title: Mast cells function as an alternative modulator of adipogenesis through 15-deoxy-delta-12, 14-prostaglandin J2.
abstract: Mast cells are one of the major producers of prostaglandins (PGs). The final metabolite of PGs 15-deoxy-delta-12,14-PGJ(2) (15-deoxy-delta PGJ(2)) is the endogenous ligand of the peroxisome proliferator-activated receptor (PPAR) γ. PPARγ modulates adipocyte differentiation; therefore, we attempted to investigate whether PGs derived from mast cells influenced on adipogenesis. We found the increase of mast cell numbers in fat tissue of obese mice fed with a high-fat diet allowed us to speculate contributions of mast cells to adipogenesis. Mast cell-mediated induction of adipogenesis was evaluated by using 3T3 L1 cells. Supernatants obtained from mast cells stimulated with calcium ionophore or the high-glucose condition contained 15-deoxy-delta PGJ(2) and induced adipogenesis of 3T3 L1 cells. Agonistic activity of PGJ(2) from the supernatants on PPARγ was confirmed by a reporter gene assay. Culture medium collected from calcium ionophore-stimulated bone marrow-derived cultured mast cells (BMCMC) activated PPAR-responsive element in NIH3T3 fibroblasts, and the specific inhibitor of PPARγ canceled the activation. Contribution of mast cells to obesity was evaluated by using mast cell-deficient mice fed with a Western diet. Weight gain of mast cell-deficient mice during high-fat feeding was impaired compared with their littermate wild-type mice; on the other hand, transplantation of bone marrow-derived cultured mast cells to mast cell-deficient mice restored the weight gain by intake of a high-fat diet. In this study, we clearly demonstrated that mast cells produced PGs in response to the high-glucose condition and induced adipocyte differentiation and possibly obesity. This is the first study that provides evidence for a novel role of mast cells in adipogenesis via PPARγ activation.
authors.affiliation: Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Graduate School, Institute of Agriculture, 3-5-8 Saiwai-cho, Fuchu, Tokyo, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Tanaka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nomura
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Keitaro
authors.initials: K
authors.lastname: Ohmori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D047495:PPAR gamma; D015230:Prostaglandin D2