Peroxisome proliferator-activated receptor-γ in capillary endothelia promotes fatty acid uptake by heart during long-term fasting.

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. METHODS AND 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.

Axially chiral monomeric and dimeric square planar Pd(II) complexes and their application to chiral tectonics.

Mononuclear and dinuclear square planar palladium(II) complexes (denoted by [(hfac)Pd(II)(L-LH)] and [(hfac)Pd(II)(L-L)Pd(II)(hfac)], respectively) were synthesized. Here hfac(-), HL-L(-) and L-L(2-) denote hexafluoroacetylacetonato, monoprotonated and non-protonated bis-ß-diketonato ligands, respectively. Three bis-ß-diketones were used as HL-LH: 1,2-diacetyl-1,2-dibenzoylethane (denoted by dabeH2), 1,2-diacetyl-1,2-bis(3-methylbutanoyl)ethane (baetH2) and 1,2-diacetyl-1,2-propanoylethane (dpeH2). Both the monomeric and dimeric Pd(II) complexes were chiral due to the orthogonal twisting of the two non-symmetric diketonato moieties in HL-L(-) and L-L(2-), respectively. Optical resolution of [(hfac)Pd(II)(dabe)Pd(II)(hfac)] was achieved chromatographically on a chiral column to obtain a pair of optical antipodes which were stable against racemization. As for the other complexes, resolution was possible only after replacing hfac(-) with a bulky ligand such as dibenzoylmethanato (dbm(-)). Although a dinuclear complex with a symmetric bis-ß-diketonato ligand, [(hfac)Pd(II)(taet)Pd(II)(hfac)] (taet(2-) = 1,1,2,2-tetraacetylethanato), was achiral, the replacement of the terminal ligands with non-symmetric ß-diketonates yielded an axially chiral complex such as [(phacac)Pd(II)(taet)Pd(II)(phacac)], wherein phacac(-) denotes 1-phenyl-1,3-butanedionato. The UV and CD spectra of the Pd(II) complexes were analyzed with the help of the TDDFT calculations. The chiral monomeric species, [(dbm)Pd(II)(R- or S-baetH)], formed a heterometallic tetranuclear complex, [Fe(III){(dbm)Pd(II)(R- or S-baet)}3], in methanol solution.

Clinical features and prognostic factors of bone metastases from colorectal cancer.

PURPOSE: To investigate the clinical features and prognoses of patients with diagnosed bone metastases from colorectal cancer (CRC). METHODS: This was a 16-year retrospective study of 32 patients with bone metastases secondary to CRC, who were seen at National Kokura Hospital between 1993 and 2008. The influence of clinical and pathologic variables on survival was assessed by univariate and multivariate analyses. RESULTS: The bone most commonly involved was the spinal column. The mean disease-free interval was 17.6 months and mean survival from the diagnosis of bone metastases was 9.3 months. On univariate analysis, the serum CEA level at the time of diagnosis of bone metastases (p = 0.020) and history of pulmonary metastases (p = 0.013) were significant. On multivariate analysis, a history of bone metastases in the ribs (hazard ratio 3.669, p = 0.025) and a history of pulmonary metastases (hazard ratio 3.854, p = 0.022) significantly affected survival. CONCLUSIONS: It is important to investigate for bone metastases in patients who complain of back pain and lumbago after CRC surgery.