Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis.

Lipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) .

An important role for triglyceride in regulating spermatogenesis.

is a powerful model to study how lipids affect spermatogenesis. Yet, the contribution of neutral lipids, a major lipid group which resides in organelles called lipid droplets (LD), to sperm development is largely unknown. Emerging evidence suggests LD are present in the testis and that loss of neutral lipid- and LD-associated genes causes subfertility; however, key regulators of testis neutral lipids and LD remain unclear.

Consideration of sex as a biological variable in diabetes research across twenty years.

Background: Sex differences exist in the risk of developing type 1 and type 2 diabetes, and in the risk of developing diabetes-associated complications. Sex differences in glucose homeostasis, islet and β cell biology, and peripheral insulin sensitivity have also been reported. Yet, we lack detailed information on the mechanisms underlying these differences, preventing the development of sex-informed therapeutic strategies for persons living with diabetes.

Auxin exposure disrupts feeding behavior and fatty acid metabolism in adult .

The ease of genetic manipulation in using the system has been beneficial in addressing key biological questions. Current modifications of this methodology to temporally induce transgene expression require temperature changes or exposure to exogenous compounds, both of which have been shown to have detrimental effects on physiological processes. The recently described auxin-inducible gene expression system (AGES) utilizes the plant hormone auxin to induce transgene expression and is proposed to be the least toxic compound for genetic manipulation, with no obvious effects on development and survival in one wild-type strain.

Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation.

The rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly.

Auxin Exposure Disrupts Feeding Behavior and Fatty Acid Metabolism in Adult .

The ease of genetic manipulation in using the system has been beneficial in addressing key biological questions. Current modifications of this methodology to temporally induce transgene expression require temperature changes or exposure to exogenous compounds, both of which have been shown to have detrimental effects on physiological processes. The recently described auxin-inducible gene expression system (AGES) utilizes the plant hormone auxin to induce transgene expression and is proposed to be the least toxic compound for genetic manipulation, with no obvious effects on development and survival in one wild-type strain.

Sex biased human thymic architecture guides T cell development through spatially defined niches.

Within the thymus, regulation of the cellular cross-talk directing T cell development is dependent on spatial interactions within specialized niches. To create a holistic, spatially defined map of tissue niches guiding postnatal T cell development we employed the multidimensional imaging platform CO-detection by indEXing (CODEX), as well as CITE-seq and ATAC-seq. We generated age-matched 4-5-month-old postnatal thymus datasets for male and female donors, and identify significant sex differences in both T cell and thymus biology.

Sex differences in islet stress responses support female β cell resilience.

Objective: Pancreatic β cells play a key role in maintaining glucose homeostasis; dysfunction of this critical cell type causes type 2 diabetes (T2D). Emerging evidence points to sex differences in β cells, but few studies have examined male-female differences in β cell stress responses and resilience across multiple contexts, including diabetes. Here, we address the need for high-quality information on sex differences in β cell and islet gene expression and function using both human and rodent samples.

Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics.

Background: Hyperinsulinemia is independently associated with increased risk and mortality of pancreatic cancer. We recently reported that genetically reduced insulin production resulted in ~ 50% suppression of pancreatic intraepithelial neoplasia (PanIN) precancerous lesions in mice. However, only female mice remained normoglycemic, and only the gene dosage of the rodent-specific Ins1 alleles was tested in our previous model.

Sex determination gene regulates the male-female difference in fat storage via the adipokinetic hormone pathway.

Sex differences in whole-body fat storage exist in many species. For example, females store more fat than males. Yet, the mechanisms underlying this sex difference in fat storage remain incompletely understood.

Developmental mechanisms of sex differences: from cells to organisms.

Male-female differences in many developmental mechanisms lead to the formation of two morphologically and physiologically distinct sexes. Although this is expected for traits with prominent differences between the sexes, such as the gonads, sex-specific processes also contribute to traits without obvious male-female differences, such as the intestine. Here, we review sex differences in developmental mechanisms that operate at several levels of biological complexity - molecular, cellular, organ and organismal - and discuss how these differences influence organ formation, function and whole-body physiology.

Female-biased upregulation of insulin pathway activity mediates the sex difference in body size plasticity.

Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work in showed that body size plasticity was higher in females, yet the mechanisms underlying increased female body size plasticity remain unclear. Here, we discover that a protein-rich diet augments body size in females and not males because of a female-biased increase in activity of the conserved insulin/insulin-like growth factor signaling pathway (IIS).

Sexual Dimorphism: Ecdysone Modulates Sex Differences in the Gut.

Sex differences in the Drosophila gut were discovered only recently. Recent work significantly extends our understanding of how steroid hormones specify these male-female differences by revealing a key role for ecdysone in regulating intestinal stem cell proliferation.

A role for triglyceride lipase brummer in the regulation of sex differences in Drosophila fat storage and breakdown.

Triglycerides are the major form of stored fat in all animals. One important determinant of whole-body fat storage is whether an animal is male or female. Here, we use Drosophila, an established model for studies on triglyceride metabolism, to gain insight into the genes and physiological mechanisms that contribute to sex differences in fat storage.

The Sex Determination Gene transformer Regulates Male-Female Differences in Drosophila Body Size.

Almost all animals show sex differences in body size. For example, in Drosophila, females are larger than males. Although Drosophila is widely used as a model to study growth, the mechanisms underlying this male-female difference in size remain unclear.

TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA.

Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and organismal growth in Drosophila.

The nutrient/target-of-rapamycin (TOR) pathway has emerged as a key regulator of tissue and organismal growth in metazoans. The signalling components of the nutrient/TOR pathway are well defined; however, the downstream effectors are less understood. Here, we show that the control of RNA polymerase (Pol) III-dependent transcription is an essential target of TOR in Drosophila.

Drosophila RNA polymerase III repressor Maf1 controls body size and developmental timing by modulating tRNAiMet synthesis and systemic insulin signaling.

The target-of-rapamycin pathway couples nutrient availability with tissue and organismal growth in metazoans. The key effectors underlying this growth are, however, unclear. Here we show that Maf1, a repressor of RNA polymerase III-dependent tRNA transcription, is an important mediator of nutrient-dependent growth in Drosophila.

Control of sexual differentiation and behavior by the doublesex gene in Drosophila melanogaster.

Doublesex proteins, which are part of the structurally and functionally conserved Dmrt gene family, are important for sex determination throughout the animal kingdom. We inserted Gal4 into the doublesex (dsx) locus of Drosophila melanogaster, allowing us to visualize and manipulate cells expressing dsx in various tissues. In the nervous system, we detected differences between the sexes in dsx-positive neuronal numbers, axonal projections and synaptic density.

Characterization of two distinct binding modes between syntaxin 4 and Munc18c.

Interaction of SM (Sec1/Munc18) proteins with their cognate syntaxins represents an important regulatory mechanism of SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor)-mediated membrane fusion. Understanding the conserved mechanisms by which SM proteins function in this process has proved challenging, largely due to an apparent lack of conservation of binding mechanisms between different SM-syntaxin pairs. In the present study, we have identified a hitherto uncharacterized mode of binding between syntaxin 4 and Munc18c that is independent of the binding mode shown previously to utilize the N-terminal peptide of syntaxin 4.