Reduced cholesterol accumulation by leptin deficient (ob/ob) mouse macrophages.
OBJECTIVE
Although presenting many aspects of the metabolic syndrome, leptin deficient (ob/ob) mice do not spontaneously develop atherosclerosis. To examine the role of leptin in foam cell formation we analyzed ob/ob leukocyte inflammation markers and macrophage cholesterol accumulation.


METHODS
Resident and thioglycollate (TG) elicited peritoneal cells of ob/ob and wildtype mice were studied. Activation markers, scavenger receptors (SR) and cholesterol accumulation were analyzed using flow cytometry and Taqman analysis. Cytokines, haptoglobin, adiponectin and amyloid A levels were analyzed with ELISA.


RESULTS
Macrophages of ob/ob mice had reduced expression of MHC class II, CD11b, CD40, SR-A and CD36 and reduced cholesterol accumulation in vitro. Plasma haptoglobin was increased and T-cell IFNgamma was reduced in ob/ob mice. Peritoneal TG instillation induced an unexpectedly weak inflammatory response in ob/ob mice.


CONCLUSIONS
The ob/ob mice had a reduced inflammatory response and reduced macrophage cholesterol accumulation in vitro. The data suggest decreased foam cell formation and atherosclerosis development in ob/ob mice.
Kjerrulf
M
M
Dept of Molecular Pharmacology, AstraZeneca R&D, Mölndal, Sweden. martin.kjerrulf@astrazeneca.com
Berke
Z
Z
Aspegren
A
A
Umaerus
M
M
Nilsson
T
T
Svensson
L
L
Hurt-Camejo
E
E
D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism*; D006242:Haptoglobins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020738:Leptin / Q000235:genetics*; D008055:Lipids / Q000737:chemistry; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese
D052242:Adiponectin; D006242:Haptoglobins; D020738:Leptin; D008055:Lipids; D007371:Interferon-gamma; D002784:Cholesterol