Childhood obesity has become a worldwide phenomenon occurring in about 43 million children and adolescents. Recent studies suggest that gut microbiota contribute to the obese phenotype probably by modulating energy intake through the formation of short chain fatty acids (SCFA) (acetate, propionate, and butyrate). Given the paucity of human data, we have recently started investigating this topic. Our preliminary data generated studying a group of lean and obese children and adolescents demonstrate that: 1) there is a strong association between plasma SCFA and the degree of obesity; 2) the circulating levels of SCFA are related to the synthetic rates of hepatic de novo lipogenesis; and 3) the gut microbiota of obese subjects have a greater ability to ferment carbohydrates than the gut microbiota of lean subjects. Based on these data we hypothesize that obese children and adolescents experience a higher amount of energy harvest for an equal amount of dietary calories than lean, as result of the higher ability of their gut microbiota to synthetize SCFA, which in turn provides an extra source of energy by serving as substrates for hepatic lipogenesis. In order to demonstrate this hypothesis and fill the knowledge void concerning the role of SCFA in the pathophysiology of childhood obesity, we will test the differences in the synthetic rates of SCFA between obese and lean adolescents, and determine how the synthetic rates of SCFA might affect hepatic lipogenesis.

Public Health Relevance

Obesity is the most common chronic disease in pediatrics, affecting 25% of children and adolescents. The key question that we plan to address here is: does the gut microbiota interact with nutrients to convey susceptibility to pediatric obesity? To answer this question, we propose: 1) to assess the synthetic rates of short chain fatty acids derived from the gut flora in lean and obese; 2) to determine whether the short chain fatty acids synthesis might affect hepatic de novo lipogenesis; and 3) to test whether the effect of the gut microbiota on the development of obesity may be mediated by certain macronutrients (namely carbohydrates).

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK114504-03
Application #
9901523
Study Section
Integrative Nutrition and Metabolic Processes Study Section (INMP)
Program Officer
Osganian, Voula
Project Start
2018-05-01
Project End
2023-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Yale University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520