Altered Energy Metabolism Research Articles

Ectotherm mitochondrial economy and responses to global warming.

Temperature is a key abiotic factor affecting ecology, biogeography, and evolution of species. Alterations of energy metabolism play an important role in adaptations and plastic responses to temperature shifts on different time scales. Mitochondrial metabolism affectscellular bioenergetics and redox balance making these organelles an important determinant of organismal performances such as growth, locomotion, or development. Here I analyze the impacts of environmental temperature on the mitochondrial functions (including oxidative phosphorylation, proton leak, production of reactive oxygen species(ROS), and ATP synthesis) of ectotherms and discuss the mechanisms underlying negative shifts in the mitochondrial energy economy caused by supraoptimal temperatures. Owing to the differences in the thermal sensitivity of different mitochondrial processes, elevated temperatures (beyond the species- and population-specific optimal range) cause reallocation of the electron flux and the protonmotive force (Δp) in a way that decreases ATP synthesis efficiency, elevates the relative cost of the mitochondrial maintenance, causes excessive production of ROS and raises energy cost for antioxidant defense. These shifts in the mitochondrial energy economy might have negative consequences for the organismal fitness traits such as the thermal tolerance or growth. Correlation between the thermal sensitivity indices of the mitochondria and the whole organism indicate that these traits experience similar selective pressures but further investigations are needed to establish whether there is a cause-effect relationship between the mitochondrial failure and loss of organismal performance during temperature change.

Hypoxia-Inducible Factor-2α Signaling in the Skeletal System.

Hypoxia-inducible factors (HIFs) are oxygen-dependent heterodimeric transcription factors that mediate molecular responses to reductions in cellular oxygen (hypoxia). HIF signaling involves stable HIF-β subunits and labile, oxygen-sensitive HIF-α subunits. Under hypoxic conditions, the HIF-α subunit is stabilized, complexes with nucleus-confined HIF-β subunit, and transcriptionally regulates hypoxia-adaptive genes. Transcriptional responses to hypoxia include altered energy metabolism, angiogenesis, erythropoiesis, and cell fate. Three isoforms of HIF-α-HIF-1α, HIF-2α, and HIF-3α-are found in diverse cell types. HIF-1α and HIF-2α serve as transcriptional activators, whereas HIF-3α restricts HIF-1α and HIF-2α. The structure and isoform-specific functions of HIF-1α in mediating molecular responses to hypoxia are well established across a wide range of cell and tissue types. The contributions of HIF-2α to hypoxic adaptation are often unconsidered if not outrightly attributed to HIF-1α. This review establishes what is currently known about the diverse roles of HIF-2α in mediating the hypoxic response in skeletal tissues, with specific focus on development and maintenance of skeletal fitness. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Vitreous metabolomic signatures of pathological myopia with complications.

Pathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications. VH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis. Bioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications. Our study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.

Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (n = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (n = 78); Nicaraguans performing non-agricultural work (n = 102); and agricultural workers in Spain (n = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (p = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.

Hepatic CCAAT/Enhancer Binding Protein (C/EBP-α and C/EBP-β) Expression Changes with Riboflavin Deficiency, Diet Restriction and Starvation in Rats , ,

To study the role of nuclear regulatory proteins in mediating dietary effects, hepatic CCAAT/enhancer binding protein (C/EBP), mRNA and transcription rate were measured for C/EBP-alpha and C/EBP-beta in nutritional states that profoundly alter energy metabolism and growth. Weanling male Sprague-Dawley rats were fed riboflavin-sufficient (R+) or deficient (R-) diets for 4 wk. A diet-restricted, pair-fed (RP) group was maintained concurrently, because riboflavin-deficient rats voluntarily decrease food consumption by approximately 50% compared with controls. Half of each group was deprived of food for 48 h. The 4-wk treatment altered hepatic levels of both proteins (P < 0.05). C/EBP-alpha protein levels were increased -twofold by diet restriction. C/ EBP-beta protein levels were increased nearly threefold by riboflavin deficiency. Starvation had no significant effect on the expression of either protein. We investigated the mechanism responsible for increased protein by measuring steady-state mRNA levels and transcription rates for C/EBP-alpha and C/EBP-beta. In both isoforms, increases in mRNA were parallel to increases in transcription rates. The nutrient-induced changes in protein, mRNA and transcription rates could not be attributed only to alterations in serum glucagon or insulin concentrations. We conclude that 1) C/EBP-alpha and C/EBP-beta expression responds to diet but may involve different dietary signals for diet restriction vs. riboflavin deficiency; 2) the dietary regulation of C/EBP-alpha and C/EBP-beta expression seems to be controlled in part at the level of gene transcription; and 3) C/EBP-alpha and C/EBP-beta nuclear proteins, by virtue of their increased quantities, may participate in regulating altered energy metabolism and growth by influencing hepatic transcription of key metabolic enzymes.

Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice

Alterations in energy metabolism are associated with depression. However, the role of glycolysis in the pathogenesis of depression and the underlying molecular mechanisms remain unexplored. Through an unbiased proteomic screen coupled with biochemical verifications, we show that the levels of glycolysis and lactate dehydrogenase A (LDHA), a glycolytic enzyme that catalyzes L-lactate production, are reduced in the dorsomedial prefrontal cortex (dmPFC) of stress-susceptible mice in chronic social defeat stress (CSDS) model. Conditional knockout of LDHA from the brain promotes depressive-like behaviors in both male and female mice, accompanied with reduced L-lactate levels and decreased neuronal excitability in the dmPFC. Moreover, these phenotypes could be duplicated by knockdown of LDHA in the dmPFC or specifically in astrocytes. In contrast, overexpression of LDHA reverses these phenotypic changes in CSDS-susceptible mice. Mechanistic studies demonstrate that L-lactate promotes neuronal excitability through monocarboxylic acid transporter 2 (MCT2) and by inhibiting large-conductance Ca2+-activated potassium (BK) channel. Together, these results reveal a role of LDHA in maintaining neuronal excitability to prevent depressive-like behaviors.

Effects of the Entomopathogenic Fungus Mucor hiemalis BO-1 on the Physical Functions and Transcriptional Signatures of Bradysia odoriphaga Larvae.

Mucor hiemalis BO-1 is an entomopathogenic fungus that infects Bradysia odoriphaga, a destructive root maggot. M. hiemalis BO-1 possesses stronger pathogenicity to the larvae than to other stages of B. odoriphaga, and provides satisfactory field control. However, the physiological response of B. odoriphaga larvae to infection and the infection mechanism of M. hiemalis are unknown. We detected some physiological indicators of diseased B. odoriphaga larvae infected by M. hiemalis BO-1. These included changes in consumption, nutrient contents, and digestive and antioxidant enzymes. We performed transcriptome analysis of diseased B. odoriphaga larvae, and found that M. hiemalis BO-1 showed acute toxicity to B. odoriphaga larvae and was as toxic as some chemical pesticides. The food consumption of diseased B. odoriphaga after inoculation with M. hiemalis spores decreased significantly, and there was a significant decrease in total protein, lipid, and carbohydrates in diseased larvae. Key digestive enzymes (protease, α-amylase, lipase, and cellulase) were significantly inhibited during infection. Peroxidase maintained high activity, and the activity of other antioxidant enzymes (catalase, superoxide dismutase, and glutathione S-transferases) first increased and then decreased. Combined with the transcriptional signatures of diseased B. odoriphaga larvae, M. hiemalis BO-1 infection resulted in decreased food consumption, reduced digestive enzyme activity, and altered energy metabolism and material accumulation. Infection was also accompanied by fluctuations in immune function, such as cytochrome P450 and the Toll pathway. Therefore, our results laid a basis for the further study of the interactions between M. hiemalis BO-1 and B. odoriphaga and promoted the genetic improvement of entomopathogenic fungi.

Multi-omics analysis unravels positive effect of rotenone on the cordycepin biosynthesis in submerged fermentation of Cordyceps militaris

Cordycepin is the key pharmacologically active compound of Cordyceps militaris, and various fermentation strategies have been developed to increase cordycepin production. This study aimed to investigate the effect of rotenone on cordycepin biosynthesis in submerged fermentation of C. militaris, and also to explore its possible induction mechanisms via multi-omics analysis. Adding 5 mg/L rotenone significantly increased the cordycepin production by 316.09 %, along with mycelial growth inhibition and cell wall destruction. Moreover, transcriptomic analysis and metabolomic analysis revealed the accumulation of cordycepin was promoted by alterations in energy metabolism and amino acid metabolism pathways. Finally, the integration analysis of the two omics confirmed rotenone altered the nucleotide metabolism pathway toward adenosine and up-regulated the cordycepin synthesis genes (cns1-3) to convert adenosine to cordycepin. This work reports, for the first time, rotenone could act as an effective inducer of cordycepin synthesis.

Plasma methylmalonic acid predicts risk of acute myocardial infarction and mortality in patients with coronary heart disease: A prospective 2-cohort study.

Elevated plasma methylmalonic acid (MMA) is reported in patients with established coronary heart disease (CHD) and is considered a marker of vitamin B12 deficiency. Moreover, MMA-dependent reactions have been linked to alterations in mitochondrial energy metabolism and oxidative stress, key features in the pathophysiology of cardiovascular diseases (CVDs). We examined whether plasma MMA prospectively predicted the long-term risk of acute myocardial infarction (AMI) and mortality. Using Cox modeling, we estimated hazard ratios (HRs) for endpoints according to per 1-SD increment of log-transformed plasma MMA in two independent populations: the Western Norway Coronary Angiography Cohort (WECAC) (patients evaluated for CHD; n=4137) and the Norwegian Vitamin Trial (NORVIT) (patients hospitalized with AMI; n=3525). In WECAC and NORVIT, 12.8% and 18.0% experienced an AMI, whereas 21.8% and 19.9% died, of whom 45.5% and 60.3% from CVD-related causes during follow-up (range 3-11 years), respectively. In WECAC, age- and gender-adjusted HRs (95% confidence interval) were 1.18 (1.09-1.28), 1.25 (1.18-1.33), and 1.28 (1.17-1.40) for future AMI, total mortality, and CVD mortality, respectively. Corresponding risk estimates were 1.19 (1.10-1.28), 1.22 (1.14-1.31), and 1.30 (1.19-1.42) in NORVIT. These estimates were only slightly attenuated after multivariable adjustments. Across both cohorts, the MMA-risk association was stronger in older adults, women, and non-smokers. Elevated MMA was associated with an increased risk of AMI and mortality in patients with suspected or verified CHD.

Abstract 102: Imaging Markers Of Energy Metabolism In The Post-stroke Mouse Brain

Introduction: Cerebral ischemia results in a lesion comprised of dying cells surrounded by a band of tissue containing cells at risk of dying, called the penumbra. Understanding the status of energy metabolism in the stroke is necessary to get a clearer picture of the formation of the lesion, and may provide insights into potential therapeutic targets. The detection and distribution of energy metabolism biomarkers, particularly in ischemic brain tissue, presents significant challenges for conventional laboratory techniques due to the labile nature of these markers and the lack of unique chemical or spectroscopic handles. Fourier Transform infrared (FTIR) spectroscopic imaging can be used to map the distribution of different biochemical parameters, such as lipids, proteins, aggregated proteins, glycogen, lactate, pyruvate, ATP/ADP, NADH and glutamate. Methods: We employed the photothrombotic stroke model in adult mice to produce a permanent focal stroke lesion. Brain tissue was collected at multiple time points (1h to 4 weeks post-stroke). FTIR imaging was employed to map the distribution of unique biochemical fingerprints for over a dozen key metabolic markers. Immunohistochemistry was also performed on adjacent tissues to correlate biomarkers revealed by FTIR with the distribution of astrocytes, myelin and macrophages. Results: During the first week poststroke, the lesion shows decreased lipid esters, protein, ATP/ADP, NADH content while showing an increase in glutamate, aggregated protein, lactate and pyruvate. Glycogen can be seen to accumulate in the penumbra starting at 1 day post-stroke until 1 week post-stroke, which correlates with the appearance of astrocytes around the border of the stroke lesion. From 1 week to 4 weeks post-stroke, we observe an increase in lipid esters in the lesion, as well as a decrease in glycogen, lactate and pyruvate, while an increase in ATP/ADP and NADH can be observed. Conclusion: We are showing for the first time novel images of multiple energy metabolism biomarkers across a range of post-stroke time points in a mammalian brain. This type of imaging will be important in studying post-stroke interventions, particularly drugs that are known to alter energy metabolism.

Metabolic heterogeneity in early-stage lung adenocarcinoma revealed by RNA-seq and scRNA-seq.

Cancer cells maintain cell growth, division, and survival through altered energy metabolism. However, research on metabolic reprogramming in lung adenocarcinoma (LUAD) is limited METHODS: We downloaded TCGA and GEO sequencing data. Consistent clustering with the ConsensusClusterPlus package was employed to detect the scores for four metabolism-related pathways. The LUAD samples in the TCGA dataset were clustered with ConsensusClusterPlus, and the optimal number of clusters was determined according to the cumulative distribution function (CDF). The cell score for each sample in the TCGA dataset was calculated using the MCPcounter estimate function of the MCPcounter package. We identified two subtypes by scoring the samples based on the 4 metabolism-related pathways and cluster dimensionality reduction. The prognosis of cluster B was obviously poorer than that of cluster A in patients with LUAD. The analysis of single-nucleotide variation (SNV) data showed that the top 15 genes in the four metabolic pathways with the most mutations were TKTL2, PGK2, HK3, EHHADH, GLUD2, PKLR, TKTL1, HADHB, CPT1C, HK1, HK2, PFKL, SLC2A3, PFKFB1, and CPT1A. The IFNγ score of cluster B was significantly higher than that of cluster A. The immune T-cell lytic activity score of cluster B was significantly higher than that of cluster A. We further identified 5 immune cell subsets from single-cell sequencing data. The top 5 marker genes of B cells were IGHM, JCHAIN, IGLC3, IGHA1, and IGKC. The C0 subgroup of monocytes had a higher pentose phosphate pathway (PPP) score than the C6 subgroup. Metabolism-related subtypes could be potential biomarkers in the prognosis prediction and treatment of LUAD.

Beta-Hydroxybutyrate Ketone Salt Supplement Alters Energy Metabolism, Blood Glucose and Ketone Levels But Not Appetite or Energy Intake

Beta-Hydroxybutyrate Ketone Salt Supplement Alters Energy Metabolism, Blood Glucose and Ketone Levels But Not Appetite or Energy Intake

PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation

The alteration of cellular energy metabolism is a hallmark of colorectal cancer (CRC). Accumulating evidence has suggested oxidative phosphorylation (OXPHOS) is upregulated to meet the demand for energy in tumor initiation and development. However, the role of OXPHOS and its regulatory mechanism in CRC tumorigenesis and progression remain unclear. Here, we reveal that Prohibitin 2 (PHB2) expression is elevated in precancerous adenomas and CRC, which promotes cell proliferation and tumorigenesis of CRC. Additionally, knockdown of PHB2 significantly reduces mitochondrial OXPHOS levels in CRC cells. Meanwhile, NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1), as a PHB2 binding partner, is screened and identified by co-immunoprecipitation and mass spectrometry. Furthermore, PHB2 directly interacts with NDUFS1 and they co-localize in mitochondria, which facilitates NDUFS1 binding to NADH:ubiquinone oxidoreductase core subunit V1 (NDUFV1), regulating the activity of complex I. Consistently, partial inhibition of complex I activity also abrogates the increased cell proliferation induced by overexpression of PHB2 in normal human intestinal epithelial cells and CRC cells. Collectively, these results indicate that increased PHB2 directly interacts with NDUFS1 to stabilize mitochondrial complex I and enhance its activity, leading to upregulated OXPHOS levels, thereby promoting cell proliferation and tumorigenesis of CRC. Our findings provide a new perspective for understanding CRC energy metabolism, as well as novel intervention strategies for CRC therapeutics.

Altered energy metabolism in Fatal Familial Insomnia cerebral organoids is associated with astrogliosis and neuronal dysfunction.

Fatal familial insomnia (FFI) is a rare neurodegenerative disease caused by a dominantly inherited single amino acid substitution (D178N) within the prion protein (PrP). No in vitro human brain tissue model for this disease has previously been available. Consequently, how this mutation exerts its damaging effect on brain cells is still unknown. Using CRISPR-Cas9 engineered induced pluripotent stem cells, we made D178N cerebral organoids and compared these with isotype control organoids. We found that, in the absence of other hallmarks of FFI, the D178N organoids exhibited astrogliosis with cellular oxidative stress. Abnormal post-translational processing of PrP was evident but no tissue deposition or propagation of mis-folded PrP isoforms were observed. Neuronal electrophysiological function was compromised and levels of neurotransmitters, particularly acetylcholine and GABA, altered. Underlying these dysfunctions were changes in cellular energy homeostasis, with substantially increased glycolytic and Krebs cycle intermediates, and greater mitochondrial activity. This increased energy demand in D178N organoids was associated with increased mitophagy and depletion of lipid droplets, in turn resulting in shifts of cellular lipid composition. Using a double mutation (178NN) we could confirm that most changes were caused by the presence of the mutation rather than interaction with PrP molecules lacking the mutation. Our data strongly suggests that shifting biosynthetic intermediates and oxidative stress, caused by an imbalance of energy supply and demand, results in astrogliosis with compromised neuronal activity in FFI organoids. They further support that many of the disease associated changes are due to a corruption of PrP function and do not require propagation of PrP mis-folding.

The Association of the Oral Microbiota with the Effects of Acid Stress Induced by an Increase of Brain Lactate in Schizophrenia Patients.

The altered cerebral energy metabolism central to schizophrenia can be linked to lactate accumulation. Lactic acid is produced by gastrointestinal bacteria, among others, and readily crosses the blood-brain barrier, leading to the brain acidity. This study aimed to examine the association of the oral microbiota with the effects of acid stress induced by an increase of brain lactate in schizophrenia patients. The study included patients with a diagnosis of acute polyphasic psychotic disorder meeting criteria for schizophrenia at 3-month follow-up. Results: Individuals with a significantly higher total score on the Positive and Negative Syndrome Scale had statistically significantly lower lactate concentrations compared to those with a lower total score and higher brain lactate. We observed a positive correlation between Actinomyces and lactate levels in the anterior cingulate cap and a negative correlation between bacteria associated with lactate metabolism and some clinical assessment scales. Conclusions: Shifts in the oral microbiota in favour of lactate-utilising bacterial genera may represent a compensatory mechanism in response to increased lactate production in the brain. Assessment of neuronal function mediated by ALA-LAC-dependent NMDA regulatory mechanisms may, thus, support new therapies for schizophrenia, for which acidosis has become a differentiating feature of individuals with schizophrenia endophenotypes.

Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia.

Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7-21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.

Alterations in energy metabolism, total protein, uric and nucleic acids in African sharptooth catfish (Clarias gariepinus Burchell) exposed to crude oil and fractions

Water contamination by crude oil is a growing challenge and little is known about the probabilistic and non-probabilistic ecosystem and species consequences. Therefore, research aimed at understanding species survival strategy in crude oil-contaminated environments with focus on cellular metabolic alterations and dynamics is vital. This study assessed the alterations in lactate dehydrogenase (LDH), glucose (GLU), glucose-6-phosphate dehydrogenase (G-6-PDH), total protein (TP), uric and nucleic acids (UA, RNA, and DNA) in the liver, heart, kidney, blood supernatants, and muscle homogenates of African sharptooth catfish ([ASC] Clarias gariepinus) exposed to varying bonny-light crude oil concentrations to understand the underlying cause of their delayed development as well as potential health and wellbeing. Three concentrations (20, 50, and 100 mg/L) of diluted whole bonny-light crude oil (DWC), water-soluble (WSF), and water-insoluble (WIF) fractions of bonny-light crude oil were used to grow ASC for 9 weeks at room temperature. Biochemical assessments revealed significant (at p < 0.05) elevations in heart LDH (48.57 ± 4.67 to 3011.34 ± 4.67 U/L) and blood G-6-PDH activities (54.86 ± 0.00 to 128 ± 18.29 mU/mL), GLU (0.22 ± 0.01 to 0.77 ± 0.01 mg/dL), TP (5.15 ± 0.14 to 22.33 ± 0.21 g/L), UA (0.29 ± 0.05 to 10.05 ± 0.27 mg/dL), as well as liver DNA (0.38 ± 0.02 to 2.33 ± 0.09 μg/mL) and RNA (12.52 ± 0.05 to 30.44 ± 0.02 μg/mL) levels for laboratory-grown ASC in DWC, WSF, WIF, and oil-impacted Ubeji river collected ASC relative to the control. Due to greater levels of cellular metabolic alterations in oil-impacted Ubeji River collected ASC, it is evident that bonny-light contamination levels in the river is greater than 100 mg/L. In conclusion, bonny-light crude oil is toxic to ASC and induces stress response. The ecological changes caused by bonny-light crude oil contamination may ultimately affect niche functioning and the development of organs in ASC.

Integrated analysis of transcriptome and metabolome data reveals insights for molecular mechanisms in overwintering Tibetan frogs, Nanorana parkeri.

Nanorana parkeri (Anura, Dicroglossidae) is a unique frog living at high altitude on the Tibetan plateau where they must endure a long winter dormancy at low temperatures without feeding. Here, we presented a comprehensive transcriptomic and metabolomic analysis of liver tissue from summer-active versus overwintering N. parkeri, providing the first broad analysis of altered energy metabolism and gene expression in this frog species. We discovered that significantly up-regulated genes (2,397) in overwintering frogs mainly participated in signal transduction and immune responses, phagosome, endocytosis, lysosome, and autophagy, whereas 2,169 down-regulated genes were mainly involved in metabolic processes, such as oxidation-reduction process, amino acid metabolic process, fatty acid metabolic process, and TCA cycle. Moreover, 35 metabolites were shown to be differentially expressed, including 22 down-regulated and 13 up-regulated in winter. These included particularly notable reductions in the concentrations of most amino acids. These differentially expressed metabolites were mainly involved in amino acid biosynthesis and metabolism. To sum up, these findings suggest that gene expression and metabolic processes show adaptive regulation in overwintering N. parkeri, that contributes to maintaining homeostasis and enhancing protection in the hypometabolic state. This study has greatly expanded our understanding of the winter survival mechanisms in amphibians.

Metformin extends the chronological lifespan of fission yeast by altering energy metabolism and stress resistance capacity.

The antiaging properties of metformin used for the treatment of type-2 diabetes mellitus have been studied extensively, but there is more to discover regarding underlying mechanisms. Here, we show that metformin significantly prolongs the chronological lifespan (CLS) of Schizosaccharomyces pombe through mechanisms similar to those observed in mammalian cells and other model organisms. While the presence of metformin in the medium caused an increase in carbohydrate consumption and ATP production, it reduced reactive oxygen species production and alleviate oxidative damage parameters such as lipid peroxidation and carbonylated proteins. We also tested whether the effect of metformin changed with the time it was added to the medium and observed that the lifespan-prolonging effect of metformin was related to the glucose concentration in the medium and did not prolong lifespan when added after glucose was completely depleted in the medium. On the other hand, cells inoculated in glucose-free medium containing metformin also showed extended lifespan suggesting that mechanisms other than that solely depend on glucose availability may be involved in extending the lifespan. These results suggest that metformin prolongs lifespan especially affecting energy metabolism and stress resistance capacity and that fission yeast can be effectively used when investigating the antiaging mechanisms of metformin.

Pork quality traits and associated muscle metabolic changes in pigs under chronic prenatal and postnatal heat stress.

Chronic heat stress (HS) is a major concern affecting pig growth performance and metabolism, with potential consequences on carcass and meat quality traits. The objective of this study was to assess the influence of prenatal (PE) and growing (GE) thermal environments, and their combination, on muscle metabolism, carcass characteristics, and pork quality. From 6 to 109 d of gestation, 12 sows (1 per block) were kept under thermoneutral (TN) conditions (cyclic 18 to 24 °C; PTN) and 12 sows under chronic HS (cyclic 28 to 34 °C; PHS). Two female offspring per sow were selected based on body weight at weaning, for a total of 48 female pigs (12 blocks of 2 sisters from each PE), and one sister was placed in each GE. Gilts were housed from 82 to 140 d of age under cyclic GTN (18 to 24 °C; n = 24) or GHS (28 to 34 °C; n = 24) environments. Data were analyzed using a mixed model including PE, GE, and PE × GE interaction as main effects, and sire, sow within PE, pen within PE × GE, and slaughter day (for plasma, muscle, and meat traits) as random effects. No significant PE × GE interaction was found on any trait under study (P ≥ 0.05). Prenatal HS did not affect growth performance and carcass traits (P ≥ 0.05). Compared with GTN, GHS pigs had lower average daily feed intake, average daily gain, and hot carcass weight (P < 0.01), but similar carcass lean meat content (P ≥ 0.05). Prenatal HS had scarce effects on pork quality, with only higher a* and C* values (P < 0.05) in the Gluteus superficialis. Growing HS led to a higher pH 24 h (P < 0.05) in the Longissimus thoracis et lumborum (LTL) and ham muscles, and higher meat quality index in the ham muscles. In contrast, quality traits of the Semispinalis capitis (SC) were not affected by either PE or GE (P > 0.05). Except a tendency for a higher citrate synthase activity in the SC (P = 0.065), PHS did not affect muscle metabolism. Growing HS induced muscle-specific metabolic responses, with reduced glycolytic potential (P < 0.01) and metabolic enzyme activities (P < 0.05) in the glycolytic LTL, but not in the oxidative SC (P > 0.05). Plasma glucose content at slaughter was lower in the GHS compared with GTN pigs (P = 0.002), indicating an altered energy metabolism in pigs under GHS. Altogether, growing HS altered growth without affecting carcass traits, but improved technological quality of loin and ham. Prenatal HS, alone or combined with GHS, had limited or even no effect on carcass and pork quality.