Effects of red meat and fiber in high fat diet on activities of sphingomyelinase, ceramidase and caspase-3 in rat colonic mucosa

2002 ◽  
Vol 13 (8) ◽  
pp. 499-504 ◽  
Author(s):  
Liping Yang ◽  
Marja Mutanen ◽  
Yajun Cheng ◽  
Rui-Dong Duan
2004 ◽  
Vol 91 (5) ◽  
pp. 715-723 ◽  
Author(s):  
Yajun Cheng ◽  
Lena Ohlsson ◽  
Rui-Dong Duan

Dietary fibre and fat affect colonic tumourigenesis and inflammation. Sphingomyelin metabolism may have implications for the pathogenesis of colonic tumours and ulcerative colitis. The present study examined the effects of psyllium and fat on the enzymes responsible for sphingomyelin metabolism and apoptosis in the colon. Mice were fed control, psyllium-containing (100 g/kg), high-fat (313 g/kg, 53 % energy as fat) or high-fat plus psyllium diets for 4 weeks. The activities of acid, neutral and alkaline sphingomyelinase (SMase), neutral ceramidase, and caspase 3, 8 and 9 in colonic mucosa were determined. The expressions of alkaline SMase and caspase 3 were examined. The psyllium-containing diet was found to increase significantly the activities of alkaline SMase and caspase 3 and decreased those of acid SMase and neutral ceramidase. The high-fat diet had opposite effects on these enzymes and attenuated the effects of psyllium. Western blotting showed that psyllium increased and high-fat decreased the levels of alkaline SMase and caspase 3 in colonic mucosa. The change in caspase 3 activity was positively correlated with that of alkaline SMase and negatively with acid SMase. No similar changes of acid and alkaline phosphatase activities in the colon or acid and neutral SMase activity in the liver were identified. In conclusion, colonic sphingomyelin metabolism and apoptosis were affected by psyllium and fat in an opposite manner. The results may have implications for colorectal tumourigenesis and inflammation.


2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Yun Jung Bae ◽  
Youn-Kyung Bak ◽  
Taesun Park ◽  
Myung-Sook Choi ◽  
Jeongseon Kim ◽  
...  

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0216072 ◽  
Author(s):  
Christina F. Butowski ◽  
David G. Thomas ◽  
Wayne Young ◽  
Nick J. Cave ◽  
Catherine M. McKenzie ◽  
...  

2020 ◽  
Vol 31 (4) ◽  
pp. 295-304
Author(s):  
Leimin Qian ◽  
◽  
Jianming Huang ◽  
Huanlong Qin ◽  
◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Yifan Zhang ◽  
Jie Ding ◽  
Yiru Wang ◽  
Xiaoteng Feng ◽  
Min Du ◽  
...  

Guanxinkang decoction (GXK), a traditional Chinese medicinal drug, is used to treat cardiovascular disease. The aim of the study was to investigate the effects of GXK on inflammation in LDLR−/− mice and RAW264.7 cells. Fed with high fat diet for 12 weeks, the mice were randomly divided into six groups, then administered with oral 0.9% saline or GXK (7.24, 14.48, and 28.96 g/kg) or Atorvastatin (1.3 mg/kg) for 12 weeks. RAW 264.7 cells were induced with ox-LDL or ox-LDL plus different concentrations of GXK (1.25, 2.5, and 5 μg/ml), or ox-LDL plus GXK plus MAPKs activators. Serum lipid profiles and inflammatory cytokines were detected by ELISA, gene expression by RT-qPCR, plaque sizes by Oil Red O, α-SMA, caspase 3, NF-κB p65 and TNF-α production by immunofluorescence staining, and protein expression by Western Blot. The phagocytic ability of cells was determined by neutral red uptake assay. Efferocytosis-related proteins (AML, MERTK, TYRO3 and MFGE8) and MAPKs pathways were detected by Western Blot. Compared to mice fed with high fat diet, the mice with GXK showed lower cholesterol, triglyceride, low-density lipoprotein cholesterol, IL-1β, IL-6, and TNF-α, smaller plaque sizes, higher α-SMA, and lower caspase 3 and NF-κB p65 in aortic roots. RAW264.7 cells treated with ox-LDL plus GXK had lower IL-1β, IL-6, and TNF-α. GXK also increased the phagocytic ability of cells. High levels of AML, MERTK, TYRO3 and MFGE8, and decreased levels of iNOS, VCAM-1, LOX-1 and MCP-1, and phosphorylation of ERK1/2, JNK, p38, and NF-κB were detected in GXK-treated group. MAPKs activators reversed the effects of GXK in repressing inflammation and promoting phagocytosis. These results suggested that GXK could attenuate atherosclerosis and resolve inflammation via efferocytosis and MAPKs signaling pathways in LDLR−/− mice and RAW264.7 cells.


2012 ◽  
Vol 37 (6) ◽  
pp. 1101-1109 ◽  
Author(s):  
Marco Aurélio Aguiar e Silva ◽  
Ivan José Vechetti-Junior ◽  
André Ferreira do Nascimento ◽  
Kelly Silva Furtado ◽  
Luciana Azevedo ◽  
...  

The present study aimed to investigate the beneficial effects of swim training on the promotion–progression stages of rat liver carcinogenesis. Male Wistar rats were submitted to chemically induced liver carcinogenesis and allocated into 4 major groups, according their dietary regimen (16 weeks) and swim training of 5 days per week (8 weeks): 2 groups were fed low-fat diet (LFD, 6% fat) and trained or not trained and 2 groups were fed high-fat diet (HFD, 21% fat) and trained or not trained. At week 20, the animals were killed and liver samples were processed for histological analyses; immunohistochemical detection of persistent or remodeling preneoplastic lesions (pPNL and rPNL) expressing placental glutathione S-transferase (GST-P) enzyme; or proliferating cell nuclear antigen (PCNA), cleaved caspase-3, and bcl-2 protein levels by Western blotting or malonaldehyde (MDA) and total glutathione detection by HPLC. Overall analysis indicated that swim training reduced the body weight and body fat in both LFD and HFD groups, normalized total cholesterol levels in the HFD group while decreased the MDA levels, increased glutathione levels and both number of GST-P-positive pPNL and hepatocellular adenomas in LFD group. Also, a favorable balance in PCNA, cleaved caspase-3, and bcl-2 levels was detected in the liver from the LFD-trained group in relation to LFD-untrained group. The findings of this study indicate that the swim training protocol as a result of exercise postconditioning may attenuate liver carcinogenesis under an adequate dietary regimen with lowered fat intake.


2013 ◽  
Vol 217 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Sara Baldassano ◽  
Antonella Amato ◽  
Francesco Cappello ◽  
Francesca Rappa ◽  
Flavia Mulè

Endogenous glucagon-like peptide-2 (GLP2) is a key mediator of refeeding-induced and resection-induced intestinal adaptive growth. This study investigated the potential role of GLP2 in mediating the mucosal responses to a chronic high-fat diet (HFD). In this view, the murine small intestine adaptive response to a HFD was analyzed and a possible involvement of endogenous GLP2 was verified using GLP2 (3–33) as GLP2 receptor (GLP2R) antagonist. In comparison with animals fed a standard diet, mice fed a HFD for 14 weeks exhibited an increase in crypt–villus mean height (duodenum, 27.5±3.0%; jejunum, 36.5±2.9%;P<0.01), in the cell number per villus (duodenum, 28.4±2.2%; jejunum, 32.0±2.9%;P<0.01), and in Ki67-positive cell number per crypt. No change in the percent of caspase-3-positive cell in the villus–crypt was observed. The chronic exposure to a HFD also caused a significant increase in GLP2 plasma levels and in GLP2R intestinal expression. Daily administration of GLP2 (3–33) (30–60 ng) for 4 weeks did not modify the crypt–villus height in control mice. In HFD-fed mice, chronic treatment with GLP2 (3–33) reduced the increase in crypt–villus height and in the cell number per villus through reduction of cell proliferation and increase in apoptosis. This study provides the first experimental evidence for a role of endogenous GLP2 in the intestinal adaptation to HFD in obese mice and for a dysregulation of the GLP2/GLP2R system after a prolonged HFD.


Author(s):  
Kunio Kawanishi ◽  
Joanna K. Coker ◽  
Kaare V. Grunddal ◽  
Chirag Dhar ◽  
Jason Hsiao ◽  
...  

Objective: Species-specific pseudogenization of the CMAH gene during human evolution eliminated common mammalian sialic acid N -glycolylneuraminic acid (Neu5Gc) biosynthesis from its precursor N -acetylneuraminic acid (Neu5Ac). With metabolic nonhuman Neu5Gc incorporation into endothelia from red meat, the major dietary source, anti-Neu5Gc antibodies appeared. Human-like Ldlr −/ − Cmah −/− mice on a high-fat diet supplemented with a Neu5Gc-enriched mucin, to mimic human red meat consumption, suffered increased atherosclerosis if human-like anti-Neu5Gc antibodies were elicited. Approach and Results: We now ask whether interventional Neu5Ac feeding attenuates metabolically incorporated Neu5Gc-mediated inflammatory acceleration of atherogenesis in this Cmah −/− Ldlr −/− model system. Switching to a Neu5Gc-free high-fat diet or adding a 5-fold excess of Collocalia mucoid-derived Neu5Ac in high-fat diet protects against accelerated atherosclerosis. Switching completely from a Neu5Gc-rich to a Neu5Ac-rich diet further reduces severity. Remarkably, feeding Neu5Ac-enriched high-fat diet alone has a substantial intrinsic protective effect against atherosclerosis in Ldlr −/− mice even in the absence of dietary Neu5Gc but only in the human-like Cmah -null background. Conclusions: Interventional Neu5Ac feeding can mitigate or prevent the red meat/Neu5Gc-mediated increased risk for atherosclerosis, and has an intrinsic protective effect, even in the absence of Neu5Gc feeding. These findings suggest that similar interventions should be tried in humans and that Neu5Ac-enriched diets alone should also be investigated further.


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