Journal article

Publication year: 2016

Pages: 113-120

Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Volume number: 1862

Issue number: 1

ISSN: 0925-4439

DOI Link: https://doi.org/10.1016/j.bbadis.2015.10.022

Publisher: Elsevier

Abstract: 
Objectives: Conflicting evidence concerning leptin in atherosclerosis has been published. Furthermore, dose-dependent effects of leptin on atherogenesis have not been studied.Methods: Leptin-deficient low-density lipoprotein receptor (LDLR) knockout (LDLR-/-;ob/ob) mice were treated with saline, 0.1, 0.5, or 3.0 mg/kg body weight (BW)/d recombinant leptin over 12 weeks starting at 8 weeks of age. Aortic root and brachiocephalic artery (BCA) atherosclerotic lesions were analyzed by oil red 0 staining. Furthermore, glucose homeostasis, lipid metabolism, and liver function including tissue studies were assessed in all animals.Results: Leptin treatment dose-dependently decreased BW in LDLR-/-;ob/ob mice as compared to saline. Mice in the 0.1 and 0.5 mg/kg BW/d groups remained heavier (i.e. subphysiological leptin dose) and in the 3.0 mg/kg BW/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.Conclusions: Leptin administration within the subphysiological to physiological range diminishes atherosclerotic lesions. Leptin appears to mediate its antiatherogenic effects indirectly through reduction of hyper-cholesterolemia and liver steatosis, as well as upregulation of insulin-sensitizing and atheroprotective adiponectin. (C) 2015 Published by Elsevier B.V.

Harvard Citation style: Hoffmann, A., Ebert, T., Klöting, N., Dokas, J., Jeromin, F., Jessnitzer, B., et al. (2016) Leptin dose-dependently decreases atherosclerosis by attenuation of hypercholesterolemia and induction of adiponectin, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1862(1), pp. 113-120. https://doi.org/10.1016/j.bbadis.2015.10.022

APA Citation style: Hoffmann, A., Ebert, T., Klöting, N., Dokas, J., Jeromin, F., Jessnitzer, B., Burkhardt, R., Fasshauer, M., & Kralisch, S. (2016). Leptin dose-dependently decreases atherosclerosis by attenuation of hypercholesterolemia and induction of adiponectin. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1862(1), 113-120. https://doi.org/10.1016/j.bbadis.2015.10.022