scholarly journals Intrarenal renin-angiotensin system mediates fatty acid-induced ER stress in the kidney

2016 ◽  
Vol 310 (5) ◽  
pp. F351-F363 ◽  
Author(s):  
Chunling Li ◽  
Yu Lin ◽  
Renfei Luo ◽  
Shaoming Chen ◽  
Feifei Wang ◽  
...  

Obesity-related kidney disease is related to caloric excess promoting deleterious cellular responses. Accumulation of saturated free fatty acids in tubular cells produces lipotoxicity involving significant cellular dysfunction and injury. The objectives of this study were to elucidate the role of renin-angiotensin system (RAS) activation in saturated fatty acid-induced endoplasmic reticulum (ER) stress in cultured human proximal tubule epithelial cells (HK2) and in mice fed with a high-fat diet. Treatment with saturated fatty acid palmitic acid (PA; 0.8 mM) for 24 h induced ER stress in HK2, leading to an unfolded protein response as reflected by increased expressions of the ER chaperone binding immunoglobulin protein (BiP) and proapoptotic transcription factor C/EBP homologous protein (CHOP) protein as evaluated by immunoblotting. PA treatment also induced increased protein expression of inositol requiring protein 1α (IRE1α), phosphorylated eukaryotic initiation factor-α (eIF2α), and activating transcription factor 4 (ATF4) as well as activation of caspase-3. PA treatment was associated with increased angiotensin II levels in cultured medium. The angiotensin II type 1 receptor (AT1R) blocker valsartan or renin inhibitor aliskiren dramatically suppressed PA-induced upregulation of BiP, CHOP, IRE1α, p-eIF2α, and ATF4 in HK2 cells. In contrast, valsartan or aliskiren did not prevent ER stress induced by tunicamycin. C57BL/6 mice fed with a high-fat diet for 14 wk exhibited increased protein expressions of BiP and CHOP compared with control mice, which were significantly attenuated by the valsartan treatment. Increased angiotensin II levels in serum and urine were observed in mice fed with a high-fat diet when compared with controls. It is suggested that the intrarenal RAS activation may play an important role in diabetic kidney injury via mediating ER stress induced by saturated fatty acid.

Author(s):  
Baojian Xue ◽  
Yang Yu ◽  
Terry G. Beltz ◽  
Fang Guo ◽  
Robert B. Felder ◽  
...  

Background Prenatal and postnatal insults can induce a physiological state that leaves offspring later in life vulnerable to subsequent challenges (stressors) eliciting cardiometabolic diseases including hypertension. In this study, we investigated whether maternal angiotensin II–induced hypertension in rats sensitizes postweaning high‐fat diet (HFD)‐elicited hypertensive response and whether this is associated with autonomic dysfunction and altered central mechanisms controlling sympathetic tone in offspring. Methods and Results When eating a low‐lard‐fat diet, basal mean arterial pressure of male offspring of normotensive or hypertensive dams were comparable. However, HFD feeding significantly increased mean arterial pressure in offspring of normotensive and hypertensive dams, but the elevated mean arterial pressure induced by HFD was greater in offspring of hypertensive dams, which was accompanied by greater sympathetic tone and enhanced pressor responses to centrally administrated angiotensin II or leptin. HFD feeding also produced comparable elevations in cardiac sympathetic activity and plasma levels of angiotensin II, interleukin‐6, and leptin in offspring of normotensive and hypertensive dams. Reverse transcriptase polymerase chain reaction analyses in key forebrain regions implicated in the control of sympathetic tone and blood pressure indicated that HFD feeding led to greater increases in mRNA expression of leptin, several components of the renin‐angiotensin system and proinflammatory cytokines in offspring of hypertensive dams when compared with offspring of normotensive dams. Conclusions The results indicate that maternal hypertension sensitized male adult offspring to HFD‐induced hypertension. Increased expression of renin‐angiotensin system components and proinflammatory cytokines, elevated brain reactivity to pressor stimuli, and augmented sympathetic drive to the cardiovascular system likely contributed.


2021 ◽  
Author(s):  
Hayoung Woo ◽  
Jung Eun Park ◽  
Youn-Soo Cha

Abstract Background: Korean fermented food, doenjang, is questioned due to its high salt content, although it has been reported an abundance of beneficial effects. Therefore, we investigated its impact on renin-angiotensin system (RAS) hypertension using 3T3-L1 adipocytes and male Sprague-Dawley rats.Results: Among the rats fed with normal diet (ND), high-fat diet (HD), high-fat diet with 8% table salt (HDS), or high-fat diet with doenjang containing 8% table salt (HDJ) for 13 weeks, the HDJ group showed significantly lower blood pressure, lesser body weight, and reduced levels of serum angiotensin II and aldosterone, compared to the HD and HDS groups. In addition, mRNA expressions levels of angiotensinogen, angiotensin converting enzyme, angiotensin II receptor type 1, and angiotensin II receptor type 2 were downregulated in epididymal fat of the HDJ group.Conclusions: In spite of its high salt content, Doenjang appears to inhibit obesity-induced hypertension through modulation of RAS by blocking the angiotensin converting enzyme, even with high fat intake.


Hypertension ◽  
2016 ◽  
Vol 67 (1) ◽  
pp. 163-170 ◽  
Author(s):  
Baojian Xue ◽  
Robert L. Thunhorst ◽  
Yang Yu ◽  
Fang Guo ◽  
Terry G. Beltz ◽  
...  

2015 ◽  
Vol 309 (9) ◽  
pp. E802-E810 ◽  
Author(s):  
Caixia Li ◽  
Silas A. Culver ◽  
Syed Quadri ◽  
Kelly L. Ledford ◽  
Qusai Y. Al-Share ◽  
...  

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.


2020 ◽  
Vol 65 ◽  
pp. 103726 ◽  
Author(s):  
Matheus Henrique Romão ◽  
Graziele Freitas de Bem ◽  
Izabelle Barcellos Santos ◽  
Ricardo de Andrade Soares ◽  
Dayane Teixeira Ognibene ◽  
...  

2020 ◽  
Vol 32 (14) ◽  
pp. 1169
Author(s):  
Arpitha Rao ◽  
Aparna Satheesh ◽  
Guruprasad Nayak ◽  
Pooja Suresh Poojary ◽  
Sandhya Kumari ◽  
...  

The present study was designed to investigate the effect of diet-induced obesity on endoplasmic reticulum (ER) stress in oocytes. Swiss albino mice (3 weeks old) were fed with a high-fat diet (HFD) for 8 weeks. Oocytes were assessed for lipid droplet accumulation, oxidative stress, ER stress and their developmental potential invitro. High lipid accumulation (P<0.01) and elevated intracellular levels of reactive oxygen species were observed in both germinal vesicle and MII oocytes of HFD-fed mice (P<0.05 and P<0.01 respectively compared with control). Further, expression of the ER stress markers X-box binding protein 1 (XBP1), glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4) and activating transcription factor 6 (ATF6) was significantly (P<0.001) higher in oocytes of the HFD than control group. Oocytes from HFD-fed mice exhibited poor fertilisation and blastocyst rates, a decrease in total cell number and high levels of DNA damage (P<0.01) compared with controls. In conclusion, diet-induced obesity resulted in elevated lipid levels and higher oxidative and ER stress in oocytes, which contributed to the compromised developmental potential of embryos.


Inflammation ◽  
2017 ◽  
Vol 40 (3) ◽  
pp. 1072-1086 ◽  
Author(s):  
Hiroki Tashiro ◽  
Koichiro Takahashi ◽  
Hironori Sadamatsu ◽  
Go Kato ◽  
Keigo Kurata ◽  
...  

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