The catalytic subunit of the system L1 amino acid transporter (S<i>lc7a5</i>) facilitates nutrient signalling in mouse skeletal muscle

The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass

Ontogeny and thermogenic role for sternal fat in female sheep

Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a critical role in preventing hypothermia in new-born sheep but is then considered to rapidly disappear during postnatal life. The extent to which the anatomical location of fat influences postnatal development and thermogenic function, particularly following feeding, in adulthood, are not known and were both examined in our study. Changes in gene expression of functionally important pathways (i.e. thermogenesis, development, adipogenesis and metabolism) were compared between sternal and retroperitoneal fat depots together with a representative skeletal muscle over the first month of postnatal life, coincident with the loss of brown fat and accumulation of white fat. In adult sheep, implanted temperature probes were used to characterise the thermogenic response of fat and muscle to feeding and the effects of reduced or increased adiposity. UCP1 was more abundant within sternal than retroperitoneal fat and was only retained in the sternal depot of adults. Distinct differences in the abundance of gene pathway markers were apparent between tissues, with sternal fat exhibiting some similarities with muscle that were not apparent in the retroperitoneal depot. In adults, the post-prandial rise in temperature was greater and more prolonged in sternal than retroperitoneal fat and muscle, a difference that was maintained with altered adiposity. In conclusion, sternal adipose tissue retains UCP1 into adulthood when it shows a greater thermogenic response to feeding than muscle and retroperitoneal fat. Sternal fat may be more amenable to targeted interventions that promote thermogenesis in large mammals

A Combined Transcriptomics and Lipidomics Analysis of Subcutaneous, Epididymal and Mesenteric Adipose Tissue Reveals Marked Functional Differences

Depot-dependent differences in adipose tissue physiology may reflect specialized functions and local interactions between adipocytes and surrounding tissues. We combined time-resolved microarray analyses of mesenteric- (MWAT), subcutaneous- (SWAT) and epididymal adipose tissue (EWAT) during high-fat feeding of male transgenic ApoE3Leiden mice with histology, targeted lipidomics and biochemical analyses of metabolic pathways to identify differentially regulated processes and site-specific functions. EWAT was found to exhibit physiological zonation. De novo lipogenesis in fat proximal to epididymis was stably low, whereas de novo lipogenesis distal to epididymis and at other locations was down-regulated in response to high-fat diet. The contents of linoleic acid and α-linolenic acid in EWAT were increased compared to other depots. Expression of the androgen receptor (Ar) was higher in EWAT than in MWAT and SWAT. We suggest that Ar may mediate depot-dependent differences in de novo lipogenesis rate and propose that accumulation of linoleic acid and α-linolenic acid in EWAT is favored by testosterone-mediated inhibition of de novo lipogenesis and may promote further elongation and desaturation of these polyunsaturated fatty acids during spermatogenesis

The prevalence of Giardia infection in dogs and cats, a systematic review and meta-analysis of prevalence studies from stool samples

Giardia has a wide range of host species and is a common cause of diarrhoeal disease in humans and animals. Companion animals are able to transmit a range of zoonotic diseases to their owners including giardiasis, but the size of this risk is not well known. The aim of this study was to analyse giardiasis prevalence rates in dogs and cats worldwide using a systematic search approach. Meta-analysis enabled to describe associations between Giardia prevalence and various confounding factors. Pooled prevalence rates were 15.2% (95% CI 13.8-16.7%) for dogs and 12% (95% CI 9.2-15.3%) for cats. However, there was very high heterogeneity between studies. Meta-regression showed that the diagnostic method used had a major impact on reported prevalence with studies using ELISA, IFA and PCR reporting prevalence rates between 2.6 and 3.7 times greater than studies using microscopy. Conditional negative binomial regression found that symptomatic animals had higher prevalence rates ratios (PRR) than asymptomatic animals 1.61 (95% CI 1.33-1.94) in dogs and 1.94 (95% CI 1.47-2.56) in cats. Giardia was much more prevalent in young animals. For cats >6 months, PRR=0.47 (0.42-0.53) and in dogs of the same age group PRR=0.36 (0.32-0.41). Additionally, dogs kept as pets were less likely to be positive (PRR=0.56 (0.41-0.77)) but any difference in cats was not significant. Faecal excretion of Giardia is common in dogs and slightly less so in cats. However, the exact rates depend on the diagnostic method used, the age and origin of the animal. What risk such endemic colonisation poses to human health is still unclear as it will depend not only on prevalence rates but also on what assemblages are excreted and how people interact with their pets

Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source

International audience: Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem and progenitor cells from which it arises. Whereas increased visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are six visceral fat depots: perirenal, gonadal, epicardial, retroperitoneal, omental and mesenteric, and it is a subject of much debate whether these have a common developmental origin and whether this differs from that for subcutaneous WAT. Here we show that all six visceral WAT depots receive a significant contribution from cells expressing Wt1 late in gestation. Conversely, no subcutaneous WAT or brown adipose tissue arises from Wt1-expressing cells. Postnatally, a subset of visceral WAT continues to arise from Wt1-expressing cells, consistent with the finding that Wt1 marks a proportion of cell populations enriched in WAT progenitors. We show that all visceral fat depots have a mesothelial layer like the visceral organs with which they are associated, and provide several lines of evidence that Wt1-expressing mesothelium can produce adipocytes. These results reveal a major ontogenetic difference between visceral and subcutaneous WAT, and pinpoint the lateral plate mesoderm as a major source of visceral WAT. They also support the notion that visceral WAT progenitors are heterogeneous, and suggest that mesothelium is a source of adipocytes

New contributions on VLF radio wave perturbations measured at high-latitudes

Abstract The Earth-ionosphere system behaves as a waveguide for the propagation of very low frequency (VLF) radio waves. If in this system the electrical conductivity of its boundaries is disturbed, the propagation of VLF waves is also disrupted, which is observed as phase and amplitude variations of VLF waves with respect to their quiescent levels. There is a diversity of physical phenomena that are able to alter significantly the conductivity of the upper boundary. These phenomena can have their origin at the Earth (e.g., lightning), in the solar system (e.g., solar flares) or even much farther away (e.g., galactic gamma-ray bursts). The aim of this thesis is to study short- and long-term VLF variations measured in Northern Finland (at the Sodankylä Geophysical Observatory) and their associations to different phenomena. The main results are as follows: [i] The minimum energy a solar flare should have in order to produce ionospheric disturbances depends on the solar cycle. This energy is understood as the ionospheric sensitivity and for daytime conditions its value lies in the range (1–12) × 10⁻⁷ J/m². [ii] The semiannual oscillation that appears in VLF measurements was determined to be related to geomagnetic activity variations. At the same time, it was found that the 27-day solar rotation oscillation is dominant during the declining phase of the solar cycle. [iii] The main characteristics of the observed VLF sunrise phase perturbation are derived from the shadowing of short wavelength solar UV radiation due to stratospheric ozone absorption when the Sun rises. [iv] VLF emissions with banded structure were observed in the 16–39 kHz frequency range, which are frequencies not usually used for the study of whistler mode VLF emissions coming from the magnetosphere. All these results are important since the VLF signals are related to variations of electron density in the ionospheric D-region, and thus have been used to identify the processes that influence the behavior of the upper atmosphere. The mentioned results can provide useful constraints on the long-term and short-term variability in coupled ion-neutral atmospheric models, thereby adding to our understanding of the response of the chemistry, dynamics and electrodynamics of the Earth’s ionosphere to solar and atmospheric forcing.Tiivistelmä Maa-ionosfäärijärjestelmä toimii aaltoputkena erittäin matalataajuisille (VLF) radioaalloille. Jos tässä järjestelmässä sen rajojen sähkönjohtavuus häiriintyy, myös VLF-aaltojen eteneminen häiriintyy, mikä havaitaan VLF-aaltojen vaihe- ja amplitudivaihteluina suhteessa niiden tasoon hiljaisina aikoina. On olemassa useita erilaisia fysikaalisia ilmiöitä, jotka pystyvät muuttamaan merkittävästi ylärajan johtavuutta. Nämä ilmiöt voivat olla peräisin maapallolta (esim. planetaariset aallot), aurinkokunnastamme (esim. auringon roihupurkaukset) tai jopa paljon kauempaa (esim. galaktiset gammapurkaukset). Tässä väitöskirjassa tutkijaan Pohjois-Suomessa (Sodankylän geofysiikan observatoriossa) mitattuja lyhyen ja pitkän aikavälin VLF-vaihteluita ja niiden yhteyksiä eri ilmiöihin. Tärkeimmät tulokset ovat seuraavat: [i] määritettiin, miten ionosfäärin päiväajan herkkyys ulkoisille häiriötekijöille riippuu auringon aktiivisuuden vaiheesta. Tämä tutkimus ymmärretään vähimmäisenergian suhteen, joka ulkoisella tapahtumalla, kuten auringon roihupurkauksella, tulisi olla, jotta se aiheuttaisi signaalin leviämiseen vaikuttavia ionosfäärisiä häiriöitä. [ii] VLF-mittauksissa esiintyvän vuotuisen vaihtelun havaittiin liittyvän mesofäärin lämpötilaan ja auringon Lyman-α-vuohon päivä- ja yöolosuhteissa. Puolivuosittaisen vaihtelun havaittiin liittyvän geomagneettisen aktiivisuuden muutoksiin. Samalla todettiin, että auringon 27 päivän pyörimisjaksoa vastaava värähtely on hallitseva auringon aktiivisuuden laskuvaiheessa. [iii] Auringonnousuvaiheen VLF-häiriöiden pääominaisuuksien havaittiin johtuvan lyhyen aallonpituuden auringon UV-vuon varjostumisesta D-alueen ionosfäärissä johtuen stratosfäärin otsonin absorptiosta auringon noustessa. [iv] VLF-aaltoja, joissa oli raitamainen rakenne, havaittiin taajuusalueella 16–39 kHz. Näitä taajuuksia ei yleensä käytetä magnetosfääristä tulevien vihellysmoodin VLF-aaltojen tutkimiseen. Tuloksemme ovat tärkeitä, koska VLF-signaalit liittyvät elektronitiheyden muutoksiin ionosfäärin D-alueella, ja siten niitä on käytetty tunnistamaan prosessit, jotka vaikuttavat ylemmän ilmakehän käyttäytymiseen. Mainitut tulokset voivat tarjota hyödyllisiä rajoja pitkä- ja lyhytaikaiseen vaihteluun ilmakehän yhdistettyissä ionineutraalimalleissa, mikä lisää ymmärrystämme Maan ionosfäärin kemiallisesta, dynaamisesta ja sähködynaamisesta vasteesta auringon ja ilmakehän pakotukseen