Biology subjects

Simpson, S. J.

Publications and source records attributed to Simpson, S. J..

6 recordsLinked to original sources

bioRxiv2024

The propensity of fructose to induce metabolic dysfunction is dependent on the baseline diet, length of the dietary exposure, and sex of the mice.

Background/ObjectivesNumerous studies have implicated high intake of sugar, particularly fructose, with the development of obesity and metabolic complications. On the other hand, fructose from fruits and vegetables has undisputed benefits for metabolic health. This paradox questions how the same fructose molecule can be associated with detrimental health effects in some studies and beneficial in others. MethodsTo answer this question, male and female mice were fed different normal chow diets and provided 30% fructose solution in water. ResultsFructose-supplemented male mice on the Boston Chow Diet (BCD=23% protein, 22% fat, 55% carbs) gained weight, developed glucose intolerance and hepatic steatosis. In contrast, male mice on the Lexington Chow Diet (LXD=24% protein, 18% fat, 58% carbs) did not gain weight, remained glucose tolerant, and had normal hepatic lipid content when supplemented with fructose. Furthermore, fructose-fed male mice on a Low-Fat Diet (LFD=20% protein, 10% fat, 70% carbs) didnt gain weight, but once switched to the BCD, they gained weight, exhibited worsening liver steatosis, and more advanced hepatic insulin resistance. The effects of fructose are sex-dependent, as female mice didnt gain weight and remained insulin-sensitive when given fructose on BCD, despite developing hepatic steatosis. ConclusionsThe differences in metabolic outcomes correlate with the propensity of the baseline diet to suppress hepatic ketohexokinase expression and the de novo lipogenesis pathway. This is likely driven by the dietary fat-to-carbohydrate ratio. Thus, metabolic dysfunction attributed to fructose intake is not a universal outcome; rather, it depends on the baseline diet, sex, and exposure length.

molecular biology↗

bioRxiv2024

Combining in vivo and in vitro approaches to better understand host-pathogen interactions

Nutrition often shapes the outcome of host-parasite interactions, however understanding the mechanisms by which this occurs is confounded by the intimate nature of the association and by the fact that the host and parasite may compete for the same limiting nutrients. One way of disentangling this interaction is to combine in vivo and in vitro approaches. Here, we explore the role of host nutrition in determining the outcome of infections using a model insect-bacterium system: the cotton leafworm Spodoptera littoralis and the blood-borne bacterium Xenorhabdus nematophila. Spodoptera littoralis larvae were reared on one of a series of 20 chemically-defined diets ranging in their protein: carbohydrate (P:C) ratio and caloric density. They were then challenged with either a fixed dose of X. nematophila cells (live or dead) or were sham-injected. Survivorship of larvae challenged with live bacterial cells was strongly dependent on the protein levels of the diet, with mortality being highest on low-protein diets. This trend was reflected in the bacterial growth rate in vivo, which peaked in larvae fed low-protein diets. To determine whether in vivo bacterial growth rates were driven by blood nutrients, rather than an enhanced host immune response, we generated 20 synthetic haemolymphs ( nutribloods) that mimicked the nutritional content of host blood. Bacterial growth rate in the nutribloods was also negatively impacted by their protein content suggesting that nutrient availability and not host immunity was driving the interaction. By comparing standardized bacterial growth rates in vivo and in vitro, we conclude that the outcome of this host-parasite interaction is largely driven by bottom-up effects of nutrients on bacterial growth, rather than by top-down effects of nutrients on host-mediated immune responses. The outcome of host-parasite interactions is typically assumed to be strongly determined by the host immune response. The direct effects of nutrition have been underexplored and may have broad consequences for host-parasite interactions across taxa.

ecology↗

bioRxiv2023

eNODAL: an experimentally guided nutriomics data clustering method to unravel complex drug-diet interactions

Unraveling the complex interplay between nutrients and drugs via their effects on omics features could revolutionize our fundamental understanding of nutritional physiology, personalized nutrition and ultimately human health-span. Experimental studies in nutrition are starting to use large-scale omics experiments to pick apart the effects of such interacting factors. However, the high dimensionality of the omics features, coupled with complex fully-factorial experimental designs together pose a challenge to the analysis. Current strategies for analyzing such types of data are based on between-feature correlations. However, these techniques risk overlooking important signals that arise from the experimental design and produce clusters that are hard to interpret. We present a novel approach for analyzing high-dimensional outcomes in nutriomics experiments, termed experiment-guided NutriOmics DatA cLustering (eNODAL). This three-step hybrid framework takes advantage of both ANOVA-type analyses and unsupervised learning methods to extract maximum information from experimental nutriomics studies. First, eNODAL categorizes the omics features into interpretable groups based on the significance of response to the different experimental variables using an ANOVA-like test. Such groups may include the main effects of a nutritional intervention, and drug exposure, or their interaction. Second, consensus clustering is performed within each interpretable group to further identify subclusters of features with similar response profiles to these experimental factors. Third, eNODAL annotates these subclusters based on their experimental responses and biological pathways enriched within the subcluster. We validate eNODAL using data from a mouse experiment to test for the interaction effects of macronutrient intake and drugs that target aging mechanisms in mice.

bioinformatics↗

bioRxiv2021

Anisotropic interaction and motion states of locusts in a hopper band

Swarming locusts present a quintessential example of animal collective motion. Juvenile locusts march and hop across the ground in coordinated groups called hopper bands. Composed of up to millions of insects, hopper bands exhibit aligned motion and various collective structures. These groups are well-documented in the field, but the individual insects themselves are typically studied in much smaller groups in laboratory experiments. We present the first trajectory data that detail the movement of individual locusts within a hopper band in a natural setting. Using automated video tracking, we derive our data from footage of four distinct hopper bands of the Australian plague locust, Chortoicetes terminifera. We reconstruct nearly twenty-thousand individual trajectories composed of over 3.3 million locust positions. We classify these data into three motion states: stationary, walking, and hopping. Distributions of relative neighbor positions reveal anisotropies that depend on motion state. Stationary locusts have high-density areas distributed around them apparently at random. Walking locusts have a low-density area in front of them. Hopping locusts have low-density areas in front and behind them. Our results suggest novel insect interactions, namely that locusts change their motion to avoid colliding with neighbors in front of them.

animal behavior and cognition↗

bioRxiv2019

Restriction of essential amino acids dictates the systemic response to dietary protein dilution

Dietary protein dilution (DPD) promotes metabolic remodelling and health but the precise nutritional components driving this response remain elusive. Here we demonstrate that dietary amino acids (AA) are sufficient and necessary to drive the response to DPD. In particular, the restriction of dietary essential AA (EAA) supply, but not non-EAA, drives the systemic metabolic response to total AA deprivation. Furthermore, systemic deprivation of Thr and Trp, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Thr is also potentially limiting in low-protein diet fed humans, and dietary Thr restriction (DTR) retarded the development of obesity-associated metabolic dysfunction in mice. Liver-derived fibroblast growth factor 21 was required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of Thr biosynthetic capacity reversed the systemic response to DTR. Taken together, our studies demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.

physiology↗

bioRxiv2018

Macronutrients modulate resistance to infection and immunity in Drosophila

Immunity and nutrition are two essential modulators of individual fitness However, while the implications of immune function and nutrition on an individual s lifespan and reproduction are known, the interplay between feeding behaviour, infection, and immune function, remains poorly understood. In this study, we used the fruit fly, Drosophila melanogaster, to investigate how infection through septic injury modulates nutritional intake, and how macronutrient balance affects survival to infection by the pathogenic Gram-positive bacterium Micrococcus luteus. Our results show that infected flies maintain carbohydrate intake, but reduce protein intake, thereby shifting from a protein-to-carbohydrate (P:C) ratio of ~1:4 to ~1:10 relative to non-infected and sham-infected flies. Strikingly, we found that the proportion of flies dying after M. luteus infection was significantly lower when flies were fed a low-P high-C diet, revealing that flies shift their macronutrient intake as means of nutritional self-medication against bacterial infection. This is likely due to the effects of macronutrient balance on the regulation of the constitutive expression of innate immune genes, as a low-P high-C diet was linked to an up-regulation in the expression of key antimicrobial peptides. Together, our results reveal the intricate relationship between macronutrient intake and resistance to infection, and integrate the molecular cross-talk between metabolic and immune pathways into the framework of nutritional immunology.

physiology↗