The nutrient sensing for whole-body homeostasis: beyond the cellular level.

Systemic nutrient sensing is a fundamental process that aligns nutrient availability with an organism's metabolic demands. This mini-review explores nutrient sensors in the intestine, pancreas, portal vein, and the brain-organs that detect and convey nutrient status to other tissues via neuronal and hormonal signaling. Unlike oral taste receptors that sense external nutrient inputs, these nutrient sensors monitor post-ingestive levels of macronutrients (carbohydrates, proteins, and lipids) and micronutrients (vitamins and essential trace elements such as calcium, magnesium, and zinc) within the body.

Encoding the glucose identity by discrete hypothalamic neurons via the gut-brain axis.

Animals need daily intakes of three macronutrients: sugar, protein, and fat. Under fasted conditions, however, animals prioritize sugar as a primary source of energy. They must detect ingested sugar-specifically D-glucose-and quickly report its presence to the brain.

A sexually transmitted sugar orchestrates reproductive responses to nutritional stress.

Seminal fluid is rich in sugars, but their role beyond supporting sperm motility is unknown. In this study, we found Drosophila melanogaster males transfer a substantial amount of a phospho-galactoside to females during mating, but only half as much when undernourished. This seminal substance, which we named venerose, induces an increase in germline stem cells (GSCs) and promotes sperm storage in females, especially undernourished ones.

Postprandial sodium sensing by enteric neurons in Drosophila.

Sodium is essential for all living organisms. Animals including insects and mammals detect sodium primarily through peripheral taste cells. It is not known, however, whether animals can detect this essential micronutrient independently of the taste system.

Starvation-induced sleep suppression requires the brain nutrient sensor.

Animals increase their locomotion activity and reduce sleep duration under starved conditions. This suggests that sleep and metabolic status are closely interconnected. The nutrient and hunger sensors in the brain, including diuretic hormone 44 (DH44)-, CN-, and cupcake-expressing neurons, detect circulating glucose levels in the internal milieu, regulate the insulin and glucagon secretion and promote food consumption.

Evaluation of mouse behavioral responses to nutritive versus nonnutritive sugar using a deep learning-based 3D real-time pose estimation system.

Animals are able to detect the nutritional content of sugar independently of taste. When given a choice between nutritive sugar and nonnutritive sugar, animals develop a preference for nutritive sugar over nonnutritive sugar during a period of food deprivation (Buchanan , 2022; Dus , 2011; 2015; Tan , 2020; Tellez , 2016). To quantify behavioral features during an episode of licking nutritive versus nonnutritive sugar, we implemented a multi-vision, deep learning-based 3D pose estimation system, termed the AI Vision Analysis for Three-dimensional Action in Real-Time (AVATAR)(Kim , 2022).

History of neurogenetic research in South Korea.

Neurogenetic research using the model has immensely expanded around the world. Likewise, scientists in South Korea have leveraged the advantages of genetic tools to understand various neurobiological processes. In this special issue, we will overview the history of neurogenetic research in South Korea that led to significant discoveries and notably implications.

Discovering signaling mechanisms governing metabolism and metabolic diseases with Drosophila.

There has been rapid growth in the use of Drosophila and other invertebrate systems to dissect mechanisms governing metabolism. New assays and approaches to physiology have aligned with superlative genetic tools in fruit flies to provide a powerful platform for posing new questions, or dissecting classical problems in metabolism and disease genetics. In multiple examples, these discoveries exploit experimental advantages as-yet unavailable in mammalian systems.

Periphery signals generated by Piezo-mediated stomach stretch and Neuromedin-mediated glucose load regulate the Drosophila brain nutrient sensor.

Nutrient sensors allow animals to identify foods rich in specific nutrients. The Drosophila nutrient sensor, diuretic hormone 44 (DH44) neurons, helps the fly to detect nutritive sugar. This sensor becomes operational during starvation; however, the mechanisms by which DH44 neurons or other nutrient sensors are regulated remain unclear.

Response of the microbiome-gut-brain axis in Drosophila to amino acid deficit.

A balanced intake of macronutrients-protein, carbohydrate and fat-is essential for the well-being of organisms. An adequate calorific intake but with insufficient protein consumption can lead to several ailments, including kwashiorkor. Taste receptors (T1R1-T1R3) can detect amino acids in the environment, and cellular sensors (Gcn2 and Tor) monitor the levels of amino acids in the cell.

Signal Amplification in Drosophila Olfactory Receptor Neurons.

Olfactory receptor neurons (ORNs) transform scant chemical inputs into significant neural signals. This transformation requires signal amplification. In this issue of Neuron, Ng et al.

A glucose-sensing neuron pair regulates insulin and glucagon in Drosophila.

Although glucose-sensing neurons were identified more than 50 years ago, the physiological role of glucose sensing in metazoans remains unclear. Here we identify a pair of glucose-sensing neurons with bifurcated axons in the brain of Drosophila. One axon branch projects to insulin-producing cells to trigger the release of Drosophila insulin-like peptide 2 (dilp2) and the other extends to adipokinetic hormone (AKH)-producing cells to inhibit secretion of AKH, the fly analogue of glucagon.

Communicating the nutritional value of sugar in .

Sweet-insensitive mutants are unable to readily identify sugar. In presence of wild-type (WT) flies, however, these mutant flies demonstrated a marked increase in their preference for nutritive sugar. Real-time recordings of starved WT flies revealed that these flies discharge a drop from their gut end after consuming nutritive sugars, but not nonnutritive sugars.

Drosophila SLC5A11 Mediates Hunger by Regulating K(+) Channel Activity.

Hunger is a powerful drive that stimulates food intake. Yet, the mechanism that determines how the energy deficits that result in hunger are represented in the brain and promote feeding is not well understood. We previously described SLC5A11-a sodium/solute co-transporter-like-(or cupcake) in Drosophila melanogaster, which is required for the fly to select a nutritive sugar over a sweeter nonnutritive sugar after periods of food deprivation.

Humidity Sensing in Drosophila.

Environmental humidity influences the fitness and geographic distribution of all animals [1]. Insects in particular use humidity cues to navigate the environment, and previous work suggests the existence of specific sensory mechanisms to detect favorable humidity ranges [2-5]. Yet, the molecular and cellular basis of humidity sensing (hygrosensation) remains poorly understood.

A quantitative feeding assay in adult Drosophila reveals rapid modulation of food ingestion by its nutritional value.

Background: Food intake of the adult fruit fly Drosophila melanogaster, an intermittent feeder, is attributed to several behavioral elements including foraging, feeding initiation and termination, and food ingestion. Despite the development of various feeding assays in fruit flies, how each of these behavioral elements, particularly food ingestion, is regulated remains largely uncharacterized.

Results: To this end, we have developed a manual feeding (MAFE) assay that specifically measures food ingestion of an individual fly completely independent of the other behavioral elements.

Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila.

Animals can detect and consume nutritive sugars without the influence of taste. However, the identity of the taste-independent nutrient sensor and the mechanism by which animals respond to the nutritional value of sugar are unclear. Here, we report that six neurosecretory cells in the Drosophila brain that produce Diuretic hormone 44 (Dh44), a homolog of the mammalian corticotropin-releasing hormone (CRH), were specifically activated by nutritive sugars.

Ionotropic glutamate receptors IR64a and IR8a form a functional odorant receptor complex in vivo in Drosophila.

Drosophila olfactory sensory neurons express either odorant receptors or ionotropic glutamate receptors (IRs). The sensory neurons that express IR64a, a member of the IR family, send axonal projections to either the DC4 or DP1m glomeruli in the antennal lobe. DC4 neurons respond specifically to acids/protons, whereas DP1m neurons respond to a broad spectrum of odorants.

Taste-independent nutrient selection is mediated by a brain-specific Na+ /solute co-transporter in Drosophila.

Animals can determine the nutritional value of sugar without the influence of taste. We examined a Drosophila mutant that is insensitive to the nutritional value of sugars, responding only to the concentration (that is, sweetness). The affected gene encodes a sodium/solute co-transporter-like protein, designated SLC5A11 (or cupcake), which is structurally similar to mammalian sodium/glucose co-transporters that transport sugar across the intestinal and renal lumen.

Dedicated olfactory neurons mediating attraction behavior to ammonia and amines in Drosophila.

Animals across various phyla exhibit odor-evoked innate attraction behavior that is developmentally programmed. The mechanism underlying such behavior remains unclear because the odorants that elicit robust attraction responses and the neuronal circuits that mediate this behavior have not been identified. Here, we describe a functionally segregated population of olfactory sensory neurons (OSNs) and projection neurons (PNs) in Drosophila melanogaster that are highly specific to ammonia and amines, which act as potent attractants.