The phospholipase A2 family's role in metabolic diseases : Focus on skeletal muscle

ACKNOWLEDGEMENT We would like to thank the Molecular Metabolism Group of the Queen's Medical Research Institute, University of Edinburgh, for useful discussions on the topic of the present review. Research Funding This work was supported by a British Heart Foundation 4Y PhD scholarship (FS/17/692/33477) to Iris Prunonosa Cervera and Nicholas M. Morton; a Wellcome Trust New Investigator Award (100981/Z/13/Z) to Nicholas M. Morton; and a Novo Nordisk Foundation—Postdoc Fellowship for research abroad—Endocrinology & Metabolism (NNF19OC0055072) to Brendan M. Gabriel.Peer reviewedPublisher PD

Effect of ration level and dietary docosahexaenoic acid content on the requirements for long-chain polyunsaturated fatty acids by juvenile barramundi (Lates calcarifer)

Juvenile barramundi were fed one of six diets containing differing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels. Fish were restricted fed on a pair-fed feeding regime to eliminate variability in feed intake, with two diets fed to satiety to examine the effects of fixed or variable feed rations on EFA requirements. Weight gain, feed intake, feed utilisation, and physical clinical signs were monitored. No effect of dietary DHA and EPA concentration, DHA:EPA ratio or total LC-PUFA level was observed on weight gain, growth rate, feed conversion ratio (FCR), survival or physical clinical health signs (P>0.05). Satiety fed fish had higher feed intake, final weight, weight gain and growth rate compared to their respective restrictively fed treatments (P<0.05). No effect of ration level on the responses to DHA concentration was observed. Body fatty acid composition was affected by diet, increasing dietary DHA resulted in higher body tissue DHA concentration, and a similar relationship was observed for EPA. Plasma haemoglobin increased with increasing DHA+EPA levels (P<0.05) while glutamate dehydrogenase increased for fish fed DHA+EPA in a 1:1 ratio, regardless of total dietary LC-PUFA (P<0.05). Juvenile barramundi may be fed diets containing as low as 1gkg-1 DHA without compromising growth or health status.&nbsp

Robo-AO Kepler Survey IV: the effect of nearby stars on 3857 planetary candidate systems

We present the overall statistical results from the Robo-AO Kepler planetary candidate survey, comprising of 3857 high-angular resolution observations of planetary candidate systems with Robo-AO, an automated laser adaptive optics system. These observations reveal previously unknown nearby stars blended with the planetary candidate host star which alter the derived planetary radii or may be the source of an astrophysical false positive transit signal. In the first three papers in the survey, we detected 440 nearby stars around 3313 planetary candidate host stars. In this paper, we present observations of 532 planetary candidate host stars, detecting 94 companions around 88 stars; 84 of these companions have not previously been observed in high-resolution. We also report 50 more-widely-separated companions near 715 targets previously observed by Robo-AO. We derive corrected planetary radius estimates for the 814 planetary candidates in systems with a detected nearby star. If planetary candidates are equally likely to orbit the primary or secondary star, the radius estimates for planetary candidates in systems with likely bound nearby stars increase by a factor of 1.54, on average. We find that 35 previously-believed rocky planet candidates are likely not rocky due to the presence of nearby stars. From the combined data sets from the complete Robo-AO KOI survey, we find that 14.5\pm0.5% of planetary candidate hosts have a nearby star with 4", while 1.2% have two nearby stars and 0.08% have three. We find that 16% of Earth-sized, 13% of Neptune-sized, 14% of Saturn-sized, and 19% of Jupiter-sized planet candidates have detected nearby stars.Comment: Accepted to the Astronomical Journa

Robo-AO Kepler Survey V: The effect of physically associated stellar companions on planetary systems

The Kepler light curves used to detect thousands of planetary candidates are susceptible to dilution due to blending with previously unknown nearby stars. With the automated laser adaptive optics instrument, Robo-AO, we have observed 620 nearby stars around 3857 planetary candidates host stars. Many of the nearby stars, however, are not bound to the KOI. In this paper, we quantify the association probability between each KOI and detected nearby stars through several methods. Galactic stellar models and the observed stellar density are used to estimate the number and properties of unbound stars. We estimate the spectral type and distance to 145 KOIs with nearby stars using multi-band observations from Robo-AO and Keck-AO. We find most nearby stars within 1" of a Kepler planetary candidate are likely bound, in agreement with past studies. We use likely bound stars as well as the precise stellar parameters from the California Kepler Survey to search for correlations between stellar binarity and planetary properties. No significant difference between the binarity fraction of single and multiple planet systems is found, and planet hosting stars follow similar binarity trends as field stars, many of which likely host their own non-aligned planets. We find that hot Jupiters are ~4x more likely than other planets to reside in a binary star system. We correct the radius estimates of the planet candidates in characterized systems and find that for likely bound systems, the estimated planetary candidate radii will increase on average by a factor of 1.77, if either star is equally likely to host the planet. We find that the planetary radius gap is robust to the impact of dilution, and find an intriguing 95%-confidence discrepancy between the radius distribution of small planets in single and binary systems.Comment: 19 pages, 12 figures, submitted to AAS Journal

Deficiency of the bone mineralization inhibitor NPP1 protects against obesity and diabetes

The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the gene that encodes NPP1 (Enpp1−/− mice). Enpp1−/− mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high-fat feeding. Enpp1−/− mice had increased levels of the insulin-sensitizing bone-derived hormone osteocalcin but unchanged insulin signalling within osteoblasts. A fuller understanding of the pathways of NPP1 could inform the development of novel therapeutic strategies for treating insulin resistance

The Robo-AO KOI survey: laser adaptive optics imaging of every Kepler exoplanet candidate

The Robo-AO Kepler Planetary Candidate Survey is observing every Kepler planet candidate host star (KOI) with laser adaptive optics imaging to hunt for blended nearby stars which may be physically associated companions. With the unparalleled efficiency provided by the first fully robotic adaptive optics system, we perform the critical search for nearby stars (0.15" to 4.0" separation with contrasts up to 6 magnitudes) that dilute the observed planetary transit signal, contributing to inaccurate planetary characteristics or astrophysical false positives. We present 3313 high resolution observations of Kepler planetary hosts from 2012-2015, discovering 479 nearby stars. We measure an overall nearby star probability rate of 14.5±0.8%. With this large data set, we are uniquely able to explore broad correlations between multiple star systems and the properties of the planets which they host, providing insight into the formation and evolution of planetary systems in our galaxy. Several KOIs of particular interest will be discussed, including possible quadruple star systems hosting planets and updated properties for possible rocky planets orbiting with in their star's habitable zone

Genome-wide screening for genetic variants in polyadenylation signal (PAS) sites in mouse selection lines for fatness and leanness

Alternative polyadenylation (APA) determines mRNA stability, localisation, translation and protein function. Several diseases, including obesity, have been linked to APA. Studies have shown that single nucleotide polymorphisms in polyadenylation signals (PAS-SNPs) can influence APA and affect phenotype and disease susceptibility. However, these studies focussed on associations between single PAS-SNP alleles with very large effects and phenotype. Therefore, we performed a genome-wide screening for PAS-SNPs in the polygenic mouse selection lines for fatness and leanness by whole-genome sequencing. The genetic variants identified in the two lines were overlapped with locations of PAS sites obtained from the PolyASite 2.0 database. Expression data for selected genes were extracted from the microarray expression experiment performed on multiple tissue samples. In total, 682 PAS-SNPs were identified within 583 genes involved in various biological processes, including transport, protein modifications and degradation, cell adhesion and immune response. Moreover, 63 of the 583 orthologous genes in human have been previously associated with human diseases, such as nervous system and physical disorders, and immune, endocrine, and metabolic diseases. In both lines, PAS-SNPs have also been identified in genes broadly involved in APA, such as Polr2c, Eif3e and Ints11. Five PAS-SNPs within 5 genes (Car, Col4a1, Itga7, Lat, Nmnat1) were prioritised as potential functional variants and could contribute to the phenotypic disparity between the two selection lines. The developed PAS-SNPs catalogue presents a key resource for planning functional studies to uncover the role of PAS-SNPs in APA, disease susceptibility and fat deposition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00335-022-09967-8

Effects of Proportions of Dietary Macronutrients on Glucocorticoid Metabolism in Diet-Induced Obesity in Rats

Tissue glucocorticoid levels in the liver and adipose tissue are regulated by regeneration of inactive glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and inactivation by 5α- and 5β-reductases. A low carbohydrate diet increases hepatic 11β-HSD1 and reduces glucocorticoid metabolism during weight loss in obese humans. We hypothesized that similar variations in macronutrient proportions regulate glucocorticoid metabolism in obese rats. Male Lister Hooded rats were fed an obesity-inducing ad libitum ‘Western’ diet (37% fat, n = 36) for 22 weeks, then randomised to continue this diet (n = 12) or to switch to either a low carbohydrate (n = 12) or a moderate carbohydrate (n = 12) diet for the final 8 weeks. A parallel lean control group were fed an ad libitum control diet (10% fat, n = 12) throughout. The low and moderate carbohydrate diets decreased hepatic 11β-HSD1 mRNA compared with the Western diet (both 0.7±0.0 vs 0.9±0.1 AU; p<0.01), but did not alter 11β-HSD1 in adipose tissue. 5α-Reductase mRNA was increased on the low carbohydrate compared with the moderate carbohydrate diet. Compared with lean controls, the Western diet decreased 11β-HSD1 activity (1.6±0.1 vs 2.8±0.1 nmol/mcg protein/hr; p<0.001) and increased 5α-reductase and 5β-reductase mRNAs (1.9±0.3 vs 1.0±0.2 and 1.6±0.1 vs 1.0±0.1 AU respectively; p<0.01) in the liver, and reduced 11β-HSD1 mRNA and activity (both p<0.01) in adipose tissue. Although an obesity-inducing high fat diet in rats recapitulates the abnormal glucocorticoid metabolism associated with human obesity in liver (but not in adipose tissue), a low carbohydrate diet does not increase hepatic 11β-HSD1 in obese rats as occurs in humans