Gut microbiota has recently emerged as a novel, metabolically active 'organ', tightly linked to obesity and related metabolic disorders such as diabetes and cardiovascular disease;and compelling evidence indicates that several key metabolites (TMAO, L-carnitine, bile acids subtypes) related to gut microbiota metabolism may play pivotal roles in mediating the metabolic effects. Diet is a major force that shapes gut microbiota and weight loss may alter metabolism of gut microbiota. The goal of this application is to examine the long-term (2 years) effects of weight-loss diets varying in macronutrients (fat, protein, and carbohydrate) on the novel cardiometabolic metabolites involved in gut microbiota metabolism in 811 overweight or obese patients from thus far one of the largest and most comprehensive comparator trials on the popular weight-loss diets - the POUNDS LOST trial. We will also assess the relation of changes in plasma gut microbiota metabolites with changes in markers of energy intake and expenditure, including gut hormones (GLP-1, ghrelin), resting metabolic rate (RMR), and total energy expenditure (TEE) measured by doubly-labeled water (DLW);as well as with changes in metabolic risk factors including insulin sensitivity, lipids, adipokines, inflammation, and amino acids. In addition, we will examine the associations between gut microbiota metabolites and global adipose gene expression. Because measurement of energy balance and metabolic markers, and adipose gene expression are funded through separate grants, the proposed project will be conducted in an extremely cost-efficient manner. We have assembled a solid group of experienced collaborators with expertise in epidemiology, metabolomics, gene expression, statistics, clinical trial, and nutrition. We believe that findings of this project will provide novel insights into the metabolic effects of gut microbiota and their relations with dietary factors;and considerably contribute to advance toward new prevention and treatment strategies for obesity and related metabolic disorders through diet intervention.
In one of the largest and most comprehensive comparator trials on the popular weight-loss diets - the POUNDS LOST trial, the proposed study integrates the newly-developed, targeted metabolomic methods and global gene expression profiling to comprehensively evaluate the effects of weight-loss diets varying in macronutrients on the long-term changes in plasma levels of the novel cardiometabolic factors involved in gut microbiota metabolism;and to investigate the mechanisms at molecular and global gene expression levels. Our findings will provide highly important and novel insights into the metabolic effects of gut microbiota and their relations with dietary factors;and significantly contribute to advance toward new prevention and treatment strategies for obesity and related metabolic disorders.
|Mendelian Randomization of Dairy Consumption Working Group (2018) Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies. Clin Chem 64:183-191|
|Heianza, Yoriko; Sun, Dianjianyi; Li, Xiang et al. (2018) Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial. Gut :|
|McKeown, Nicola M; Dashti, Hassan S; Ma, Jiantao et al. (2018) Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis. Diabetologia 61:317-330|
|Sun, D; Wang, T; Heianza, Y et al. (2018) Birthweight and cardiometabolic risk patterns in multiracial children. Int J Obes (Lond) 42:20-27|
|Han, Liyuan; Duan, Donghui; Zhang, Shuang et al. (2018) Effects of the interaction between glycated haemoglobin genetic risk score and postpartum weight reduction on glycaemic changes: A gene-weight interaction analysis. Diabetes Obes Metab 20:2733-2739|
|Goni, Leticia; Sun, Dianjianyi; Heianza, Yoriko et al. (2018) Macronutrient-specific effect of the MTNR1B genotype on lipid levels in response to 2 year weight-loss diets. J Lipid Res 59:155-161|
|Heianza, Yoriko; Sun, Dianjianyi; Smith, Steven R et al. (2018) Changes in Gut Microbiota-Related Metabolites and Long-term Successful Weight Loss in Response to Weight-Loss Diets: The POUNDS Lost Trial. Diabetes Care 41:413-419|
|Nisa, Hoirun; Qi, Kevin H T; Leng, Junhong et al. (2018) The Circadian Rhythm-Related MTNR1B Genotype, Gestational Weight Gain, and Postpartum Glycemic Changes. J Clin Endocrinol Metab 103:2284-2290|
|Sun, Dianjianyi; Li, Xiang; Heianza, Yoriko et al. (2018) History of Asthma From Childhood and Arterial Stiffness in Asymptomatic Young Adults: The Bogalusa Heart Study. Hypertension 71:928-936|
|Wang, Tiange; Heianza, Yoriko; Sun, Dianjianyi et al. (2018) Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene-diet interaction analysis in two prospective cohort studies. BMJ 360:j5644|
Showing the most recent 10 out of 50 publications