Intermittent hypoxia in obese Zucker rats: cardiometabolic and inflammatory effects.
What is the central question of this study? This study addresses the relative impact of obesity and intermittent hypoxia in the pathophysiological process of obstructive sleep apnoea by investigating the metabolic, inflammatory and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker rats. What is the main finding and its importance? We found that obesity and intermittent hypoxia have mainly distinct consequences on the investigated inflammatory and cardiometabolic parameters in Zucker rats. This suggests that, for a given severity of sleep apnea, the association of obesity and obstructive sleep apnoea may not necessarily be deleterious. Obstructive sleep apnoea is associated with obesity with a high prevalence, and both co-morbidities are independent cardiovascular risk factors. Intermittent hypoxia (IH) is thought to be the main factor responsible for the obstructive sleep apnoea-related cardiometabolic alterations. The aim of this study was to assess the respective impact of obesity and IH on the inflammatory and cardiometabolic state in rats. Lean and obese Zucker rats were exposed to normoxia or chronic IH, and we assessed metabolic and inflammatory parameters, such as plasma lipids and glucose, serum leptin and adiponectin, liver cytokines, nuclear factor-κB activity and cardiac endothelin-1 levels. Myocardial infarct size was also evaluated following in vitro ischaemia-reperfusion. Circulating lipids, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels were higher in obese versus lean rats. Chronic IH did not have a significant impact on metabolic parameters in lean rats. In obese rats, IH increased glycaemia and HOMA-IR. Liver interleukin-6 and tumour necrosis factor-α levels were elevated in lean rats exposed to IH; obesity prevented the increase in interleukin-6 but not in tumour necrosis factor-α. Finally, IH exposure enhanced myocardial sensitivity to infarction in both lean and obese rats and increased cardiac endothelin-1 in lean but not obese rats. In conclusion, this study shows that the dyslipidaemia and insulin resistance induced by obesity of genetic origin does not enhance the deleterious cardiovascular response to IH and may even partly protect against IH-induced inflammation.
Univ Grenoble Alpes, HP2, F-38041 Grenoble Cedex, France. anne.briancon@univ-grenoble-alpes.fr.|INSERM U1042, F-38041 Grenoble Cedex, France. anne.briancon@univ-grenoble-alpes.fr.
Anne
A
Briançon-Marjollet
Univ Grenoble Alpes, HP2, F-38041 Grenoble Cedex, France.|INSERM U1042, F-38041 Grenoble Cedex, France.|CHU Institut de Biologie et Pathologies, F-38043 Grenoble, France.
Denis
D
Monneret
Univ Grenoble Alpes, HP2, F-38041 Grenoble Cedex, France.|INSERM U1042, F-38041 Grenoble Cedex, France.
Marion
M
Henri
Univ Grenoble Alpes, HP2, F-38041 Grenoble Cedex, France.|INSERM U1042, F-38041 Grenoble Cedex, France.
Marie
M
Joyeux-Faure
Univ Grenoble Alpes, HP2, F-38041 Grenoble Cedex, France.|INSERM U1042, F-38041 Grenoble Cedex, France.
Perle
P
Totoson
Univ Grenoble Alpes, HP2, F-38041 Grenoble Cedex, France.|INSERM U1042, F-38041 Grenoble Cedex, France.
Sandrine
S
Cachot
Univ Grenoble Alpes, HP2, F-38041 Grenoble Cedex, France.|INSERM U1042, F-38041 Grenoble Cedex, France.|CHU Institut de Biologie et Pathologies, F-38043 Grenoble, France.
Patrice
P
Faure
Univ Grenoble Alpes, HP2, F-38041 Grenoble Cedex, France.|INSERM U1042, F-38041 Grenoble Cedex, France.
Diane
D
Godin-Ribuot
D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; D001786:Blood Glucose; D016207:Cytokines; D019332:Endothelin-1; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D008055:Lipids; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha