scholarly journals Oxidised plant sterols as well as oxycholesterol increase the proportion of severe atherosclerotic lesions in female LDL receptor+/ − mice

2013 ◽  
Vol 111 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Jogchum Plat ◽  
Elke Theuwissen ◽  
Constanze Husche ◽  
Dieter Lütjohann ◽  
Marion J. J. Gijbels ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Control Diet ◽  
Ldl Receptor ◽  
Atherosclerotic Lesion ◽  
Serum Levels ◽  
Plant Sterols ◽  
Atherosclerotic Lesions ◽  
Human Situation ◽  
Diet Control ◽  
Lesion Severity

Oxysterols (oxidised cholesterol) may play a role in the pathogenesis of CVD. Similar to cholesterol, plant sterols are susceptible to oxidation. However, less is known about the potential atherogenicity of oxidised plant sterols (oxyphytosterols). In the present study, the atherogenicity of a mixture of oxyphytosterols was examined by feeding female LDL receptor-deficient (LDLR+/ −) mice for 35 weeks a control diet (atherogenic high-fat diet; n 9), an oxysterol diet (control diet+0·025 % (w/w) oxysterols; n 12) or an oxyphytosterol diet (control diet+0·025 % (w/w) oxyphytosterols; n 12). In the LDLR+/ − mice, serum levels of cholesterol, lipoprotein profiles, cholesterol exposure and inflammatory markers at the end of the experiment were comparable between the three diet groups. Nevertheless, the proportion of severe atherosclerotic lesions was significantly higher after oxysterol (41 %; P= 0·004) and oxyphytosterol (34 %; P= 0·011) diet consumption than after control diet consumption (26 %). Oxyphytosterol levels in the lesions were the highest in the oxyphytosterol group. Here, we show that not only dietary oxysterols but also dietary oxyphytosterols increase the proportion of severe atherosclerotic lesions. This suggests that plant sterols when oxidised may increase atherosclerotic lesion severity instead of lowering the size and severity of lesions when fed in their non-oxidised form. Therefore, this finding might give an indication as to where to find the answer in the current hot debate about the potential atherogenicity of plant sterols. However, to what extent these results can be extrapolated to the human situation warrants further investigation.

scholarly journals Hypocholesterolaemic effect of whole-grain highland hull-less barley in rats fed a high-fat diet

2018 ◽  
Vol 119 (10) ◽  
pp. 1102-1110 ◽  
Author(s):  
Xuejuan Xia ◽  
Guannan Li ◽  
Jiaxin Song ◽  
Jiong Zheng ◽  
Jianquan Kan
Keyword(s):  
Bile Acid ◽  
High Fat Diet ◽  
Control Diet ◽  
Ldl Receptor ◽  
Acid Synthesis ◽  
Farnesoid X Receptor ◽  
High Dose ◽  
Whole Grain ◽  
Sprague Dawley ◽  
High Fat

AbstractWhole-grain highland hull-less barley (WHLB) contains high amounts of bioactive compounds that potentially exhibit cholesterol-lowering effects. This study investigated the hypocholesterolaemic effect of WHLB. A total of seventy-two male Sprague–Dawley rats were divided into four groups and were fed with the normal control diet, high-fat diet (HFD) and HFD containing low or high dose (10 or 48·95 %) of WHLB. High dose of WHLB significantly decreased the organ indexes of liver and abdominal fat and lipid levels of plasma and liver in HFD rats. The lipid regulation effect of WHLB, which was reconfirmed through hepatocyte morphologic observation, was accompanied by a large excretion of bile acids in the small intestinal contents and the faeces. Real-time PCR analyses, which were further reconfirmed through Western blot analyses, revealed that a high dose of WHLB significantly enhanced the hepatic expressions of AMP-activated protein kinase α, cholesterol 7α-hydroxylase, LDL receptor, liver X receptor, and PPARα and decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. It also enhanced the ileal expression of farnesoid X receptor and resulted in the decrease of expression of apical sodium-dependent bile acid transporter. WHLB exhibited hypocholesterolaemic effects mainly by inhibiting cholesterol synthesis, cholesterol accumulation in peripheral tissue, and bile acid reabsorption and by stimulating bile acid synthesis.

P4141Lack of IkBNS promotes cholate-containing high-fat diet-induced inflammation and atherogenesis in low-density lipoprotein (LDL) receptor-deficient mice

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Kitamura ◽  
K Isoda ◽  
K Akita ◽  
K Miyosawa ◽  
T Kadoguchi ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Aortic Root ◽  
High Fat Diet ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Endotoxin Shock ◽  
High Fat ◽  
Lps Challenge ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

Abstract Background IκBNS is one of the nuclear IκB proteins and regulates a subset of Toll-like receptor (TLR) dependent genes. LPS acts as extremely strong stimulator of innate immunity. We tried to investigate whether stimulation of innate immunity could promote atherosclerosis in the IκBNS-deficient atherogenic mice. However all IκBNS-deficient mice died of LPS challenge at a dose of which almost all wild-type mice survived, because IκBNS-deficient mice are highly sensitive to LPS-induced endotoxin shock. Then, we decided to use a cholate-containing high fat diet (HFD(CA(+))), which has been widely used as an atherogenic diet in mice. Furthermore, HFD(CA(+)) has been shown to induce TLR4 mediated early inflammatory response. The present study aims to clarify the lack of IκBNS promotes atherogenesis in LDL receptor-deficient (LDLr−/−) mice fed HFD(CA(+)) compared with those fed a cholate-free HFD (HFD(CA(−)). Methods and results Mice that lacked IκBNS (IκBNS−/−) were crossed with LDLr−/− mice and formation of atherosclerotic lesions was analyzed after 6 weeks consumption of HFD(CA(+)) or HFD(CA(−)). The extent of atherosclerosis in the aorta (en face) was significantly increased in IκBNS−/−/LDLr−/−(CA(+)) mice compared with others after 6-week consumption of HFD (p<0.01) (Figure). Interestingly, HFD(CA(−)) did not induce significant atherosclerotic lesions in IκBNS−/−/LDLr−/− compared with LDLr−/− mice after 6-week consumption (Figure). Immunostaining of aortic root lesion revealed that HFD(CA(+)) significantly increased positive area of Mac-3 (macrophage) by 1.5-fold (p=0.01) and TLR4, interleukin-6 (IL-6) expression by 1.7-fold (P<0.05) and 1.5-fold (p<0.05) respectively in IκBNS−/−/LDLr−/− (CA(+)) compared to LDLr−/− (CA(+)) mice. Furthermore, active STAT3 (pSTAT3)-positive cells were significantly increased by 1.7-fold in the atherosclerotic lesions of IκBNS−/−/LDLr−/− (CA(+)) compared with LDLr−/− (CA(+)) mice (p<0.01). TLR4 positive areas, IL-6 positive areas, and pSTAT3 positive cells were overlapped with Mac-3, indicating that TLR4-IL-6-STAT3 axis was activated in macrophages in IκBNS−/−/LDLr−/− (CA(+)) mice. On the other hand, HFD(CA(−)) could not induce any difference in these immunoreactivities of arteriosclerotic lesions between IκBNS−/−/LDLr−/− (CA(−)) compared with LDLr−/− (CA(−)) mice. These findings suggest that IκBNS deficiency and HFD(CA(+)) promote atherogenesis in LDLr−/− mice via TLR4/IL-6/STAT3 pathway. Finally, we show the monocytes from peripheral blood of IκBNS−/−/LDLr−/− (CA(+)) mice were found to contain the most mounts of Ly6Chi among four groups, suggesting that lack of IκBNS enhances inflammation in the response HFD(CA(+)) feeding and thereby influence atherogenesis in IκBNS−/−/LDLr−/− mice. Aortic root atherosclerotic lesions Conclusions The present study is the first to demonstrate that the activation of innate immune system using HFD(CA(+)) induced significant inflammation and atherogenesis in IκBNS−/−/LDLr−/− compared with LDLr−/− mice.

scholarly journals Cysteamine Decreases Low‐Density Lipoprotein Oxidation, Causes Regression of Atherosclerosis, and Improves Liver and Muscle Function in Low‐Density Lipoprotein Receptor–Deficient Mice

2021 ◽  
Vol 10 (18) ◽  
Author(s):  
Feroz Ahmad ◽  
Robert D. Mitchell ◽  
Tom Houben ◽  
Angela Palo ◽  
Tulasi Yadati ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Muscle Function ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
High Fat ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

Background We have shown previously that low‐density lipoprotein (LDL) can be oxidized in the lysosomes of macrophages, that this oxidation can be inhibited by cysteamine, an antioxidant that accumulates in lysosomes, and that this drug decreases atherosclerosis in LDL receptor–deficient mice fed a high‐fat diet. We have now performed a regression study with cysteamine, which is of more relevance to the treatment of human disease. Methods and Results LDL receptor–deficient mice were fed a high‐fat diet to induce atherosclerotic lesions. They were then reared on chow diet and drinking water containing cysteamine or plain drinking water. Aortic atherosclerosis was assessed, and samples of liver and skeletal muscle were analyzed. There was no regression of atherosclerosis in the control mice, but cysteamine caused regression of between 32% and 56% compared with the control group, depending on the site of the lesions. Cysteamine substantially increased markers of lesion stability, decreased ceroid, and greatly decreased oxidized phospholipids in the lesions. The liver lipid levels and expression of cluster of differentiation 68, acetyl–coenzyme A acetyltransferase 2, cytochromes P450 (CYP)27, and proinflammatory cytokines and chemokines were decreased by cysteamine. Skeletal muscle function and oxidative fibers were increased by cysteamine. There were no changes in the plasma total cholesterol, LDL cholesterol, high‐density lipoprotein cholesterol, or triacylglycerol concentrations attributable to cysteamine. Conclusions Inhibiting the lysosomal oxidation of LDL in atherosclerotic lesions by antioxidants targeted at lysosomes causes the regression of atherosclerosis and improves liver and muscle characteristics in mice and might be a promising novel therapy for atherosclerosis in patients.

The treatment with an extract from Calafate (Berberis microphylla) induces transcript and protein expression of molecules involved in thermogenesis and adipocyte browning in adipose tissue from obese mice

2021 ◽  
pp. 1-11
Author(s):  
Lissette Duarte ◽  
Javier Quezada ◽  
Luisa A. Ramirez ◽  
Karla Vasquez ◽  
Juan F. Orellana ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Control Diet ◽  
Obese Mice ◽  
High Fat ◽  
Total Polyphenols ◽  
Adipose Tissues ◽  
Protein Levels ◽  
Brown Adipose ◽  
Diet Control

BACKGROUND: Polyphenols intake increases the function of brown adipose tissue (BAT), stimulating energy expenditure (EE). Calafate (Berberis microphylla) is a polyphenol-rich Chilean native fruit. OBJECTIVE: To analyse the effect of a treatment with a Calafate extract in the thermogenic activity of mice adipose tissues. METHODS: Forty adult C57BL/6J male mice were subdivided into four groups (n=10 each): control diet, control+Calafate (extract: 50mg total polyphenols/kg weight), high-fat diet (HF) and HF+Calafate. RESULTS: Calafate prevented the increase in body weight and the decrease EE induced by HF. In BAT, Ucp-1 transcript was influenced by the interaction between diet and Calafate (p<0.01), Pparα showed the same expression pattern as Ucp-1 and both, diet (p<0.01) and Calafate (p<0.05), induced significant effects in Sirt1. In inguinal adipose tissue, Pgc1α, Pparα, Prdm16, Sirt1, and Dio2 transcripts presented a decreased expression caused by HF, that was reversed by Calafate. In BAT, an effect of diet (p<0.05) and an interaction between diet and Calafate (p<0.01) was observed in UCP-1 protein levels. CONCLUSIONS: A treatment with Calafate drives less weight gain in mice fed with HF, and reverses the effects generated by it on the expression of thermogenic and browning markers.

scholarly journals Chronic NaHS Treatment Is Vasoprotective in High-Fat-Fed ApoE−/−Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Asha Ford ◽  
Mohammad Al-Magableh ◽  
Tracey A. Gaspari ◽  
Joanne L. Hart
Keyword(s):  
High Fat Diet ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Atherosclerotic Lesion ◽  
Vascular Changes ◽  
High Fat ◽  
Superoxide Generation ◽  
Atherosclerotic Lesions ◽  
Atherosclerotic Lesion Development

Hydrogen sulfide is emerging as an important mediator of vascular function that has antioxidant and cytoprotective effects. The aim of this study was to investigate the role of endogenous H2S and the effect of chronic exogenous H2S treatment on vascular function during the progression of atherosclerotic disease. ApoE−/−mice were fed a high-fat diet for 16 weeks and treated with the H2S donor NaHS or the cystathionine-γ-lyase (CSE) inhibitor D,L-propargylglycine (PPG), to inhibit endogenous H2S production for the final 4 weeks. Fat-fed ApoE−/−mice displayed significant aortic atherosclerotic lesions and significantly impaired endothelial function compared to wild-type mice. Importantly, 4 weeks of NaHS treatment significantly reduced vascular dysfunction and inhibited vascular superoxide generation. NaHS treatment significantly reduced the area of aortic atherosclerotic lesions and attenuated systolic blood pressure. Interestingly, inhibiting endogenous, CSE-dependent H2S production with PPG did not exacerbate the deleterious vascular changes seen in the untreated fat-fed ApoE−/−mice. The results indicate NaHS can improve vascular function by reducing vascular superoxide generation and impairing atherosclerotic lesion development. Endogenous H2S production via CSE is insufficient to counter the atherogenic effects seen in this model; however exogenous H2S treatment has a significant vasoprotective effect.

scholarly journals Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anandini Swaminathan ◽  
Andrej Fokin ◽  
Tomas Venckūnas ◽  
Hans Degens
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Body Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
Metabolic Health ◽  
High Fat ◽  
Methionine Restriction ◽  
Old Mice

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

scholarly journals Effect of dietary copper sources on performance, gastric ghrelin-RNA expression, and growth hormone concentrations in serum in piglets

2019 ◽  
Vol 97 (10) ◽  
pp. 4242-4247 ◽  
Author(s):  
Ricardo Gonzalez-Esquerra ◽  
Raquel B Araujo ◽  
Douglas Haese ◽  
Joao L Kill ◽  
Anderson F Cunha ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Copper Chloride ◽  
Block Design ◽  
Control Diet ◽  
Phase 1 ◽  
Serum Levels ◽  
Control Group ◽  
Feed Conversion ◽  
Growth Promoters ◽  
Serum Growth Hormone

Abstract Two performance studies were conducted to investigate the effects of 3 different sources of Cu on production parameters of piglets. A total of 256 piglets weaned at 24 ± 2 d were randomly allocated into 4 treatments with 10 or 8 replicates per treatment of 4 or 3 piglets per pen in Exp. 1 and 2, respectively. The experimental period was divided into 3 feeding phases: Phase 1 (24 to 35 d), Phase 2 (36 to 49 d), and Phase 3 (50 to 70 d). Treatments included a Control group (fed 10 mg/kg of Cu from CuSO4), a group fed 160 mg/kg of either CuSO4 (CuSO4-160) or tri-basic copper chloride (TBCC), and a group fed Cu methionine hydroxy analogue chelated (Cu-MHAC) at 150, 80, and 50 mg/kg in Phases 1, 2, and 3, respectively. The methionine value of Cu-MHAC was accounted during diet formulation to achieve the same levels of methionine across treatments. Phases 1 and 2 diets contained 2,200 and 1,500 ppm of ZnO, respectively; and antibiotics were used as growth promoters. Performance parameters were analyzed as completely randomized block design, in which each experiment was considered as a block. In trial 2, blood serum and mucosal samples, from the fundic region of the stomach, were collected from 1 piglet per replicate at day 70 and tested for serum growth hormone levels (GH) and ghrelin mRNA expression, respectively. The contrast between Cu-MHAC vs. CuSO4-160 + TBCC showed that piglets fed Cu-MHAC exhibited better feed conversion ratio (FCR) in all feeding phases compared with feeding inorganic Cu (P < 0.05). Overall, feeding Cu-MHAC improved body weight (BW), BW gain, feed intake (FI), and FCR vs. Control diet fed piglets; yet, it improved BW and FCR vs. TBCC fed piglets, and improved BW, BW gain, and FI vs. CuSO4-160 fed piglets (P < 0.05). Feeding TBCC promoted similar performance than feeding CuSO4-160, regardless of age (P > 0.05). Both ghrelin expression and growth hormone serum levels were significantly increased by feeding Cu-MHAC vs. Control diet fed animals (P < 0.01). Feeding CuSO4-160 upregulated ghrelin expression vs. Control (P < 0.01) while GH serum levels and ghrelin expression did no change by feeding TBCC compared with Control diet fed animals (P > 0.05). It was concluded that feeding Cu-MHAC at the levels tested herein can improve growth performance of piglets beyond feeding 160 ppm of either CuSO4 or TBCC, which may be partially explained by the increased expression of ghrelin and GH serum levels.

scholarly journals Perinatal High-Fat Diet Influences Ozone-Induced Responses on Pulmonary Oxidant Status and the Molecular Control of Mito-Phagy in Female Rat Offspring

2021 ◽  
Vol 22 (14) ◽  
pp. 7551
Author(s):  
Sven H. Rouschop ◽  
Samantha J. Snow ◽  
Urmila P. Kodavanti ◽  
Marie-José Drittij ◽  
Lou M. Maas ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
High Fat Diet ◽  
Control Diet ◽  
Ozone Exposure ◽  
Female Rat ◽  
Induced Responses ◽  
High Fat ◽  
Molecular Control ◽  
Rat Offspring ◽  
Oxidant Status

Previous research has shown that a perinatal obesogenic, high-fat diet (HFD) is able to exacerbate ozone-induced adverse effects on lung function, injury, and inflammation in offspring, and it has been suggested that mitochondrial dysfunction is implicated herein. The aim of this study was to investigate whether a perinatal obesogenic HFD affects ozone-induced changes in offspring pulmonary oxidant status and the molecular control of mitochondrial function. For this purpose, female Long-Evans rats were fed a control diet or HFD before and during gestation, and during lactation, after which the offspring were acutely exposed to filtered air or ozone at a young-adult age (forty days). Directly following this exposure, the offspring lungs were examined for markers related to oxidative stress; oxidative phosphorylation; and mitochondrial fusion, fission, biogenesis, and mitophagy. Acute ozone exposure significantly increased pulmonary oxidant status and upregulated the molecular machinery that controls receptor-mediated mitophagy. In female offspring, a perinatal HFD exacerbated these responses, whereas in male offspring, responses were similar for both diet groups. The expression of the genes and proteins involved in oxidative phosphorylation and mitochondrial biogenesis, fusion, and fission was not affected by ozone exposure or perinatal HFD. These findings suggest that a perinatal HFD influences ozone-induced responses on pulmonary oxidant status and the molecular control of mitophagy in female rat offspring.

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