Abstract-Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity.We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using meanϪ1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; nϭ9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; nϭ7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.

Abstract. Recently, several extensions of massive vector theory in curved space-time have been proposed in many literatures. In this paper, we consider the most general vector-tensor theories that contain up to two derivatives with respect to metric and vector field. By imposing a degeneracy condition of the Lagrangian in the context of ADM decomposition of space-time to eliminate an unwanted mode, we construct a new class of massive vector theories where five degrees of freedom can propagate, corresponding to three for massive vector modes and two for massless tensor modes. We find that the generalized Proca and the beyond generalized Proca theories up to the quartic Lagrangian, which should be included in this formulation, are degenerate theories even in curved space-time. Finally, introducing new metric and vector field transformations, we investigate the properties of thus obtained theories under such transformations.arXiv:1608.07066v4 [gr-qc]

RAS blockade decreases adipocyte size without change in epididymal %fat pads accompanied by improvement in insulin sensitivity.

We find new, simple cosmological solutions with flat, open, and closed spatial geometries, contrary to the previous wisdom that only the open model is allowed. The metric and the Stückelberg fields are given explicitly, showing nontrivial configurations of the Stückelberg in the usual FriedmannLemaître-Robertson-Walker coordinates. The solutions exhibit self-acceleration, while being free from ghost instabilities. Our solutions can accommodate inhomogeneous dust collapse represented by the Lemaître-Tolman-Bondi metric as well. Thus, our results can be used not only to describe homogeneous and isotropic cosmology but also to study gravitational collapse in massive gravity.It is very intriguing to explore whether or not the graviton can have a mass. The first attempt to add a mass term to the gravity action was made by Fierz and Pauli [1], who considered the quadratic action for the graviton h µν in flat space with the mass termThe linear theory with the Fierz-Pauli mass term is ghost-free. However, the theory does not reproduce general relativity in the massless limit m → 0. The extra three degrees of freedom in a massive spin 2 survive even in this limit, and therefore the prediction for light bending is away from that of general relativity, which clearly contradicts solar-system tests. This is called the vDVZ discontinuity [2]. As pointed out by Vainshtein [3], the discontinuity can in fact be cured by going beyond the linear theory. Massive gravity has a new length scale called the Vainshtein radius, below which the nonlinearities of the theory come in and the effect of the extra degrees of freedom is screened safely. The Vainshtein radius becomes larger as m gets smaller, and thereby a smooth massless limit is attained.However, the very nonlinearities turned out to cause another trouble. Boulware and Deser argued that there appears a sixth scalar degree of freedom at nonlinear order, which has a wrong sign kinetic term, i.e., the sixth mode is a ghost [4]. The ghost issue was emphasized in the effective field theory approach in Ref. [5]. The presence of the Boulware-Deser (BD) ghost has hindered us from constructing a consistent theory of massive gravity.Recently, a theoretical breakthrough in this field has been made. Adding higher-order self-interaction terms and tuning appropriately their coefficients, de Rham and collaborators successfully eliminated the dangerous scalar mode from the theory in the decoupling limit [6,7]. Then, Hassan and Rosen established a complete proof that the theory does not suffer from the BD ghost instability to all orders in perturbations and away from the decoupling limit [8]. Thus, there certainly exists a nonlinear theory of massive gravity that is free of the BD ghost.In addition to the theoretical interests described above, the mystery of the accelerated expansion of the Universe [9] motivates massive gravity theories as a possible alternative to dark energy. Since the attractive force mediated by a massive graviton is Yukawa-suppressed by a factor e −mr , massive gravity t...

We revisit nonsingular cosmologies in which the limiting curvature hypothesis is realized. We study the cosmological perturbations of the theory and determine the general criteria for stability. For the simplest model, we find generic Ostrogradski instabilities unless the action contains the Weyl tensor squared with the appropriate coefficient. When considering two specific nonsingular cosmological scenarios (one inflationary and one genesis model), we find ghost and gradient instabilities throughout most of the cosmic evolution. Furthermore, we show that the theory is equivalent to a theory of gravity where the action is a general function of the Ricci and Gauss-Bonnet scalars, and this type of theory is known to suffer from instabilities in anisotropic backgrounds. This leads us to construct a new type of curvature-invariant scalar function. We show that it does not have Ostrogradski instabilities, and it avoids ghost and gradient instabilities for most of the interesting background inflationary and genesis trajectories. We further show that it does not possess additional new degrees of freedom in an anisotropic spacetime. This opens the door for studying stable alternative nonsingular very early Universe cosmologies.

We consider a new form of theories of gravity in which the action is written in terms of the Ricci scalar and its first and second derivatives. Despite the higher derivative nature of the action, the theory is free from ghost under an appropriate choice of the functional form of the Lagrangian. This model possesses 2 + 2 physical degrees of freedom, namely 2 scalar degrees and 2 tensor degrees. We exhaust all such theories with the Lagrangian of the form f (R, (∇R) 2 , ✷R), where R is the Ricci scalar, and then show some examples beyond this ansatz. In course of analysis, we prove the equivalence between these examples and generalized bi-Galileon theories.

Exosomes play a critical role in cell-to-cell communication by delivering cargo molecules to recipient cells. However, the mechanism underlying the generation of the exosomal multivesicular endosome (MVE) is one of the mysteries in the field of endosome research. Although sphingolipid metabolites such as ceramide and sphingosine 1-phosphate (S1P) are known to play important roles in MVE formation and maturation, the detailed molecular mechanisms are still unclear. Here, we show that Rho family GTPases, including Cdc42 and Rac1, are constitutively activated on exosomal MVEs and are regulated by S1P signaling as measured by fluorescence resonance energy transfer (FRET)-based conformational changes. Moreover, we detected S1P signaling-induced filamentous actin (F-actin) formation. A selective inhibitor of Gβγ subunits, M119, strongly inhibited both F-actin formation on MVEs and cargo sorting into exosomal intralumenal vesicles of MVEs, both of which were fully rescued by the simultaneous expression of constitutively active Cdc42 and Rac1. Our results shed light on the mechanism underlying exosomal MVE maturation and inform the understanding of the physiological relevance of continuous activation of the S1P receptor and subsequent downstream G protein signaling to Gβγ subunits/Rho family GTPases-regulated F-actin formation on MVEs for cargo sorting into exosomal intralumenal vesicles.

Extendibility of inflationary spacetimes with flat spatial geometry is investigated. We find that the past boundary of an inflationary spacetime becomes a so-called parallely propagated curvature singularity if the ratioḢ/a 2 diverges at the boundary, whereḢ and a represent the time derivative of the Hubble parameter and the scale factor, respectively. On the other hand, if the ratioḢ/a 2 converges, then the past boundary is regular and continuously extendible. We also develop a method to judge the continuous (C 0 ) extendibility of spacetime in the case of slow-roll inflation driven by a canonical scalar field. As applications of this method, we find that Starobinsky inflation has a C 0 parallely propagated curvature singularity, but a small field inflation model with a Higgs-like potential does not. We also find that an inflationary solution in a modified gravity theory with limited curvature invariants is free of such a singularity and is smoothly extendible.