title: Peroxisome proliferator-activated receptor-γ in capillary endothelia promotes fatty acid uptake by heart during long-term fasting.
abstract: BACKGROUND
  Endothelium is a crucial blood-tissue interface controlling energy supply according to organ needs. We investigated whether peroxisome proliferator-activated receptor-γ (PPARγ) induces expression of fatty acid-binding protein 4 (FABP4) and fatty acid translocase (FAT)/CD36 in capillary endothelial cells (ECs) to promote FA transport into the heart.
  
  
  RESULTS
  Expression of FABP4 and CD36 was induced by the PPARγ agonist pioglitazone in human cardiac microvessel ECs (HCMECs), but not in human umbilical vein ECs. Real-time PCR and immunohistochemistry of the heart tissue of control (Pparg(fl/null)) mice showed an increase in expression of FABP4 and CD36 in capillary ECs by either pioglitazone treatment or 48 hours of fasting, and these effects were not found in mice deficient in endothelial PPARγ (Pparg(▵)(EC)(/null)). Luciferase reporter constructs of the Fabp4 and CD36 promoters were markedly activated by pioglitazone in HCMECs through canonical PPAR-responsive elements. Activation of PPARγ facilitated FA uptake by HCMECs, which was partially inhibited by knockdown of either FABP4 or CD36. Uptake of an FA analogue, (125)I-BMIPP, was significantly reduced in heart, red skeletal muscle, and adipose tissue in Pparg(▵)(EC)(/null) mice as compared with Pparg(fl/null) mice after olive oil loading, whereas those values were comparable between Pparg(fl/null) and Pparg(▵)(EC)(/null) null mice on standard chow and a high-fat diet. Furthermore, Pparg(▵)(EC)(/null) mice displayed slower triglyceride clearance after olive oil loading.
  
  
  CONCLUSIONS
  These findings identified a novel role for capillary endothelial PPARγ as a regulator of FA handing in FA-metabolizing organs including the heart in the postprandial state after long-term fasting.
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Goto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iso
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suga
authors.forename: Akinari
authors.initials: A
authors.lastname: Hattori
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Irie
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shinagawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsui
authors.forename: Mas Rizky A A
authors.initials: MR
authors.lastname: Syamsunarno
authors.forename: Miki
authors.initials: M
authors.lastname: Matsui
authors.forename: Anwarul
authors.initials: A
authors.lastname: Haque
authors.forename: Masashi
authors.initials: M
authors.lastname: Arai
authors.forename: Fumio
authors.initials: F
authors.lastname: Kunimoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Keigo
authors.initials: K
authors.lastname: Endo
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005215:Fasting / Q000097:blood*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D000069463:Olive Oil; D047495:PPAR gamma / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D010938:Plant Oils / Q000008:administration & dosage / Q000378:metabolism; D019518:Postprandial Period; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens; C493410:FABP4 protein, human; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000069463:Olive Oil; D047495:PPAR gamma; D010938:Plant Oils; D045162:Thiazolidinediones; D014280:Triglycerides; D000077205:Pioglitazone