Nutrition & Metabolism最新文献

{"title":"A comparative study on indicators of vitamin A status and risk factors for sensitivity and specificity of the methods to detect vitamin A deficiency.","authors":"Olivier O Sombié, Augustin N Zeba, Jérome W Somé, Adama Kazienga, Michael Grahn, Sherry A Tanumihardjo, Stefaan De Henauw, Souheila Abbeddou","doi":"10.1186/s12986-023-00768-7","DOIUrl":"10.1186/s12986-023-00768-7","url":null,"abstract":"<p><strong>Background: </strong>Serum retinol (SR) and retinol-binding protein (RBP) are commonly used indicators, but they are affected by infections and inflammation. This study aimed to assess the sensitivity and specificity of VA indicators to detect vitamin A deficiency (VAD) in 36-59-month-old children living in a rural area in Burkina Faso.</p><p><strong>Methods: </strong>In a community-based study, two cross-sectional surveys were carried out from November 2016 to September 2017 in the health district of Dandé in Burkina Faso. The surveys included 115 children 36-59 months old. Indicators of VA and inflammation assessed in all children included SR, RBP and total liver VA reserves (TLR) estimated by retinol isotope dilution, and inflammation markers (C-reactive protein (CRP) and alpha 1-acid glycoprotein (AGP)). We calculated the sensitivity, specificity, positive and negative predictive values. In addition, the effects of inflammation, helminth infection, and season on sensitivity and specificity were assessed.</p><p><strong>Results: </strong>The prevalence of VAD assessed by SR (< 0.7 µmol/L), RBP (< 0.7 µmol/L), and TLR (< 0.1 µmol/g liver) were, respectively, 30.9%, 33.3%, and 0%. Compared to TLR, the specificity, positive predictive value, and negative predictive value of SR were 71.1%, 0%, and 100%, and of RBP, were 68.9%, 0%, and 100%, respectively. The sensitivity was indeterminable for SR and RBP. The specificity of SR and RBP was lower during the dry season. Elevated CRP (> 5.0 mg/L) and AGP (> 1.0 g/L) were detected in 1.9% and 28.6% of children, respectively. The adjustment of VA indicators for inflammation improved SR's specificity to 75.9% and decreased RBP's specificity to 67.8%.</p><p><strong>Conclusion: </strong>No cases of VAD were identified by TLR. However, (inflammation-adjusted) SR and RBP had varying accuracy in the estimation of VAD.</p><p><strong>Trial registration: </strong>The study was registered, retrospectively, on 22 March 2018 as a clinical trial with the Pan African Clinical Trials Registry under the number Cochrane South Africa; PACTR201803002999356.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early adulthood weight change, midlife \"Life's essential 8\" health status and risk of cardiometabolic diseases: a chinese nationwide cohort study.","authors":"Qiuyu Cao,&nbsp;Mian Li,&nbsp;Guijun Qin,&nbsp;Li Yan,&nbsp;Jiang He,&nbsp;Min Xu,&nbsp;Yu Xu,&nbsp;Tiange Wang,&nbsp;Yuhong Chen,&nbsp;Shuangyuan Wang,&nbsp;Hong Lin,&nbsp;Zhiyun Zhao,&nbsp;Zhengnan Gao,&nbsp;Tianshu Zeng,&nbsp;Ruying Hu,&nbsp;Xuefeng Yu,&nbsp;Gang Chen,&nbsp;Qing Su,&nbsp;Yiming Mu,&nbsp;Lulu Chen,&nbsp;Xulei Tang,&nbsp;Qin Wan,&nbsp;Guixia Wang,&nbsp;Feixia Shen,&nbsp;Zuojie Luo,&nbsp;Yingfen Qin,&nbsp;Li Chen,&nbsp;Yanan Huo,&nbsp;Qiang Li,&nbsp;Zhen Ye,&nbsp;Yinfei Zhang,&nbsp;Chao Liu,&nbsp;Youmin Wang,&nbsp;Shengli Wu,&nbsp;Tao Yang,&nbsp;Huacong Deng,&nbsp;Jiajun Zhao,&nbsp;Lixin Shi,&nbsp;Guang Ning,&nbsp;Weiqing Wang,&nbsp;Jieli Lu,&nbsp;Yufang Bi","doi":"10.1186/s12986-023-00765-w","DOIUrl":"10.1186/s12986-023-00765-w","url":null,"abstract":"<p><strong>Background: </strong>The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by \"Life's Essential 8\" has not been characterized. We aim to examine the associations of early adulthood weight change and midlife \"Life's Essential 8\" CVH status with cardiometabolic outcomes in a Chinese cohort.</p><p><strong>Methods: </strong>The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in \"Life's Essential 8\" was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria.</p><p><strong>Results: </strong>72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04-1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25-1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01-2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90-2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife.</p><p><strong>Conclusions: </strong>Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healthy lifestyle scores associate with incidence of type 2 diabetes mediated by uric acid.","authors":"Xinyue He,&nbsp;Wei Shao,&nbsp;Senhai Yu,&nbsp;Jiazhou Yu,&nbsp;Changzhen Huang,&nbsp;Haiqing Ren,&nbsp;Chengguo Liu,&nbsp;Yuying Xu,&nbsp;Yimin Zhu","doi":"10.1186/s12986-023-00763-y","DOIUrl":"10.1186/s12986-023-00763-y","url":null,"abstract":"<p><strong>Background: </strong>Whether and to what extent serum uric acid (SUA) mediates the association between combined lifestyle behaviors and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to investigate the role of SUA in the relationship between healthy lifestyle scores (HLS) and the incidence of T2DM.</p><p><strong>Methods: </strong>This prospective study used data from Zhejiang Metabolic Syndrome cohort. A HLS (5-point scale including healthy waist circumference (WC), never smoking, high physical activity, healthy diet and moderate alcohol intake) was estimated in 13,919 participants, who had SUA at baseline examination in 2009-2014, and were followed-up to 2021-2022 to ascertain incident of T2DM. Cox proportional hazards models and mediation analysis were used to examine the associations between HLS, SUA and T2DM.</p><p><strong>Results: </strong>We included 13,919 participants aged 18 years or older without diabetes at baseline (mean age 54.6 [SD 13.9] years, 58.7% female). During a median follow-up of 9.94 years, 645 cases of T2DM occurred. Compared with participants with a poor HLS, those with 4-5 low-risk lifestyle factors showed a 60% reduction in the risk of developing T2DM (adjusted HR, 0.40; 95% CI: 0.28-0.57). Further, the population-attributable risk percent (95% CI) of T2DM for poor adherence to the overall healthy lifestyle (< 4 low-risk factors) was 43.24% (30.02%, 56.46%). The HLS was inversely associated with SUA level. With per score increased in HLS, the beta (95% CI) of SUA (log transformed) was - 0.03 (- 0.03, - 0.02), and the odds ratio (95% CI) of hyperuricemia was 0.82 (0.77, 0.86). The relationship between the HLS and risk of T2DM was mediated by SUA with a 13.06% mediation effect. There was no significant combined effect of HLS and SUA on risk of T2DM (P = 0.097).</p><p><strong>Conclusions: </strong>The relationship between overall healthy lifestyle behaviors and T2DM was reconfirmed and the association appeared to be mediated by SUA. The mediation effect of baseline SUA was more pronounced among women who were below 60 years old.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of serum betaine concentrations with the risk of new-onset cancers: results from two independent nested case-control studies.","authors":"Hailun Xie,&nbsp;Kangping Zhang,&nbsp;Yaping Wei,&nbsp;Guotian Ruan,&nbsp;Heyang Zhang,&nbsp;Shuqun Li,&nbsp;Yun Song,&nbsp;Ping Chen,&nbsp;Lishun Liu,&nbsp;Binyan Wang,&nbsp;Hanping Shi","doi":"10.1186/s12986-023-00755-y","DOIUrl":"10.1186/s12986-023-00755-y","url":null,"abstract":"<p><p>Evidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the \"H-type Hypertension Prevention and Control Public Service Project\" (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99-1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine < 5.01 mmol/L, OR = 0.82, 95%CI = 0.59-1.14, p = 0.228; betaine ≥ 5.01 mmol/L, OR = 1.08, 95%CI = 1.01-1.17, p = 0.036). In the validation cohort, a significant association between serum betaine as a continuous variable and total cancer (OR = 1.48, 95%CI = 1.06-2.05, P = 0.020) was also found. High serum betaine was associated with increased risk of total cancer and lung cancer, and a U-shaped association was found with the risk of digestive cancers, with a turning point at about 5.01 mmol/L.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does dietary nitrate boost the effects of caloric restriction on brain health? Potential physiological mechanisms and implications for future research.","authors":"Mushari Alharbi, Blossom Cm Stephan, Oliver M Shannon, Mario Siervo","doi":"10.1186/s12986-023-00766-9","DOIUrl":"10.1186/s12986-023-00766-9","url":null,"abstract":"<p><p>Dementia is a highly prevalent and costly disease characterised by deterioration of cognitive and physical capacity due to changes in brain function and structure. Given the absence of effective treatment options for dementia, dietary and other lifestyle approaches have been advocated as potential strategies to reduce the burden of this condition. Maintaining an optimal nutritional status is vital for the preservation of brain function and structure. Several studies have recognised the significant role of nutritional factors to protect and enhance metabolic, cerebrovascular, and neurocognitive functions. Caloric restriction (CR) positively impacts on brain function via a modulation of mitochondrial efficiency, endothelial function, neuro-inflammatory, antioxidant and autophagy responses. Dietary nitrate, which serves as a substrate for the ubiquitous gasotransmitter nitric oxide (NO), has been identified as a promising nutritional intervention that could have an important role in improving vascular and metabolic brain regulation by affecting oxidative metabolism, ROS production, and endothelial and neuronal integrity. Only one study has recently tested the combined effects of both interventions and showed preliminary, positive outcomes cognitive function. This paper explores the potential synergistic effects of a nutritional strategy based on the co-administration of CR and a high-nitrate diet as a potential and more effective (than either intervention alone) strategy to protect brain health and reduce dementia risk.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effects of plant-based flours on metabolic homeostasis and the gut microbiota in high-fat fed rats.","authors":"Taylor M Martinez, Hallie R Wachsmuth, Rachel K Meyer, Savanna N Weninger, Adelina I Lane, Archana Kangath, Gabriele Schiro, Daniel Laubitz, Jennifer H Stern, Frank A Duca","doi":"10.1186/s12986-023-00767-8","DOIUrl":"10.1186/s12986-023-00767-8","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiome is a salient contributor to the development of obesity, and diet is the greatest modifier of the gut microbiome, which highlights the need to better understand how specific diets alter the gut microbiota to impact metabolic disease. Increased dietary fiber intake shifts the gut microbiome and improves energy and glucose homeostasis. Dietary fibers are found in various plant-based flours which vary in fiber composition. However, the comparative efficacy of specific plant-based flours to improve energy homeostasis and the mechanism by which this occurs is not well characterized.</p><p><strong>Methods: </strong>In experiment 1, obese rats were fed a high fat diet (HFD) supplemented with four different plant-based flours for 12 weeks. Barley flour (BF), oat bran (OB), wheat bran (WB), and Hi-maize amylose (HMA) were incorporated into the HFD at 5% or 10% total fiber content and were compared to a HFD control. For experiment 2, lean, chow-fed rats were switched to HFD supplemented with 10% WB or BF to determine the preventative efficacy of flour supplementation.</p><p><strong>Results: </strong>In experiment 1, 10% BF and 10% WB reduced body weight and adiposity gain and increased cecal butyrate. Gut microbiota analysis of WB and BF treated rats revealed increases in relative abundance of SCFA-producing bacteria. 10% WB and BF were also efficacious in preventing HFD-induced obesity; 10% WB and BF decreased body weight and adiposity, improved glucose tolerance, and reduced inflammatory markers and lipogenic enzyme expression in liver and adipose tissue. These effects were accompanied by alterations in the gut microbiota including increased relative abundance of Lactobacillus and LachnospiraceaeUCG001, along with increased portal taurodeoxycholic acid (TDCA) in 10% WB and BF rats compared to HFD rats.</p><p><strong>Conclusions: </strong>Therapeutic and preventative supplementation with 10%, but not 5%, WB or BF improves metabolic homeostasis, which is possibly due to gut microbiome-induced alterations. Specifically, these effects are proposed to be due to increased concentrations of intestinal butyrate and circulating TDCA.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases.","authors":"Chiara Murgia, Ankush Dehlia, Mark A Guthridge","doi":"10.1186/s12986-023-00764-x","DOIUrl":"10.1186/s12986-023-00764-x","url":null,"abstract":"<p><p>Riboflavin, or vitamin B2, is an essential nutrient that serves as a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). The binding of the FAD and/or FMN cofactors to flavoproteins is critical for regulating their assembly and activity. There are over 90 proteins in the human flavoproteome that regulate a diverse array of biochemical pathways including mitochondrial metabolism, riboflavin transport, ubiquinone and FAD synthesis, antioxidant signalling, one-carbon metabolism, nitric oxide signalling and peroxisome oxidative metabolism. The identification of patients with genetic variants in flavoprotein genes that lead to adult-onset pathologies remains a major diagnostic challenge. However, once identified, many patients with adult-onset inborn errors of metabolism demonstrate remarkable responses to riboflavin therapy. We review the structure:function relationships of mutant flavoproteins and propose new mechanistic insights into adult-onset riboflavin-responsive pathologies and metabolic dysregulations that apply to multiple biochemical pathways. We further address the vexing issue of how the inheritance of genetic variants in flavoprotein genes leads to an adult-onset disease with complex symptomologies and varying severities. We also propose a broad clinical framework that may not only improve the current diagnostic rates, but also facilitate a personalized approach to riboflavin therapy that is low cost, safe and lead to transformative outcomes in many patients.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of the modified fat-protein unit algorithm compared with that of carbohydrate counting on postprandial glucose in adults with type-1 diabetes when consuming meals with differing macronutrient compositions: a randomized crossover trial.","authors":"Yunying Cai, Mengge Li, Lun Zhang, Jie Zhang, Heng Su","doi":"10.1186/s12986-023-00757-w","DOIUrl":"10.1186/s12986-023-00757-w","url":null,"abstract":"<p><strong>Background: </strong>The optimization of glucose control in type-1 diabetes is challenged by postprandial glycemic variability. This study aimed to compare the postprandial glycemic effects of carbohydrate counting and the modified fat-protein unit (FPU) algorithms following meals with different protein and fat emphases in adults with type-1 diabetes.</p><p><strong>Methods: </strong>Thirty adults with type-1 diabetes aged 18 to 45 years participated in a randomized crossover trial. In a random order, participants consumed four test meals with equivalent energy and different macronutrient emphases on four separate mornings. The modified FPU algorithms and carbohydrate counting were used to determine the insulin dose for the test meals. A continuous glucose monitoring system was used to measured postprandial glycemia.</p><p><strong>Results: </strong>Compared with carbohydrate counting, the modified FPU algorithm significantly decreased the late postprandial mean glucose levels (p = 0.026) in high protein-fat meals. The number of hypoglycemia episodes was similar between insulin dosing algorithms for the high protein-fat meals; hypoglycemic events were considerably higher for the modified FPU in the normal protein-fat meal (p = 0.042).</p><p><strong>Conclusions: </strong>The modified FPU algorithm may improve postprandial glycemic control after consuming high protein-fat meals in adults with type-1 diabetes but may result in increased hypoglycemia risk when used with a normal protein-fat meal.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective association between an obesogenic dietary pattern in early adolescence and metabolomics derived and traditional cardiometabolic risk scores in adolescents and young adults from the ALSPAC cohort.","authors":"Eduard Martínez Solsona, Laura Johnson, Kate Northstone, Genevieve Buckland","doi":"10.1186/s12986-023-00754-z","DOIUrl":"10.1186/s12986-023-00754-z","url":null,"abstract":"<p><strong>Background: </strong>Dietary intake during early life may be a modifying factor for cardiometabolic risk (CMR). Metabolomic profiling may enable more precise identification of CMR in adolescence than traditional CMR scores. We aim to assess and compare the prospective associations between an obesogenic dietary pattern (DP) score at age 13 years with a novel vs. traditional CMR score in adolescence and young adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC).</p><p><strong>Methods: </strong>Study participants were ALSPAC children with diet diary data at age 13. The obesogenic DP z-score, characterized by high energy-density, high % of energy from total fat and free sugars, and low fibre density, was previously derived using reduced rank regression. CMR scores were calculated by combining novel metabolites or traditional risk factors (fat mass index, insulin resistance, mean arterial blood pressure, triacylglycerol, HDL and LDL cholesterol) at age 15 (n = 1808), 17 (n = 1629), and 24 years (n = 1760). Multivariable linear regression models estimated associations of DP z-score with log-transformed CMR z-scores.</p><p><strong>Results: </strong>Compared to the lowest tertile, the highest DP z-score tertile at age 13 was associated with an increase in the metabolomics CMR z-score at age 15 (β = 0.20, 95% CI 0.09, 0.32, p trend < 0.001) and at age 17 (β = 0.22, 95% CI 0.10, 0.34, p trend < 0.001), and with the traditional CMR z-score at age 15 (β = 0.15, 95% CI 0.05, 0.24, p trend 0.020). There was no evidence of an association at age 17 for the traditional CMR z-score (β = 0.07, 95% CI -0.03, 0.16, p trend 0.137) or for both scores at age 24.</p><p><strong>Conclusions: </strong>An obesogenic DP was associated with greater CMR in adolescents. Stronger associations were observed with a novel metabolite CMR score compared to traditional risk factors. There may be benefits from modifying diet during adolescence for CMR health, which should be prioritized for further research in trials.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10310479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 exacerbates insulin resistance in hepatocytes by regulating m⁶A modification of cytochrome P450 2B6.","authors":"Yongqing Li, Dantong Zhang, Yinan Gao, Peijun Wang, Zejun Wang, Bingyang Zhang, Junjun Liu, Diwen Ye, Wanshan Ma, Sumei Lu","doi":"10.1186/s12986-023-00762-z","DOIUrl":"10.1186/s12986-023-00762-z","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance (IR) in hepatocytes endangers human health, and frequently results in the development of non-alcoholic fatty liver disease (NAFLD). Research on m⁶A methylation of RNA molecules has gained popularity in recent years; however, the molecular mechanisms regulating the processes of m⁶A modification and IR are not known. The cytochrome P450 (CYP450) enzyme system, which is mainly found in the liver, is associated with the pathogenesis of NAFLD. However, few studies have been conducted on CYP450 related m⁶A methylation. Here, we investigated the role of the methyltransferase METTL3 in exacerbating IR in hepatocytes, mainly focusing on the regulation of m⁶A modifications in CYP2B6.</p><p><strong>Methods and results: </strong>Analysis using dot blot and epitranscriptomic chips revealed that the m⁶A modification pattern of the transcriptome in high-fat diet (HFD)-induced fatty liver and free fatty acid (FFA)-induced fatty hepatocytes showed significant changes. CYP450 family members, especially Cyp2b10, whose homolog in humans is CYP2B6, led to a noticeable increase in m⁶A levels in HFD-induced mice livers. Application of the METTL3 methyltransferase inhibitor, STM2457, increased the level of insulin sensitivity in hepatocytes. We then analyzed the role of METTL3 in regulating m⁶A modification of CYP2B6 in hepatocytes. METTL3 regulated the m⁶A modification of CYP2B6, and a positive correlation was found between the levels of CYP2B6 translation and m⁶A modifications. Furthermore, interference with METTL3 expression and exposure to STM2457 inhibited METTL3 activity, which in turn interfered with the phosphorylated insulin receptor substrate (pIRS)-glucose transporter 2 (GLUT2) insulin signaling pathway; overexpression of CYP2B6 hindered IRS phosphorylation and translocation of GLUT2 to membranes, which ultimately exacerbated IR.</p><p><strong>Conclusion: </strong>These findings offer unique insights into the role that METTL3-mediated m⁶A modifications of CYP2B6 play in regulating insulin sensitivity in hepatocytes and provide key information for the development of strategies to induce m⁶A modifications for the clinical treatment of NAFLD.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}