title: Regulation of Dipeptidyl Peptidase-4, its Substrate Chemokines, and Their Receptors in Adipose Tissue of ob/ob Mice.
abstract: The physiological function of DPP-4 in proteolytic inactivation of incretins has been well established, however, there is limited information on the expression and the significance of DPP-4 in white adipose tissue with regard to obesity. The objective of the work was to reveal the expression and regulation of DPP-4 in adipocytes and compare the expression and activity of DPP-4 in white adipose tissue and several other organs such as the liver, muscle and kidney. We also investigated the gene expression levels of DPP-4 substrate chemokines, and their receptors in white adipose tissue. DPP-4 was mainly expressed in stromal vascular fraction (SVF), and downregulated in adipose tissue of ob/ob compared with C57BL6/J mice. Mimetic conditions of obese fat in vitro showed that differentiation of mouse primary preadipocytes into adipocytes was associated with marked downregulation of DPP-4 expression. Treatment with TNF-α or ROS even decreased DPP-4 expression in mouse primary adipocytes. Various DPP-4 substrate chemokines were expressed in white adipose tissue and regulated by obesity. The expression of receptors for DPP-4 substrate chemokines was markedly high and tightly regulated by obesity in white adipose tissue. Expression of DPP-4 was reduced in adipose tissues of ob/ob mice. Actions of several substrate chemokines might be potentiated by downregulation of DPP-4, synergistically with upregulation of chemokines and their receptors in adipose tissues of obese mice.
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Fukuhara
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Onodera
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Yokoyama
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Otsuki
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018925:Chemokines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D018819:Dipeptidyl Peptidase 4