title: Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats.
abstract: OBJECTIVE
  We assessed the relationship between a high-fat (HF) diet and central apnea during rapid eye movement and non-rapid eye movement sleep stages by recording ventilatory parameters in 28 non-obese rats in which insulin resistance had been induced by an HF diet. We also studied whether metformin (an anti-hyperglycemic drug frequently used to treat insulin resistance) could reverse sleep apnea or prevent its occurrence in this experimental paradigm.
  
  
  METHODS
  Rats were fed with a standard diet (10 rats), an HF diet (8 rats), or an HF diet concomitantly with metformin treatment (10 rats). Each animal was instrumented for electroencephalographic and electromyographic recording. After 3 weeks, ventilatory parameters during sleep were recorded with a body plethysmograph. All rats were treated with metformin for 1 week, after which time the ventilatory measurements were measured again.
  
  
  RESULTS
  Our results showed that the three groups of animals did not differ in terms of body growth over the entire experimental period. The HF diet did not modify sleep structure or minute ventilation in the different sleep stages. A great increase (+266 +/- 48%) in central apnea frequency was observed in insulin-resistant rats. This was explained by an increase in both post-sigh (+195 +/- 35%) and spontaneous apnea (+437 +/- 65%) in the different sleep stages. These increases were suppressed by metformin treatment.
  
  
  CONCLUSIONS
  Insulin resistance induced by the HF diet could be the promoter of sleep apnea in non-obese rats. Metformin is an efficient curative and preventive treatment for sleep apnea, suggesting that insulin resistance modifies the ventilatory drive independently of obesity.
authors.affiliation: EA 3901, Dysrégulations Métaboliques Acquises et Génétiques, Université de Picardie Jules Verne, Faculté de Médecine, 3 Rue des Louvels, F-80036 Amiens cedex 1, France. wiam.ramadan@etud.u-picardie.fr
authors.forename: Wiâm
authors.initials: W
authors.lastname: Ramadan
authors.forename: Gérard
authors.initials: G
authors.lastname: Dewasmes
authors.forename: Michel
authors.initials: M
authors.lastname: Petitjean
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wiernsperger
authors.forename: Stéphane
authors.initials: S
authors.lastname: Delanaud
authors.forename: Alain
authors.initials: A
authors.lastname: Geloen
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Libert
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D012891:Sleep Apnea Syndromes / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control*
chemical_list: D004041:Dietary Fats; D007004:Hypoglycemic Agents; D008687:Metformin