scholarly journals IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice

2021 ◽  
Author(s):  
Dae Hwan Kim ◽  
So Young Chun ◽  
EunHye Lee ◽  
Bomi Kim ◽  
BoHyun Yoon ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Immune Cell ◽  
Periodic Acid ◽  
Total Serum ◽  
Obese Mice ◽  
High Fat ◽  
Low Fat ◽  
Renal Inflammation ◽  
Functional Failure

Abstract BACKGROUND: High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. METHODS: To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High‐fat dieted C57BL/6 mice and (4) High‐fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. RESULTS: At week 12, high‐fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro‐inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. CONCLUSION: IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.

scholarly journals Altered Gut Microbiota Is a Novel Mechanism for the Adverse Effects Induced by Foodborne Titanium Dioxide Nanoparticles in Obese and Non-obese Mice (P21-021-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hengjun Du ◽  
Xiaoqiong Cao ◽  
Yanhui Han ◽  
Min Gu ◽  
Hang Xiao
Keyword(s):  
Titanium Dioxide ◽  
Adverse Effects ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Low Fat ◽  
Colonic Inflammation ◽  
Tio2 Nps ◽  
Low Fat Diet

Abstract Objectives Many food products contain inorganic nanoparticles (NPs), such as titanium dioxide (TiO2) NPs. There is increasing concern about the potential unintended health risks associated with foodborne TiO2 NPs in certain populations, such as the obese. The purpose of this study was to determine the adverse effects of TiO2 NPs in obese individuals, the molecular mechanism involved and the potential role of gut microbiota in mediating the adverse effects. Methods Two types of TiO2 (30 nm and E171-Food grade TiO2) were mixed with mouse diet at 0.1 wt% and fed to two populations of mice (high-fat diet-fed obese mice and non-obese mice). Meanwhile, fecal samples from the above groups of mice were collected weekly for transplanting to four groups of mice fed a low-fat diet for 10 weeks. 16 s rRNA gene amplicon sequencing, histological analysis, immunohistochemistry, ELISA and SCFAs analysis were utilized to characterize the composition of the microbiota, inflammation status, and the effects of altered gut microbiota on the inflammation status of the mouse colon. Results TiO2 NPs significantly altered the composition of gut microbiota with stronger alterations in the high-fat diet-fed obese mice than the low-fat diet-fed non-obese mice. The abundance of inflammation-related cytokines (e.g., IL-10, IL-12p70, and IL-17) and myeloperoxidase (MPO) in the mouse colonic mucosa were significantly altered by TiO2 NPs to produce an inflammatory state. TiO2 NPs decreased the cecal levels of SCFAs such as butyrate. Moreover, the magnitude of the above alteration was higher in the obese mice than in the non-obese mice. After 10 weeks of microbial transplant, microbiota from the mice consuming a high-fat diet with TiO2 NPs led to an increase of pro-inflammatory cytokines, loss of healthy colonic morphology, and infiltration of immune cells in the colon of the low-fat diet-fed recipient mice, indicating a significant colonic inflammation. Conclusions TiO2 NPs altered gut microbiota in both obese and non-obese mice, with stronger effects in the obese mice, and the alteration of gut microbiota led to colonic inflammation in the mice. Overall, these findings provided a valuable new perspective on the potential adverse effects and appropriate mechanisms of foodborne TiO2 NPs among populations with different obese status. Funding Sources USDA/NIFA competitive grants to Hang Xiao.

Obese Adipose Tissue Modulates Pro-inflammatory Responses of Mouse Airway Epithelial Cells

2021 ◽  
Author(s):  
Jennifer L Ather ◽  
Katherine E Van Der Vliet ◽  
Madeleine M Mank ◽  
Leah F Reed ◽  
Anne E Dixon ◽  
...  
Keyword(s):  
Weight Loss ◽  
Epithelial Cells ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Obese Mice ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet

Although recognized as an important endocrine organ, little is known about the mechanisms through which adipose tissue can regulate inflammatory responses in distant tissues, such as lung, that are affected by obesity. To explore potential mechanisms, male C57BL/6J mice were provided either high-fat diet, low-fat diet, or were provided a high-fat diet then switched to the low-fat diet to promote weight loss. Visceral adipocytes were then cultured in vitro to generate conditioned media (CM) that was used to treat both primary (MTEC) and immortalized (MTCC) airway epithelial cells. Adiponectin levels were greatly depressed in the CM from both obese and diet-switched adipocytes relative to mice continually fed the low-fat diet. MTEC from obese mice secreted higher baseline levels of inflammatory cytokines than MTEC from lean or diet-switched mice. MTEC treated with obese adipocyte CM increased their secretion of these cytokines compared to MTEC treated with lean CM. Diet-switched CM modestly decreased the production of cytokines compared to obese CM, and these effects were recapitulated when the CM was used to treat MTCC. Adipose stromal vascular cells from obese mice expressed genes consistent with an M1 macrophage phenotype and decreased eosinophil abundance compared to lean SVF, a profile that persisted in the lean diet-switched mice despite substantial weight loss. Soluble factors secreted from obese adipocytes exert a pro-inflammatory effect on airway epithelial cells, and these alterations are attenuated by diet-induced weight loss, which could have implications for the airway dysfunction related to obese asthma and its mitigation by weight loss.

scholarly journals IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Yinyin Zhang ◽  
Kun Zhang ◽  
Yuling Zhang ◽  
Lingqu Zhou ◽  
Hui Huang ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Vascular Calcification ◽  
High Fat Diet ◽  
Calcium Content ◽  
Serum Levels ◽  
High Fat ◽  
P38 Inhibitor ◽  
Cardiovascular Morbidity And Mortality ◽  
Mapk Inhibitors

Objective: Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality in patients with chronic renal failure (CRF). It is well-known that obesity and metabolic syndrome (OB/MS) predicts poor prognosis of CRF patients. However, the influence of OB/MS on VC in CRF patients isn't clear. IL-18 mediates OB/MS-related inflammation, but whether IL-18 is involved in OB/MS -mediated VC in CRF patients hasn't been studied. In this study, it was explored that whether OB/MS caused by high-fat diet (HFD) can affect the level of serum IL-18 and aggravate the degree of VC in CRF rats. Furthermore, it was studied that whether IL-18 induces rat vascular smooth muscle cells (VSMCs) calcification by activating the MAPK pathways.Approach: The rats were randomly assigned to the sham-operated, CRF and CRF + HFD groups. CRF was induced by 5/6 nephrectomy. Serum IL-18 levels and aortic calcification indicators were compared in each group. Primary rat VSMCs calcification were induced by β-glycerophosphate and exposed to IL-18. VSMCs were also treated with MAPK inhibitors.Results: The weight, serum levels of hsCRP, TG and LDL-C in CRF + HFD group were significantly higher than those in sham-operated and CRF groups (p < 0.05). Compared with the sham-operated group, the calcium content and the expression of BMP-2 of aorta in CRF and CRF + HFD groups were significantly increased (p < 0.05). Moreover, the calcium content and the expression of BMP-2 of aorta in CRF + HFD group was significantly higher than those in CRF group (p < 0.05). And the serum IL-18 level was positively correlated with aortic calcium content. It was also found that p38 inhibitor SB203580 can suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18. But the JNK inhibitor SP600125 can't suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18.Conclusions: These findings suggest that obesity-related inflammation induced by high-fat diet could exacerbate VC in CRF rats. Furthermore, serum IL-18 level had a positive correlation with the degree of VC. It is also found that IL-18 promoted osteogenic differentiation and calcification of rat VSMCs via p38 pathway activation.

scholarly journals Vascular Endothelial Glycocalyx Plays a Role in the Obesity Paradox According to Intravital Observation

2021 ◽  
Vol 8 ◽  
Author(s):  
Shingo Mitsuda ◽  
Kohji Uzawa ◽  
Marie Sawa ◽  
Tadao Ando ◽  
Takahiro Yoshikawa ◽  
...  
Keyword(s):  
Obesity Paradox ◽  
Diet Group ◽  
Endothelial Glycocalyx ◽  
Vascular Endothelial ◽  
Obese Mice ◽  
High Fat ◽  
Low Fat ◽  
Positive Correlation ◽  
Cranial Window ◽  
Low Fat Diet

According to the “obesity paradox,” for severe conditions, individuals with obesity may be associated with a higher survival rate than those who are lean. However, the physiological basis underlying the mechanism of the obesity paradox remains unknown. We hypothesize that the glycocalyx in obese mice is thicker and more resistant to inflammatory stress than that in non-obese mice. In this study, we employed intravital microscopy to elucidate the differences in the vascular endothelial glycocalyx among three groups of mice fed diets with different fat concentrations. Male C57BL/6N mice were divided into three diet groups: low-fat (fat: 10% kcal), medium-fat (fat: 45% kcal), and high-fat (fat: 60% kcal) diet groups. Mice were fed the respective diet from 3 weeks of age, and a chronic cranial window was installed at 8 weeks of age. At 9 weeks of age, fluorescein isothiocyanate-labeled wheat germ agglutinin was injected to identify the glycocalyx layer, and brain pial microcirculation was observed within the cranial windows. We randomly selected arterioles of diameter 15–45 μm and captured images. The mean index of the endothelial glycocalyx was calculated using image analysis and defined as the glycocalyx index. The glycocalyx indexes of the high-fat and medium-fat diet groups were significantly higher than those of the low-fat diet group (p < 0.05). There was a stronger positive correlation between vessel diameter and glycocalyx indexes in the high-fat and medium-fat diet groups than in the low-fat diet group. The glycocalyx indexes of the non-sepsis model in the obese groups were higher than those in the control group for all vessel diameters, and the positive correlation was also stronger. These findings indicate that the index of the original glycocalyx may play an important role in the obesity paradox.

scholarly journals The Impact of Different Animal-Derived Protein Sources on Adiposity and Glucose Homeostasis during Ad Libitum Feeding and Energy Restriction in Already Obese Mice

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1153 ◽  
Author(s):  
Lene Secher Myrmel ◽  
Kristin Røen Fauske ◽  
Even Fjære ◽  
Annette Bernhard ◽  
Ulrike Liisberg ◽  
...  
Keyword(s):  
Body Mass ◽  
Fat Mass ◽  
Energy Restriction ◽  
High Protein ◽  
Protein Source ◽  
Obese Mice ◽  
High Fat ◽  
Low Fat ◽  
Protein Sources ◽  
Ad Libitum

Low-fat diets and energy restriction are recommended to prevent obesity and to induce weight loss, but high-protein diets are popular alternatives. However, the importance of the protein source in obesity prevention and weight loss is unclear. The aim of this study was to investigate the ability of different animal protein sources to prevent or reverse obesity by using lean or obese C57BL/6J mice fed high-fat/high-protein or low-fat diets with casein, cod or pork as protein sources. Only the high-fat/high-protein casein-based diet completely prevented obesity development when fed to lean mice. In obese mice, ad libitum intake of a casein-based high-fat/high-protein diet modestly reduced body mass, whereas a pork-based high-fat/high-protein diet aggravated the obese state and reduced lean body mass. Caloric restriction of obese mice fed high-fat/high-protein diets reduced body weight and fat mass and improved glucose tolerance and insulin sensitivity, irrespective of the protein source. Finally, in obese mice, ad libitum intake of a low-fat diet stabilized body weight, reduced fat mass and increased lean body mass, with the highest loss of fat mass found in mice fed the casein-based diet. Combined with caloric restriction, the casein-based low-fat diet resulted in the highest loss of fat mass. Overall, the dietary protein source has greater impact in obesity prevention than obesity reversal.

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