title: Leptin dose-dependently decreases atherosclerosis by attenuation of hypercholesterolemia and induction of adiponectin.
abstract: Conflicting evidence concerning leptin in atherosclerosis has been published. Furthermore, dose-dependent effects of leptin on atherogenesis have not been studied.
  
  
  
  Leptin-deficient low-density lipoprotein receptor (LDLR) knockout (LDLR(-/-);ob/ob) mice were treated with saline, 0.1, 0.5, or 3.0mg/kg body weight (BW)/d recombinant leptin over 12weeks starting at 8weeks of age. Aortic root and brachiocephalic artery (BCA) atherosclerotic lesions were analyzed by oil red O staining. Furthermore, glucose homeostasis, lipid metabolism, and liver function including tissue studies were assessed in all animals.
  
  
  
  Leptin treatment dose-dependently decreased BW in LDLR(-/-);ob/ob mice as compared to saline. Mice in the 0.1 and 0.5mg/kgBW/d groups remained heavier (i.e. subphysiological leptin dose) and in the 3.0mg/kgBW/d group had similar weight (i.e. physiological leptin dose) as compared to non-leptin-deficient LDLR(-/-) animals. Recombinant leptin dose-dependently reduced plaque area in the aortic root and the BCA by 36% and 58%, respectively. Leptin-mediated reductions of plasma total and LDL-cholesterol (Chol) remained independent predictors for aortic root plaque area. Chol content in liver, as well as hepatic expression of key lipid and proinflammatory genes, were dose-dependently regulated by leptin. Furthermore, leptin treatment increased circulating levels and adipose tissue mRNA expression of the adipokine adiponectin.
  
  
  
  Leptin administration within the subphysiological to physiological range diminishes atherosclerotic lesions. Leptin appears to mediate its antiatherogenic effects indirectly through reduction of hypercholesterolemia and liver steatosis, as well as upregulation of insulin-sensitizing and atheroprotective adiponectin.
authors.affiliation: University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Hoffmann
authors.affiliation: University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB AdiposityDiseases, 04103 Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ebert
authors.affiliation: Leipzig University Medical Center, IFB AdiposityDiseases, 04103 Leipzig, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
authors.affiliation: University of Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 04103 Leipzig, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Dokas
authors.affiliation: University of Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 04103 Leipzig, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Jeromin
authors.affiliation: University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Jessnitzer
authors.affiliation: University of Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 04103 Leipzig, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Burkhardt
authors.affiliation: University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB AdiposityDiseases, 04103 Leipzig, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Fasshauer
authors.affiliation: University of Leipzig, Department of Endocrinology and Nephrology, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB AdiposityDiseases, 04103 Leipzig, Germany. Electronic address: susan.kralisch@medizin.uni-leipzig.de.
authors.forename: Susan
authors.initials: S
authors.lastname: Kralisch
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D052242:Adiponectin; D000924:Anticholesteremic Agents; D007328:Insulin; D020738:Leptin; D011994:Recombinant Proteins; D002784:Cholesterol
keywords: Adipokine; Adiponectin; Atherosclerosis; Insulin resistance; Leptin; Obesity