Renal Expression of AQP1 in the High-fat Nutritional Obesity of Rat

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.

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Expression of V2R and AQPs in the Renal Medulla of High-fat Nutritional Obesity of Rat

International Journal of Morphology ◽

10.4067/s0717-95022019000200459 ◽

2019 ◽

Vol 37 (2) ◽

pp. 459-465

Author(s):

Jinbao Wang ◽

Pei Wang ◽

Zhisheng Wang ◽

Linwu Ran ◽

Li Yang ◽

...

Keyword(s):

Renal Medulla ◽

High Fat ◽

Nutritional Obesity

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Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/9032792 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 7

Author(s):

Weijie Yi ◽

Xiao Xie ◽

Miying Du ◽

Yongjun Bu ◽

Nannan Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Green Tea ◽

High Fat Diet ◽

Tea Polyphenols ◽

Green Tea Polyphenols ◽

Activity Levels ◽

High Fat ◽

Sirt3 Expression ◽

Renal Expression ◽

Expression And Activity

Scope. Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results. Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) and sirtuin 3(SIRT3) were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE) level and the acetyl-MnSOD (K122)/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion. The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.

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Abstract P189: Disruption of Cyp2c44 Increases Sodium Chloride Cotransporter Expression and Activity in the Distal Convoluted Tubule

Hypertension ◽

10.1161/hyp.68.suppl_1.p189 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Xiao-Tong Su ◽

Lijun Wang ◽

Zhongxiuzi Gao ◽

Dao-Hong Lin ◽

VarunKumar Pandey ◽

...

Keyword(s):

High Fat Diet ◽

Collecting Duct ◽

Renal Tubules ◽

Epoxyeicosatrienoic Acid ◽

High Fat ◽

Sodium Chloride Cotransporter ◽

Renal Expression ◽

Clearance Study ◽

Late Part

Cytochrome-P450 (CYP) epoxygenase plays an important role in the regulation of renal sodium transport. Previous studies have demonstrated that global disruption of Cyp2c44 , a major epoxygenase in the renal tubules, increased ENaC activity in the collecting duct. In addition, we have demonstrated that an increase in dietary Na intake significantly increased the mRNA expression of CYP2c44 in the DCT. DCT is responsible for the reabsorption of 5-9% of filter Na load and is the target for thiazide diuretic. Na absorption in the DCT is mediated by NaCl cotransporter (NCC) and also by ENaC in the late part of DCT. However, the role of epoxyeicosatrienoic acid (EET) in the regulation Na transport in the DCT is not clear. We now examine the role of CYP2c44 and EET in the regulation of NCC expression. The disruption of Cyp2c44 increases the expression of NCC and ENaC activity in the DCT. The disruption of CYP2c44 also suppressed the renal expression of GPR75, a receptor which is activated by 20-hydroxyeicosatetraenoic acid (20-HETE). Renal Na clearance study also demonstrates that the effect of hydrochlorothiazide on Na excretion in Cyp2c44 knockout (KO) mice was significantly higher than those of WT mice. In addition, the disruption of Cyp2c44 significantly increased the expression of ste20-proline and alanine-rich kinase (SPAK) which is known to stimulate NCC activity by phosphorylation. Increased dietary Na intake decreases NCC expression and this effect is blunted in Cyp2c44 KO mice. The role of EET in the regulation of NCC expression is further suggested by the finding that high fat-diet induced increase in NCC expression is inhibited by application of EET. We conclude that CYP2c44-derived EET plays an important role in inhibiting NCC and ENaC in the DCT.

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High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00158.2015 ◽

2015 ◽

Vol 309 (9) ◽

pp. E802-E810 ◽

Cited By ~ 12

Author(s):

Caixia Li ◽

Silas A. Culver ◽

Syed Quadri ◽

Kelly L. Ledford ◽

Qusai Y. Al-Share ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Angiotensin Converting Enzyme ◽

High Fat Diet ◽

Renin Angiotensin System ◽

Converting Enzyme ◽

High Fat ◽

Angiotensin System ◽

Collagen Iii ◽

Renal Expression

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene ( Cc1−/−) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type ( Cc1+/+) and Cc1−/− mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1−/− mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr508) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1+/+ mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1−/− mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr508) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1−/− mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis.

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Adipocytes play an etiological role in the podocytopathy of high-fat diet-fed rats

Journal of Endocrinology ◽

10.1530/joe-16-0064 ◽

2016 ◽

Vol 231 (2) ◽

pp. 109-120 ◽

Cited By ~ 5

Author(s):

Jinn-Yang Chen ◽

Deng-Yuan Jian ◽

Chih-Chan Lien ◽

Yu-Ting Lin ◽

Ching-Heng Ting ◽

...

Keyword(s):

Renal Function ◽

Kidney Disease ◽

Conditioned Medium ◽

Diet Group ◽

Normal Diet ◽

Sprague Dawley ◽

High Fat ◽

Urine Protein ◽

Renal Histology ◽

Renal Expression

Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy.

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Abstract # P-20: 11b-Hydroxysteroid Dehydrogenase 1 Regulation in High Fat Diet Induced Insulin Resistant Rats and Rats Treated with Sutherlandia Frutescens

Endocrine Practice ◽

10.1016/s1530-891x(20)43833-9 ◽

2016 ◽

Vol 22 ◽

pp. 23

Author(s):

Ngozi F. Nnolum-Orji ◽

Saartjie Roux ◽

Janine Mackenzie ◽

Disang Lekutlane

Keyword(s):

High Fat Diet ◽

Hydroxysteroid Dehydrogenase ◽

High Fat ◽

Insulin Resistant ◽

Sutherlandia Frutescens

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Abstract #64: A Comparative Pharmacokinetic Study of Metformin Hydrochloride Oral Solution (100 mg/mL) in Healthy Adult Male Patients Under Fasting, Low-Fat, and High-fat Meal Conditions

Endocrine Practice ◽

10.1016/s1530-891x(20)46341-4 ◽

2004 ◽

Vol 10 ◽

pp. 23

Author(s):

Kiran Marthak

Keyword(s):

Adult Male ◽

Pharmacokinetic Study ◽

Healthy Adult ◽

Oral Solution ◽

Metformin Hydrochloride ◽

High Fat ◽

Comparative Pharmacokinetic ◽

Healthy Adult Male ◽

Male Patients ◽

Fat Meal

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Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000259 ◽

2019 ◽

Vol 89 (1-2) ◽

pp. 45-54

Author(s):

Akemi Suzuki ◽

André Manoel Correia-Santos ◽

Gabriela Câmara Vicente ◽

Luiz Guillermo Coca Velarde ◽

Gilson Teles Boaventura

Keyword(s):

Thyroid Hormones ◽

High Fat Diet ◽

Female Offspring ◽

Flaxseed Oil ◽

Diabetic Rats ◽

High Fat ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Flaxseed Flour ◽

Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

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