Uncoupling Protein 3: Its Possible Biological Role and Mode of Regulation in Rodents and Humans

The recently discovered uncoupling protein 3 (UCP3) is highly homologous to the mitochondrialinner membrane protein UCP1, which generates heat by uncoupling the respiratory chainfrom oxidative phosphorylation. The thermogenic function of UCP1 protects against cold andregulates the energy balance in rodents. We review in vitro studies investigating the uncouplingactivity of UCP3 and in vivo studies, which address UCP3 gene expression in brown adiposetissue and skeletal muscle under various metabolic conditions. The data presented are, for themost, consistent with an uncoupling role for UCP3 in regulatory thermogenesis. We alsodiscuss mediators of UCP3 regulation and propose a potential role for intracellular fatty acidsin the mechanism of UCP3 modulation. Finally, we hypothesize a role for UCP3 in themetabolic adaptation of the mitochondria to the degradation of fatty acid

Fatty acids do not activate UCP2 in pancreatic beta cells: comparison with UCP1

UCP2 is expressed in pancreatic β cells where its postulated uncoupling activity will modulate glucose-induced changes in ATP/ADP ratio and insulin secretion. The consequences of UCP2 over/underexpression on β-cell function has mainly been studied in the basal state; however, a UCP has no uncoupling activity unless stimulated by fatty acids and/or reactive oxygen species. Here, UCP2 was overexpressed in INS-1 cells and parameters reflecting mitochondrial coupling measured in the basal state and after stimulation by fatty acids. For comparison, UCP1 was expressed to similar levels and the same parameters measured. Neither UCP1 expression nor UCP2 overexpression modified basal or glucose-stimulated metabolic changes. Upon addition of fatty acids, UCP1-expressing cells displayed the expected mitochondrial uncoupling effect, while UCP2 did not elicit any measurable change in mitochondrial function. Taken together, our data demonstrate that, in pancreatic β-cells, UCP2 has no uncoupling activity in the basal state or after fatty acid stimulatio

Uncoupling protein-3 as a molecular determinant of the action of 3,5,3′-triiodothyronine on energy metabolism

Thyroid hormones are known to stimulate thermogenesis in rodents by exerting a permissive effect on norepinephrine that affects uncoupling protein-1 (UCP1) expression in brown adipose tissue (BAT). The aim of this study was to identify new targets of the thermogenic effects of T3 in tissues other than the BAT, such as skeletal muscle. In β1/β2/β3-adrenoceptor knockout (β-less) mice, that are dramatically cold intolerant, a normal body temperature was maintained throughout 48h of cold exposure by T3 administration. In these mice, BAT UCP1 protein expression was not modified either by cold exposure or by T3 administration. To test the possibility that T3 might act via muscle uncoupling protein-3 (UCP3), an UCP3 knockout (KO) model was used. This model exhibited a normal phenotype except that, upon T3 administration, stimulated oxygen consumption of the UCP3KO mice was significantly lower by 6% than that of the wild-type (WT) mice. This difference was observed only during the dark period (between 7.00p.m. and 7.00a.m.), i.e. when the mice are the most active at consuming food. Therefore, UCP3 might participate in the correction by T3 of the dramatic cold intolerance of the β-less mice. These results reactivate the idea that UCP3 might play a role in the control of energy balanc

Near-Infrared Properties of Moderate-Redshift Galaxy Clusters: Halo Occupation Number, Mass-to-Light Ratios and Omega(M)

Using K-band imaging for 15 of the Canadian Network for Observational Cosmology (CNOC1) clusters we examine the near-infrared properties of moderate-redshift (0.19 < z < 0.55) galaxy clusters. We find that the number of K-band selected cluster galaxies within R{sub 500} (the Halo Occupation Number, HON) is well-correlated with the cluster dynamical mass (M{sub 500}) and X-ray Temperature (T{sub x}); however, the intrinsic scatter in these scaling relations is 37% and 46% respectively. Comparison with clusters in the local universe shows that the HON-M{sub 500} relation does not evolve significantly between z = 0 and z {approx} 0.3. This suggests that if dark matter halos are disrupted or undergo significant tidal-stripping in high-density regions as seen in numerical simulations, the stellar mass within the halos is tightly bound, and not removed during the process. The total K-band cluster light (L{sub 200},K) and K-band selected richness (parameterized by B{sub gc,K}) are also correlated with both the cluster T{sub x} and M{sub 200}. The total (intrinsic) scatter in the L{sub 200,K}-M{sub 200} and B{sub gc,K}-M{sub 200} relations are 43%(31%) and 35%(18%) respectively and indicates that for massive clusters both L{sub 200,K} and B{sub gc,K} can predict M{sub 200} with similar accuracy as T{sub x}, L{sub x} or optical richness (B{sub gc}). Examination of the mass-to-light ratios of the clusters shows that similar to local clusters, the K-band mass-to-light ratio is an increasing function of halo mass. Using the K-band mass-to-light ratios of the clusters, we apply the Oort technique and find {Omega}{sub m,0} = 0.22 {+-} 0.02, which agrees well with recent combined concordance cosmology parameters, but, similar to previous cluster studies, is on the low-density end of preferred values

3D-HST: A wide-field grism spectroscopic survey with the Hubble Space Telescope

We present 3D-HST, a near-infrared spectroscopic Treasury program with the Hubble Space Telescope for studying the processes that shape galaxies in the distant Universe. 3D-HST provides rest-frame optical spectra for a sample of ~7000 galaxies at 1<z<3.5, the epoch when 60% of all star formation took place, the number density of quasars peaked, the first galaxies stopped forming stars, and the structural regularity that we see in galaxies today must have emerged. 3D-HST will cover 3/4 (625 sq.arcmin) of the CANDELS survey area with two orbits of primary WFC3/G141 grism coverage and two to four parallel orbits with the ACS/G800L grism. In the IR these exposure times yield a continuum signal-to-noise of ~5 per resolution element at H~23.1 and a 5sigma emission line sensitivity of 5x10-17 erg/s/cm2 for typical objects, improving by a factor of ~2 for compact sources in images with low sky background levels. The WFC3/G141 spectra provide continuous wavelength coverage from 1.1-1.6 um at a spatial resolution of ~0."13, which, combined with their depth, makes them a unique resource for studying galaxy evolution. We present the preliminary reduction and analysis of the grism observations, including emission line and redshift measurements from combined fits to the extracted grism spectra and photometry from ancillary multi-wavelength catalogs. The present analysis yields redshift estimates with a precision of sigma(z)=0.0034(1+z), or sigma(v)~1000 km/s. We illustrate how the generalized nature of the survey yields near-infrared spectra of remarkable quality for many different types of objects, including a quasar at z=4.7, quiescent galaxies at z~2, and the most distant T-type brown dwarf star known. The CANDELS and 3D-HST surveys combined will provide the definitive imaging and spectroscopic dataset for studies of the 1<z<3.5 Universe until the launch of the James Webb Space Telescope.Comment: Replacement reflects version now accepted by ApJS. A preliminary data release intended to provide a general illustration of the WFC3 grism data is available at http://3dhst.research.yale.edu

Anatomy of a post-starburst minor merger: a multi-wavelength WFC3 study of NGC 4150

(Abridged) We present a spatially-resolved near-UV/optical study of NGC 4150, using the Wide Field Camera 3 (WFC3) on board the Hubble Space Telescope. Previous studies of this early-type galaxy (ETG) indicate that it has a large reservoir of molecular gas, exhibits a kinematically decoupled core (likely indication of recent merging) and strong, central H_B absorption (indicative of young stars). The core of NGC 4150 shows ubiquitous near-UV emission and remarkable dusty substructure. Our analysis shows this galaxy to lie in the near-UV green valley, and its pixel-by-pixel photometry exhibits a narrow range of near-UV/optical colours that are similar to those of nearby E+A (post-starburst) galaxies. We parametrise the properties of the recent star formation (age, mass fraction, metallicity and internal dust content) in the NGC 4150 pixels by comparing the observed near-UV/optical photometry to stellar models. The typical age of the recent star formation (RSF) is around 0.9 Gyrs, consistent with the similarity of the near-UV colours to post-starburst systems, while the morphological structure of the young component supports the proposed merger scenario. The RSF metallicity, representative of the metallicity of the gas fuelling star formation, is around 0.3 - 0.5 Zsun. Assuming that this galaxy is a merger and that the gas is sourced mainly from the infalling companion, these metallicities plausibly indicate the gas-phase metallicity (GPM) of the accreted satellite. Comparison to the local mass-GPM relation suggests (crudely) that the mass of the accreted system is around 3x10^8 Msun, making NGC 4150 a 1:20 minor merger. A summation of the pixel RSF mass fractions indicates that the RSF contributes about 2-3 percent of the stellar mass. This work reaffirms our hypothesis that minor mergers play a significant role in the evolution of ETGs at late epochs.Comment: 28 pages, 2 tables, accepted for publication in Ap

Hyperoxia-mediated oxidative stress increases expression of UCP3 mRNA and protein in skeletal muscle

The uncoupling protein-3 (UCP3) is a mitochondrial protein expressed mainly in skeletal muscle. Among several hypotheses for its physiological function, UCP3 has been proposed to prevent excessive production of reactive oxygen species. In the present study, we evaluated the effect of an oxidative stress induced by hyperoxia on UCP3 expression in mouse skeletal muscle and C2C12 myotubes. We found that the hyperoxia-mediated oxidative stress was associated with a 5-fold and 3-fold increase of UCP3 mRNA and protein levels, respectively, in mouse muscle. Hyperoxia also enhanced reactive oxygen species production and UCP3 mRNA expression in C2C12 myotubes. Our findings support the view that both in vivo and in vitro UCP3 may modulate reactive oxygen species production in response to an oxidative stress