A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice.

It is well known that the ω-3 fatty acids (ω-3-FAs; also known as n-3 fatty acids) can exert potent anti-inflammatory effects. Commonly consumed as fish products, dietary supplements and pharmaceuticals, ω-3-FAs have a number of health benefits ascribed to them, including reduced plasma triglyceride levels, amelioration of atherosclerosis and increased insulin sensitivity. We reported that Gpr120 is the functional receptor for these fatty acids and that ω-3-FAs produce robust anti-inflammatory, insulin-sensitizing effects, both in vivo and in vitro, in a Gpr120-dependent manner. Indeed, genetic variants that predispose to obesity and diabetes have been described in the gene encoding GPR120 in humans (FFAR4). However, the amount of fish oils that would have to be consumed to sustain chronic agonism of Gpr120 is too high to be practical, and, thus, a high-affinity small-molecule Gpr120 agonist would be of potential clinical benefit. Accordingly, Gpr120 is a widely studied drug discovery target within the pharmaceutical industry. Gpr40 is another lipid-sensing G protein-coupled receptor, and it has been difficult to identify compounds with a high degree of selectivity for Gpr120 over Gpr40 (ref. 11). Here we report that a selective high-affinity, orally available, small-molecule Gpr120 agonist (cpdA) exerts potent anti-inflammatory effects on macrophages in vitro and in obese mice in vivo. Gpr120 agonist treatment of high-fat diet-fed obese mice causes improved glucose tolerance, decreased hyperinsulinemia, increased insulin sensitivity and decreased hepatic steatosis. This suggests that Gpr120 agonists could become new insulin-sensitizing drugs for the treatment of type 2 diabetes and other human insulin-resistant states in the future

High-Resolution Submillimeter and Near-Infrared Studies of the Transition Disk around Sz 91

To reveal the structures of a transition disk around a young stellar object in Lupus, Sz 91, we have performed aperture synthesis 345 GHz continuum and CO(3--2) observations with the Submillimeter Array (\sim1\arcsec--3\arcsec resolution), and high-resolution imaging of polarized intensity at the $K_s$-band by using the HiCIAO instrument on the Subaru Telescope (0\farcs25 resolution). Our observations successfully resolved the inner and outer radii of the dust disk to be 65 AU and 170 AU, respectively, which indicates that Sz 91 is a transition disk source with one of the largest known inner holes. The model fitting analysis of the spectral energy distribution reveals an H$_2$ mass of $2.4\times10^{-3}$ M_\sun in the cold ($T<$30 K) outer part at $65<r<170$ AU by assuming a canonical gas-to-dust mass ratio of 100, although a small amount ($>3\times10^{-9}$ M_\sun) of hot ($T\sim$180 K) dust possibly remains inside the inner hole of the disk. The structure of the hot component could be interpreted as either an unresolved self-luminous companion body (not directly detected in our observations) or a narrow ring inside the inner hole. Significant CO(3--2) emission with a velocity gradient along the major axis of the dust disk is concentrated on the Sz 91 position, suggesting a rotating gas disk with a radius of 420 AU. The Sz 91 disk is possibly a rare disk in an evolutionary stage immediately after the formation of protoplanets because of the large inner hole and the lower disk mass than other transition disks studied thus far

Radial decoupling of small and large dust grains in the transitional disk RX J1615.3-3255

We present H-band (1.6 {\mu}m) scattered light observations of the transitional disk RX J1615.3-3255, located in the ~1 Myr old Lupus association. From a polarized intensity image, taken with the HiCIAO instrument of the Subaru Telescope, we deduce the position angle and the inclination angle of the disk. The disk is found to extend out to 68 $\pm$ 12 AU in scattered light and no clear structure is observed. Our inner working angle of 24 AU does not allow us to detect a central decrease in intensity similar to that seen at 30 AU in the 880 {\mu}m continuum observations. We compare the observations with multiple disk models based on the Spectral Energy Distribution (SED) and submm interferometry and find that an inner rim of the outer disk at 30 AU containing small silicate grains produces a polarized intensity signal which is an order of magnitude larger than observed. We show that a model in which the small dust grains extend smoothly into the cavity found for large grains is closer to the actual H-band observations. A comparison of models with different dust size distributions suggests that the dust in the disk might have undergone significant processing compared to the interstellar medium.Comment: 8 pages, 7 figures, 4 tables. Accepted for publication in A&

A Substellar Companion to Pleiades HII 3441

We find a new substellar companion to the Pleiades member star, Pleiades HII 3441, using the Subaru telescope with adaptive optics. The discovery is made as part of the high-contrast imaging survey to search for planetary-mass and substellar companions in the Pleiades and young moving groups. The companion has a projected separation of 0".49 +/- 0".02 (66 +/- 2 AU) and a mass of 68 +/- 5 M_J based on three observations in the J-, H-, and K_S-band. The spectral type is estimated to be M7 (~2700 K), and thus no methane absorption is detected in the H band. Our Pleiades observations result in the detection of two substellar companions including one previously reported among 20 observed Pleiades stars, and indicate that the fraction of substellar companions in the Pleiades is about 10.0 +26.1/-8.8 %. This is consistent with multiplicity studies of both the Pleiades stars and other open clusters.Comment: Main text (14 pages, 4 figures, 4 tables), and Supplementary data (8 pages, 3 tables). Accepted for Publications of Astronomical Society of Japa

Extreme Asymmetry in the Disk of V1247 Ori

We present the first near-infrared scattered-light detection of the transitional disk around V1247 Ori, which was obtained using high-resolution polarimetric differential imaging observations with Subaru/HiCIAO. Our imaging in the H band reveals the disk morphology at separations of ~0.14"-0.86" (54-330 au) from the central star. The polarized intensity (PI) image shows a remarkable arc-like structure toward the southeast of the star, whereas the fainter northwest region does not exhibit any notable features. The shape of the arm is consistent with an arc of 0.28" $\pm$ 0.09" in radius (108 au from the star), although the possibility of a spiral arm with a small pitch angle cannot be excluded. V1247 Ori features an exceptionally large azimuthal contrast in scattered, polarized light; the radial peak of the southeastern arc is about three times brighter than the northwestern disk measured at the same distance from the star. Combined with the previous indication of an inhomogeneous density distribution in the gap at $\lesssim$46 au, the notable asymmetry in the outer disk suggests the presence of unseen companions and/or planet-forming processes ongoing in the arc.Comment: 21 pages, 5 figures, accepted for publication in PAS

High-Resolution Submillimeter and Near-Infrared Studies of the Transition Disk around Sz 91

To reveal the structures of a transition disk around a young stellar object in Lupus, Sz 91, we have performed aperture synthesis 345 GHz continuum and CO(32) observations with the Submillimeter Array ( 13 resolution), and high-resolution imaging of polarized intensity at the Ks-band by using the Hi-CIAO instrument on the Subaru Telescope (0.25 resolution). Our observations successfully resolved the inner and outer radii of the dust disk to be 65 and 170AU, respectively, which indicates that Sz 91 is a transition disk source with one of the largest known inner holes. The model fitting analysis of the spectral energy distribution reveals an H2 mass of 2.4 103 M in the cold (T 30 K) outer part at 65 r 170 AU by assuming a canonical gas-to-dust mass ratio of 100, although a small amount ( 3109 M) of hot (T 180 K) dust possibly remains inside the inner hole of the disk. The structure of the hot component could be interpreted as either an unresolved self-luminous companion body (not directly detected in our observations) or a narrow ring inside the inner hole. Significant CO(32) emission with a velocity gradient along the major axis of the dust disk is concentrated on the Sz 91 position, suggesting a rotating gas disk with a radius of 420 AU. The Sz 91 disk is possibly a rare disk in an evolutionary stage immediately after the formation of protoplanets because of the large inner hole and the lower disk mass than other transition disks studied thus far

Extreme Asymmetry in the Polarized Disk of V1247 Orionis *

We present the first near-infrared scattered-light detection of the transitional disk around V1247 Ori, which was obtained using high-resolution polarimetric differential imaging observations with Subaru/HiCIAO. Our imaging in the H band reveals the disk morphology at separations of 0.′′14–0.′′86 (54–330 au) from the central star. The polarized intensity (PI) image shows a remarkable arc-like structure toward the southeast of the star, whereas the fainter northwest region does not exhibit any notable features. The shape of the arm is consistent with an arc of 0.′′28 0.′′09 in radius (108 au from the star), although the possibility of a spiral arm with a small pitch angle cannot be excluded. V1247 Ori features an exceptionally large azimuthal contrast in scattered, polarized light; the radial peak of the southeastern arc is about three times brighter than the northwestern disk measured at the same distance from the star. Combined with the previous indication of an inhomogeneous density distribution in the gap at < 46 au, the notable asymmetry in the outer disk suggests the presence of unseen companions and/or planet-forming processes ongoing in the arc.This work is supported by MEXT KAKENHI Nos. 23103005. S.K. acknowledges support from an STFC Ernest Rutherford Fellowship (ST/J004030/1) and Marie Curie CIG grant (SH-06192)