CB(1) antagonism restores hepatic insulin sensitivity without normalization of adiposity in diet-induced obese dogs

The endocannabinoid system is highly implicated in the development of insulin resistance associated with obesity. It has been shown that antagonism of the CB(1) receptor improves insulin sensitivity (S(I)). However, it is unknown whether this improvement is due to the direct effect of CB(1) blockade on peripheral tissues or secondary to decreased fat mass. Here, we examine in the canine dog model the longitudinal changes in S(I) and fat deposition when obesity was induced with a high-fat diet (HFD) and animals were treated with the CB(1) antagonist rimonabant. S(I) was assessed (n = 20) in animals fed a HFD for 6 wk to establish obesity. Thereafter, while HFD was continued for 16 additional weeks, animals were divided into two groups: rimonabant (1.25 mg·kg(-1)·day(-1) RIM; n = 11) and placebo (n = 9). Euglycemic hyperinsulinemic clamps were performed to evaluate changes in insulin resistance and glucose turnover before HFD (week -6) after HFD but before treatment (week 0) and at weeks 2, 6, 12, and 16 of treatment (or placebo) + HFD. Magnetic resonance imaging was performed to determine adiposity- related changes in S(I). Animals developed significant insulin resistance and increased visceral and subcutaneous adiposity after 6 wk of HFD. Treatment with RIM resulted in a modest decrease in total trunk fat with relatively little change in peripheral glucose uptake. However, there was significant improvement in hepatic insulin resistance after only 2 wk of RIM treatment with a concomitant increase in plasma adiponectin levels; both were maintained for the duration of the RIM treatment. CB(1) receptor antagonism appears to have a direct effect on hepatic insulin sensitivity that may be mediated by adiponectin and independent of pronounced reductions in body fat. However, the relatively modest effect on peripheral insulin sensitivity suggests that significant improvements may be secondary to reduced fat mass.     

The Small Interfering RNA Pathway Is Not Essential for Wolbachia-Mediated Antiviral Protection in Drosophila melanogaster

Wolbachia pipientis delays RNA virus-induced mortality in Drosophila spp. We investigated whether Wolbachia-mediated protection was dependent on the small interfering RNA (siRNA) pathway, a key antiviral defense. Compared to Wolbachia-free flies, virus-induced mortality was delayed in Wolbachia-infected flies with loss-of-function of siRNA pathway components, indicating that Wolbachia-mediated protection functions in the absence of the canonical siRNA pathway.     

In vivo deuteration strategies for neutron scattering analysis of bacterial polyhydroxyoctanoate

The cultivation of microorganisms on deuterated substrates has allowed us to control deuterium incorporation into biopolymer systems which is important for characterisation using neutron scattering techniques. Bacterial polyhydroxyoctanoate (PHO) is a polyester formed within inclusions inside bacterial cells and was deuterated in vivo under various conditions to characterise the formation of these inclusions by neutron scattering. Manipulation of deuterated media during microbial growth and PHO production phases resulted in polymer with partial or complete substitution of hydrogen by deuterium, as shown by gas chromatography. Sequential feeding of hydrogenated and deuterated forms of the same precursor was used to demonstrate that neutron scattering analysis could be used to differentiate between chemically similar phases in these polymer inclusions.     

Impact of soil warming and shading on colonization and community structure of arbuscular mycorrhizal fungi in roots of a native grassland community

Arbuscular mycorrhizal (AM) fungi have a major influence on the structure, responses and below‐ground C allocation of plant communities. Our lack of understanding of the response of AM fungi to factors such as light and temperature is an obstacle to accurate prediction of the impact of global climate change on ecosystem functioning. In order to investigate this response, we divided a grassland site into 24 plots, each either unshaded or partly shaded with soil either unheated or heated by 3°C at 2 cm depth. In both short‐term studies in spring and autumn, and in a 1‐year‐long study, we measured root length colonization (L_RC) by AM and non‐AM fungi. For selected root samples, DNA sequences were amplified by PCR with fungal‐specific primers for part of the small sub‐unit (SSU) rRNA gene. In spring, the total L_RC increased over 6 weeks from 12% to 25%. Shading significantly reduced AM but increased non‐AM fungal colonization, while soil warming had no effect. In the year‐long study, colonization by AM fungi peaked in summer, whereas non‐AM colonization peaked in autumn, when there was an additive effect of shading and soil warming that reduced AM but increased non‐AM fungi. Stepwise regression revealed that light received within the 7 days prior to sampling was the most significant factor in determining AM L_RC and that mean temperature was the most important influence on non‐AM L_RC. Loglinear analysis confirmed that there were no seasonal or treatment effects on the host plant community. Ten AM fungal sequence types were identified that clustered into two families of the Glomales, Glomaceae and Gigasporaceae. Three other sequence types were of non‐AM fungi, all Ascomycotina. AM sequence types showed seasonal variation and shading impacts: loglinear regression analysis revealed changes in the AM fungal community with time, and a reduction of one Glomus sp. under shade, which corresponded to a decrease in the abundance of Trifolium repens. We suggest that further research investigating any impacts of climate change on ecosystem functioning must not only incorporate their natural AM fungal communities but should also focus on niche separation and community dynamics of AM fungi.     

Phosphorylation of p70S6k correlates with increased skeletal muscle mass following resistance exercise

High-resistance exercise training results in an increase inmuscle wet mass and protein content. To begin to address the acute changes following a single bout of high-resistance exercise, a newmodel has been developed. Training rats twice a week for 6 wk resultedin 13.9 and 14.4% hypertrophy in the extensor digitorum longus (EDL)and tibialis anterior (TA) muscles, respectively. Polysome profilesafter high-resistance lengthening contractions suggest that the rate ofinitiation is increased. The activity of the 70-kDa S6 protein kinase(p70^S6k), a regulator oftranslation initiation, is also increased following high-resistancelengthening contractions (TA, 363 ± 29%; EDL, 353 ± 39%).Furthermore, the increase inp70^S6k activity 6 h after exercisecorrelates with the percent change in muscle mass after 6 wk oftraining (r = 0.998). The tightcorrelation between the activation ofp70^S6k and the long-term increasein muscle mass suggests thatp70^S6k phosphorylation may be agood marker for the phenotypic changes that characterize musclehypertrophy and may play a role in load-induced skeletal muscle growth.