title: Effect of dietary manipulation on substrate flux and energy balance in obese women taking the appetite suppressant dexfenfluramine.
abstract: 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.
authors.affiliation: MRC Dunn Clinical Nutrition Centre, Addenbrooke's Hospital, Cambridge, United Kingdom. S.Poppitt@auckland.ac.nz
authors.forename: S D
authors.initials: SD
authors.lastname: Poppitt
authors.forename: D L
authors.initials: DL
authors.lastname: Swann
authors.forename: P R
authors.initials: PR
authors.lastname: Murgatroyd
authors.forename: M
authors.initials: M
authors.lastname: Elia
authors.forename: R M
authors.initials: RM
authors.lastname: McDevitt
authors.forename: A M
authors.initials: AM
authors.lastname: Prentice
mesh_terms: 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
chemical_list: D001067:Appetite Depressants; D004041:Dietary Fats; D020372:Dexfenfluramine