The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) has important roles in adipogenesis and immune response as well as roles in both lipid and carbohydrate metabolism. Although synthetic agonists for PPARgamma are widely used as insulin sensitizers, the identity of the natural ligand(s) for PPARgamma is still not clear. Suggested natural ligands include 15-deoxy-delta12,14-prostaglandin J2 and oxidized fatty acids such as 9-HODE and 13-HODE. Crystal structures of PPARgamma have revealed the mode of recognition for synthetic compounds. Here we report structures of PPARgamma bound to oxidized fatty acids that are likely to be natural ligands for this receptor. These structures reveal that the receptor can (i) simultaneously bind two fatty acids and (ii) couple covalently with conjugated oxo fatty acids. Thermal stability and gene expression analyses suggest that such covalent ligands are particularly effective activators of PPARgamma and thus may serve as potent and biologically relevant ligands.

Taste is essential for animals to evaluate food quality and make important decisions about food choice and intake. How complex brains process sensory information to produce behavior is an essential question in the field of sensory neurobiology. Currently, little is known about higher-order taste circuits in the brain as compared with those of other sensory systems. Here, we used the common vinegar fly, Drosophila melanogaster, to screen for candidate neurons labeled by different transgenic GAL4 lines in controlling feeding behaviors. We found that activation of one line (VT041723-GAL4) produces 'proboscis holding' behavior (extrusion of the mouthpart without withdrawal). Further analysis showed that the proboscis holding phenotype indicates an aversive response, as flies pre-fed with either sucrose or water prior to neuronal activation exhibited regurgitation. Anatomical characterization of VT041723-GAL4-labeled neurons suggests that they receive sensory input from peripheral taste neurons. Overall, our study identifies a subset of brain neurons labeled by VT041723-GAL4 that may be involved in a taste circuit that controls regurgitation.

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Taste is essential for humans and animals alike to evaluate food quality and make important decisions about food choice and intake . How complex brains process sensory information to produce behavior is an essential question in the field of sensory neurobiology. Currently, little is known about taste circuits in the brain as compared to other sensory systems. Here, we used the common vinegar fly, Drosophila melanogaster, to explore the potential role of brain neurons labeled by a transgenic line (VT041723-GAL4) in producing "proboscis holding" behavior (extrusion of the mouthpart without withdrawal) . By utilizing the GAL4/UAS binary expression system, we expressed a heat-activated cation channel (UAS-dTrpA1) in these brain neurons and artificially activated them by elevation of temperature, subsequently examining behavior in the heat-activated proboscis extension reflex (PER) assay . We found that activation of these neurons induced proboscis holding . Interestingly, the proboscis holding phenotype was sexually dimorphic. Male flies rarely showed proboscis holding and those that did had shorter proboscis holding durations . On the other hand, both mated and virgin females showed significantly more proboscis holding and had longer proboscis holding durations than male flies. Overall, we identified a subset of brain neurons labeled by the VT041723-GAL4 line that controls a sexually dimorphic feeding response (proboscis holding) upon activation .