Transmembrane protein 126B protects against high fat diet (HFD)-induced renal injury by suppressing dyslipidemia via inhibition of ROS

A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and molecular levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1, and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. Also, 14(15)-EET (a major substrate of sEH), but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1, and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may positively regulate Ampk transcriptionally in mRMCs. This study provides insights into and therapeutic target for the HFD-mediated renal injury.

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Abstract 084: Activation Of Trpv1-expressing Renal Sensory Nerves With N-oleoyldopamine Attenuates High Fat Diet-induced Impairment In Renal Function

Hypertension ◽

10.1161/hyp.64.suppl_1.084 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Shuang-Quan Yu ◽

Donna H Wang

Keyword(s):

Renal Function ◽

Renal Injury ◽

High Fat Diet ◽

Sympathetic Nerve Activity ◽

Intrathecal Injection ◽

Renal Nerves ◽

High Fat ◽

Nerve Activity ◽

Renal Sympathetic Nerve Activity ◽

Renal Sympathetic

Renal injury occurs in obesity. Accumulating evidence indicates that activation of the transient receptor potential vanilloid 1 (TRPV1) protects tissues from injury albeit the mechanisms are largely unknown. We test the hypothesis that high fat diet (HFD) intake impairs afferent renal nerves expressing TRPV1 channels, leading to increased renal sympathetic nerve activity (RSNA), decreased renal function, and hypertension, and that chronic activation of TRPV1 positive afferent renal nerves attenuates HFD-induced impairment. N-oleoyldopamine (OLDA, 1 ng/kg, daily), a selective TRPV1 agonist, was administrated intrathecally (T8-L3) via a indwelled catheter to chronically activate TRPV1 positive afferent renal nerves in rats fed a HFD or normal fat diet (Con) for 8 weeks. HFD decreased renal TRPV1 expression and afferent renal nerve activity (ARNA, Con: 133±8, Con+OLDA: 127±15, HFD: 84±5, HFD+OLDA: 115±7, p<0.05) in response to intra-pelvis perfusion of capsaicin (4 μM, 3 min, 20 ml/min), a selective TRPV1 agonist, which were prevented by OLDA. HFD increased RSNA responses to intrathecal injection of muscimol (3 nmol/kg), a GABA-A receptor agonist, and urinary norepinephrine levels, which were prevented by OLDA. HFD decreased creatinine clearance and increased urinary albumin levels, which were prevented by OLDA (Creatinine clearance, Con: 0.52±0.09, Con+OLDA: 0.54±0.12, HFD: 0.24±0.04, HFD+OLDA: 0.40±0.06 ml/min/100 gbwt, p<0.05). HFD increased levels of collagen deposition, connective tissue growth factor (CTGF), and matrix metalloproteinase-2 (MMP-2) in the kidney, which were prevented by OLDA. HFD increased systolic blood pressure by the week of 6 after HFD, which was prevented by OLDA. Thus, HFD impairs TRPV1-positive afferent renal nerves, increases renal sympathetic nerve activity, and leads to renal injury and hypertension. Segment-specific intrathecal injection of OLDA protects against HFD-induced impairment in afferent renal nerves and prevents HFD-induced renal injury and hypertension. Our data illustrate that preservation of TRPV1 positive afferent renal nerves may be a therapeutic strategy in preventing obesity- or type 2 diabetes-induced renal injury and hypertension.

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Punicalagin alleviates renal injury via the gut-kidney axis in high-fat diet-induced diabetic mice

Food & Function ◽

10.1039/d1fo03343c ◽

2022 ◽

Author(s):

Qinglian Hua ◽

Ya Ling Han ◽

Haifeng Zhao ◽

Haowen Zhang ◽

Bei Yan ◽

...

Keyword(s):

Renal Function ◽

Gut Microbiota ◽

Renal Injury ◽

High Fat Diet ◽

Intestinal Barrier ◽

Diabetic Mice ◽

High Fat ◽

Microbial Ecosystem

Diabetic renal injury was associated with dysbiosis of the gut microbiota and intestinal barrier. Punicalagin (PU) from pomegranates potentially impacts the microbial ecosystem, intestinal barrier, and renal function. Therefore, we...

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Dietary calcium regulates the risk renal injury in high fat diet induced obese rats by regulating renal lipid metabolism, oxidative stress and inflammation

Archives of Physiology and Biochemistry ◽

10.1080/13813455.2020.1746812 ◽

2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Sandeep Das ◽

Dipayan Choudhuri

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Renal Injury ◽

High Fat Diet ◽

Dietary Calcium ◽

High Fat ◽

Obese Rats

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Simvastatin and tempol protect against endothelial dysfunction and renal injury in a model of obesity and hypertension

AJP Renal Physiology ◽

10.1152/ajprenal.00351.2009 ◽

2010 ◽

Vol 298 (1) ◽

pp. F86-F94 ◽

Cited By ~ 34

Author(s):

Sarah F. Knight ◽

Jianghe Yuan ◽

Siddhartha Roy ◽

John D. Imig

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Endothelial Dysfunction ◽

Renal Injury ◽

High Fat Diet ◽

Glomerular Injury ◽

High Fat ◽

Simvastatin Treatment ◽

Wky Rats ◽

Wistar Kyoto

Obesity and hypertension are risk factors for the development of chronic kidney disease. The mechanisms by which elevated blood pressure and fatty acids lead to the development of renal injury are incompletely understood. Here, we investigated the contributions of cholesterol and oxidative stress to renal endothelial dysfunction and glomerular injury in a model of obesity and hypertension. Male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were fed a normal diet, a high-fat diet, a high-fat diet with tempol, or a high-fat diet with simvastatin for up to 10 wk. Blood pressure was not altered by a high-fat diet or treatments. After 3 wk, renal afferent dilatory responses to acetylcholine were impaired in WKY rats and SHR fed a high-fat diet. Tempol treatment prevented this vascular dysfunction in both strains; however, simvastatin treatment demonstrated greater beneficial effects in the SHR. Albuminuria was observed in the SHR and was exacerbated by a high-fat diet. Tempol and simvastatin treatment significantly ameliorated albuminuria in the SHR fed a high-fat diet. Ten weeks on a high-fat resulted in an increase in urinary 8-isoprostane in WKY rats and SHR, and tempol and simvastatin treatment prevented this increase, indicating a reduction in renal oxidative stress. Monocyte chemoattractant protein-1 (MCP-1) excretion was significantly elevated by a high-fat diet in both strains, and tempol prevented this increase. Interestingly, simvastatin treatment had no effect on MCP-1 levels. These data indicate that tempol and simvastatin treatment via a reduction in oxidative stress improve renal endothelial function and decrease glomerular injury in a model of obesity and hypertension.

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Role of Altered Renal Lipid Metabolism in the Development of Renal Injury Induced by a High-Fat Diet

Journal of the American Society of Nephrology ◽

10.1681/asn.2007010089 ◽

2007 ◽

Vol 18 (10) ◽

pp. 2715-2723 ◽

Cited By ~ 148

Author(s):

Shinji Kume ◽

Takashi Uzu ◽

Shin-ichi Araki ◽

Toshiro Sugimoto ◽

Keiji Isshiki ◽

...

Keyword(s):

Lipid Metabolism ◽

Renal Injury ◽

High Fat Diet ◽

High Fat

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Epigallocatechin Gallate (EGCG) Promotes the Immune Function of Ileum in High Fat Diet Fed Mice by Regulating Gut Microbiome Profiling and Immunoglobulin Production

Frontiers in Nutrition ◽

10.3389/fnut.2021.720439 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaoxia Liu ◽

Ke Zhao ◽

Nana Jing ◽

Qingjun Kong ◽

Xingbin Yang

Keyword(s):

Gut Microbiome ◽

High Fat Diet ◽

Transmembrane Protein ◽

Epigallocatechin Gallate ◽

Intragastric Administration ◽

High Fat ◽

Immunoglobulin Production ◽

Transcriptomic Profiling ◽

Egcg Treatment ◽

Microbiome Profiling

This study aimed to investigate the regulatory effect of epigallocatechin gallate (EGCG) on the composition of the gut microbiome, the transcriptomic profiling of ileum, and their interplay in high fat diet (HFD) induced obese mice. Intragastric administration of EGCG to C57BL/6J mice for 14 consecutive weeks remarkably decreased HFD induced excessive fat deposition (p < 0.001), and the increment of serum TG, TC, HDL-C (p < 0.05), as well as improved glucose tolerance (p < 0.001). EGCG shifted the gut microbiota mainly by elevating the relative abundance of Parasutterrlla, Bacteroides, and Akkermansia (p < 0.01), decreasing that of norank_f_Erysipelotrichaceae, unclassified_f_Ruminococcaceae, Anaerotruncus, Roseburia, norank_Lachnospiraceae, and Lachnospiraceae_UCG_006 (p < 0.01) at the genus level. In addition, EGCG affected the transcriptomic profiling of ileum, and the differentially expressed (DE) genes after HFD or/and EGCG treatment were mostly enriched in the immune reaction of ileum, such as the GO term of “immune effector process” and “phagocytosis, recognition.” Furthermore, the KEGG category of “immune diseases,” “immune system,” and “infection diseases: bacterial” were commonly enriched by the DE genes of the two treatments. Among those DE genes, 16 immunoglobulins heavy chain variable region encoded genes (Ighvs) and other immunity-related genes, such as complement component 2 (C2), interferon-induced transmembrane protein 1 (Iftm1), polymeric immunoglobulin receptor (pigR), and alanyl aminopeptidase (Anpep), were highly correlated with the shifted microbes in the gut (p < 0.05, absolute r > 0.5). Overall, the results suggested that EGCG ameliorated the HFD induced metabolic disorder mainly by regulating gut microbiome profiling and the immunoglobulin production of ileum, while the genes expressed in the ileum, especially Ighvs, C2, Iftm1, pigR, and Anpep, might play important roles in coordinating the immunity of mice regarding the gut microbes and the host interactions.

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