The role of macrophage leptin receptor in aortic root lesion formation.
Plasma leptin is often elevated in obese individuals, and previous studies have suggested leptin as a factor that links obesity and atherosclerosis. Because macrophages play a key role in atherogenesis and are responsive to leptin, we hypothesized that leptin increases aortic root lesion formation, in part, through macrophage leptin receptor (LepR). Three different bone marrow transplantation studies were conducted in which bone marrow, with or without LepR, was transplanted into lethally irradiated 1) LDL receptor-deficient (LDLR(-/-)) mice with moderate hyperleptinemia due to Western diet (WD) feeding, 2) LDLR(-/-) mice with WD feeding plus pharmacologically induced hyperleptinemia (daily injection of 125 microg leptin), or 3) obese, hyperleptinemic, LepR-deficient LDLR(-/-) (LepR(db/db);LDLR(-/-)) mice. Minor differences in plasma parameters such as cholesterol, triglycerides, and insulin were observed in some groups; however, a consistent trend for the role of LepR on these parameters was not detected. In each of the studies, macrophage LepR expression did not have an effect on aortic root atherosclerotic lesion formation. These results suggest that nonhematopoietic cells may have a more significant role than macrophages in leptin-mediated effects on aortic root lesion formation.
Surmi
Bonnie K
BK
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232-0615, USA.
Atkinson
Robin D
RD
Gruen
Marnie L
ML
Coenen
Kimberly R
KR
Hasty
Alyssa H
AH
D000818:Animals; D001018:Aortic Diseases / Q000209:etiology*; D050197:Atherosclerosis / Q000209:etiology; D016026:Bone Marrow Transplantation; D004032:Diet; D005260:Female; D006207:Half-Life; D020738:Leptin / Q000008:administration & dosage / Q000097:blood*; D008264:Macrophages / Q000737:chemistry*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications; D011973:Receptors, LDL / Q000172:deficiency / Q000502:physiology*; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D020738:Leptin; D011973:Receptors, LDL; D054411:Receptors, Leptin