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  • 1
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 117, No. 2 ( 2021-01-21), p. 435-449
    Abstract: The microbiome-derived metabolite trimethylamine-N-oxide (TMAO) has attracted major interest and controversy both as a diagnostic biomarker and therapeutic target in atherothrombosis. Methods and results Plasma TMAO increased in mice on ‘unhealthy’ high-choline diets and notably also on ‘healthy’ high-fibre diets. Interestingly, TMAO was found to be generated by direct oxidation in the gut in addition to oxidation by hepatic flavin-monooxygenases. Unexpectedly, two well-accepted mouse models of atherosclerosis, ApoE−/− and Ldlr−/− mice, which reflect the development of stable atherosclerosis, showed no association of TMAO with the extent of atherosclerosis. This finding was validated in the Framingham Heart Study showing no correlation between plasma TMAO and coronary artery calcium score or carotid intima-media thickness (IMT), as measures of atherosclerosis in human subjects. However, in the tandem-stenosis mouse model, which reflects plaque instability as typically seen in patients, TMAO levels correlated with several characteristics of plaque instability, such as markers of inflammation, platelet activation, and intraplaque haemorrhage. Conclusions Dietary-induced changes in the microbiome, of both ‘healthy’ and ‘unhealthy’ diets, can cause an increase in the plasma level of TMAO. The gut itself is a site of significant oxidative production of TMAO. Most importantly, our findings reconcile contradictory data on TMAO. There was no direct association of plasma TMAO and the extent of atherosclerosis, both in mice and humans. However, using a mouse model of plaque instability we demonstrated an association of TMAO plasma levels with atherosclerotic plaque instability. The latter confirms TMAO as being a marker of cardiovascular risk.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1499917-1
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Cardiovascular Research Vol. 117, No. 2 ( 2021-01-21), p. 386-401
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 117, No. 2 ( 2021-01-21), p. 386-401
    Abstract: Carbohydrates are the major source of dietary energy, but their role in health and disease remains controversial. Recent epidemiological evidence suggests that the increased consumption of carbohydrates is associated with obesity and increased risk of mortality and dietary trials show that carbohydrate restriction leads to weight loss and improved glycaemic status in obese and diabetic subjects. In contrast, the diets of populations with long and healthy lifespans (e.g. traditional Okinawans from Japan) are high in carbohydrate and low in protein, and several clinical and preclinical studies have linked low-carbohydrate–high-protein diets with increased mortality risk. In this paper we attempt to reconcile these contradictory findings by moving beyond traditional single-nutrient analyses to consider the interactions between nutrients on health outcomes. We do so using the Geometric Framework (GF), a nutritional modelling platform that explicitly considers the main and interactive effects of multiple nutrients on phenotypic characteristics. Analysis of human data by GF shows that weight loss and improved cardio-metabolic outcomes under carbohydrate restriction derive at least in part from reduced caloric intake due to the concomitantly increased proportion of protein in the diet. This is because, as in many animals, a specific appetite for protein is a major driver of food intake in humans. Conversely, dilution of protein in the diet leverages excess food intake through compensatory feeding for protein (‘protein leverage’). When protein is diluted in the diet by readily digestible carbohydrates and fats, as is the case in modern ultra-processed foods, protein leverage results in excess calorie intake, leading to rising levels of obesity and metabolic disease. However, when protein is diluted in the diet by increased quantities of less readily digestible forms of carbohydrate and fibre, energy balance is maintained and health benefits accrue, especially during middle age and early late-life. We argue that other controversies in carbohydrate research can be resolved using the GF methodology in dietary studies.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1499917-1
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Nutrition Reviews Vol. 80, No. 5 ( 2022-04-08), p. 1160-1178
    In: Nutrition Reviews, Oxford University Press (OUP), Vol. 80, No. 5 ( 2022-04-08), p. 1160-1178
    Abstract: Consumption of dietary macronutrients is associated with the progression of a wide range of inflammatory diseases, either by direct modulation of host immune response or via microbiome. This includes periodontitis, a disease affecting tooth-supporting tissues. Objective The aim of this work was to systematically review studies focusing on the effect of macronutrient (ie, carbohydrate, protein, fat) intake on periodontitis in rodents. Data Sources Electronic searches were performed in February 2021 using the PubMed and Web of Science databases. Out of 883 articles reviewed, 23 studies were selected for additional analysis. Data Extraction Investigators extracted relevant data, including author names; the year of publication; article title; macronutrient composition; number and species of animals and their age at the start of the experiment; intervention period; method of periodontitis induction; and primary and secondary periodontitis outcomes. Quality assessment was done using the risk-of-bias tool for animal studies. After completing the data extraction, descriptive statistical information was obtained. Data Analysis High intakes of dietary cholesterol, saturated fatty acids, and processed carbohydrates such as sucrose, and protein-deficient diets were positively associated with periodontitis in rodents. This included greater amounts of alveolar bone loss, more lesions on periodontal tissues, and dental plaque accumulation. In contrast, high doses of milk basic protein in diets and diets with a high ratio of ω-3 to ω-6 fatty acids were negatively associated with periodontitis in rodents. Conclusion This work highlights the fact that, despite the large body of evidence linking macronutrients with inflammation and ageing, overall there is little information on how dietary nutrients affect periodontitis in animal models. In addition, there is inconsistency in data due to differences in methodology, outcome measurement, and dietary formulation. More studies are needed to examine the effects of different dietary macronutrients on periodontitis and investigate the underlying biological mechanisms.
    Type of Medium: Online Resource
    ISSN: 0029-6643 , 1753-4887
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2066844-2
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  • 4
    Online Resource
    Online Resource
    MDPI AG ; 2013
    In:  Cells Vol. 2, No. 2 ( 2013-04-26), p. 266-283
    In: Cells, MDPI AG, Vol. 2, No. 2 ( 2013-04-26), p. 266-283
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2013
    detail.hit.zdb_id: 2661518-6
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  • 5
    Online Resource
    Online Resource
    Informa UK Limited ; 2014
    In:  Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
    In: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Informa UK Limited
    Type of Medium: Online Resource
    ISSN: 1178-7007
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2494854-8
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  • 6
    In: Cell Reports, Elsevier BV, Vol. 25, No. 8 ( 2018-11), p. 2234-2243.e6
    Type of Medium: Online Resource
    ISSN: 2211-1247
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2649101-1
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  • 7
    In: The FASEB Journal, Wiley, Vol. 33, No. 7 ( 2019-07), p. 8033-8042
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1468876-1
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Biology Vol. 10, No. 4 ( 2021-04-16), p. 336-
    In: Biology, MDPI AG, Vol. 10, No. 4 ( 2021-04-16), p. 336-
    Abstract: Obesity caused by the overconsumption of calories has increased to epidemic proportions. Insulin resistance is often associated with an increased adiposity and is a precipitating factor in the development of cardiovascular disease, type 2 diabetes, and altered metabolic health. Of the various factors contributing to metabolic impairments, nutrition is the major modifiable factor that can be targeted to counter the rising prevalence of obesity and metabolic diseases. However, the macronutrient composition of a nutritionally balanced “healthy diet” are unclear, and so far, no tested dietary intervention has been successful in achieving long-term compliance and reductions in body weight and associated beneficial health outcomes. In the current review, we briefly describe the role of the three major macronutrients, carbohydrates, fats, and proteins, and their role in metabolic health, and provide mechanistic insights. We also discuss how an integrated multi-dimensional approach to nutritional science could help in reconciling apparently conflicting findings.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661517-4
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  • 9
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-03-18)
    Abstract: Inorganic arsenic (iAs) exposure has been reported to have an impact on cardiovascular diseases (CVD). However, there is not much known about the cardiac tissue injury of CVD patients in relation to iAs exposure and potential role of single nucleotide polymorphisms (SNPs) of genes related to iAs metabolism, oxidative stress, endothelial dysfunction and inflammation which may play important roles in such CVD cases. In this dual center cross-sectional study, based on the exclusion and inclusion criteria, we have recruited 50 patients out of 270, who came from known arsenic-affected and- unaffected areas of mainly Chittagong, Dhaka and Rajshahi divisions of Bangladesh and underwent open-heart surgery at the selected centers during July 2017 to June 2018. We found that the patients from arsenic affected areas contained significantly higher average iAs concentrations in their urine (6.72 ± 0.54 ppb, P  = 0.028), nail (529.29 ± 38.76 ppb, P   〈  0.05) and cardiac tissue (4.83 ± 0.50 ppb, P   〈  0.05) samples. Patients’ age, sex, BMI, hypertension and diabetes status adjusted analysis showed that patients from arsenic-affected areas had significantly higher iAs concentration in cardiac tissue (2.854, 95%CI 1.017–8.012, P  = 0.046) reflecting higher cardiac tissue injury among them (1.831, 95%CI 1.032–3.249, P  = 0.039), which in turn allowed the analysis to assume that the iAs exposure have played a vital role in patients’ disease condition. Adjusted analysis showed significant association between urinary iAs concentration with AA ( P  = 0.012) and AG ( P  = 0.034) genotypes and cardiac iAs concentration with AA ( P  = 0.017) genotype of AS3MT rs10748835. The AG genotype of AS3MT rs10748835 (13.333 95%CI 1.280–138.845, P  = 0.013), AA genotype of NOS3 rs3918181 (25.333 95%CI 2.065–310.757, P  = 0.002), GG genotype of ICAM1 rs281432 (12.000 95%CI 1.325–108.674, P  = 0.010) and AA genotype of SOD2 rs2758331 (13.333 95%CI 1.280–138.845, P  = 0.013) were found significantly associated with CVD patients from arsenic-affected areas. Again, adjusted analysis showed significant association of AA genotype of AS3MT rs10748835 with CVD patients from arsenic affected areas. In comparison to the reference genotypes of the selected SNPs, AA of AS3MT 10748835, AG of NOS3 rs3918181 and AC of rs3918188, GG of ICAM1 rs281432, TT of VCAM1 rs3176867, AA of SOD2 rs2758331 and GT of APOE rs405509 significantly increased odds of cardiac tissue injury of CVD patients from arsenic affected areas. The results showed that the selected SNPs played a susceptibility role towards cardiac tissue iAs concentration and injury among CVD patients from iAs affected areas.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 10
    In: Journal of Diabetes Research, Hindawi Limited, Vol. 2015 ( 2015), p. 1-16
    Abstract: Pancreatic β -cell loss induced by saturated free fatty acids (FFAs) is believed to contribute to type 2 diabetes. Previous studies have shown induction of endoplasmic reticulum (ER) stress, increased ubiquitinated proteins, and deregulation of the Bcl-2 family in the pancreas of type 2 diabetic patients. However, the precise mechanism of β -cell death remains unknown. In the present study we demonstrate that the FFA palmitate blocks the ubiquitin-proteasome system (UPS) and causes apoptosis through induction of ER stress and deregulation of Bcl-2 proteins. We found that palmitate and the proteasome inhibitor MG132 induced ER stress in β -cells, resulting in decreased expression of the prosurvival proteins Bcl-2, Mcl-1, and Bcl-XL, and upregulation of the prodeath BH3-only protein PUMA. On the other hand, pharmacological activation of the UPS by sulforaphane ameliorated ER stress, upregulated prosurvival Bcl-2 proteins, and protected β -cells from FFA-induced cell death. Furthermore, transgenic overexpression of Bcl-2 protected islets from FFA-induced cell death in vitro and improved glucose-induced insulin secretion in vivo . Together our results suggest that targeting the UPS and Bcl-2 protein expression may be a valuable strategy to prevent β -cell demise in type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 2314-6745 , 2314-6753
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2015
    detail.hit.zdb_id: 2711897-6
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