The purpose of this study is to test the hypothesis that the disruption of the "normal" (three meals a day) eating pattern and prolonged overnight fasting caused by skipping breakfast: i) alters the expression of specific clock genes and clock gene targets involved in regulating adipose tissue lipolysis (breakdown or destruction); ii) increases basal adipose tissue lipolytic (breakdown) activity and plasma free fatty acid (FFA) concentrations; iii) reduces skeletal muscle insulin sensitivity; and iv) increases daylong plasma glucose, FFA, and insulin concentrations. The investigator will do this by studying healthy, lean persons either randomized to consume either 3 standard meals per day or omit breakfast and consume 2 meals per day without changing daily calorie intake (skipping breakfast group).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
30
Washington University School of Medicine
St Louis, Missouri, United States
Determine the effect of skipping breakfast on basal adipose tissue lipolytic activity and skeletal muscle insulin sensitivity
Hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled trace infusions will be conducted before and after the diet intervention to asses the changes on basal adipose tissue lipolytic activity and skeletal muscle insulin sensitivity.
Time frame: 3 weeks
Determine the effect of skipping breakfast on 24-hour plasma substrate, hormone concentrations and intramyocellular fatty acid mediators of lipotoxicity.
Multiple blood and skeletal muscle biopsy samples will be obtained during a 24-hour feeding study before and after the diet intervention to assess 24-hour plasma substrate, hormone concentrations and intramyocellular fatty acid mediators of lipotoxicity.
Time frame: 3 weeks
Determine the effect of skipping breakfast on the diurnal expression of clock genes and downstream metabolic targets involved in regulating adipose tissue lipolytic activity and skeletal muscle insulin action.
Serial biopsy samples (every 6 hours) of adipose tissue and muscle will be obtained during the 24-hour feeding study to evaluate diurnal expression patterns of i) clock genes \[CLOCK, brain and muscle Arnt-like protein-1(BMAL1), period1 (PER1), period2 (PER2), and Dbp D site albumin promoter binding protein (DBP)\] in adipose tissue and muscle and ii) putative downstream clock gene targets associated with lypolysis in adipose tissue \[hormone-sensitive lipase(HSL) and adipocyte triglyceride lipase (ATGL)\], skeletal muscle insulin action \[glucose transporter type 4(GLUT4)\] and skeletal muscle fatty acid metabolism \[cluster of differentiation 36(CD36), uncoupling protein 3 (UCP3) and pyruvate dehydrogenase kinase, isozyme 4(PDK4)\].
Time frame: 3 weeks
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