Effect of dietary manipulation on substrate flux and energy balance in obese women taking the appetite suppressant dexfenfluramine.
BACKGROUND
Studies in lean men show poor regulation of energy (EB) and fat balance (FB) during manipulation of dietary ratios of fat to carbohydrate. High-fat (HF), high-energy diets cause hyperphagia and a positive EB and FB.


OBJECTIVE
The protocol was designed to measure substrate flux and EB in obese women taking dexfenfluramine (DF) or placebo (PL) during an HF (50% of energy) or low-fat (25% of energy; LF) diet. We hypothesized that alterations in dietary fat would not be regulated and would lead to a positive EB and FB.


METHODS
The study was double-blind, randomized, and placebo-controlled, with 4 treatments (LF/DF, HF/DF, LF/PL, and HF/PL) and a crossover. Five days of continuous, whole-body calorimetry measurements were made in 6 subjects after 8 d of home DF/PL treatment. Macronutrient balance and EB were measured within the chamber as the cumulative difference between ad libitum intake and oxidation.


RESULTS
The HF diet increased energy (HF, 10.50 MJ/d; LF, 8.13 MJ/d; P < 0.0001) and fat intakes (HF, 5.34 MJ/d; LF, 2.06 MJ/d; P < 0.0001), leading to a positive EB (delta = 2.37 MJ/d) and FB (delta = 2.31 MJ/d). DF reduced energy (DF, 8.96 MJ/d; PL, 9.66 MJ/d; P < 0.01) and macronutrient intakes, but did not increase energy expenditure (delta = -0.31 MJ/d; P < 0.01), or 24-h fat oxidation (delta = 0.03 MJ/d; P = 0.46).


CONCLUSIONS
EB and FB are poorly regulated with HF, energy-dense diets in obese women, which leads to fat deposition and weight gain.
Poppitt
S D
SD
MRC Dunn Clinical Nutrition Centre, Addenbrooke's Hospital, Cambridge, United Kingdom. S.Poppitt@auckland.ac.nz
Swann
D L
DL
Murgatroyd
P R
PR
Elia
M
M
McDevitt
R M
RM
Prentice
A M
AM
D001067:Appetite Depressants / Q000494:pharmacology* / Q000627:therapeutic use; D002151:Calorimetry; D018592:Cross-Over Studies; D020372:Dexfenfluramine / Q000494:pharmacology* / Q000627:therapeutic use; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism* / Q000494:pharmacology; D004311:Double-Blind Method; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism*; D010084:Oxidation-Reduction; D012527:Satiation / Q000187:drug effects
D001067:Appetite Depressants; D004041:Dietary Fats; D020372:Dexfenfluramine