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A recent hypothesis postulates the existence of an 'immune-metabolic depression' (IMD) dimension characterized by metabolic dysregulations. Combining data on metabolomics and depressive symptoms, we aimed to identify depressions associated with an increased risk of adverse metabolic alterations. Clustering data were from 1094 individuals with major depressive disorder in the last 6 months and measures of 149 metabolites from a H-NMR platform and 30 depressive symptoms (IDS-SR30). Canonical correlation analyses (CCA) were used to identify main independent metabolite-symptom axes of variance. Then, for the replication, we examined the association of the identified dimensions with metabolites from the same platform and cardiometabolic diseases in an independent population-based cohort ( = 6572). CCA identified an overall depression dimension and a dimension resembling IMD, in which symptoms such as sleeping too much, increased appetite, and low energy level had higher relative loading. In the independent sample, the overall depression dimension was associated with lower cardiometabolic risk, such as (i.e. per s.d.) HOMA-1B -0.06 (95% CI -0.09 - -0.04), and visceral adipose tissue -0.10 cm (95% CI -0.14 - -0.07). In contrast, the IMD dimension was associated with well-known cardiometabolic diseases such as higher visceral adipose tissue 0.08 cm (95% CI 0.04-0.12), HOMA-1B 0.06 (95% CI 0.04-0.09), and lower HDL-cholesterol levels -0.03 mmol/L (95% CI -0.05 - -0.01). Combining metabolomics and clinical symptoms we identified a replicable depression dimension associated with adverse metabolic alterations, in line with the IMD hypothesis. Patients with IMD may be at higher cardiometabolic risk and may benefit from specific treatment targeting underlying metabolic dysregulations.

Widespread coral bleaching has generally been linked to high water temperatures at larger geographic scales. However, the bleaching response can be highly variable among individual of the same species, between different species, and across localities; what causes this variability remains unresolved. Here, we tracked bleached and non-bleached colonies of Acropora muricata to see if they recovered or died following a stress event inside the semi-enclosed lagoon of Bouraké (New Caledonia), where corals are long-term acclimatized to extreme conditions of temperature, pH and dissolved oxygen, and at a nearby control reef where conditions are more benign. We describe Symbiodiniaceae community changes based on next-generation sequencing of the ITS2 marker, metabolic responses, and energetic reserve measures (12 physiological traits evaluated) during the La Niña warm and rainy summer in 2021. Widespread coral bleaching (score 1 and 2 on the coral colour health chart) was observed only in Bouraké, likely due to the combination of the high temperatures (up to 32°C) and heavy rain. All colonies (i.e., Bouraké and reference site) associated predominantly with Symbiodinaceae from the genera Cladocopium . Unbleached colonies in Bouraké had a specific ITS2-type profile (proxies for Symbiodiniaceae genotypes), while the bleached colonies in Bouraké had the same ITS2-type profile of the reef control colonies during the stress event. After four months, the few bleached colonies that survived in Bouraké (B2) acquired the same ITS2 type profiles of the unbleached colonies in Bouraké. In terms of physiological performances, all bleached corals showed metabolic depression (e.g., P gross and R dark ). In contrast, unbleached colonies in Bouraké maintained higher metabolic rates and energetic reserves compared to control corals. Our study suggests that Acropora muricata enhanced their resistance to bleaching thanks to specific Symbiodiniaceae associations, while energetic reserves may increase their resilience after stress.

Metabolic depression and dormancy (i.e., stopping/greatly reducing activity and feeding) are strategies used by many animals to survive winter conditions characterized by food shortages and cold temperatures. However, controversy exists on whether the reduced metabolism of some fishes at cold temperatures is due to dormancy alone, or also involves active metabolic depression. Thus, we acclimated winter-dormant cunner [ Tautogolabrus adspersus , a north temperate wrasse which in Newfoundland is at the northern limit of its distribution] and winter-active Atlantic salmon ( Salmo salar ) to winter (0°C; 8h light: 16h dark) and summer (10°C; 16h light: 8 h dark) conditions, and measured the thermal sensitivity of ATP-producing and O 2 -consuming processes in isolated liver mitochondria and hepatocytes when exposed in vitro to temperatures from 20 to 0°C and 10 to 0°C, respectively. We found that: 1) liver mitochondrial State 3 respiration and hepatocyte O 2 consumption in cunner were only ~ one-third and two-thirds of that measured in salmon, respectively, at all measurement temperatures; 2) cunner mitochondria also have proton conductance and leak respiration (State 4) values that are only approximately one-third of those in salmon; 3) the mitochondria of cunner show a dramatic reduction in respiratory control ratio (from ~ 8 to 3), and a much greater drop in State 3 respiration, between 10 and 5°C (Q 10 values in 10- and 0°C-acclimated fish of 14.5 and 141.2, respectively), as compared with salmon (3.9 and 9.6, respectively); and 4) lowering temperature from 5 to 0°C resulted in ~ 40 and 30% reductions in hepatocyte O 2 consumption due to non-mitochondrial respiration and Na + -K + -ATPase activity, respectively, in cunner, but not in salmon. Collectively, these results highlight the intrinsic capacity for metabolic depression in hepatocytes and mitochondria of cunner, and clearly suggest that several cellular processes play a role in the reduced metabolic rates exhibited by some fishes at cold temperatures.

Depression is one of the most prevalent psychiatric disorders worldwide, with a steadily increasing incidence and complex, multifactorial pathophysiology. Beyond classical neurochemical mechanisms, growing evidence points to the role of systemic low-grade inflammation and immuno-metabolic disturbances in its development. Gut microbiota dysbiosis has emerged as a key factor linking metabolic, immune, and neuroendocrine pathways, potentially exacerbating neuroinflammation and contributing to the onset and progression of depressive symptoms. Immune activation, which is a result of gut dysbiosis, may play a crucial role in the pathogenesis of immuno-metabolic depression. Thyroid dysfunction appears to be an important, yet insufficiently understood component of this network. Thyroid hormones play a crucial role in regulating metabolism, immune responses, and central nervous system function. Alterations in thyroid function, even within subclinical ranges, have been associated with mood disturbances and may share common inflammatory and metabolic pathways with depression. Furthermore, emerging data suggest that gut microbiota may influence thyroid hormone metabolism, including deiodinase activity, linking dysbiosis with thyroid axis dysregulation. Despite these insights, the integrated interactions between thyroid function, gut microbiota, metabolic syndrome, and inflammation in depression remain largely unexplored. This review explores current evidence to highlight gaps in existing research and synthesizes current knowledge, aiming to clarify mechanisms underlying immuno-metabolic depression. Understanding these relationships may provide a rationale for redefining depression as an immuno-metabolic disorder and support the development of more integrative therapeutic strategies targeting not only the brain, but also the gut-thyroid axis.

Rising sea surface temperatures are increasingly causing breakdown in the nutritional relationship between corals and algal endosymbionts (Symbiodiniaceae), threatening the basis of coral reef ecosystems and highlighting the critical role of coral reproduction in reef maintenance. The effects of thermal stress on metabolic exchange (i.e., transfer of fixed carbon photosynthates from symbiont to host) during sensitive early life stages, however, remains understudied. We exposed symbiotic Montipora capitata coral larvae in Hawaiʻi to high temperature (+2.5°C for 3 days), assessed rates of photosynthesis and respiration, and used stable isotope tracing (4 mM 13 C sodium bicarbonate; 4.5 h) to quantify metabolite exchange. While larvae did not show any signs of bleaching and did not experience declines in survival and settlement, metabolic depression was significant under high temperature, indicated by a 19% reduction in respiration rates, but with no change in photosynthesis. Larvae exposed to high temperature showed evidence for maintained translocation of a major photosynthate, glucose, from the symbiont, but there was reduced metabolism of glucose through central carbon metabolism (i.e., glycolysis). The larval host invested in nitrogen cycling by increasing ammonium assimilation, urea metabolism, and sequestration of nitrogen into dipeptides, a mechanism that may support the maintenance of glucose translocation under thermal stress. Host nitrogen assimilation via dipeptide synthesis appears to be used for nitrogen limitation to the Symbiodiniaceae, and we hypothesize that nitrogen limitation contributes to retention of fixed carbon by favoring photosynthate translocation to the host. Collectively, our findings indicate that although these larvae are susceptible to metabolic stress under high temperature, diverting energy to nitrogen assimilation to maintain symbiont population density, photosynthesis, and carbon translocation may allow larvae to avoid bleaching and highlights potential life stage specific metabolic responses to stress.

Harsh thermal environments in the rocky intertidal zone pose serious physiological and molecular challenges to the inhabitants. Metabolic depression is regarded as an energy-conserving feature of intertidal species. To understand the molecular mechanism of metabolic depression, we investigated physiological and transcriptomic responses in the intertidal snail Echinolittorina radiata. The metabolic rate and expression of most genes were insensitive to temperatures ranging from 33 to 45 °C and then increased with further heating to 52 °C. Different from other genes, the genes involved in heat shock response (HSR) and oxidative stress response (OSR) (e.g., genes encoding heat shock protein 70 (HSP70) and cytochrome P450 protein (CYP450)) kept upregulating during metabolic depression. These high levels of HSR and OSR genes should be important for surviving the harsh thermal environments on the rocky shore. In the population experiencing more frequent moderate heat events, the depression breadth was larger, and the change in magnitude of upregulation was insensitive for HSR genes (e.g., HSP70s) but heat-sensitive for OSR genes (e.g., CYP450s) at the temperature of 37 to 45 °C. These findings indicate that both the thermal sensitivity of HSR and OSR genes and the insensitivity of metabolic genes are crucial for surviving extreme intertidal environments, and different populations of the same species rely on various physiological mechanisms to differing extents to deal with heat stress. The cellular stress response is not a “one size fits all” response across populations largely depending on local thermal regimes.

Physiological responses to temperature are known to be a major determinant of species distributions and can dictate the sensitivity of populations to global warming. In contrast, little is known about how other major global change drivers, such as ocean acidification (OA), will shape species distributions in the future. Here, by integrating population genetics with experimental data for growth and mineralization, physiology and metabolomics, we demonstrate that the sensitivity of populations of the gastropod Littorina littorea to future OA is shaped by regional adaptation. Individuals from populations towards the edges of the natural latitudinal range in the Northeast Atlantic exhibit greater shell dissolution and the inability to upregulate their metabolism when exposed to low pH, thus appearing most sensitive to low seawater pH. Our results suggest that future levels of OA could mediate temperature-driven shifts in species distributions, thereby influencing future biogeography and the functioning of marine ecosystems. Global warming is expected to lead to shifts in species' geographic ranges to track preferred temperatures. Here, the authors show that populations of the common periwinkle vary in their sensitivity to ocean acidification, another major global change driver, which could further restrict range shifts caused by warming.

Increases in thermal variability elevate metabolic rate due to Jensen's inequality, and increased metabolic rate decreases the fitness of dormant ectotherms by increasing consumption of stored energy reserves. Theory predicts that ectotherms should respond to increased thermal variability by lowering the thermal sensitivity of metabolism, which will reduce the impact of the warm portion of thermal variability. We examined the thermal sensitivity of metabolic rate of overwintering Erynnis propertius (Lepidoptera: Hesperiidae) larvae from a stable or variable environment reared in the laboratory in a reciprocal common garden design, and used these data to model energy use during the winters of 1973-2010 using meteorological data to predict the energetic outcomes of metabolic compensation and phenological shifts. Larvae that experienced variable temperatures had decreased thermal sensitivity of metabolic rate, and were larger than those reared at stable temperatures, which could partially compensate for the increased energetic demands. Even with depressed thermal sensitivity, the variable environment was more energy-demanding than the stable, with the majority of this demand occurring in autumn. Autumn phenology changes thus had disproportionate influence on energy consumption in variable environments, and variable-reared larvae were most susceptible to overwinter energy drain. Therefore the energetic impacts of the timing of entry into winter dormancy will strongly influence ectotherm fitness in northern temperate environments. We conclude that thermal variability drives the expression of metabolic suppression in this species; that phenological shifts will have a greater impact on ectotherms in variable thermal environments; and that E. propertius will be more sensitive to shifts in phenology in autumn than in spring. This suggests that increases in overwinter thermal variability and/or extended, warm autumns, will negatively impact all non-feeding dormant ectotherms which lack the ability to suppress their overwinter metabolic thermal sensitivity.

Thermal acclimation is hypothesized to offer a selective advantage in seasonal habitats and may underlie disparities in geographic range size among closely‐related species with similar ecologies. Understanding this relationship is also critical for identifying species that are more sensitive to warming climates. Here, we study North American plethodontid salamanders to investigate whether acclimation ability is associated with species’ latitudinal extents and the thermal range of the environments they inhabit. We quantified variation in thermal physiology by measuring standard metabolic rate (SMR) at different test and acclimation temperatures for 16 species of salamanders with varying latitudinal extents. A phylogenetically‐controlled Markov chain Monte Carlo generalized linear mixed model (MCMCglmm) was then employed to determine whether there are differences in SMR between wide‐ and narrow‐ranging species at different acclimation temperatures. In addition, we tested for a relationship between the acclimation ability of species and the environmental temperature ranges they inhabit. Further, we investigated if there is a trade‐off between critical thermal maximum (CTMax) and thermal acclimation ability. MCMCglmm results show a significant difference in acclimation ability between wide and narrow‐ranging temperate salamanders. Salamanders with wide latitudinal distributions maintain or slightly increase SMR when subjected to higher test and acclimation temperatures, whereas several narrow‐ranging species show significant metabolic depression. We also found significant, positive relationships between acclimation ability and environmental thermal range, and between acclimation ability and CTMax. Wide‐ranging salamander species exhibit a greater capacity for thermal acclimation than narrow‐ranging species, suggesting that selection for acclimation ability may have been a key factor enabling geographic expansion into areas with greater thermal variability. Further, given that narrow‐ranging salamanders are found to have both poor acclimation ability and lower tolerance to warm temperatures, they are likely to be more susceptible to environmental warming associated with anthropogenic climate change. Thermal acclimation is hypothesized to offer a selective advantage in seasonal habitats and may underlie disparities in geographic range size among closely related species with similar ecologies. Here, we find wide‐ranging salamanders exhibit a greater capacity for thermal acclimation than narrow‐ranging species. Associations between acclimation ability and thermal environments indicate an important role for physiological tolerances in range expansions and the susceptibility of heat‐intolerant narrow‐ranging species to rises in global temperature.