Metabolic Effects of Differential Organ Growth Rates

Young children have a high resting energy expenditure (REE) relative to their body weight and metabolically active compartment, fat-free mass (FFM). Both body weight and FFM are, however, metabolically heterogeneous and include organs and tissues varying widely in specific metabolic rate (i.e., organ REE/kg/d). One prevailing hypothesis is that most, if not all, of the higher REE observed in young animals and children compared to adults can be accounted for by a larger proportion of high metabolic rate components such as brain, liver, and heart..

Study Overview

• Status: Completed
• Conditions: Resting Energy Expenditure

Detailed Description

FFM was the traditional and only means of adjusting REE for between-individual differences in metabolically active tissue components. The investigators seek to improve the understanding of variation in REE by developing new and improved rapid magnetic resonance imaging (MRI) methods of quantifying some of the major heat producing organs and tissues in children and adults. The long-term aim is to provide an improved understanding of human energy requirements. Specifically, the investigators propose to test whether: 1) a portion of the elevated daily REE adjusted for FFM observed in young children (Tanner Stage 1) could be accounted for by the relative fractions of body mass as high metabolic activity tissues (heart, liver, kidney, brain) and low metabolic activity tissues (skeletal muscle, adipose tissue), 2) a portion of the age-related decline in daily REE adjusted for FFM observed in children could be accounted for by changes in the relative fractions of body mass as high and low metabolic rate tissues during growth.

• Study Type: Observational
• Enrollment (Actual): 49

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Dympna Gallagher

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 11 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be healthy African-American, Asian (Chinese, Korean, Japanese), and Caucasian pre-pubertal females and males (ages 7-11 years) at baseline. Lean (Body mass index (BMI) < 85th by age and sex) and obese (BMI > 95th percentile by age and sex.

Description

Inclusion Criteria:

• Healthy
• Aged from 7-11 years
• Pre-pubertal (based on Tanner staging)
• Africa-American, Asian, and Caucasian (by self-report of all 4 grandparents of same race group)

Exclusion Criteria:

• Actively involved in a weight management program
• Have co-morbidities of obesity (Blounts disease, hypertension, diabetes; sleep apnea)
• Have entered puberty
• Precocious puberty
• Have known metabolic abnormalities
• Were born prematurely, or were small or large for gestational age
• Lean individuals who have a family history (parents or siblings) of obesity or Type 2 diabetes
• Current or previous significant use of any medication known to affect any of the variables being measured

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Prepubertal children; Healthy 7-11 year old girls and boys.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting energy expenditure in kilocalories	REE is measured by indirect calorimetry over a 30 minute period and extrapolated to a 24 hour period	Day 1
Fat mass in kilograms	Measured from a whole-body dual energy X-ray absorptiometry (DXA) scan	Day 1
Fat-free mass in kilograms	Measured from a whole-body dual energy X-ray absorptiometry (DXA) scan	Day 1
Height in meters	Measured using a stadiometer	Day 1
Weight in kilograms	Measured using a calibrated scale	Day 1
Liver in kilograms	Total volume measured by MRI	Day 1
Heart in kilogram	Left ventricular mass measured by cardiac gated MRI	Day 1
Kidneys in kilogram	Total volume measured by MRI	Day 1
Spleen in kilograms	Total volume measured by MRI	Day 1
Trunk high metabolic rate organs in kilograms	The sum of liver, kidneys, spleen, and heart	Day 1
Brain mass in kilogram	Total volume measured by MRI	Day 1
Skeletal muscle mass in kilograms	Skeletal muscle volume measured by MRI	Day 1
Residual fat-free mass in kilograms	Fat-free mass minus the sum of kidneys, liver, spleen, heart, and skeletal muscle	Day 1
Total body adipose tissue mass in kilogram	Represents the sum of visceral, subcutaneous, and intermuscular adipose tissue by MRI	Day 1
Body mass index in kg/m2	Weight and height will be combined to report BMI	Day 1
Variability in resting energy expenditure	The collected measures will be aggregated to statistically test the following question: How much of the variability in resting energy expenditure can be accounted for by the mass of the measured organs (liver, kidneys, spleen, heart) and tissues (fat, skeletal muscle, brain) and is the explained variance greater than the variance explained when predicting resting energy explained from a model using fat and fat-free mass alone.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in resting energy expenditure in relation to changes in body composition and organ mass.	A portion of age-related decline (2-years) in daily REE adjusted for FFM observed in children is explainable in part by changes in the relative fractions of body mass as high (brain, heart, liver, kidney) and low (skeletal muscle, adipose tissue) metabolic activity tissues with growth and pubertal progress	From baseline measure to follow-up, approximately 2 years

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Dympna Gallagher, Columbia University

Publications and helpful links

General Publications

• Bauer J, Thornton J, Heymsfield S, Kelly K, Ramirez A, Gidwani S, Gallagher D. Dual-energy X-ray absorptiometry prediction of adipose tissue depots in children and adolescents. Pediatr Res. 2012 Oct;72(4):420-5. doi: 10.1038/pr.2012.100. Epub 2012 Jul 20.
• Dorsey KB, Thornton JC, Heymsfield SB, Gallagher D. Greater lean tissue and skeletal muscle mass are associated with higher bone mineral content in children. Nutr Metab (Lond). 2010 May 11;7:41. doi: 10.1186/1743-7075-7-41.
• Shen W, Velasquez G, Chen J, Jin Y, Heymsfield SB, Gallagher D, Pi-Sunyer FX. Comparison of the relationship between bone marrow adipose tissue and volumetric bone mineral density in children and adults. J Clin Densitom. 2014 Jan-Mar;17(1):163-9. doi: 10.1016/j.jocd.2013.02.009. Epub 2013 Mar 21.
• Gao Y, Zong K, Gao Z, Rubin MR, Chen J, Heymsfield SB, Gallagher D, Shen W. Magnetic resonance imaging-measured bone marrow adipose tissue area is inversely related to cortical bone area in children and adolescents aged 5-18 years. J Clin Densitom. 2015 Apr-Jun;18(2):203-8. doi: 10.1016/j.jocd.2015.03.002. Epub 2015 Apr 1.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2004
• Primary Completion (Actual): February 20, 2007
• Study Completion (Actual): February 20, 2007

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): July 18, 2017
• Last Update Submitted That Met QC Criteria: July 14, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Fat-free mass; Tanner stage 1; Pre-pubertal
• Other Study ID Numbers: AAAO3053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No