title: Differential regulation of metabolic parameters by energy deficit and hunger.
abstract: OBJECTIVE
  Hypocaloric diet decreases both energy expenditure (EE) and respiratory exchange rate (RER), affecting the efficacy of dieting inversely. Energy deficit and hunger may be modulated separately both in human and animal studies by drug treatment or food restriction. Thus it is important to separate the effects of energy deficit and hunger on EE and RER.
  
  
  METHODS
  Three parallel and analogous experiments were performed using three pharmacologically distinct anorectic drugs: rimonabant, sibutramine and tramadol. Metabolic parameters of vehicle- and drug-treated and pair-fed diet-induced obese mice from the three experiments underwent common statistical analysis to identify effects independent of the mechanisms of action. Diet-induced obesity (DIO) test of tramadol was also performed to examine its anti-obesity efficacy.
  
  
  RESULTS
  RER was decreased similarly by drug treatments and paired feeding throughout the experiment irrespective of the cause of reduced food intake. Contrarily, during the passive phase, EE was decreased more by paired feeding than by both vehicle and drug treatment irrespective of the drug used. In the active phase, EE was influenced by the pharmacological mechanisms of action. Tramadol decreased body weight in the DIO test.
  
  
  CONCLUSIONS
  Our results suggest that RER is mainly affected by the actual state of energy balance; conversely, EE is rather influenced by hunger. Therefore, pharmacological medications that decrease hunger may enhance the efficacy of a hypocaloric diet by maintaining metabolic rate. Furthermore, our results yield the proposal that effects of anorectic drugs on EE and RER should be determined compared to vehicle and pair-fed groups, respectively, in animal models.
authors.affiliation: Gedeon Richter Plc., Division of Pharmacological and Drug Safety Research, Hungary. Electronic address: kitkatamas@yahoo.com.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kitka
authors.affiliation: Gedeon Richter Plc., Division of Pharmacological and Drug Safety Research, Hungary.
authors.forename: Sebestyén
authors.initials: S
authors.lastname: Tuza
authors.affiliation: Gedeon Richter Plc., Division of Pharmacological and Drug Safety Research, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Varga
authors.affiliation: Gedeon Richter Plc., Division of Pharmacological and Drug Safety Research, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Horváth
authors.affiliation: Gedeon Richter Plc., Division of Pharmacological and Drug Safety Research, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Kovács
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001069:Appetite Regulation / Q000187:drug effects; D031204:Caloric Restriction; D003503:Cyclobutanes / Q000494:pharmacology; D004032:Diet; D004734:Energy Metabolism / Q000187:drug effects; D005508:Food Deprivation / Q000502:physiology*; D006815:Hunger / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D014147:Tramadol / Q000494:pharmacology
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; D014147:Tramadol; C058254:sibutramine
keywords: Energy expenditure; Indirect calorimetry; Obesity; Respiratory exchange rate; Respiratory quotient