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Biology subjects

Wanek, T.

Publications and source records attributed to Wanek, T..

3 recordsLinked to original sources

Stress-induced Metabolic Remodeling of Adipose and Brain Tissue revealed by Positron Emission Tomography

Stress impacts our health and triggers physiological adaptations, yet the metabolic programs engaged during stress remain incompletely understood. To fill this knowledge gap, we utilized total-body positron emission tomography (PET), multi-OMICS, and endocrine profiling to assess how various murine stress models affect systemic metabolic remodeling. We found that acute immobilization and surgery activate brown adipose tissue as part of the stress response, independently of hypothermia, thereby acting as a highly stress-sensitive metabolic hub. Additionally, we identified stress-specific hypo- and hypermetabolic signatures in different brain regions, and distinguished networks between brain and adipose tissue depots across the different stress groups. Our work presents a novel perspective on stress and its mobilization of metabolic resources and identifies PET imaging of brain and adipose tissue as a valuable, minimally invasive technique for tracking metabolic stress responses in mice, with relevance for animal welfare and disease models, and translational impact for mental health studies and preventive medicine.

physiology↗

Injury size regulates glucose allocation locally and systemically during vertebrate tissue regeneration

Tissue regeneration requires careful allocation of metabolic resources, yet how organisms adjust this allocation in response to varying amounts of tissue loss remains poorly understood. Here, we show that the regenerative metabolic response is not fixed: the size of an injury regulates how glucose is allocated at both local and organism-wide levels. We first demonstrate that tail regeneration requires glucose metabolism in the axolotl (Ambystoma mexicanum), a salamander capable of regenerating centimetre-scale tissues. We then mapped glucose uptake in axolotls regenerating from small or large tail injuries using positron emission tomography/magnetic resonance imaging (PET/MRI) and the radiolabelled glucose analogue [18F]FDG. Glucose uptake was elevated in regenerating tails compared to uninjured tails. During early regeneration, larger injuries induced higher glucose uptake than smaller injuries, correlating with faster regenerative outgrowth. Larger injuries also increased glucose uptake in distant organs, indicating a systemic metabolic response. Together, our findings suggest that metabolic responses tuned to injury size underlie faithful tissue regeneration and establish PET/MRI as a powerful approach for studying whole-body metabolic dynamics in large regenerating vertebrates.

developmental biology↗

CD8+ T cells regulate the bioenergetic reprogramming of lymphoid organs and the heart during viral infection

The activation of the immune system is a bioenergetically-costly process1. Yet, essential bodily functions require a continuous energy supply, imposing energy constraints and trade-offs between competing processes2. Our understanding of the underlying bioenergetic adaptations reconciling rapid immune activation with other vital processes remains scarce. 3-6 Here, by using experimental models of viral infections, we identified an unexpected CD8+ T cell-driven redistribution of energy substrates between lymphoid organs and the heart. Viral infection promoted systemic hypoglycaemia and ketogenesis, together with systemic reallocation of energy substrates. Across organs analysed, secondary lymphoid organs and the heart showed the most dramatic changes. The former increased glucose uptake and oxidation while the heart showed the opposite, switching to preferential fatty acid utilization. These bioenergetic adaptations were absent in infected mice lacking CD8+ T cells or with T cells lacking the glucose transporter GLUT1. Pharmacological inhibition of fatty acid oxidation forced a systemic switch to glucose oxidation. This was associated with metabolic decompensation, reduced cardiac energetics, left ventricular stress, and mortality in otherwise nonlethal viral infections. Our results reveal how the energetic cost of immune cell activation imposes bioenergetic adaptations on non-lymphoid organs, posing a major challenge for the heart by completely relying on fatty acids.

immunology↗