Mechanisms of Obesity and Its Metabolic Complications in Youth
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Obesity, Childhood
- Sponsor
- Yale University
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Rate of Appearance of Acetate
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
The overarching goal of this project is to determine whether the effect of gut microbiota on human metabolism might be mediated by short chain fatty acids (SCFA) and whether the SCFA might modulate lipid metabolism.
Detailed Description
This would be the first study determining the effect of SCFA synthesis on hepatic de novo lipogenesis and to assess whether and how isocaloric dietary changes (namely low carbohydrates) might modify the composition of the gut microbiota and reduce the synthesis of SCFA during adolescence, a sensitive period for the development of obesity.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Good general health,
- •Taking no medication on a chronic basis
- •Age 15 to 21 years,
- •In puberty (girls and boys: Tanner stage III - V)
- •BMI \>25th and \<85th for lean cohort; BMI \>95th for obese cohort
- •Girls who begin menstruating must have a negative pregnancy test during the study.
- •Exclusion criteria:
- •Baseline creatinine \>1.0 mg
- •Food allergies
- •Pregnancy
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Rate of Appearance of Acetate
Time Frame: Pre lactulose (average values at 2, 2.5, 3 hours) and Post lactulose (average of values at 7, 8, 9 and 10 hours)
Starting at 08:00, we began a 10-h, primed, continuous, peripheral venous infusion of 99% sodium \[d3\]-acetate with a priming dose of 200 μg · kg-1 · min-1 for 4 min and a continuous infusion rate of 59.5 μg · kg-1 · min-1 for 10 h. After 180 min from the start of the infusion, subjects received 20 g of lactulose per os, dissolved in 30 mL of water.
Percent of Hepatic de Novo Lipogenesis.
Time Frame: Pre lactulose (average values at 2, 2.5, 3 hours) and Post lactulose (average of values at 7, 8, 9 and 10 hours)
The percent of hepatic de novo lipogenesis (DNL) refers to the proportion of fatty acids in the liver that are derived from a de novo synthesis pathway, rather than from dietary sources.
Change in the Rate of Appearance of Acetate
Time Frame: Pre lactulose (average values at 2, 2.5, 3 hours) and Post lactulose (average of values at 7, 8, 9 and 10 hours)
The changes in rate of appearance of acetate (RaAcetate) are measured averaging the basal RaAcetate 9 timepoints (2 and 3 hours) and the post-lactulose RaAcetate (timepoints 7, 8, 9 and 10 hours).