Davina Derous

Obesity results from a gene by environment interaction. Understanding the impacts of environmental factors like diet on body weight/fatness has been greatly facilitated by rodent models. We previously identified the responses of males of five mouse strains fed 30 different diets. Two of these strains showed much greater weight gain and two were resistant. Sixty-six marker SNPs in 57 genes were identified, which have a genetic motif across the four strains reflecting their protection or susceptibility to high-fat diet (HFD). We used two of these strains: C57BL/6 and BALB/c, in a classic approach of cross-breeding the strains, to generate a F1 generation, and then cross-breeding their offspring to generate an F2 population. The F2 males were fed HFD and phenotyped for body weight, fat mass, and energy intake and genotyped for the 66 SNPs. Body mass gain on HFD was influenced by 17 SNPs in 11 genes explaining 87% of the individual variation in weight gain. We then measured gene expression of these 11 genes in 16 tissues of male and female C57BL/6 and Balb/c mice when fed high- or low-fat diets, and in 6 tissues of mice exposed to different levels of calorie restriction, to map their expression profiles. The genes were widely expressed in a diversity of tissues including several not normally suspected to be important for fat storage regulation (e.g., testis, lungs, and spleen) with only four expressed predominantly in the hypothalamus. Body fat regulation is probably more complex than current models focused on the brain–adipose axis suppose.

Harbour porpoises ( Phocoena phocoena ) in the North and Baltic Seas are increasingly impacted by anthropogenic pressures, including underwater noise, fisheries and pollution. These pressures correlate with declining population health, particularly affecting the respiratory system. Growing pathological lesions, partly resulting from high prevalence of parasitic infestations and subsequent diseases, can impair tissue function and oxygen supply to distant end-organs. In this study, we applied an integrative MultiOmics approach (proteomics, metabolomics, lipidomics) to analyse the lungs and muscles of 12 wild harbour porpoises with compromised respiratory health. Our aim was to identify dysregulated biological pathways across omics layers to advance insights into adaptive physiological responses and to define disease-associated molecular signatures that could assist health assessments. Our analysis revealed pronounced immune system and antioxidative responses in the lungs and muscles, indicated by enhanced immunoglobulins, plasmalogens and glutathione-related proteins. In the lungs, high cardiolipin levels and reduced collagen suggest impaired tissue structure and function, while tissue maintenance processes were elevated in the muscle. Both tissues exhibited metabolic alterations suggestive of energetic imbalance, including increased purine metabolism in the lung and decreased lipid metabolism in the muscle. Several dysregulated molecules were shared across tissues, pointing to pathophysiological effects. The proposed disease-associated molecular signatures included the protein SLC25A4, the metabolite O-phosphoethanolamine and the lipid TG O-16:0_16:0_20:4 for the lung, and the protein SPEG, the metabolite pipecolic acid, and the lipid BMP 18:1_22:6 in the muscle. Our findings elucidate the complexity of molecular mechanisms linking anthropogenic and environmental stressors with vulnerability and resilience in a marine sentinel species. Furthermore, this study highlights the potential of integrative omics to define disease-related marker panels, thereby supporting ongoing and future health monitoring and conservation efforts.

Alternative splicing (AS) involves production of several different RNA molecules from a single pre-mRNA. Calorie restriction (CR) is a sustained calorie deficit without malnutrition, which extends health and lifespan. AS is dysregulated in aging but less so following CR, suggesting a role for AS in the beneficial effects of CR. To test the hypothesis that AS is involved in the CR response and explore its tissue specificity, male C57BL/6 mice were exposed to 3 months of graded CR (0–40% at 10% increments) and RNA sequencing data from six tissues (epididymal white adipose tissue [eWAT], liver, hypothalamus, gastrocnemius muscle, testes, and stomach) were analyzed to provide a multi-tissue characterization of differential AS (DAS). The number of differentially expressed splicing regulators increased with CR levels in all tissues but primarily the muscle, eWAT, and liver. The total number of DAS genes also increased with increasing CR levels and was largely tissue-specific. Most DAS genes were not differentially expressed. DAS was functionally integrated across tissues with the same processes being overrepresented: namely, mitochondria and oxidative phosphorylation, transcription and translation, and quality checking and degradation of RNA and especially proteins. This study demonstrates that short-term CR evokes a functionally integrated cross-tissue AS response in mice that is largely independent of expression changes.

Introduction: Marine mammals have long been affected by human activities. Aims: To understand the state of knowledge regarding anthropogenic threats, we systematically mapped peer‐reviewed and grey literature on this topic for 19 marine mammal species found in the North Atlantic. Methods: Searches in 2022 and 2024 resulted in 3390 relevant documents for review. Relevant records were extracted from each document ( n = 6964 records), and threats were grouped into 13 major classes (e.g., climate change, fisheries, acoustic disturbance). Results & Discussion: Of the 19 species, bottlenose dolphins had the most records ( n = 1365), and of the threat classes, fisheries had the most records ( n = 2124), with 59% being associated with mortality. Mapping the study locations highlighted how records were unevenly distributed across each IUCN‐defined species range. Furthermore, species of conservation concern (i.e., globally assessed by IUCN as ‘Endangered’) often received comparatively little study effort. We highlight the species and threats that have to date received limited attention and discuss the potential reasons for disparities in research effort. Conclusion: Increased efforts to understand and appropriately mitigate threats are critical, given the continued co‐existence of marine mammals and human threats in the ‘Anthropocene’.

Calorie restriction (CR) is the reduction in calorie intake while avoiding malnutrition. CR increases longevity and attenuates the development of many age-related diseases, although some unfavorable responses have been reported. In response to CR, energy is withdrawn from tissues to correct the energy deficit. Changes in tissue mass over short-term, 3 months graded CR (STCR) were complex and while most tissues reduced size, some grew. Employing a graded long-term CR (LTCR) protocol in male C57BL/6J mice, tissue utilization, digestive efficiency, bone health and motor coordination was investigated. Mice were restricted by 10%-40% over 580 days/19 months and sacrificed at 24-month old. Control mice fed ad libitum in the 12-hr darkphase only (12AL) were regarded as 0CR. The patterns of tissue weights, digestive efficiency, and bone measurements across the levels of CR were consistent between the STCR and LTCR studies, highlighting shared similarities over both experiments. Notable differences were enhanced utilization of the reproductive accessory organs which could be linked to a shutdown of the reproductive axis; reduced utilization of the spleen, changes in the hierarchy of investment in the digestive organs which was not linked to digestive efficiency. The vital organs were protected from utilization, with preservation of the brain by CR, presumably linked to reduced neurodegeneration and sustained coordination. The favorable effects of LTCR on bone health contradict previous negative reports. Overall, morphological changes determined within 3 months of CR, persisted to 19 months. The pattern of tissue utilization may be critical to the beneficial effects of CR.

Over 25% of cetacean species worldwide are listed as critically endangered, endangered or vulnerable by the International Union for Conservation of Nature. Objective and widely applicable tools to assess cetacean health are therefore vital for population monitoring and to inform conservation initiatives. Novel blubber biomarkers of physiological state are examples of such tools that could be used to assess overall health. Proteins extracted from blubber likely originate from both the circulation and various cell types within the tissue itself, and their expression is responsive to signals originating from other organs and the nervous system. Blubber proteins can therefore capture information on physiological stressors experienced by individuals at the time of sampling. For the first time, we assess the feasibility of applying shotgun proteomics to blubber biopsy samples collected from free-ranging baleen whales. Samples were collected from minke whales (Balaenoptera acutorostrata) (n = 10) in the Gulf of St Lawrence, Canada. Total protein was extracted using a RIPA cell lysis and extraction buffer-based protocol. Extracted proteins were separated and identified using nanoflow Liquid Chromatography Electrospray Ionization in tandem with Mass Spectrometry. We mapped proteins to known biological pathways and determined whether they were significantly enriched based on the proteome profile. A pathway enrichment map was created to visualize overlap in tissue-level biological processes. Amongst the most significantly enriched biological pathways were those involved in immune system function: inflammatory responses, leukocyte-mediated immunity and the humoral immune response. Pathways associated with responses to oxidative stress were also enriched. Using a suite of such protein biomarkers has the potential to better assess the overall health and physiological state of live individuals through remote biopsy sampling. This information is vital for population health assessments to predict population trajectories, and ultimately guide and monitor conservation priorities and initiatives.

Prolonged exposure to food dyes, even for those considered safe for consumption, are known to have toxic effects. However, we lack a proper understanding of the underlying compounds that are responsible for the observed toxicity. In this study, we tested the toxic physiological effects of three common commercially available natural food dyes (red, green, blue), and their main ingredients (turmeric and spirulina), on Drosophila melanogaster oviposition, larval development, and larval foraging behaviour. Larval development and egg-to-adult survival was significantly impacted by blue and green dyes. These effects were recapitulated when flies were fed with increasing concentrations of turmeric and spirulina, suggesting that turmeric is a toxic component of the food dye. Red dye, which contains neither turmeric or spirulina, had little impact on fly health and behaviour. Green and blue food dyes decreased egg laying, an effect similar to that observed in increasing concentrations of turmeric and, to a lesser extent, spirulina. When given a choice, larvae preferred to feed as follows: control > red > blue > green diet patches, a pattern inversely correlating with the previously observed toxicity. Our results show that, despite turmeric being often considered a super food, it can have toxic effects that the impact organismal physiology and health.

Calorie restriction (CR) typically promotes a reduction in body mass, which correlates with increased lifespan. We evaluated the overall changes in survival, body mass dynamics, and body composition following long-term graded CR (580 days/19 months) in male C57BL/6J mice. Control mice (0% restriction) were fed ad libitum in the dark phase only (12-hour ad libitum [12AL]). CR groups were restricted by 10%–40% of their baseline food intake (10CR, 20CR, 30CR, and 40CR). Body mass was recorded daily, and body composition was measured at 8 time points. At 728 days/24 months, all surviving mice were culled. A gradation in survival rate over the CR groups was found. The pattern of body mass loss differed over the graded CR groups. Whereas the lower CR groups rapidly resumed an energy balance with no significant loss of fat or fat-free mass, changes in the 30 and 40CR groups were attributed to higher fat-free mass loss and protection of fat mass. Day-to-day changes in body mass were less variable under CR than for the 12AL group. There was no indication that body mass was influenced by external factors. Partial autocorrelation analysis examined the relationship between daily changes in body masses. A negative correlation between mass on Day 0 and Day +1 declined with age in the 12AL but not the CR groups. A reduction in the correlation with age suggested body mass homeostasis is a marker of aging that declines at the end of life and is protected by CR.