scholarly journals Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats

2020 ◽  
Vol 245 (2) ◽  
pp. 193-205 ◽  
Author(s):  
Myat Theingi Swe ◽  
Laongdao Thongnak ◽  
Krit Jaikumkao ◽  
Anchalee Pongchaidecha ◽  
Varanuj Chatsudthipong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
High Fat ◽  
Enzyme Expression ◽  
Renal Gluconeogenesis ◽  
Glucose Reabsorption ◽  
Obese Rats ◽  
Gluconeogenic Enzyme

The kidneys release glucose into the systemic circulation through glucose reabsorption and renal gluconeogenesis. Currently, the significance of renal glucose release in pathological conditions has become a subject of interest. We examined the effect of sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i) on renal gluconeogenic enzyme expression in obese rats. Male Wistar rats (180–200 g) were fed either a normal diet (ND, n = 6) or a high-fat diet. At 16 weeks, after confirming the degree of glucose intolerance, high-fat diet-fed rats were randomly subdivided into three groups (n = 6/group): untreated group (HF), treated with dapagliflozin 1 mg/kg/day (HFSG) and treated with metformin 30 mg/kg/day (HFM). The treatment was continued for 4 weeks. We observed that dapagliflozin or metformin mitigated the enhanced expression of renal gluconeogenic enzymes, PEPCK, G6Pase and FBPase, as well as improved glucose tolerance and renal function in obese rats. Dapagliflozin downregulated the elevated expression of gluconeogenic transcription factors p-GSK3β, p-CREB and coactivator PGC1α in the renal cortical tissue. Metformin reduced the expression levels of renal cortical FOXO1 and CREB. Furthermore, reduced renal insulin signaling was improved and renal oxidative stress was attenuated by either dapagliflozin or metformin treatment in obese rats. We concluded that glucose tolerance was improved by dapagliflozin in obese prediabetic rats by suppressing renal glucose release from not only glucose reabsorption but also renal gluconeogenesis through improving renal cortical insulin signaling and oxidative stress. The efficacy of dapagliflozin in improving renal insulin signaling, oxidative stress and renal function was greater than that of metformin.

scholarly journals Strawberry Intake Ameliorates Oxidative Stress and Decreases GABA Levels Induced by High-Fat Diet in Frontal Cortex of Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 70 ◽  
Author(s):  
Cuauhtémoc Sandoval-Salazar ◽  
Cecilia Oviedo-Solís ◽  
Edmundo Lozoya-Gloria ◽  
Herlinda Aguilar-Zavala ◽  
Martha Solís-Ortiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Oxidative Damage ◽  
Frontal Cortex ◽  
Protein Oxidation ◽  
High Fat Diet ◽  
High Fat ◽  
Gaba Concentration ◽  
Obese Rats ◽  
Lipid And Protein Oxidation

It has been proposed that there is a correlation between high-fat diet (HFD), oxidative stress and decreased γ-aminobutyric acid (GABA) levels, but this has not been thoroughly demonstrated. In the present study, we determined the effects of strawberry extract intake on the oxidative stress and GABA levels in the frontal cortex (FC) of obese rats. We observed that an HFD increased lipid and protein oxidation, and decreased GABA levels. Moreover, UV-irradiated strawberry extract (UViSE) decreased lipid peroxidation but not protein oxidation, whereas non-irradiated strawberry extract (NSE) reduced protein oxidation but not lipid peroxidation. Interestingly, NSE increased GABA concentration, whereas UViSE was not as effective. In conclusion, our results suggest that an HFD increases oxidative damage in the FC, whereas strawberry extract intake may ameliorate the disturbances associated with HFD-induced oxidative damage.

scholarly journals Catalase-dependent H2O2consumption by cardiac mitochondria and redox-mediated loss in insulin signaling

2016 ◽  
Vol 311 (5) ◽  
pp. H1091-H1096 ◽  
Author(s):  
Paul M. Rindler ◽  
Angela Cacciola ◽  
Michael Kinter ◽  
Luke I. Szweda
Keyword(s):  
Oxidative Stress ◽  
Glutathione Peroxidase ◽  
Binding Affinity ◽  
Insulin Signaling ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Cardiac Mitochondria ◽  
High Fat ◽  
Akt Phosphorylation ◽  
Selective Increase

We have recently demonstrated that catalase content in mouse cardiac mitochondria is selectively elevated in response to high dietary fat, a nutritional state associated with oxidative stress and loss in insulin signaling. Catalase and various isoforms of glutathione peroxidase and peroxiredoxin each catalyze the consumption of H2O2. Catalase, located primarily within peroxisomes and to a lesser extent mitochondria, has a low binding affinity for H2O2relative to glutathione peroxidase and peroxiredoxin. As such, the contribution of catalase to mitochondrial H2O2consumption is not well understood. In the current study, using highly purified cardiac mitochondria challenged with micromolar concentrations of H2O2, we found that catalase contributes significantly to mitochondrial H2O2consumption. In addition, catalase is solely responsible for removal of H2O2in nonrespiring or structurally disrupted mitochondria. Finally, in mice fed a high-fat diet, mitochondrial-derived H2O2is responsible for diminished insulin signaling in the heart as evidenced by reduced insulin-stimulated Akt phosphorylation. While elevated mitochondrial catalase content (∼50%) enhanced the capacity of mitochondria to consume H2O2in response to high dietary fat, the selective increase in catalase did not prevent H2O2-induced loss in cardiac insulin signaling. Taken together, our results indicate that mitochondrial catalase likely functions to preclude the formation of high levels of H2O2without perturbing redox-dependent signaling.

scholarly journals Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Mahdieh Abbasalizad Farhangi ◽  
Ghazaleh Nameni ◽  
Ghazaleh Hajiluian ◽  
Mehran Mesgari-Abbasi
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
High Fat Diet ◽  
Cardiac Tissue ◽  
High Fat ◽  
Obese Rats

scholarly journals Effects of Vitamin D and Simvastatin on Inflammatory and Oxidative Stress Markers of High-Fat Diet-Induced Obese Rats

2021 ◽  
Vol 2 (3) ◽  
pp. 39-50
Author(s):  
Abdel-Moniem A. Makhlouf ◽  
Atef M. Mahmoud ◽  
Rania G. Ibrahim ◽  
Yasmeen S. Abdel Aziz
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
High Fat Diet ◽  
Male Rats ◽  
Antioxidant Defenses ◽  
Control Group ◽  
High Fat ◽  
Stress Markers ◽  
Obese Rats ◽  
Markers Of Oxidative Stress

Purpose: This study was aimed to evaluate the antioxidant and anti-inflammatory effects of vitamin D and Simvastatin (SIM) on a high-fat diet (HFD) induced-obese rats. Methods: 40 adult male rats were divided into four groups: control group, HFD, HFD + vitamin D, and HFD + SIM for 14 weeks. Vitamin D or SIM supplementation was done for the last 6 weeks. Vitamin D dosage was 500 IU/kg, while SIM dosage was 10 mg/kg. Interleukin-6 (IL-6) concentration and markers of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione(GSH) concentrations in serum were determined using ELISA kits and spectrophotometry methods, respectively. Results: Treatment with vitamin D or SIM could significantly reduce IL-6 and MDA and increases SOD, GPx activities, and GSH levels. Oxidative stress can result not only from increased ROS production but also from dysfunctional antioxidant defenses. Conclusion: From the experimental results, it was observed that SIM and vitamin D could attenuate oxidative stress and inflammation markers associated with obesity.

scholarly journals High-Fat Diet Increased Oxidative Stress and Mitochondrial Dysfunction Induced by Renal Ischemia-Reperfusion Injury in Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Priyanka N. Prem ◽  
Gino A. Kurian
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Ischemia Reperfusion ◽  
Protein Translation ◽  
Renal Ischemia ◽  
High Fat ◽  
Dietary Regimen ◽  
The Impact

Renal ischemia-reperfusion (IR) injury is one of the major causes of acute kidney injury influenced by the ischemic duration and the presence of comorbidities. Studies have reported that high-fat diet consumption can induce renal lipotoxicity and metabolic dyshomeostasis that can compromise the vital functions of kidney. This study aimed to evaluate the impact of a high-fat diet in the recovery of renal tissue from IR and explored the cellular pathology. In this study, 24 male Wistar rats were divided into two groups: normal diet (ND; n = 12) and high-fat diet (HD; n = 12), which were further subdivided into sham and IR groups at the end of the dietary regimen. The high-fat diet was introduced in 4-week-old rats and continued for 16 weeks. IR was induced by bilateral clamping of the renal peduncle for 45 min, followed by 24 h of reperfusion. Blood chemistry, estimated glomerular filtration rate (eGFR), mitochondrial function, and oxidative stress analysis were carried out to study the pathological changes. The rats fed with HD showed a decreased eGFR and elevated plasma creatinine, thereby compromised kidney function. Subcellular level changes in HD rats are deceased mitochondrial copy number, low PGC-1α gene expression, and declined electron transport chain (ETC) enzymes and adenosine triphosphate (ATP) level. Upon IR induction, HD rats exhibited severely impaired renal function (eGFR-0.09 ml/min) and elevated injury markers compared with ND rats. A histological analysis displayed increased tubular necrosis and cast formation in HD-IR in comparison to ND-IR. The oxidative stress and mitochondrial dysfunction were more prominent in HD-IR. In vitro protein translation assessment revealed impaired translational capacity in HD-IR mitochondria, which suggests mitochondrial changes with diet that may adversely affect the outcome of IR injury. High-fat diet consumption alters the normal renal function by modifying the cellular mitochondria. The renal changes compromise the ability of the kidney to recover from ischemia during reperfusion.

scholarly journals Antioxidants preserve redox balance and inhibit c-Jun-N-terminal kinase pathway while improving insulin signaling in fat-fed rats: evidence for the role of oxidative stress on IRS-1 serine phosphorylation and insulin resistance

2008 ◽  
Vol 197 (2) ◽  
pp. 287-296 ◽  
Author(s):  
R Vinayagamoorthi ◽  
Zachariah Bobby ◽  
M G Sridhar
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Redox Balance ◽  
Serine Phosphorylation ◽  
Control Group ◽  
High Fat ◽  
Jnk Pathway

The oxidative stress-sensitive c-Jun-N-terminal kinase (JNK) pathway is known to be activated in diabetic condition and is involved in the progression of insulin resistance. However, the effect of antioxidants on JNK pathway and insulin resistance has not been investigated. The present study was aimed to investigate the effect of antioxidants on redox balance, insulin sensitivity, and JNK pathway in high-fat-fed rats. Male Wistar rats were divided into four groups: the control group – received a rodent chow; control+antioxidant group – fed with rodent chow supplemented with 0.2% (w/w) vitamin E, 0.3% (w/w) vitamin C, and 0.5% (w/w) α-lipoic acid; high-fat group – received high-fat diet; and high fat+antioxidant group – fed with high-fat diet supplemented with above antioxidants. Fat feeding to rats for 9 weeks significantly increased IRS-1 serine phoshorylation, reduced insulin-stimulated IRS-1 tyrosine phosphorylation and insulin sensitivity. High-fat diet also impaired redox balance and activated the redox-sensitive serine kinase – JNK pathway. Antioxidant supplementation along with high-fat diet preserved the free radical defense system, inhibited the activation of JNK pathway, and improved insulin signaling and insulin sensitivity. The present study shows for the first time that antioxidants inhibit JNK pathway and IRS-1 serine phosphorylation while improving insulin sensitivity in fat-fed rats. These findings implicate the beneficial effect of antioxidants in obesity-/dyslipidemia-induced insulin resistance in humans.

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