Indole Alleviates Diet-Induced Hepatic Steatosis and Inflammation in a Manner Involving Myeloid Cell 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3.

BACKGROUND AND AIMS: Indole is a microbiota metabolite that exerts anti-inflammatory responses. However, the relevance of indole to human non-alcoholic fatty liver disease (NAFLD) is not clear. It also remains largely unknown whether and how indole acts to protect against NAFLD. The present study sought to examine the association between the circulating levels of indole and liver fat content in human subjects and explore the mechanisms underlying indole actions in mice with diet-induced NAFLD. APPROACH AND RESULTS: In a cohort of 137 subjects, the circulating levels of indole were reversely correlated with body mass index. In addition, the circulating levels of indole in obese subjects were significantly lower than those in lean subjects and were accompanied with increased liver fat content. At the whole-animal level, treatment of high-fat diet (HFD)-fed C57BL/6J mice with indole caused significant decreases in the severity of hepatic steatosis and inflammation. In cultured cells, indole treatment stimulated the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a master regulatory gene of glycolysis, and suppressed macrophage proinflammatory activation in a PFKFB3-dependent manner. Moreover, myeloid cell-specific PFKFB3 disruption exacerbated the severity of HFD-induced hepatic steatosis and inflammation and blunted the effect of indole on alleviating diet-induced NAFLD phenotype. CONCLUSIONS: Taken together, our results demonstrate that indole is relevant to human NAFLD and capable of alleviating diet-induced NAFLD phenotypes in mice in a myeloid cell PFKFB3-dependent manner. Therefore, indole mimetic and/or macrophage-specific PFKFB3 activation may be the viable preventive and/or therapeutic approaches for inflammation-associated diseases including NAFLD.

How far is too close? restricted, sex-biased dispersal in black-capped vireos.

Understanding the interplay of dispersal and how it translates into gene flow is key to understanding population processes, and especially so for endangered species occupying fragmented habitats. In migratory songbirds, there is evidence that long-distance movement capabilities do not translate well into observed dispersal. Our objectives were to (i) define the fine-scale spatial genetic structure in endangered black-capped vireos to characterize dispersal patterns and (ii) to correlate dispersal dynamics to overall population genetic structure using a simulation approach. We sampled 160 individuals over 2 years to (i) describe the fine-scale genetic structuring and (ii) used this information to model scenarios to compare with actual data on change in population structuring over a 100-year interval. We found that black-capped vireos exhibit male philopatry and restricted dispersal distances, relative to females. Our simulations also support a sex-biased dispersal model. Additionally, we find that fragmentation related changes in rates of dispersal might be a likely cause for increasing levels of population structure over a 100-year period. We show that restricted sex-biased dispersal can explain population structuring in this species and that changes in dispersal rates due to fragmentation may be a continuing threat to genetic viability in this species.

Genetic isolation within the malaria mosquito Anopheles melas.

Anopheles melas is a brackish water-breeding member of the Anopheles gambiae complex that is distributed along the coast of West Africa and is a major malaria vector within its range. Because little is known about the population structure of this species, we analysed 15 microsatellite markers and 1161 bp of mtDNA in 11 A. melas populations collected throughout its range. Compared with its sibling species A. gambiae, A. melas populations have a high level of genetic differentiation between them, representing its patchy distribution due to its fragmented larval habitat that is associated with mangroves and salt marsh grass. Populations clustered into three distinct groups representing Western Africa, Southern Africa and Bioko Island populations that appear to be mostly isolated. Fixed differences in the mtDNA are present between all three clusters, and a Bayesian clustering analysis of the microsatellite data found no evidence for migration from mainland to Bioko Island populations, and little migration was evident between the Southern to the Western cluster. Surprisingly, mtDNA divergence between the three A. melas clusters is on par with levels of divergence between other species of the A. gambiae complex, and no support for monophyly was observed in a maximum-likelihood phylogenetic analysis. Finally, an approximate Bayesian analysis of microsatellite data indicates that Bioko Island A. melas populations were connected to the mainland populations in the past, but became isolated, presumably when sea levels rose after the last glaciation period (≥10 000-11 000 bp). This study has exposed species-level genetic divergence within A. melas and also has implications for control of this malaria vector.

Population structure in an endangered songbird: maintenance of genetic differentiation despite high vagility and significant population recovery.

Black-capped vireos (Vireo atricapilla), an endangered, migratory species dependent upon early successional habitat, have experienced significant recovery since its protection. In light of its vagility and known increase in population size and range, limited genetic differentiation would be expected in the species. Using 15 microsatellite loci and an extensive sampling regime, we detected significant overall genetic differentiation (F(ST) = 0.021) and high interpopulation differentiation compared to other migratory birds. Although proximate sites (separated by < 20 km) tended to be genetically similar, there was no apparent association of either geographical distance or landscape attributes with differentiation between sites. Evidence of a population bottleneck was also detected in a site located near other large concentrations of birds. Although black-capped vireos are capable of large-scale movements and the population has experienced a recent expansion, dispersal appears too insufficient to eliminate the genetic differentiation resulting from restricted colonization of ephemeral habitats.