title: Impact of macrophage inflammatory protein-1α deficiency on atherosclerotic lesion formation, hepatic steatosis, and adipose tissue expansion.
abstract: Macrophage inflammatory protein-1α (CCL3) plays a well-known role in infectious and viral diseases; however, its contribution to atherosclerotic lesion formation and lipid metabolism has not been determined. Low density lipoprotein receptor deficient (LDLR(-/-)) mice were transplanted with bone marrow from CCL3(-/-) or C57BL/6 wild type donors. After 6 and 12 weeks on western diet (WD), recipients of CCL3(-/-) marrow demonstrated lower plasma cholesterol and triglyceride concentrations compared to recipients of C57BL/6 marrow. Atherosclerotic lesion area was significantly lower in female CCL3(-/-) recipients after 6 weeks and in male CCL3(-/-) recipients after 12 weeks of WD feeding (P<0.05). Surprisingly, male CCL3(-/-) recipients had a 50% decrease in adipose tissue mass after WD-feeding, and plasma insulin, and leptin levels were also significantly lower. These results were specific to CCL3, as LDLR(-/-) recipients of monocyte chemoattractant protein(-/-) (CCL2) marrow were not protected from the metabolic consequences of high fat feeding. Despite these improvements in LDLR(-/-) recipients of CCL3(-/-) marrow in the bone marrow transplantation (BMT) model, double knockout mice, globally deficient in both proteins, did not have decreased body weight, plasma lipids, or atherosclerosis compared with LDLR(-/-) controls. Finally, there were no differences in myeloid progenitors or leukocyte populations, indicating that changes in body weight and plasma lipids in CCL3(-/-) recipients was not due to differences in hematopoiesis. Taken together, these data implicate a role for CCL3 in lipid metabolism in hyperlipidemic mice following hematopoietic reconstitution.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Arion
authors.initials: A
authors.lastname: Kennedy
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Gruen
authors.forename: Dario A
authors.initials: DA
authors.lastname: Gutierrez
authors.forename: Bonnie K
authors.initials: BK
authors.lastname: Surmi
authors.forename: Jeb S
authors.initials: JS
authors.lastname: Orr
authors.forename: Corey D
authors.initials: CD
authors.lastname: Webb
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Hasty
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology*; D001835:Body Weight; D016026:Bone Marrow Transplantation; D054405:Chemokine CCL3 / Q000172:deficiency* / Q000502:physiology; D004032:Diet; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D006949:Hyperlipidemias; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D054405:Chemokine CCL3; D008055:Lipids