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) an d fat balance (FB) during manipulation of dietary ratios of fat to car bohydrate. High-fat (HF), high-energy diets cause hyperphagia and a po sitive EB and FB. Objective: The protocol was designed to measure subs trate flux and EB in obese women taking dexfenfluramine (DF) or placeb o (PL) during an HF (50% of energy) or low-fat (25% of energy; LF) die t. We hypothesized that alterations in dietary fat would not be regula ted and would lead to a positive EB and FB. Design: The study was doub le-blind, randomized, and placebo-controlled, with 4 treatments (LF/DF , HF/DF, LF/PL, and HF/PL) and a crossover. Five days of continuous, w hole-body calorimetry measurements were made in 6 subjects after 8 d o f home DF/PL treatment. Macronutrient balance and EB were measured wit hin 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 (D elta = 2.31 MJ/d). DF reduced energy (DF, 8.96 MJ/d; FL, 9.66 MJ/d; P< 0.01) and macronutrient intakes, but did not increase energy expendit ure (Delta = -0.31 MJ/d; P < 0.01), or 24-h fat oxidation (Delta = 0.0 3 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.