Mammalian hibernation is a physiological and behavioural adaptation that permits survival during seasonal periods of energy shortage via a combination of pre-hibernal energy storage and hibernal metabolic depression (torpor). There is both seasonal preparation for the expression of torpor, and the spontaneous termination of hibernation at the end of the season. Small hibernating mammals repeatedly alternate between the torpid state, and the interbout euthermic state over a relatively short timescale (days-weeks) for the entire hibernation season. This is known as torpor arousal cycling (T-A cycling). Hibernation is therefore characterised by extreme shifts in energy homeostasis. Rheostasis is term referring to a change in a regulated homeostatic level or set point. Hibernation can be viewed as rheostasis both over the annual timescale of the seasonal hibernation cycle and over the much shorter T-A cycle. The brain sites through which these homeostatic shifts are controlled have not been identified. A specialised glial cell type lining the 3rd ventricle of the mediobasal hypothalamus (MBH tanycytes), are of particular interest. MBH tanycytes have a privileged anatomical position contacting the periphery and the hypothalamic control centres of the brain. They have documented sensing and signalling function within the hypothalamus, making them a strong candidate cell type for the control of energy homeostasis. Here, I propose that the MBH tanycytes could act as a "rheostat", shifting their sensitivity to metabolic feedback over the annual timescale and the T-A cycle, and therefore are a promising cell type to investigate in relation to the brain control of hibernation.

Small mammals in the temperate zone often face environmental changes such as photoperiod and temperature, that may influence hematological parameters, innate immunity, and cytokines, all of which are indicative of host immunity and reflective of overall health. In order to test the winter immunoenhancement hypothesis which states that animals use short day length to up-regulate immune responses in winter, 34 adult female striped hamsters (Cricetulus barabensis) were randomly divided into long day (16 L:8D) and short day (8 L:16D) treatment groups, which were further assigned to either mild (23 ± 1℃) or low temperature (5 ± 1℃) treatment groups, respectively. We found that low temperature treatment, regardless of photoperiod, significantly increased red blood cell (RBC), and haematocrit (PCV), haemoglobin concentrations (HGB), and short photoperiod also increased RBC and PCV, implying their enhancing effect on the oxygen-transport in hamsters. However, low temperature treatment, but not photoperiod, decreased white blood cells (WBC), intermediate granulocytes (MID), percent of intermediate granulocytes (MID%), neutrophil granulocytes (GRAN), and percent of neutrophil granulocytes (GRAN%), suggesting its suppressive effect on immune function. In addition, bacteria killing capacity indicative of innate immunity increased in short day hamsters, which supported the winter immunoenhancement hypothesis. Interleukin-4 (IL-4) was reduced in low temperature-adapted hamsters, while IL-2, tumor necrosis factor alpha (TNF-α), interferon-γ (INF-γ) were not affected by low temperature treatment or short day length. Overall, low temperature and photoperiod exerted different influences on hematological parameters, innate immunity, and cytokines in striped hamsters.

Climate change is predicted to continue elevating regional sea surface temperatures (SST) and increase the frequency and severity of localized heating events, phenomena which may threaten the biodiversity, integrity, and function of tropical coral reef ecosystems. The primary objective of this study was to determine physiological and behavioral responses to elevated SST in a Hawaiian surgeonfish, the yellow tang, Zebrasoma flavescens. We assessed standard metabolic rate (SMR), maximum metabolic rate (MMR), aerobic scope (AS), and swimming performance, as well as temperature preference (T) in this ecologically and economically important coral reef fish. The Z. flavescens were acclimated to either the current maximum monthly summer SST around O'ahu, 27 °C, or an elevated SST, 31 °C. Acclimation temperature had no significant effect on SMR, MMR, AS, or swimming performance. Temperature preference was tested over a 24-hour period in an annular preference chamber with a gradient ranging from 24 to 34 °C. Our study found that Z. flavescens in both acclimation temperatures had a similar T (median) of 27 °C with first and third quartiles of 25.7 to 29 °C. Analysis of relative use of available temperatures (compositional analysis) indicated a preference for the lowest available temperatures of 24 to 26 °C in both acclimation groups. These findings indicate that Z. flavescens can completely compensate AS and swimming ability to the elevated SST conditions, although T remains near or below the current summer SST, suggesting other factors explain behavioral temperature preference.

Deep metabolic transitions promoted by anoxia and diapause are tolerated for years by embryos of the brine shrimp, Artemia franciscana, whereas even short metabolic disruptions in mammals are accompanied by bursts of reactive oxygen species (ROS) that cause tissue damage during ischemia-reperfusion. We hypothesized mitochondria from these embryos are mechanistically poised to avoid ROS bursts and the associated oxidative stress during metabolic recovery. Isolated mitochondria that exhibited robust functional coupling were exposed to anoxia-reoxygenation (A/R) or continuous normoxia. HO efflux was statistically identical between A/R versus normoxia groups (p = 0.221). Addition of auranofin and dinitrochlorobenzene, inhibitors of ROS scavenging pathways, promoted a five-fold increase in HO release for the normoxic mitochondria, which confirmed that scavenging mechanisms substantially suppress routine ROS efflux. Yet when these same inhibitors were added to the A/R group, maximum HO efflux was no greater than for normoxia. Treatment with rotenone, an inhibitor of Complex I and reverse electron transport (RET), produced only a modest decrease in HO efflux. This result indicates that RET, a major contributor to ROS bursts in mammalian mitochondria, is not stimulated by A/R in A. franciscana. Lack of aconitase inactivation, protein carbonyl accumulation, and lipid hydroperoxide production demonstrate that bouts of A/R do not cause significant oxidative damage in A. franciscana mitochondria. Finally, the capacity to downregulate Complex I activity through active-deactive conformations was tested and is not operative. These data collectively suggest that Complex I from A. franciscana may not possess the capacity for RET and the associated ROS surge.

Fish face a functional trade-off at the gills between minimizing ion movement and maximizing oxygen uptake - the osmorespiratory compromise, but the extent of this trade-off remains poorly understood in elasmobranchs. Using the Pacific dogfish shark, we assessed the impacts of progressive hypoxia in animals acclimated to 25, 30 and 36 ppt for 4 days at 12 °C. Plasma osmolality increased with water osmolality at 36 ppt (osmoconformation) and decreased at 25 ppt. Plasma urea decreased at 25 ppt, though to a lesser extent than plasma Cl, while plasma urea increased to a greater extent than plasma Cl at 36 ppt. In normoxia, oxygen consumption rate (MO) was elevated by 60% at 36 ppt, and ventilatory index (frequency x amplitude) was elevated by 70%, reflecting increases in both components of ventilation, but these parameters remained unchanged in sharks exposed to 25 ppt. During progressive hypoxia, MO and ventilation exhibited different patterns at the three salinities, but in all three, MO fell linearly below a water PO of ~ 80 Torr (10.7 kPa), indicating oxyconformation. Under hypoxia (45 to 5 Torr; 6.0 to 0.7 kPa) MO was the same at all salinities, while ventilatory amplitude was elevated at both 25 and 30 ppt. At 36 ppt, frequency decreased during hypoxia. Ventilatory index increased during hypoxia only at 30 ppt and not at the other salinities. From these data it is clear that dogfish sharks face an osmorespiratory compromise balancing the needs for urea retention against those of O uptake.

Limited freshwater availability and increasing salinisation of inland water bodies pose significant challenges to sustainable aquaculture. In the context of climate change, the use of inland saline water (ISW) offers a practical alternative, enabling the expansion of aquaculture into water-scarce and non-arable regions. The combined effects of elevated temperature and salinity on genetically improved farmed tilapia fingerlings (initial weight: 2.73 ± 0.02 g) were evaluated after a 60-day experimental trial. Fish were distributed across six treatments in triplicates (n = 15/tank): Control (T X FW), T1 (T × 10), T2 (T × 15), T3 (T X FW), T4 (T × 10), T5 (T × 15 ), representing combinations of temperature (28.5-33.5 °C) and salinity (Freshwater, 10 ppt, or 15 ppt). Growth and physiological parameters were assessed after 60-day rearing in the designated treatments. Results revealed significant interactive effects on growth, with control achieving the highest final body weight (18.26 g) while T5 showed a 47% reduction. Hepatosomatic index showed no significant response to either factor, while the viscero-somatic index increased from 7.54% in control to 8.43% at 15 ppt. Haematological parameters increased with stressors, with T5 treatment showing a 32% increase in WBC count compared to the control. Serum protein profiles showed complex responses, with total protein in T × 10 (10.82 g/dL) being higher than in the control (~ 2.7 times). Branchial LDH activity remained unchanged across treatments, while hepatic LDH activity in T × 15 was 3-fold higher than that of the control. Aminotransferases (AST, ALT) and serum lipids also showed a similar trend, peaking at T5. Branchial NKA enzyme activity increased 5-fold in T5 compared to the control. Hepatic igf1 expression was downregulated with increasing salinity (70% reduction at 15 ppt) and temperature. These findings demonstrate that combined exposure to elevated temperature and salinity impairs growth and physiological alterations in GIFT tilapia, with implications for inland saline aquaculture under climate change scenarios.

East Pacific green turtles (Chelonia mydas) inhabit tropical and subtropical waters along the western coast of the Americas. This population uses the Gulf of California, Mexico, as a primary area for feeding and refuge, where they face various stressors. This study aimed to establish hematological reference intervals for healthy green turtles in this area (n = 326), as well as evaluate seasonal variations in blood parameters and compare values between healthy turtles and individuals affected by fibropapillomatosis (n = 25). Reference intervals for hematological analytes were estimated following the American Society for Veterinary Clinical Pathology guidelines. Seasons significantly influenced hemoglobin, hematocrit and heterophils, which were lower during the cold season, while monocytes and eosinophils were significantly higher. These variations were attributed to physiological effects of cooler water temperatures, shorter photoperiods, reduced food intake, and immune response to seasonal stressors during the colder months. Turtles with visible fibropapillomatosis tumors were mildly affected, with tumor sizes not exceeding 5-cm diameter (tumor score 1). While significant alterations were observed in some hematological analytes (i.e., lower hemoglobin and hematocrit, and higher WBC, lymphocytes and heterophil: lymphocyte ratio), these values remained within the reference intervals estimated for healthy turtles. Additionally, no abnormalities commonly associated with severe fibropapillomatosis were observed, suggesting minimal structural or functional damage at tumor score 1 stage. This baseline information will help evaluate intra-population trends, assess potential impacts from future ecosystem changes, and develop effective conservation strategies for this threatened population.

This study investigates the scaling exponent (b) of standard metabolic rate (SMR) in western mosquitofish, focusing on both among- and within-individual levels while exploring the influences of growth and sex on within-individual b values. For group-reared fish, the intraspecific b value was determined by analyzing the relationship between SMR and body mass across individuals of varying sizes and ages. For individually-reared fish, the SMR of each fish was measured five times between 60 and 150 days of age, and both among- and within-individual b values were calculated. The among- and within-individual b values of the individually-reared fish across ages did not differ significantly from the intraspecific b value of the group-reared fish. The among-individual b values showed a nonsignificant V-shaped change with increasing age in the individually-reared fish, suggesting that the ontogenetic decrease of b value related to growth slowdown can be reversed post-maturation. Although there was no significant difference in within-individual b values between females and males, greater variability was observed among females. Furthermore, the relationship between within-individual b values and specific growth rate displayed sexual dimorphism, with females exhibiting a stronger positive correlation, suggesting higher energy demands associated with both somatic and gonadal development compared to males.

High-fat diets (HFDs) are increasingly being studied in aquaculture because of their complex species-specific effects on fish physiology. While moderate fat levels can lower feed costs, supply essential fatty acids, and promote growth in some carnivorous and fast-growing species, excessive fat intake is linked to negative outcomes, such as impaired lipid metabolism, hepatic steatosis, immune suppression, and reduced growth. Although some studies have reported improved growth in zebrafish and other tolerant species, most finfish exhibited growth inhibition, metabolic dysfunction, and greater disease susceptibility under prolonged HFD exposure. Mechanistically, HFDs disrupt lipid homeostasis by downregulating lipolytic genes (e.g., cpt1a, pparα, and atgl) and upregulating lipogenic genes (e.g., srebp-1, fas, and acc), resulting in hepatic lipid accumulation. These shifts are associated with mitochondrial dysfunction, reduced fatty acid β-oxidation, oxidative stress, and activation of ER stress pathways such as ire1/xbp1. HFDs also stimulate inflammatory pathways through tlrs, nf-κb, and cytokines (il-6, tnf-α, and il-1β), contributing to immunometabolic imbalances. Additionally, HFDs negatively affect intestinal health by altering morphology, weakening barrier function, and disrupting microbiota composition, leading to poor nutrient absorption and increased infection risk. This review provides current evidence of HFD-induced changes in growth, immunity, lipid metabolism, mitochondrial function, and gut health in finfish. This emphasizes the importance of species-specific dietary fat optimization to improve feed efficiency, safeguard fish health, and ensure sustainable aquaculture practices.

During hibernation, golden-mantled ground squirrels (Spermophilus lateralis) breathe in distinct multi-breath episodes separated by prolonged periods of apnea. We hypothesized that vagal afferent feedback from pulmonary stretch receptors, and N-methyl-D-aspartate (NMDA) type glutamate receptor-mediated processes in the pons are instrumental in the production of this breathing pattern and analyzed the effects of disrupting vagal feedback, and blockade of NMDA type receptors by the non-competitive antagonist (+)-5-methyl-10,11-dihydro-5 H-dibenzo[a, d]-cyclohepten-5,10-imine maleate (MK-801), on breathing pattern and ventilatory responses to hypoxia and hypercapnia in ground squirrels during natural hibernation. The hibernating squirrels breathed episodically and exhibited a robust ventilatory response to hypercapnia but not hypoxia. The breathing episode (not the individual breath) was the major regulated variable in the breathing pattern. Vagal blockade did not alter breathing on a breath-by-breath basis but did decrease the breaths per episode decreasing overall ventilation and abolished the hypercapnic ventilatory response. MK-801 increased the number of breaths per episode and the frequency of breathing during episodes but did not alter overall ventilation nor the hypercapnic ventilatory response. Combined treatment with MK-801 and vagal blockade abolished episodic breathing but also initiated arousal from hibernation. The data suggest that in golden-mantled ground squirrels hibernating at 5°C body temperature, vagal feedback and NMDA receptor mediated processes still modulate breathing. Whether they are responsible for clustering breaths into episodes is suggested but remains equivocal.

Oxidative damage and inflammation are mechanisms proposed to contribute to physiological senescence. Variation in oxidative damage and inflammation may reflect differential allocation of resources to reproduction and survival, contributing to differences in species-typical longevity and resulting from distinct, evolved life-history strategies. To investigate the link between molecular processes and physiological senescence, we compared urinary biomarkers of oxidative stress (8-isoprostane and 8-OHdG) and inflammation (neopterin) in a cross-sectional sample of two species that differ in life-history schedules: the relatively fast-paced ring-tailed lemur (Lemur catta; n = 41; ages = 1-32 years) and slow-paced Coquerel's sifaka (Propithecus coquereli; n = 49; ages = 1-27 years). Consistent with a faster life-history pace, ring-tailed lemurs showed significantly higher average levels of DNA damage than did sifakas (8-OHdG: ring-tailed lemur mean: 18.6 ± 10.3 ng/mg Cr, sifaka mean 8.0 ± 9.0 ng/mg Cr, p = 0.001). Species differences in lipid damage and inflammatory biomarkers were not significant (8-isoprostane: ring-tailed lemur mean: 0.5 ± 0.3 ng/mg Cr, sifaka mean: 0.3 ± 0.2 ng/mg Cr, p = 0.11), although sifakas tended to show greater inflammation (neopterin: ring-tailed lemur mean: 0.01 ± 0.02 ng/mg Cr, sifaka mean: 0.02 ± 0.02 ng/mg Cr; p = 0.14), which may reflect health challenges faced by this species in captivity. Contrary to our predictions, neither species showed age-related change in either marker of oxidative stress. Thus, although lemurs appear not to experience an increase in the rate of oxidative damage incurred with age, we cannot exclude the possibility that accumulated damage contributes to aging. Neither lemur species exhibited age-related change in inflammation; if anything, contrary to our prediction, ring-tailed lemurs showed marginal declines in inflammation with age. This finding, consistent with a few recent studies of other non-human primates, suggests that lemurs avoid the phenomenon of "inflammaging" widely observed in humans.

Hibernation is an adaptive strategy that conserves energy in response to environmental challenges. While mitochondrial proteomic adaptations are well-documented in deep hibernators, the proteomic changes underlying daily torpor remain less clear. We investigated mitochondrial proteomic adaptations in the liver of a daily hibernator, the Djungarian hamster (Phodopus sungorus), across different hibernation phases. Hamsters were maintained under long-day (summer) or short-day photoperiods (winter), to induce torpor. Livers from summer, torpor, and interbout euthermia phases were analyzed by liquid chromatography-mass spectrometry with labelled standards of mitochondrial energy metabolism proteins, resulting in accurate quantitative proteomics. Differential protein regulation was assessed using empirical Bayes models with false discovery rate correction. Increased abundance of fatty acid oxidation enzymes during hibernation indicates a seasonal metabolic shift toward lipid utilization, similar to deep hibernators. Additionally, torpor featured elevated complex II subunits and tricarboxylic acid cycle enzymes representing evolutionary adaptations specific to daily torpor, likely to cater higher energy demands necessary to maintain torpid body temperature above 15 °C in near-freezing ambient temperatures. This represents evolutionary adaptations specific to daily torpor. Increased levels of the mitochondrial uncoupling-related solute carrier family 25 member 5 (SLC25A5) may be responsible for both thermogenesis and limiting production of reactive oxygen species. Furthermore, the selective upregulation of SOD2 during torpor underscores its critical role in mitigating reactive oxygen species accumulation during metabolic transitions. In summary, daily torpor exhibits unique mitochondrial proteomic adaptations that distinguish it from deep torpor, which may be necessary to enable torpor at body temperatures well above the ambient temperature.

Cyclic changes in snowshoe hare (Lepus americanus) fecundity have been attributed to changes in winter forage availability and predation pressure. Disentangling how nutrition and predation pressure affect snowshoe hare physiology is complex. As an herbivore of the northern boreal forests, snowshoe hares cope with extreme seasonal changes in diet, ambient temperature, and energy demands. We examined seasonal variation in the body condition index, blood biomarkers indicative of nutritional status, and fecal cortisol metabolite concentrations, in snowshoe hares across five ecologically distinct times of year in relation to adult survival rates. Snowshoe hares sampled from a high-density population in northern Alaska during 2018 showed decreases in survival and in plasma concentrations of total protein (TP), blood urea nitrogen (BUN), hematocrit (Hct), Chloride (Cl) and glucose during March and October. Increased survival and concentrations of Cl, TP, BUN, Hct, sodium (Na) and glucose were observed during August. Decreases in mass and survival from August to October suggest limited forage. Increases in TP, BUN, Hct and glucose in December suggest higher metabolic turnover. Fecal cortisol concentrations were not significantly associated with seasonal nutritional condition. A two-fold increase in mean cortisol was observed during August, potentially associated with energetically costly processes such as increased movement and reproduction. This work provides seasonal observations of snowshoe hare plasma biochemical values (N = 164) indicative of nutritional status, and supports the idea of using a collective biomarker approach to advance our understanding of how seasonality may play a role in snowshoe hare physiology.

The pineal gland synchronizes the body's circadian rhythms by producing melatonin in response to changes in the light-dark cycle. Our study evaluated how prolonged exposure to constant lighting (LL) or darkness (DD) affects pineal physiology by monitoring the transcription of genes critical for rhythmic endocrine activity. To achieve this, rats were exposed to LL, DD, or LD (control) from P21 to P90. LL and DD impacted the rats' physiology, as evidenced by the shift from a bimodal voluntary activity pattern to a free-running one. Serum melatonin and the transcription of genes encoding key enzymes involved in melatonin synthesis and adrenergic receptors changed their characteristic diurnal pattern observed in the LD group. The transcription of clock genes important for pineal rhythmicity was disturbed under both LL and DD: LL attenuated or flattened the expression of core clock genes, while DD showed a weaker effect and shifted the peak of expression. In LL, altered expression of clock genes was associated with increased transcription of regulators of mitochondrial biogenesis, and markers of mitophagy and mitochondrial dynamics, resulting in elevated ATP production. Oppositely, in DD conditions, ATP decreased. Principal Component Analysis (PCA) revealed distinct clusters comprising clock and mitochondria-related genes, indicating a close association between the circadian clock and mitochondrial function. These findings suggest that long-term exposure to LL environment poses more significant challenges to the pineal gland than DD. This might be associated with the heightened blood corticosterone levels observed in LL conditions, indicating potential chronobiological stress.

Calorie restriction has been shown to dramatically extend lifespan in a range of species. Beyond longevity, calorie restriction is also reported to improve cognitive function, ameliorate neurodegeneration and peripheral nerve damage, reduce cancer incidence, and is commonly used to increase motivation in studies of behaviour. The mouse has been the most common species for these experiments and whilst efforts are ongoing to demonstrate the benefits of calorie restriction in humans, the evidence in mice is most compelling. Many mechanisms have been proposed for the beneficial effects of calorie restriction, but we note that one potentially important factor has seldom been considered: namely that mice readily enter torpor in response to food restriction. Torpor is a remarkable protective physiological state characterized by profound reductions in body temperature, oxygen consumption, heart rate, and activity. In this review, we describe the dietary protocols used to study the effects of calorie restriction and present the case that mice in these studies are highly likely to have entered torpor. We discuss the extent to which torpor might influence or mediate the measured outcomes. We highlight that induction of torpor is an important confound that is rarely, if at all, considered in calorie restriction research and make recommendations for the design and conduct of future studies.

Classical mammalian hibernators, such as the golden-mantled ground squirrel, exploit cold temperatures typical of torpor (~ 4 °C) as a robust cue for an imprecisely-coordinated depression of homeostatic processes such as protein synthesis and degradation. As a result, torpid metabolic rates may be 1/100th of active rates in ground squirrels. Tenrecs have profound thermal and metabolic plasticity; active tenrecs housed at low ambient temperatures may have body temperatures and resting metabolic rates similar to torpid tenrecs or more similar to that of the basal metabolic rate of comparably sized mammals. Importantly, tenrecs may be more or less active or torpid at both high and low body temperatures. Thus, temperature is likely an inappropriate cue for the regulation of homeostatic processes. Here, we demonstrate tenrecs have low but highly variable (~ tenfold) ubiquitylated protein concentrations, maintain robust ubiquitylation rates in the cold, have depressed proteolytic activities in the cold, and do not experience a marked depression of proteolysis in the torpid state. These data suggest an inability to regulate protein degradation when torpid or when body temperatures are reduced. We suggest that in ancestral-like mammals, a suitable approach was 'Life in the Slow Lane', wherein rates of processes like protein degradation (and presumably protein synthesis) were simply slow regardless of body temperature or torpor status. Low rates of processes are congruent with observed low metabolic rates and would help mitigate homeostatic mismatches incurred by a lack of coordination that might otherwise be deleterious.

To provide knowledge on growth performance and data that are helpful for resource assessment of Homatula variegata (Dabry de Thiersant, 1874) living in northern Guizhou, China, the current study focused on the length-weight relationship (LWR), the growth pattern, the condition factor (CF), as well as the relationship between muscle metabolomics and growth in H. variegata. A total of 135 H. variegata were collected during 19 months using our patented hookless fishing tackles. The lengths (from the snout tip to the base of the caudal fin) and weights were measured, and the LWR and CF was calculated. Furthermore, the muscle tissues from fin tissues of 8 fish in winter were used for the analyses of metabolomics. The lengths and weights of 135 individuals varied by seasons, and there were opposite changes of the parameter a and the parameter b among different seasons. The parameters of LWR indicated that the growth pattern of H. variegata was the negative allometric growth. Furthermore, the CF of H. variegata was consistent with the seasonal variations of the lengths. Our results displayed that H. variegata exhibited better growth during spring and winter in northern Guizhou. Moreover, the positive correlation between triglycerides (TG) metabolites and CF found in the metabolomics analysis of muscle tissue in winter revealed the potential importance of lipid-rich food for the well-being and growth performance of H. variegata. Taken together, our findings provided basic information on the growth patterns and the relationship between metabolic characteristics and CF of H. variegata.

This study investigated the impacts of Camel whey protein hydrolysate (CPH) supplementation on hepatocellular damage in Nile tilapia (Oreochromis niloticus) under hypoxic stress condition. Specifically, to elucidate the fundamental impacts of chronic hypoxia stress on the expression of key genes, cyp1a, hif-a, pk, cpt-1, pdk, and hsp70 in Oreochromis niloticus. Additionally, we aim to explore the involvement of the Nrf-2-Keap-1 expression as a potential mechanism through which chronic hypoxia stress may induce hepatic tissue damage. Also, other genes that catalyze the oxidative decarboxylation of pyruvate and glucose metabolism (pdk-1, cpt-1, pk, and ldh) reflect liver stress and vitality in hypoxic and normoxic conditions in Nile tilapia. Four groups of fish, each containing 40 fish (17.40 ± 0.50 g), were included for 4 weeks. The experimental diets embraced basal and 75 g CPH/kg enriched diets. Two fish groups persisted in normoxic conditions, while the others were restrained in hypoxic conditions (DO around 1.7 mg/L). The results revealed that a fortified diet with CPH significantly reversed the hypoxia-induced reduction in the antioxidants (CAT, GSH, and SOD), liver enzymes, and lipid profile changes. However, the hypoxic states caused the downregulation of cyp1a1 but up-regulated the expression of hif-a, and hsp-70 via nrf-2-keap-1 signaling pathways. Moreover, hypoxia stress-induced histopathological alterations in the fish liver tissue were substantially reversed by CPH dietary supplementation. These results concluded that CPH is a beneficial dietary supplement for mitigating the impacts of hypoxia stress on the liver.