Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats.
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.
Ramadan
Wiâm
W
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
Dewasmes
Gérard
G
Petitjean
Michel
M
Wiernsperger
Nicolas
N
Delanaud
Stéphane
S
Geloen
Alain
A
Libert
Jean-Pierre
JP
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*
D004041:Dietary Fats; D007004:Hypoglycemic Agents; D008687:Metformin