Diet-induced obesity leads to dysfunctional feeding behavior. However, the precise molecular nodes underlying diet-induced feeding motivation dysregulation are poorly understood. The fruit fly is a simple genetic model system yet displays significant evolutionary conservation to mammalian nutrient sensing and energy balance. Using a longitudinal high sugar regime in Drosophila, we sought to address how diet-induced changes in adipocyte lipid composition regulate feeding behavior. We observed that subjecting adult Drosophila to a prolonged high-sugar diet degrades the hunger-driven feeding response. Lipidomics analysis reveals that longitudinal exposure to high-sugar diets significantly alters whole-body phospholipid profiles. By performing a systematic genetic screen for phospholipid enzymes in adult fly adipocytes, we identify Pect as a critical regulator of hunger-driven feeding. Pect is a rate-limiting enzyme in the phosphatidylethanolamine (PE) biosynthesis pathway and the fly ortholog of human PCYT2. We show that disrupting Pect activity only in the Drosophila fat cells causes insulin resistance, dysregulated lipoprotein delivery to the brain, and a loss of hunger-driven feeding. Previously human studies have noted a correlation between PCYT2/Pect levels and clinical obesity. Now, our unbiased studies in Drosophila provide causative evidence for adipocyte Pect function in metabolic homeostasis. Altogether, we have uncovered that PE phospholipid homeostasis regulates hunger response.
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures
- Akhila Rajan
- Kevin P Kelly
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Tania Reis, University of Colorado Anschutz Medical Campus, United States
© 2022, Kelly et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Plasmids enable the dissemination of antimicrobial resistance (AMR) in common Enterobacterales pathogens, representing a major public health challenge. However, the extent of plasmid sharing and evolution between Enterobacterales causing human infections and other niches remains unclear, including the emergence of resistance plasmids. Dense, unselected sampling is essential to developing our understanding of plasmid epidemiology and designing appropriate interventions to limit the emergence and dissemination of plasmid-associated AMR. We established a geographically and temporally restricted collection of human bloodstream infection (BSI)-associated, livestock-associated (cattle, pig, poultry, and sheep faeces, farm soils) and wastewater treatment work (WwTW)-associated (influent, effluent, waterways upstream/downstream of effluent outlets) Enterobacterales. Isolates were collected between 2008 and 2020 from sites <60 km apart in Oxfordshire, UK. Pangenome analysis of plasmid clusters revealed shared ‘backbones’, with phylogenies suggesting an intertwined ecology where well-conserved plasmid backbones carry diverse accessory functions, including AMR genes. Many plasmid ‘backbones’ were seen across species and niches, raising the possibility that plasmid movement between these followed by rapid accessory gene change could be relatively common. Overall, the signature of identical plasmid sharing is likely to be a highly transient one, implying that plasmid movement might be occurring at greater rates than previously estimated, raising a challenge for future genomic One Health studies.
Microbial plankton play a central role in marine biogeochemical cycles, but the timing in which abundant lineages diversified into ocean environments remains unclear. Here, we reconstructed the timeline in which major clades of bacteria and archaea colonized the ocean using a high-resolution benchmarked phylogenetic tree that allows for simultaneous and direct comparison of the ages of multiple divergent lineages. Our findings show that the diversification of the most prevalent marine clades spans throughout a period of 2.2 Ga, with most clades colonizing the ocean during the last 800 million years. The oldest clades – SAR202, SAR324, Ca. Marinimicrobia, and Marine Group II – diversified around the time of the Great Oxidation Event, during which oxygen concentration increased but remained at microaerophilic levels throughout the Mid-Proterozoic, consistent with the prevalence of some clades within these groups in oxygen minimum zones today. We found the diversification of the prevalent heterotrophic marine clades SAR11, SAR116, SAR92, SAR86, and Roseobacter as well as the Marine Group I to occur near to the Neoproterozoic Oxygenation Event (0.8–0.4 Ga). The diversification of these clades is concomitant with an overall increase of oxygen and nutrients in the ocean at this time, as well as the diversification of eukaryotic algae, consistent with the previous hypothesis that the diversification of heterotrophic bacteria is linked to the emergence of large eukaryotic phytoplankton. The youngest clades correspond to the widespread phototrophic clades Prochlorococcus, Synechococcus, and Crocosphaera, whose diversification happened after the Phanerozoic Oxidation Event (0.45–0.4 Ga), in which oxygen concentrations had already reached their modern levels in the atmosphere and the ocean. Our work clarifies the timing at which abundant lineages of bacteria and archaea colonized the ocean, thereby providing key insights into the evolutionary history of lineages that comprise the majority of prokaryotic biomass in the modern ocean.