Impaired Thermogenesis and Adipose Tissue Development in Mice with Fat-Specific Disruption of Insulin and IGF-1 Signalling

Insulin and insulin-like growth factor 1 (IGF-1) play important roles in adipocyte differentiation, glucose tolerance and insulin sensitivity. Here, to assess how these pathways can compensate for each other, we created mice with a double tissue-specific knockout of insulin and IGF-1 receptors to eliminate all insulin/IGF-1 signaling in fat. These FIGIRKO mice had markedly decreased white and brown fat mass and were completely resistant to high fat diet (HFD) induced obesity and age- and HFD-induced glucose intolerance. Energy expenditure was increased in FIGIRKO mice despite a >85% reduction in brown fat mass. However, FIGIRKO mice were unable to maintain body temperature when placed at $4^{\circ}C$. Brown fat activity was markedly decreased in FIGIRKO mice but was responsive to $\beta3$-receptor stimulation. Thus, insulin/IGF-1 signaling has a crucial role in the control of brown and white fat development, and, when disrupted, leads to defective thermogenesis and a paradoxical increase in basal metabolic rate

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

Transcriptional analysis of adipose tissue during development reveals depot-specific responsiveness to maternal dietary supplementation

Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specifc uncoupling protein (UCP)1 and rapid fat growth. The extent to which this adaptation may vary between anatomical locations remains unknown, or whether the process is sensitive to maternal dietary supplementation. We, therefore, conducted a data mining based study on the major fat depots (i.e. epicardial, perirenal, sternal (which possess UCP1 at 7 days), subcutaneous and omental) (that do not possess UCP1) of young sheep during the frst month of life. Initially we determined what effect adding 3% canola oil to the maternal diet has on mitochondrial protein abundance in those depots which possessed UCP1. This demonstrated that maternal dietary supplementation delayed the loss of mitochondrial proteins, with the amount of cytochrome C actually being increased. Using machine learning algorithms followed by weighted gene co-expression network analysis, we demonstrated that each depot could be segregated into a unique and concise set of modules containing co-expressed genes involved in adipose function. Finally using lipidomic analysis following the maternal dietary intervention, we confrmed the perirenal depot to be most responsive. These insights point at new research avenues for examining interventions to modulate fat development in early life

Review of Environmental Monitoring by Means of Radio Waves in the Polar Regions: From Atmosphere to Geospace

The Antarctic and Arctic regions are Earth's open windows to outer space. They provide unique opportunities for investigating the troposphere–thermosphere–ionosphere–plasmasphere system at high latitudes, which is not as well understood as the mid- and low-latitude regions mainly due to the paucity of experimental observations. In addition, different neutral and ionised atmospheric layers at high latitudes are much more variable compared to lower latitudes, and their variability is due to mechanisms not yet fully understood. Fortunately, in this new millennium the observing infrastructure in Antarctica and the Arctic has been growing, thus providing scientists with new opportunities to advance our knowledge on the polar atmosphere and geospace. This review shows that it is of paramount importance to perform integrated, multi-disciplinary research, making use of long-term multi-instrument observations combined with ad hoc measurement campaigns to improve our capability of investigating atmospheric dynamics in the polar regions from the troposphere up to the plasmasphere, as well as the coupling between atmospheric layers. Starting from the state of the art of understanding the polar atmosphere, our survey outlines the roadmap for enhancing scientific investigation of its physical mechanisms and dynamics through the full exploitation of the available infrastructures for radio-based environmental monitoring

A longitudinal study on the occurrence of Cryptosporidium and Giardia in dogs during their first year of life

<p>Abstract</p> <p>Background</p> <p>The primary aim of this study was to obtain more knowledge about the occurrence of <it>Cryptosporidium </it>and <it>Giardia </it>in young dogs in Norway.</p> <p>The occurrence of these parasites was investigated in a longitudinal study by repeated faecal sampling of dogs between 1 and 12 months of age (litter samples and individual samples). The dogs were privately owned and from four large breeds. Individual faecal samples were collected from 290 dogs from 57 litters when the dogs were approximately 3, 4, 6, and 12 months old. In addition, pooled samples were collected from 43 of the litters, and from 42 of the mother bitches, when the puppies were approximately 1 and/or 2 months old.</p> <p>Methods</p> <p>The samples were purified by sucrose gradient flotation concentration and examined by immunofluorescent staining.</p> <p>Results</p> <p>128 (44.1%) of the young dogs had one or more <it>Cryptosporidium </it>positive samples, whilst 60 (20.7%) dogs had one or more <it>Giardia </it>positive samples. The prevalence of the parasites varied with age. For <it>Cryptosporidium</it>, the individual prevalence was between 5.1% and 22.5%, with the highest level in dogs < 6 months old, and declining with age. For <it>Giardia</it>, the individual prevalence was between 6.0% and 11.4%, with the highest level in dogs > 6 months old, but the differences between age groups were not statistically significant. Significant differences in prevalences were found in relation to geographic location of the dogs. Both parasites occurred at low prevalences in Northern Norway.</p> <p>Conclusion</p> <p>Both <it>Cryptosporidium </it>and <it>Giardia </it>are common in Norwegian dogs, with <it>Cryptosporidium </it>more prevalent than <it>Giardia</it>. Prevalences of the parasites were found to be influenced by age, geographical location, and infection status before weaning.</p

The Number of X Chromosomes Causes Sex Differences in Adiposity in Mice

Sexual dimorphism in body weight, fat distribution, and metabolic disease has been attributed largely to differential effects of male and female gonadal hormones. Here, we report that the number of X chromosomes within cells also contributes to these sex differences. We employed a unique mouse model, known as the “four core genotypes,” to distinguish between effects of gonadal sex (testes or ovaries) and sex chromosomes (XX or XY). With this model, we produced gonadal male and female mice carrying XX or XY sex chromosome complements. Mice were gonadectomized to remove the acute effects of gonadal hormones and to uncover effects of sex chromosome complement on obesity. Mice with XX sex chromosomes (relative to XY), regardless of their type of gonad, had up to 2-fold increased adiposity and greater food intake during daylight hours, when mice are normally inactive. Mice with two X chromosomes also had accelerated weight gain on a high fat diet and developed fatty liver and elevated lipid and insulin levels. Further genetic studies with mice carrying XO and XXY chromosome complements revealed that the differences between XX and XY mice are attributable to dosage of the X chromosome, rather than effects of the Y chromosome. A subset of genes that escape X chromosome inactivation exhibited higher expression levels in adipose tissue and liver of XX compared to XY mice, and may contribute to the sex differences in obesity. Overall, our study is the first to identify sex chromosome complement, a factor distinguishing all male and female cells, as a cause of sex differences in obesity and metabolism

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