Compelling evidence has implicated human gut microbiota in development of obesity and related cardiometabolic disorders. Recent studies identified a group of circulating metabolites that are functionally related to gut microbiota. These microbial metabolites act as ?transducers? in the microbiota-host communications and ?sensors? in gut-organ/tissue crosstalk, and affect ectopic fat distribution in various metabolic organs and tissues. Diet is among the most important regulators of gut microbiota; however, no study has assessed how weight-loss diets may affect the long-term changes of the newly identified microbial metabolites. The proposed systems study aims to fill this significant research gap. In two of the longest and largest comparator trials on the popular weight-loss diets - POUNDS LOST and CENTRAL, we propose to identify novel plasma microbial metabolites associated with long-term weight loss in response to diet interventions. We will examine relations of plasma levels of identified microbial metabolites and ectopic fat distribution in the liver, heart, pancreas, and kidney, as well as adipose and skeletal muscle tissues. In addition, we will assess whether changes in plasma microbial metabolites mediate the relations between weight loss and changes in cardiometabolic markers. Moreover, we will examine the dynamic associations between microbial metabolites and changes in plasma miRNAs related to obesity and cardiometabolic risk. The findings from our study will considerably improve development of novel prevention and treatment strategies for obesity and related cardiometabolic disorders.

Public Health Relevance

The study proposes to detect novel circulating microbial metabolites associated with long-term weight loss in response to diet interventions. We will perform innovative analyses on the dynamic interrelationships of weight- loss diets, microbial metabolites, gut-organ/tissue cross talk, miRNAs, biochemical and clinical measures. Our study would lead to identification of novel modifiable targets for diet interventions, and improve precision obesity management.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK100383-06
Application #
10124378
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Maruvada, Padma
Project Start
2014-09-15
Project End
2023-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
6
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Tulane University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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
Heianza, Yoriko; Sun, Dianjianyi; Ma, Wenjie et al. (2018) Gut-microbiome-related LCT genotype and 2-year changes in body composition and fat distribution: the POUNDS Lost Trial. Int J Obes (Lond) 42:1565-1573
Sun, Dianjianyi; Heianza, Yoriko; Li, Xiang et al. (2018) Genetic, epigenetic and transcriptional variations at NFATC2IP locus with weight loss in response to diet interventions: The POUNDS Lost Trial. Diabetes Obes Metab 20:2298-2303
Goni, Leticia; Sun, Dianjianyi; Heianza, Yoriko et al. (2018) A circadian rhythm-related MTNR1B genetic variant modulates the effect of weight-loss diets on changes in adiposity and body composition: the POUNDS Lost trial. Eur J Nutr :
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

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