title: Inhibition of Lipolysis Ameliorates Diabetic Phenotype in a Mouse Model of Obstructive Sleep Apnea.
abstract: Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH). C57BL6/J mice were exposed for 14 days to IH or control conditions. IH was created by decreasing the fraction of inspired oxygen from 20.9 to 6.5%, 60 times/h. Control exposure was air (fraction of inspired oxygen, 20.9%) delivered at an identical flow rate. Acipimox was provided in drinking water (0.5 g/ml) during exposures. After exposures, intraperitoneal insulin (0.5 IU/kg) and glucose (1 g/kg) tolerance tests were performed, and primary adipocytes were isolated for lipolysis experiments. IH elevated fasting glucose by 51% and worsened glucose tolerance and insulin sensitivity by 33 and 102%, respectively. In parallel, IH increased spontaneous lipolysis by 264%, and reduced epididymal fat mass by 15% and adipocyte size by 8%. Acipimox treatment prevented IH-induced lipolysis and increased epididymal fat mass and adipocyte size by 19 and 10%, respectively. Acipimox fully prevented IH-induced impairments in fasting glycemia, glucose tolerance, and insulin sensitivity. For all reported results, P less than 0.05 was considered significant. Augmented lipolysis contributes to insulin resistance and glucose intolerance observed in mice exposed to IH. Acipimox treatment ameliorated the metabolic consequences of IH and might represent a novel treatment option for patients with obstructive sleep apnea.
authors.affiliation: 1 Center for Research on Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine.|2 Center of Toxicology and Health Safety, National Institute of Public Health, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Weiszenstein
authors.affiliation: 3 Division of Pulmonary and Critical Care Medicine, Asthma and Allergy Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Shimoda
authors.affiliation: 4 Sports Medicine Department, Third Faculty of Medicine, and.
authors.forename: Michal
authors.initials: M
authors.lastname: Koc
authors.affiliation: 5 Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; and.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Seda
authors.affiliation: 1 Center for Research on Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine.|2 Center of Toxicology and Health Safety, National Institute of Public Health, Prague, Czech Republic.|3 Division of Pulmonary and Critical Care Medicine, Asthma and Allergy Center, Johns Hopkins School of Medicine, Baltimore, Maryland.|6 Second Internal Medicine Department, Vinohrady Teaching Hospital, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Polak
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011719:Pyrazines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology*
chemical_list: D005227:Fatty Acids; D007328:Insulin; D011719:Pyrazines; D005947:Glucose; C027696:acipimox
keywords: diabetes; insulin resistance; intermittent hypoxia; lipolysis; obstructive sleep apnea