a b s t r a c t GPR41 is reportedly expressed in murine adipose tissue and mediates short chain fatty acid (SCFA)-stimulated leptin secretion by activating Ga i . Here, we agree with a contradictory report in finding no expression of GPR41 in murine adipose tissue. Nevertheless, in the presence of adenosine deaminase to minimise Ga i signalling via the adenosine A1 receptor, SCFA stimulated leptin secretion by adipocytes from wild-type but not GPR41 knockout mice. Expression of GPR43 was reduced in GPR41 knockout mice. Acetate but not butyrate stimulated leptin secretion in wild-type mesenteric adipocytes, consistent with mediation of the response by GPR43 rather than GPR41. Pertussis toxin prevented stimulation of leptin secretion by propionate in epididymal adipocytes, implicating Ga i signalling mediated by GPR43 in SCFA-stimulated leptin secretion.

Bioinformatics is now intrinsic to life science research, but the past decade has witnessed a continuing deficiency in this essential expertise. Basic data stewardship is still taught relatively rarely in life science education programmes, creating a chasm between theory and practice, and fuelling demand for bioinformatics training across all educational levels and career roles. Concerned by this, surveys have been conducted in recent years to monitor bioinformatics and computational training needs worldwide. This article briefly reviews the principal findings of a number of these studies. We see that there is still a strong appetite for short courses to improve expertise and confidence in data analysis and interpretation; strikingly, however, the most urgent appeal is for bioinformatics to be woven into the fabric of life science degree programmes. Satisfying the relentless training needs of current and future generations of life scientists will require a concerted response from stakeholders across the globe, who need to deliver sustainable solutions capable of both transforming education curricula and cultivating a new cadre of trainer scientists.

We have determined the phosphorylation pattern of circulating insulin-like growth factor-binding protein-1 (IGFBP-1) in normal subjects and assessed how this changes in pregnancy. Two RIAs employing different monoclonal antibodies (MAbs 6303 or 6305) were used to measure IGFBP-1. In normal subjects, RIA 6303 measured 11-fold higher levels than RIA 6305 (72.8 vs. 6.6 micrograms/L; P < 0.008). However, in amniotic fluid (AF), the two assays gave similar results. Immunoprecipitation of plasma and AF with MAb 6303 and 6305 before nonsodium dodecyl sulfate-electrophoresis and Western ligand blotting revealed different IGFBP-1 isoforms and differential antibody recognition as the cause of this discrepancy. In AF, both MAbs precipitated nonphosphorylated and phosphorylated isoforms, whereas in plasma, only a single highly phosphorylated species, not seen in AF, was observed. This form of IGFBP-1 was precipitated by MAb 6303 only. During pregnancy, the phosphorylation state of IGFBP-1 in the maternal circulation was altered, as nonphosphorylated IGFBP-1 and three lesser phosphoforms were also observed. The appearance of these other variants resulted in a significant increase in IGFBP-1 measured by RIA 6305 (37, 51, and 83 micrograms/L in first, second, and third trimesters, respectively; P < 0.0005 vs. controls). The changes in IGFBP-1 phosphorylation induced by pregnancy may influence the modulatory effects of IGFBP-1 on IGF bioavailability and, hence, fetal growth.

Objective: To investigate the relationship of percent body fat (%fat), assessed by dual energy-X-ray absorptiometry (DXA) or a four-compartment model, with upper body and lower limb skinfolds. Design: Cross-sectional design involving forward stepwise and hierarchical multiple regression analyses to assess the relationship of %fat with skinfolds and a combination of four commonly used upper body skinfolds (biceps, triceps, subscapular and iliac crest) with the calf and thigh skinfolds. Setting: University research laboratory. Subjects: In all, 31 females, mean age 20.9 (72.0) y, and 21 males, mean age 22.3 (75.5) y volunteered for this study, which was approved by the Ethics Committee of the School of Sport, Health and Exercise Sciences, University of Wales, Bangor. Measurements: %fat from DXA in both groups, and %fat from a four-compartment (water, bone mineral mass, fat and residual) model (%fat4C) in females only. Skinfolds were measured at the abdomen, iliac crest, biceps, triceps, subscapular, calf and thigh. Results: All skinfolds were positively associated with DXA estimates of %fat (Po0.01). In males and females, the thigh skinfold had the highest correlation with %fat. This was also observed when %fat4C was used as the criterion in females. Stepwise multiple regression analysis using %fatDXA as the criterion selected the thigh (R 2 ¼ 0.82), calf (R 2 change 0.04) and iliac crest (R 2 change ¼ 0.03) for females, and the thigh (R 2 ¼ 0.79), iliac crest (R 2 change ¼ 0.11) and abdomen (R 2 change ¼ 0.03) for males (all Po0.01). When %fat4C was used as the criterion in the females, only the thigh was selected as a significant predictor (R 2 ¼ 0.76). Independent prediction factors were created from the sum of biceps, triceps, subscapular and iliac crest ( P 4skf) and from the sum of the thigh and calf ( P thigh þ calf). These factors were then entered into a hierarchical multiple linear regression analysis to predict percent fat. Order of entry was varied to allow the assessment of unique variance accounted for by each predictor. The sum of the thigh and calf explained more variance in %fatDXA than that explained by the P 4skf alone, irrespective of the order of entry in both males and females. This was also observed when %fat4C was used as the criterion in the females. Conclusions:The results of this study confirm that lower body skinfolds are highly related to percent body fat in fit and healthy young men and women, and uphold current recommendations by the British Olympic Association to include the thigh skinfold with P 4skf. Conventional use of the P 4skf to estimate percent body fat is significantly enhanced by the inclusion of the thigh and calf skinfolds, either independently or in combination. In this group of males and females, the sum of the thigh and calf skinfolds accounted for the most variance in percent fat.

Background and objectiveMaternal overnutrition has been implicated in affecting the offspring by programming metabolic disorders such as obesity and diabetes, by mechanisms that are not clearly understood. This study aimed to determine the long-term impact of maternal high-fat (HF) diet feeding on epigenetic changes in the offspring’s hypothalamic Pomc gene, coding a key factor in the control of energy balance. Further, it aimed to study the additional effects of postnatal overnutrition on epigenetic programming by maternal nutrition.MethodsEight-week-old female Sprague–Dawley rats were fed HF diet or low-fat (LF) diet for 6 weeks before mating, and throughout gestation and lactation. At postnatal day 21, samples were collected from a third offspring and the remainder were weaned onto LF diet for 5 weeks, after which they were either fed LF or HF diet for 12 weeks, resulting in four groups of offspring differing by their maternal and postweaning diet.ResultsWith maternal HF diet, offspring at weaning had rapid early weight gain, increased adiposity, and hyperleptinemia. The programmed adult offspring, subsequently fed LF diet, retained the increased body weight. Maternal HF diet combined with offspring HF diet caused more pronounced hyperphagia, fat mass, and insulin resistance. The ARC Pomc gene from programmed offspring at weaning showed hypermethylation in the enhancer (nPE1 and nPE2) regions and in the promoter sequence mediating leptin effects. Interestingly, hypermethylation at the Pomc promoter but not at the enhancer region persisted long term into adulthood in the programmed offspring. However, there were no additive effects on methylation levels in the regulatory regions of Pomc in programmed offspring fed a HF diet.ConclusionMaternal overnutrition programs long-term epigenetic alterations in the offspring’s hypothalamic Pomc promoter. This predisposes the offspring to metabolic disorders later in life.