controls sugar reward valuation in .

The genes - which include and ( ) - evolved from Ty3 retrotransposons and encode proteins that form virus-like capsids. These capsids enable a novel form of intercellular communication by transferring RNAs between cells. However, the specific neuronal circuits and brain processes Arc intercellular signaling regulates remain unknown.

Obesity- and diet-induced plasticity in systems that control eating and energy balance.

In April 2023, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in partnership with the National Institute of Child Health and Human Development, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research, hosted a 2-day online workshop to discuss neural plasticity in energy homeostasis and obesity. The goal was to provide a broad view of current knowledge while identifying research questions and challenges regarding neural systems that control food intake and energy balance. This review includes highlights from the meeting and is intended both to introduce unfamiliar audiences with concepts central to energy homeostasis, feeding, and obesity and to highlight up-and-coming research in these areas that may be of special interest to those with a background in these fields.

regulates gustatory habituation in sweet taste neurons and mediates sugar ingestion in .

Similar to other animals, the fly, reduces its responsiveness to tastants with repeated exposure, a phenomenon called gustatory habituation. Previous studies have focused on the circuit basis of gustatory habituation in the fly chemosensory system. However, gustatory neurons reduce their firing rate during repeated stimulation, suggesting that cell-autonomous mechanisms also contribute to habituation.

N-adenosine methylation controls the translation of insulin mRNA.

Control of insulin mRNA translation is crucial for energy homeostasis, but the mechanisms remain largely unknown. We discovered that insulin mRNAs across invertebrates, vertebrates and mammals feature the modified base N-methyladenosine (mA). In flies, this RNA modification enhances insulin mRNA translation by promoting the association of the transcript with polysomes.

Nutrigenomic regulation of sensory plasticity.

Diet profoundly influences brain physiology, but how metabolic information is transmuted into neural activity and behavior changes remains elusive. Here, we show that the metabolic enzyme O-GlcNAc Transferase (OGT) moonlights on the chromatin of the gustatory neurons to instruct changes in chromatin accessibility and transcription that underlie sensory adaptations to a high-sugar diet. OGT works synergistically with the Mitogen Activated Kinase/Extracellular signal Regulated Kinase (MAPK/ERK) rolled and its effector stripe (also known as EGR2 or Krox20) to integrate activity information.

Food memory circuits regulate eating and energy balance.

In mammals, learning circuits play an essential role in energy balance by creating associations between sensory cues and the rewarding qualities of food. This process is altered by diet-induced obesity, but the causes and mechanisms are poorly understood. Here, we exploited the relative simplicity and wealth of knowledge about the D.

High-sucrose diet exposure is associated with selective and reversible alterations in the rat peripheral taste system.

Elevated sugar consumption is associated with an increased risk for metabolic diseases. Whereas evidence from humans, rodents, and insects suggests that dietary sucrose modifies sweet taste sensation, understanding of peripheral nerve or taste bud alterations is sparse. To address this, male rats were given access to 30% liquid sucrose for 4 weeks (sucrose rats).

Crème de la Créature: Dietary Influences on Behavior in Animal Models.

In humans, alterations in cognitive, motivated, and affective behaviors have been described with consumption of processed diets high in refined sugars and saturated fats and with high body mass index, but the causes, mechanisms, and consequences of these changes remain poorly understood. Animal models have provided an opportunity to answer these questions and illuminate the ways in which diet composition, especially high-levels of added sugar and saturated fats, contribute to brain physiology, plasticity, and behavior. Here we review findings from invertebrate (flies) and vertebrate models (rodents, zebrafish) that implicate these diets with changes in multiple behaviors, including eating, learning and memory, and motivation, and discuss limitations, open questions, and future opportunities.

Brain on food: The neuroepigenetics of nutrition.

Humans have known for millennia that nutrition has a profound influence on health and disease, but it is only recently that we have begun mapping the mechanisms via which the dietary environment impacts brain physiology and behavior. Here we review recent evidence on the effects of energy-dense and methionine diets on neural epigenetic marks, gene expression, and behavior in invertebrate and vertebrate model organisms. We also discuss limitations, open questions, and future directions in the emerging field of the neuroepigenetics of nutrition.

Confection Confusion: Interplay Between Diet, Taste, and Nutrition.

Although genetics shapes our sense of taste to prefer some foods over others, taste sensation is plastic and changes with age, disease state, and nutrition. We have known for decades that diet composition can influence the way we perceive foods, but many questions remain unanswered, particularly regarding the effects of chemosensory plasticity on feeding behavior. Here, we review recent evidence on the effects of high-nutrient diets, especially high dietary sugar, on sweet taste in vinegar flies, rodents, and humans, and discuss open questions about molecular and neural mechanisms and research priorities.

NIH Workshop Report: sensory nutrition and disease.

In November 2019, the NIH held the "Sensory Nutrition and Disease" workshop to challenge multidisciplinary researchers working at the interface of sensory science, food science, psychology, neuroscience, nutrition, and health sciences to explore how chemosensation influences dietary choice and health. This report summarizes deliberations of the workshop, as well as follow-up discussion in the wake of the current pandemic. Three topics were addressed: A) the need to optimize human chemosensory testing and assessment, B) the plasticity of chemosensory systems, and C) the interplay of chemosensory signals, cognitive signals, dietary intake, and metabolism.

Persistent epigenetic reprogramming of sweet taste by diet.

Diets rich in sugar, salt, and fat alter taste perception and food preference, contributing to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here, we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.

Dietary sugar inhibits satiation by decreasing the central processing of sweet taste.

From humans to vinegar flies, exposure to diets rich in sugar and fat lowers taste sensation, changes food choices, and promotes feeding. However, how these peripheral alterations influence eating is unknown. Here we used the genetically tractable organism to define the neural mechanisms through which this occurs.

Rapid metabolic shifts occur during the transition between hunger and satiety in Drosophila melanogaster.

Metabolites are active controllers of cellular physiology, but their role in complex behaviors is less clear. Here we report metabolic changes that occur during the transition between hunger and satiety in Drosophila melanogaster. To analyze these data in the context of fruit fly metabolic networks, we developed Flyscape, an open-access tool.

High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster.

Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear. To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster. On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity.

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.

Benzoyl chloride derivatization with liquid chromatography-mass spectrometry for targeted metabolomics of neurochemicals in biological samples.

Widely targeted metabolomic assays are useful because they provide quantitative data on large groups of related compounds. We report a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method that utilizes benzoyl chloride labeling for 70 neurologically relevant compounds, including catecholamines, indoleamines, amino acids, polyamines, trace amines, antioxidants, energy compounds, and their metabolites. The method includes neurotransmitters and metabolites found in both vertebrates and insects.

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.

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.

Taste-independent detection of the caloric content of sugar in Drosophila.

Feeding behavior is influenced primarily by two factors: nutritional needs and food palatability. However, the role of food deprivation and metabolic needs in the selection of appropriate food is poorly understood. Here, we show that the fruit fly, Drosophila melanogaster, selects calorie-rich foods following prolonged food deprivation in the absence of taste-receptor signaling.

Clock and cycle limit starvation-induced sleep loss in Drosophila.

Neural systems controlling the vital functions of sleep and feeding in mammals are tightly interconnected: sleep deprivation promotes feeding, whereas starvation suppresses sleep. Here we show that starvation in Drosophila potently suppresses sleep, suggesting that these two homeostatically regulated behaviors are also integrated in flies. The sleep-suppressing effect of starvation is independent of the mushroom bodies, a previously identified sleep locus in the fly brain, and therefore is regulated by distinct neural circuitry.

Drosophila RISC component VIG and its homolog Vig2 impact heterochromatin formation.

Heterochromatin formation plays an important role in gene regulation and the maintenance of genome integrity. Here we present results from a study of the D. melanogaster gene vig, encoding an RNAi complex component and its homolog vig2 (CG11844) that support their involvement in heterochromatin formation and/or maintenance.

Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary.

In Drosophila gonads, Piwi proteins and associated piRNAs collaborate with additional factors to form a small RNA-based immune system that silences mobile elements. Here, we analyzed nine Drosophila piRNA pathway mutants for their impacts on both small RNA populations and the subcellular localization patterns of Piwi proteins. We find that distinct piRNA pathways with differing components function in ovarian germ and somatic cells.

An endogenous small interfering RNA pathway in Drosophila.

Drosophila endogenous small RNAs are categorized according to their mechanisms of biogenesis and the Argonaute protein to which they bind. MicroRNAs are a class of ubiquitously expressed RNAs of approximately 22 nucleotides in length, which arise from structured precursors through the action of Drosha-Pasha and Dicer-1-Loquacious complexes. These join Argonaute-1 to regulate gene expression.