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.
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 (FST = 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.
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. 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 with indole caused significant decreases in the severity of hepatic steatosis and inflammation. In cultured cells, indole treatment stimulated the expression of 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 is capable of alleviating diet-induced NAFLD phenotypes in mice in a myeloid cell PFKFB3-dependnet 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.
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.
Interest in monitoring the population viability of the Brown Pelican (Pelecanus occidentalis) has recently risen in the context of the species' 2009 delisting as endangered, rapid degradation of ...nesting habitat, and recent oil spills. To assess the Brown Pelican's patterns of movement (across natal colony, nonnatal colony, and noncolony islands), age and sex structure, and survival probabilities, we banded 1177 chicks in Louisiana from 2007 to 2009. In band-resighting surveys within the Isles Dernieres archipelago from 2008 to 2010, we detected 92 of our banded birds. Neither age nor sex appeared to influence where we observed pelicans resting on beaches across the islands, and we found the highest proportions of pelicans at their natal island. Yet few observations of banded birds suggest either movement outside our study area or mortality. Conditions at colonies and proximity to other sites of loafing or colonies may in part explain the disparity in proportions of resightings of individuals banded on different islands. Finally, the apparent probability of survival of one-year-old pelicans was lower than that of two- and three-year olds. Insights into these trends in movement and survival of young Brown Pelicans can improve future management of colony sites.
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.
Abstract 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 mt DNA 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 mt DNA 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, mt DNA 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.
Within the context of a limited number of Brown Pelican (Pelecanus occidentalis) breeding sites, promoting new colonies can mitigate localized threats to regional populations. To assess the efficacy ...of short-distance (∼5 km) translocations and use of decoys to establish new colonies, and thereby increase statewide population viability, research was conducted within the Isles Dernieres archipelago, Louisiana. Translocations of 323 Brown Pelican chicks to an un-colonized island were performed from 2007 to 2009, and from 2008 to 2010, 108 Brown Pelican decoys were deployed on a separate island void of nesting. From 2008 to 2010 band re-sighting surveys detected only one transplanted Brown Pelican chick that returned to the release site. Further, < 1 % of translocated individuals were observed throughout the archipelago, compared to 5% and 9% of banded individuals encountered that fledged from nearby islands. Low detection of translocated Brown Pelicans may be due to translocation stress that can result in disorientation and social disorganization, which may promote increased roaming. At sites with decoys, no loafing or nesting Brown Pelicans were observed. Further, behavioral surveys suggest there was no difference in interest of passing Brown Pelicans to decoys compared to paired control survey areas without decoys. Despite past successes of translocations and decoys for establishing new colonies of Brown Pelicans and other waterbird species, Brown Pelican conservation may be best promoted via restoration and protection of current colony sites.
Laporte and Charlesworth (2002) also illustrated that when males have higher variance in reproductive success and a lower dispersal rate than females, there is a sharp decrease in the difference in ...population structure expected between mtDNA and nDNA. Because males are more philopatric than females (Grzybowski 1995) and extrapair copulations are common in songbirds, this scenario is quite likely in Black-capped Vireos. ... we reported that "once distances separating pairs of populations exceed 100 km, there appears to be little evidence that genetic differentiation increases with greater distances" (Barr et al. 2008:3635).
PDF
