title: Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia.
abstract: Chronic intermittent hypoxia (IH) during sleep can result from obstructive sleep apnea (OSA), a disorder that is particularly prevalent in obesity. OSA is associated with high levels of circulating leptin, cardiovascular dysfunction, and dyslipidemia. Relationships between leptin and cardiovascular function in OSA and chronic IH are poorly understood. We exposed lean wild-type (WT) and obese leptin-deficient ob/ob mice to IH for 4 wk, with and without leptin infusion, and measured cardiovascular indices including aortic vascular stiffness, endothelial function, cardiac myocyte morphology, and contractile properties. At baseline, ob/ob mice had decreased vascular compliance and endothelial function vs. WT mice. We found that 4 wk of IH decreased vascular compliance and endothelial relaxation responses to acetylcholine in both WT and leptin-deficient ob/ob animals. Recombinant leptin infusion in both strains restored IH-induced vascular abnormalities toward normoxic WT levels. Cardiac myocyte morphology and function were unaltered by IH. Serum cholesterol and triglyceride levels were significantly decreased by leptin treatment in IH mice, as was hepatic stearoyl-Coenzyme A desaturase 1 expression. Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH.
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Yang
authors.forename: Gautam
authors.initials: G
authors.lastname: Sikka
authors.forename: Jill
authors.initials: J
authors.lastname: Larson
authors.forename: Vabren L
authors.initials: VL
authors.lastname: Watts
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Niu
authors.forename: Carla L
authors.initials: CL
authors.lastname: Ellis
authors.forename: Karen L
authors.initials: KL
authors.lastname: Miller
authors.forename: Andre
authors.initials: A
authors.lastname: Camara
authors.forename: Christian
authors.initials: C
authors.lastname: Reinke
authors.forename: Vladimir
authors.initials: V
authors.lastname: Savransky
authors.forename: Vsevolod Y
authors.initials: VY
authors.lastname: Polotsky
authors.forename: Christopher P
authors.initials: CP
authors.lastname: O'Donnell
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
authors.forename: Lili A
authors.initials: LA
authors.lastname: Barouch
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D006949:Hyperlipidemias / Q000188:drug therapy*; D000860:Hypoxia / Q000188:drug therapy*; D020738:Leptin / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D020738:Leptin; D008055:Lipids; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D000109:Acetylcholine