Fatty Acid Oxidation Disorders & Body Weight Regulation Grant

Oregon Health & Science University (OHSU)

Status: Completed

Conditions: Trifunctional Protein Deficiency

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT00654004

DK71869

K01DK071869 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Several hormones involved in body weight regulation increase the subject's ability to burn fat for energy. The purpose of this study is to investigate how burning fat for energy may affect those hormones and body weight in children. The study will also determine if eating a diet higher in protein alters the amount of fat you burn and how these hormones control body weight.

Full description

A role for mitochondrial fatty acid oxidation in the peripheral signaling cascade of leptin, adiponectin and insulin has recently been proposed from animal studies but has not been investigated in humans. Children with trifunctional protein (TFP, including deficiency of long-chain hydroxyacyl-CoA dehydrogenase) and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, inherited disorders of long-chain fatty acid ß-oxidation, lack an ability to oxidize fatty acids for energy. They have increased levels of body fat and circulating leptin and a high incidence of obesity. Current therapy for children with these disorders is based on frequent meals and consuming a low fat, very high carbohydrate diet. Despite treatment, exercise induced rhabdomyolysis is a common complication of TFP and VLCAD deficiency that frequently leads to exercise avoidance. The effects of these genetic defects on body composition and weight regulation have not been investigated. The contribution of fatty-acid oxidation during moderate intensity exercise in children has also not been reported.

Two groups of subjects were recruited: one group of subjects had a long-chain fatty acid oxidation disorder (n=13). The other group is a group of controls (n=16). We studied peripheral signals of body weight regulation, glucose tolerance, body composition, and exercise metabolism in subjects with a long-chain fatty acid oxidation disorder compared to normal controls.

Enrollment: 26 patients

Sex: All

Ages: 7 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• confirmed diagnosis of TFP, LCHAD, CPT2 or VLCAD deficiency
• at least 7 years of age
• willingness to complete overnight admission
• generally healthy

Exclusion criteria

• inclusion in another research project that alters macronutrient intake
• diabetes, thyroid disease or other endocrine dysfunction that alters body composition.
• pregnancy
• anemia

Trial design

26 participants in 2 patient groups

Subjects

Description:

Subjects are patients with a long-chain fatty acid oxidation disorder including CPT2, VLCAD, TFP or LCHAD deficiency.

Controls

Description:

Subjects do not have a fatty acid oxidation disorder.