Biology subjects

Ja, W. W.

Publications and source records attributed to Ja, W. W..

6 recordsLinked to original sources

bioRxiv2026

Time-restricted eating promotes sustained fat loss in Drosophila

While current therapeutics restricting calorie intake, such as GLP-1 agonists, induce fat loss for many people, they are ineffective for others and concerns remain about their long-term effects on health, particularly loss of lean muscle mass. Moreover, many quickly regain fat if they stop treatment. In contrast, time-restricted eating does not restrict calorie intake but instead restricts the time window for eating and prevents obesity in mice and humans. Here we investigated the effects of intermittent Time-Restricted Feeding (iTRF), which extends lifespan and delays markers of aging, on stored fat in Drosophila. Ten days of iTRF caused significant fat loss relative to ad lib diet, an effect that persisted even after return to ad lib diet. Unlike iTRF-induced lifespan extension, iTRF-induced fat loss did not depend on circadian-regulated autophagy. iTRF treated both diet-induced and genetically induced obesity and significantly reduced lipid droplet size in the fat body (adipose tissue). Instead of causing muscle loss, iTRF increased total and muscle-specific protein levels and enhanced flight performance, suggesting a shift in body composition. We found that iTRF evoked fasting-induced hyperactivity, partially mediated by octopamine, the fly ortholog of the human stress hormone norepinephrine. Ablation of octopaminergic neurons (OANs) prevented iTRF-mediated effects: fat loss, increased protein, and enhanced flight performance. Our results suggest that Drosophila iTRF causes rapid, permanent fat loss and increased muscle function through a "fight or flight" response. Understanding the mechanisms driving differences between Drosophila and human responses to TRE could be critical for identifying effective therapeutic targets for obesity.

physiology↗

bioRxiv2025

easyClock: A User-Friendly Desktop Application for Circadian Rhythm Analysis and Visualization

Circadian rhythms regulate a wide range of biological processes, and their precise characterization is essential for understanding behavioral and physiological fluctuations. However, existing tools to analyze circadian data often require coding expertise or rely on specific data acquisition software, limiting their general applicability. Here, we present easyClock, an intuitive and interactive application designed to streamline circadian rhythm analysis and visualization. The easyClock application enables simultaneous processing of multiple files, allowing users to preview, batch-analyze, and plot diverse sets of time series generated from high-throughput experiments. To enhance data analysis efficiency and provide comparable results, this application integrates four different analysis methods for handling data with various waveforms. Results are easily viewed and exported for any selected range of data. This free-to-use application is open-source and can be deployed on macOS computers by users without coding experience. AvailabilityThe source code for the latest version of easyClock is available at https://github.com/HungryFly/easyClock_for_CircadianRhythms. To download the installation package and access version updates, please refer to https://github.com/Dr-WUBINBIN/easyClock/releases.

bioinformatics↗

bioRxiv2024

Chemosensation drives divergent social behavior in Drosophila

The social environment can have a considerable impact on animal behavior. However, the molecular signals that drive socially sensitive behaviors are not completely defined. Using the model organism, Drosophila melanogaster, we investigated behavioral responses to housing status. Group housing of male flies induces robust social interactions--composed of chasing and touching--in the Dahomey strain, but not in other commonly used parental lines. Testing mixed-strain groups revealed that strain-specific variation in chemosensation, rather than in the generation of chemosignals, likely underlies the divergent group behaviors. Using locomotor activity as a higher throughput readout for increased social interactions, we found that manipulations that decrease or ablate olfaction--through surgical removal of olfactory organs, silencing of olfactory neurons, or mutations in odorant receptor co-receptor (Orco)--decrease Dahomey social sensitivity. Females of all tested strains, including Dahomey, show no evidence of increased group activity. These results demonstrate that Dahomey social sensitivity is a sexually dimorphic, olfaction-dependent group behavior. The OR43a receptor, as well as signaling through Or43a+ neurons, contributes to Dahomey group hyperactivity. Additional studies also suggest that strain-specific single nucleotide polymorphisms (SNPs) in the Or43a gene are associated with Dahomey social sensitivity. Our studies reveal insights on the mechanisms that regulate sensory recognition and behavioral responses to the social environment, and how divergent strategies may have evolved within the same species.

animal behavior and cognition↗

bioRxiv2024

Energy Deficit is a Key Driver of Sleep Homeostasis

Sleep and feeding are vital homeostatic behaviors, and disruptions in either can result in substantial metabolic consequences. Distinct neuronal manipulations in Drosophila can dissociate sleep loss from subsequent homeostatic rebound, offering an optimal platform to examine the precise interplay between these fundamental behaviors. Here, we investigate concomitant changes in sleep and food intake in individual animals, as well as respiratory metabolic expenditure, that accompany behavioral and genetic manipulations that induce sleep loss in Drosophila melanogaster. We find that sleep disruptions resulting in energy deficit through increased metabolic expenditure and manifested as increased food intake were consistently followed by rebound sleep. In contrast, "soft" sleep loss, which does not induce rebound sleep, is not accompanied by increased metabolism and food intake. Our results demonstrate that homeostatic sleep rebound is linked to energy deficit accrued during sleep loss. Collectively, these findings support the notion that sleep functions to conserve energy and highlight the need to examine the effects of metabolic therapeutics on sleep.

neuroscience↗

bioRxiv2019

Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila

Neurofibromatosis type 1 (NF1) is a genetic disorder predisposing patients to a range of features, the most characteristic of which include areas of abnormal skin pigmentation and benign tumors associated with peripheral nerves, termed neurofibromas. Less common, but more serious symptoms also include malignant peripheral nerve sheath tumors, other malignancies, and learning disabilities. The NF1 gene encodes neurofibromin, a large protein that functions as a negative regulator of Ras signaling and mediates pleiotropic cellular and organismal function. Recent evidence suggests NF1 may regulate metabolism, though the mechanisms are unknown. Here we show that the Drosophila ortholog of NF1, dNf1 regulates metabolic homeostasis in fruit flies by functioning within a discrete brain circuit. Loss of dNf1 increases metabolic rate and feeding, enhances starvation susceptibility, and decreases lipid stores while increasing lipid turnover rate. The increase in metabolic rate is independent of locomotor activity (grooming), and maps to a subset of neurons in the ventral nervous system. The feeding and metabolic rate effects are due to loss of dNf1 in the same set of neurons, suggesting that increased feeding may be a compensatory effect driven by the increase in metabolic rate and lipid turnover. Finally, we show that the Ras GAP-related domain of neurofibromin is required for normal metabolism, demonstrating that Ras signaling downstream of dNf1 mediates the metabolic effects. These data demonstrate that dNf1 regulates metabolic rate via neuronal mechanisms, suggest that cellular and systemic metabolic alterations may represent a pathophysiological mechanism in NF1, and provide a platform for investigating the cellular role of neurofibromin in metabolic homeostasis.

neuroscience↗

bioRxiv2019

Phospholipase D Transduces Force to TREK-1 Channels in a Biological Membrane

Rapid conversion of force into a biological signal enables living cells to respond to mechanical forces in their environment. The force is believed to initially affect the plasma membrane and then alter the behavior of membrane proteins. Phospholipase D2 (PLD2) is a mechanosensitive enzyme that is regulated by a structured membrane-lipid site comprised of cholesterol and saturated ganglioside (GM1). Here we show stretch activation of TWIK-related K+ channel (TREK-1) is mechanically evoked by PLD2 and spatial patterning involving ordered GM1 and 4,5- bisphosphate (PIP2) clusters. First, mechanical force deforms the ordered lipids, which lowers membrane cholesterol, disrupts the interaction of PLD2 with the GM1 lipids, and allows a complex of TREK-1 and PLD2 to associate with PIP2 clusters. The association with PIP2 activates the enzyme, which produces the second messenger phosphatidic acid (PA) that gates the channel. Co-expression of catalytically inactive PLD2 inhibits TREK-1 stretch currents in a biological membrane. Cellular uptake of cholesterol inhibits TREK-1 currents in culture and depletion of cholesterol from astrocytes releases TREK-1 from GM1 lipids in mouse brain. Depletion of the PLD2 ortholog in flies results in hypersensitivity to mechanical force. We conclude PLD2 mechanosensitivity combines with TREK-1 ion permeability to elicit a mechanically evoked response. SummaryShear thinning activates TREK-1 through a second messenger.

neuroscience↗