diet-switch protocol'. Gastrocnemius muscle was isolated and used for total RNA isolation.
2012-09-07 | E-GEOD-36717 | biostudies-arrayexpress
Project description:Male Sprague-Dawley rats were used to establish exhausted-exercise model by motorized rodent treadmill. Yu-Ping-Feng-San at doses of 2.18 g/kg was administrated by gavage before exercise training for 10 consecutive days. Quantitative proteomics was performed for assessing the related mechanism of Yu-Ping-Feng-San.
2022-08-12 | PXD032737 | Pride