Imbalance In Energy Metabolism Research Articles

Sulforaphane modulates some stress parameters in TPT-exposed Cyprinus carpio in relation to liver metabolome

This study aimed to investigate the protective effect of sulforaphane (SFN) on liver injury induced by triphenyltin (TPT) in Cyprinus carpio (C. carpio). The fish (average weight of 56.9±0.4 g) were divided into 4 groups with four replicates: the control, TPT, SFN+TPT and SFN groups. Twenty fish were selected from each tank and cultured for 8 weeks. Then, serum and liver samples were collected for physiological, biochemical and metabolomic analyses. In the present study, TPT downregulated the expression of the lysozyme gene, upregulated HSP70 and Hsp90 gene expression, and decreased the activities of serum antioxidant enzymes (SOD, CAT, and GPX). However, dietary SFN alleviated oxidative stress, and prevented changes in immune genes. Metabolomic analysis revealed that TPT exposure changed key metabolites in the main phenylalanine, fatty acid and glycerophosphatide metabolic pathways, which are related to inflammation, oxidative stress and immunity and might also lead to an imbalance of liver energy and lipid metabolism. Dietary SFN promoted amino acid metabolism and increased metabolites related to immunity, anti-inflammation, antioxidation, and protein synthesis in liver of C. carpio. In summary, dietary SFN supplementation reversed TPT-induced decreases in immunity and oxidative stress and regulated amino acid metabolism, lipid metabolism, inflammation and immunity-related metabolic pathways.

Sodium butyrate improves renal injury in diabetic nephropathy through AMPK/SIRT1/PGC-1α signaling pathway

Diabetic nephropathy (DN) is a prototypical chronic energy metabolism imbalance disease. The AMPK/Sirt1/PGC-1α signaling pathway plays a pivotal role in regulating energy metabolism throughout the body. Gut microbiota ferment indigestible carbohydrates to produce a variety of metabolites, particularly short-chain fatty acids (SCFAs), which exert positive effects on energy metabolism. However, the potential for SCFAs to ameliorate DN-associated renal injury via the AMPK/Sirt1/PGC-1α pathway remains a matter of debate. In this study, we investigated the effects of sodium butyrate (NaB), a SCFA, on energy metabolism in mice with spontaneous DN at two different doses. Body weight, blood glucose and lipid levels, urinary protein excretion, liver and kidney function, interleukin-6 (IL-6) levels, and the expressions of AMPK, phosphorylated AMPK (p-AMPK), mitofusin 2 (MFN2), optic atrophy 1 (OPA1), and glucagon-like peptide-1 receptor (GLP-1R) were monitored in mice. Additionally, butyrate levels, gut microbiota composition, and diversity in colonic stool were also assessed. Our findings demonstrate that exogenous NaB supplementation can improve hyperglycemia and albuminuria, reduce renal tissue inflammation, inhibit extracellular matrix accumulation and glomerular hypertrophy, and could alter the gut microbiota composition in DN. Furthermore, NaB was found to upregulate the expressions of MFN2, OPA1, p-AMPK, and GLP-1R in DN renal tissue. These results suggest that NaB could improve the composition of gut microbiota in DN, activate the AMPK/Sirt1/PGC-1α signaling pathway, and enhance mitochondrial function to regulate energy metabolism throughout the body. Collectively, our findings indicate that NaB may be a novel therapeutic agent for the treatment of DN.

Tissue-specific roles of mitochondrial unfolded protein response during obesity.

Obesity is a worldwide multifactorial disease caused by an imbalance in energy metabolism, increasing adiposity, weight gain, and promoting related diseases such as diabetes, cardiovascular diseases, neurodegeneration, and cancer. Recent findings have reported that metabolic stress related to obesity induces a mitochondrial stress response called mitochondrial unfolded protein response (UPRmt), a quality control pathway that occurs in a nuclear DNA-mitochondria crosstalk, causing transduction of chaperones and proteases under stress conditions. The duality of UPRmt signaling, with both beneficial and detrimental effects, acts in different contexts depending on the tissue, cell type, and physiological states, affecting the mitochondrial function and efficiency and the metabolism homeostasis during obesity, which remains not fully clarified. Therefore, this review discusses the most recent findings regarding UPRmt signaling during obesity, bringing an overview of UPRmt across different metabolic tissues.

An exploratory metabolomic study reveals the Dipsacus asper-Achyranthes bidentate herb pair against osteoarthritis by modulating imbalance in polyunsaturated fatty acids and energy metabolism

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the cartilage. The therapeutic potential of the Dipsacus asper-Achyranthes bidentate herb pair for OA has been acknowledged, yet its precise mechanism remains elusive. In this study, we conducted a comprehensive analysis of metabolomic changes and therapeutic outcomes in osteoarthritic rats, employing a gas chromatography-mass spectrometry-based metabolomics approach in conjunction with histopathological and biochemical assessments. The rats were divided into six groups: control, model, positive control, Dipsacus asper treated, Achyranthes bidentata treated, and herb pair treated groups. Compared to the model group, significant reductions in levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and iNOS were observed in the treated groups. Multivariate statistical analyses were employed to investigate metabolite profile changes in serum samples and identify potential biomarkers, revealing 45 differential biomarkers, with eighteen validated using standard substances. These analytes exhibited excellent linearity across a wide concentration range (R2>0.9990), with intra- and inter-day precision RSD values below 4.69% and 4.83%, respectively. Recoveries of the eighteen analytes ranged from 93.97% to 106.59%, with RSD values under 5.72%, underscoring the method's reliability. Treatment with the herbal pair effectively restored levels of unsaturated fatty acids such as linoleic acid and arachidonic acid, along with glucogenic amino acids. Additionally, levels of phosphoric acid and citric acid were reversed, indicating restoration of energy metabolism. Collectively, these findings highlight the utility of metabolomic analysis in evaluating therapeutic efficacy and elucidating the underlying molecular mechanisms of herb pairs in OA treatment.

Low-dose BPA-induced neuronal energy metabolism dysfunction and apoptosis mediated by PINK1/parkin mitophagy pathway in juvenile rats

Bisphenol A (BPA) is related to neurological disorders involving mitochondrial dysfunction, while the mechanism remains elusive. Therefore, we explored it through in vitro and in vivo experiments. In vitro, hippocampal neurons derived from neonatal rats of different genders were exposed to 1–100 nM and 100 μM BPA, autophagy activator Rapa and inhibitor 3-MA for 7 d. The results suggested that even nanomolar BPA (1–100 nM) disturbed Ca2+ homeostasis and damaged the integrity of mitochondrial cristae in neurons (p < 0.05). Furthermore, BPA increased the number of autophagic lysosomes, LC3II/LC3I ratio, and p62 expression, and decreased parkin expression (p < 0.05), suggesting that the entry of damaged mitochondria into autophagic pathway was prompted, while the autophagic degradation pathway was blocked. This further disrupts neuronal energy metabolism and promotes neuronal apoptosis. However, Rapa attenuated the adverse effects caused by BPA, while 3-MA exacerbated these reactions. In vivo, exposure of juvenile rats to 0.5, 50, 5000 μg/kg‧bw/day BPA during PND 7–21 markedly impaired the structure of hippocampal mitochondria, increased the number of autophagosomes, the rate of neuronal apoptosis, and the expression levels of pro-apoptotic proteins Cyt C, Bax, Bak1, and Caspase3, and decreased the expression of anti-apoptotic protein Bcl2 (p < 0.05). Particularly, male rats are more sensitive to low-dose BPA than females. Overall, environmental-doses BPA can induce the imbalance of energy metabolism in hippocampal neurons via PINK1/parkin mitophagy, thereby inducing their apoptosis. Importantly, this study provides a theoretical basis for attenuating BPA-related neurological diseases.

Targeted Metabolomics Highlights Dramatic Antioxidant Depletion, Increased Oxidative/Nitrosative Stress and Altered Purine and Pyrimidine Concentrations in Serum of Primary Myelofibrosis Patients.

To date, little is known concerning the circulating levels of biochemically relevant metabolites (antioxidants, oxidative/nitrosative stress biomarkers, purines, and pyrimidines) in patients with primary myelofibrosis (PMF), a rare form of myeloproliferative tumor causing a dramatic decrease in erythropoiesis and angiogenesis. In this study, using a targeted metabolomic approach, serum samples of 22 PMF patients and of 22 control healthy donors were analyzed to quantify the circulating concentrations of hypoxanthine, xanthine, uric acid (as representative purines), uracil, β-pseudouridine, uridine (as representative pyrimidines), reduced glutathione (GSH), ascorbic acid (as two of the main water-soluble antioxidants), malondialdehyde, nitrite, nitrate (as oxidative/nitrosative stress biomarkers) and creatinine, using well-established HPLC method for their determination. Results showed that PMF patients have dramatic depletions of both ascorbic acid and GSH (37.3- and 3.81-times lower circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001), accompanied by significant increases in malondialdehyde (MDA) and nitrite + nitrate (4.73- and 1.66-times higher circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001). Additionally, PMF patients have remarkable alterations of circulating purines, pyrimidines, and creatinine, suggesting potential mitochondrial dysfunctions causing energy metabolism imbalance and consequent increases in these cell energy-related compounds. Overall, these results, besides evidencing previously unknown serum metabolic alterations in PMF patients, suggest that the determination of serum levels of the aforementioned compounds may be useful to evaluate PMF patients on hospital admission for adjunctive therapies aimed at recovering their correct antioxidant status, as well as to monitor patients' status and potential pharmacological treatments.

Changes and Significance of Central Carbon Metabolism before and after Metformin Treatment of Type 2 Diabetes Based on Mass Spectrometry.

An imbalance in energy metabolism serves as a causal factor for type 2 diabetes (T2D). Although metformin has been known to ameliorate the overall energy metabolism imbalance, but the direct correlation between metformin and central carbon metabolism (CCM) has not been thoroughly investigated. In this study, we employed a high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) technique to examine the alterations and significance of CCM both before and after metformin treatment for T2D. We recruited 29 participants, comprising 10 individuals recently diagnosed with T2D (T2D group). Among these, 10 patients underwent a 4-6-week treatment with metformin (MET group). Additionally, we included 9 healthy subjects (CON group). Employing HPIC-MS/MS, we quantitatively analyzed 56 metabolites across 18 biologically relevant metabolic pathways associated with CCM. Univariate and multivariate statistical analyses were utilized to identify differential metabolites. Subsequently, correlation analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted on the identified differential metabolites. We identified seven distinct metabolites in individuals with T2D (p < 0.05). Notably, cyclic 3',5'-Adenosine MonoPhosphate (AMP), Glucose 6-phosphate, L-lactic acid, Maleic acid, and Malic acid exhibited a reversal to normal levels following metformin treatment. Furthermore, Malic acid demonstrated a positive correlation with L-lactic acid (r = 0.94, p < 0.05), as did succinic acid with malic acid (r = 0.81, p < 0.05), L-lactic acid with succinic acid (r = 0.78, p < 0.05), and L-lactic acid with glucose-6-phosphate (r = 0.72, p < 0.05). These metabolites were notably enriched in pyruvate metabolism (p = 0.005), tricarboxylic acid cycle (TCA) (p = 0.007), propanoate metabolism (p = 0.007), and glycolysis or gluconeogenesis (p = 0.009), respectively. We employed HPIC-MS/MS to uncover alterations in CCM among individuals recently diagnosed with T2D before and after metformin treatment. The findings suggest that metformin may ameliorate the energy metabolism imbalance in T2D by reducing intermediates within the CCM pathway.

Tetrad stage transient cold stress skews auxin-mediated energy metabolism balance in Chinese cabbage pollen.

Changing ambient temperature often impairs plant development and sexual reproduction, particularly pollen ontogenesis. However, mechanisms underlying cold stress-induced male sterility are not well understood. Here, we exposed Chinese cabbage (Brassica campestris) to different cold conditions during flowering and demonstrated that the tetrad stage was the most sensitive. After completion of pollen development at optimal conditions, transient cold stress at the tetrad stage still impacted auxin levels, starch and lipid accumulation, and pollen germination, ultimately resulting in partial male sterility. Transcriptome and metabolome analyses and histochemical staining indicated that the reduced pollen germination rate was due to the imbalance of energy metabolism during pollen maturation. The investigation of β-glucuronidase (GUS)-overexpressing transgenic plants driven by the promoter of DR5 (DR5::GUS report system) combined with cell tissue staining and metabolome analysis further validated that cold stress during the tetrad stage reduced auxin levels in mature pollen grains. Low-concentration auxin treatment on floral buds at the tetrad stage before cold exposure improved the cold tolerance of mature pollen grains. Artificially changing the content of endogenous auxin during pollen maturation by spraying chemical reagents and loss-of-function investigation of the auxin biosynthesis gene YUCCA6 by artificial microRNA technology showed that starch overaccumulation severely reduced the pollen germination rate. In summary, we revealed that transient cold stress at the tetrad stage of pollen development in Chinese cabbage causes auxin-mediated starch-related energy metabolism imbalance that contributes to the decline in pollen germination rate and ultimately seed set.

Insights into neurometabolic diseases

&lt;abstract&gt;&lt;sec&gt; &lt;title&gt;Background&lt;/title&gt; &lt;p&gt;Neurometabolic diseases are the results of genetic changes that lead to an imbalance in energy utilization and metabolism.&lt;/p&gt; &lt;/sec&gt;&lt;sec&gt; &lt;title&gt;Aim&lt;/title&gt; &lt;p&gt;Our aim was to explore the update in treatment and diagnosis of neurometabolic disease.&lt;/p&gt; &lt;/sec&gt;&lt;sec&gt; &lt;title&gt;Methods&lt;/title&gt; &lt;p&gt;PubMed, Scopus, Google scholar, and the web of science were searched for studies reported in the last 20 years (1997–30/10/2020). The data was searched and archived by keywords like “Neurometabolic”, “neurogenesis”, and “role of neuro-degeneration in neurometabolic disease” without narrowing or limiting search items. Only abstracts of searched publications were reviewed. A total of 389 publications were found in the initial research, in which 62 publications were considered for the study and the remaining were excluded because of their specificity to the subject.&lt;/p&gt; &lt;/sec&gt;&lt;sec&gt; &lt;title&gt;Study update&lt;/title&gt; &lt;p&gt;The neurometabolic disease affects one in 500 newborns, causing a major burden of illness and infant mortality. However, the cause of the disease is unclear in up to 50% of neurological-like cases. Thus, we ask why are they referred to as neurometabolic disorders (NMD), despite extensive genetic and biochemistry investigations? Treatment is possible for some metabolic diseases. For instance, the devastating neurological effects of phenylketonuria have been recognized for many years. Except for some notable exceptions, treatment remains largely unsatisfactory. Therefore, research efforts concentrate on corrective genetic approaches applicable after early detection by newborn screening or before fertilization. We considered recent studies on treating neurometabolic diseases. We focused on the most common neurometabolic diseases and the associated clinical advancements in their therapy.&lt;/p&gt; &lt;/sec&gt;&lt;/abstract&gt;

Cell Reprogramming Strategies for Treating Osteoarthritis and Intervertebral Disc Degeneration.

Osteoarthritis (OA) and intervertebral disc degeneration (IVDD) are the most common degenerative bone and joint diseases, posing a major threat to patients' physical and mental health due to the occurrence of chronic pain and disability. Within this context, the absence of efficacious therapies has led to a growing interest in regenerative medicine. In particular, as a method that can erase the memory of differentiation and re-endow cells with pluripotency, cell reprogramming technologies have ushered in a new era of personalized therapy, which not only show great potential for the treatment of degenerative osteoarthropathies but also promise to achieve tissue regenerative and repair. However, compared to other areas of research, reprogramming technologies to treat OA and IVDD are still in the preliminary stages and require further investigation. This paper briefly introduces the characteristics of cell reprogramming; summarizes the pathological mechanisms of reprogramming to improves energy metabolism, aging, inflammation, oxidative stress, and immune imbalance in OA and IVDD under the background of microenvironment and immunity; highlights the significant advantages of reprogramming-derived cells compared to embryonic stem cells and mesenchymal stem cells, based on these advances, providing important strategies for its development and clinical application in OA and IVDD.

Monochasma savatieri Franch. protects against acute lung injury via α7nAChR-TLR4/NF-κB p65 signaling pathway based on integrated pharmacology analysis

Ethnopharmacological relevanceAcute lung injury (ALI) is a life-threatening condition with high morbidity and mortality, underscoring the urgent need for novel treatments. Monochasma savatieri Franch. (LRC) is commonly used clinically to treat wind-heat cold, bronchitis, acute pneumonia and acute gastroenteritis. However, its role in the treatment of ALI and its mechanism of action are still unclear. Aim of the studyThis study aimed to demonstrate the pharmacological effects and underlying mechanisms of LRC extract, and provide important therapeutic strategies and theoretical basis for ALI. Materials and methodsIn this study, a research paradigm of integrated pharmacology combining histopathological analysis, network pharmacology, metabolomics, and biochemical assays was used to elucidate the mechanisms underlaying the effects of LRC extract on LPS-induced ALI in BALB/c mice. ResultsThe research findings demonstrated that LRC extract significantly alleviated pathological damage in lung tissues and inhibited apoptosis in alveolar epithelial cells, and the main active components were luteolin, isoacteoside, and aucubin. Lung tissue metabolomic and immunohistochemical methods confirmed that LRC extract could restore metabolic disorders in ALI mice by correcting energy metabolism imbalance, activating cholinergic anti-inflammatory pathway (CAP), and inhibiting TLR4/NF-κB signaling pathway. ConclusionsThis study showed that LRC extract inhibited the occurrence and development of ALI inflammation by promoting the synthesis of antioxidant metabolites, balancing energy metabolism, activating CAP and suppressing the α7nAChR-TLR4/NF-κB p65 signaling pathway. In addition, our study provided an innovative research model for exploring the effective ingredients and mechanisms of traditional Chinese medicine. To the best of our knowledge, this is the first report describing the protective effects of LRC extract in LPS-induced ALI mice.

Altered Energy Metabolism, Mitochondrial Dysfunction, and Redox Imbalance Influencing Reproductive Performance in Granulosa Cells and Oocyte During Aging.

Female fertility decreases during aging. The development of effective therapeutic strategies to address the age-related decline in oocyte quality and quantity and its accurate diagnosis remain major challenges. In this review, we summarize our current understanding of the study of aging and infertility, focusing primarily on the molecular basis of energy metabolism, mitochondrial function, and redox homeostasis in granulosa cells and oocytes, and discuss perspectives on future research directions. Mitochondria serve as a central hub sensing a multitude of physiological processes, including energy production, cellular redox homeostasis, aging, and senescence. Young granulosa cells favor glycolysis and actively produce pyruvate, NADPH, and other metabolites. Oocytes rely on oxidative phosphorylation fueled by nutrients, metabolites, and antioxidants provided by the adjacent granulosa cells. A reduced cellular energy metabolism phenotype, including both aerobic glycolysis and mitochondrial respiration, is characteristic of older female granulosa cells compared with younger female granulosa cells. Aged oocytes become more susceptible to oxidative damage to cells and mitochondria because of further depletion of antioxidant-dependent ROS scavenging systems. Molecular perturbations of gene expression caused by a subtle change in the follicular fluid microenvironment adversely affect energy metabolism and mitochondrial dynamics in granulosa cells and oocytes, further causing redox imbalance and accelerating aging and senescence. Furthermore, recent advances in technology are beginning to identify biofluid molecular markers that may influence follicular development and oocyte quality. Accumulating evidence suggests that redox imbalance caused by abnormal energy metabolism and/or mitochondrial dysfunction is closely linked to the pathophysiology of age-related subfertility.

The effects of polyethylene microplastics on the growth, reproduction, metabolic enzymes, and metabolomics of earthworms Eisenia fetida

The existing data regarding the effects of polyethylene (PE) microplastics (MPs) smaller than 5 mm in size on earthworms are insufficient to fully comprehend their toxicity. In this study, earthworms Eisenia fetida were exposed to artificially added PE at a concentration ranging from 0.05 to 20 g/kg soil (0.005%−2%) for 60 days to determine the concentration range causing negative effects on earthworms and to uncover the potential toxic mechanisms. The individual growth, reproduction, and metabolic enzyme activities, including phase I enzymes (cytochrome P450 [CYP] 1A2, 2B6, 2C9, and 3A4), and phase II metabolic enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione sulfotransferase (GST)), and metabolomics were measured. The observed variations in responses of multiple cross-scale endpoints indicated that individual indices are less responsive to PE MPs than metabolic enzymes or metabolomics. Despite the absence of significant alterations in growth inhibition based on body weight, PE MPs at concentrations equal to or exceeding 2.5 g/kg were found to exert a toxic effect on earthworms, which was evidenced by significant changes in metabolic enzyme activities (CYP1A2, 2B6, 2C9, and 3A4, SOD, CAT, and GST) and important small molecule metabolites screened based on metabolomics, likely due to the bioaccumulation of PE. The toxicity of PE MPs to earthworms is inferred to be associated with neurotoxicity, oxidative damage, decreased detoxification capacity, energy metabolism imbalance, and impaired amino acid and purine metabolism due to bioaccumulation. The findings of this study will enhance our understanding of the molecular toxicity mechanisms of PE MPs and contribute to a more accurate assessment of the ecological risks posed by PE MPs in soil.

Anxiety adds the risk of cognitive progression and is associated with axon/synapse degeneration among cognitively unimpaired older adults.

Mental symptoms have been shown to be associated with dementia. As the most common neuropsychiatric disorder, it is unclear whether and why anxiety increases the risk of cognitive progression in elderly. The aim of this study was to investigate the longitudinal effects of anxiety on cognitive impairment in non-dementia elderly and to explore the underlying biological processes using multi-omics including microarray-based transcriptomics, mass spectrometry-based proteomics and metabolomics, cerebrospinal fluid (CSF) biochemical markers, and brain diffusion tensor imaging (DTI). The Alzheimer's Disease Neuroimaging Initiative (ADNI), Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Shanghai Mental Health Centre (SMHC) cohorts were included. Anxiety was found to increase the risk of subsequent cognitive progression in the ADNI, and a similar result was observed in the CLHLS cohort. Enrichment analysis indicated activated axon/synapse pathways and suppressed mitochondrial pathways in anxiety, the former confirmed by deviations in frontolimbic tract morphology and altered levels of axon/synapse markers, and the latter supported by decreased levels of carnitine metabolites. Mediation analysis revealed that anxiety's effect on the longitudinal cognition was mediated by brain tau burden. Correlations of mitochondria-related expressed genes with axon/synapse proteins, carnitine metabolites, and cognitive changes were found. This study provides cross-validated epidemiological and biological evidence that anxiety is a risk factor for cognitive progression in non-dementia elderly, and that axon/synapse damage in the context of energy metabolism imbalance may contribute to this phenomenon. The National Natural Science Foundation of China (82271607, 81971682, and 81830059) for data analysis and data collection.

Venlafaxine's effect on resilience to stress is associated with a shift in the balance between glucose and fatty acid utilization.

Brain metabolism is a fundamental process involved in the proper development of the central nervous system and in the maintenance of the main higher functions in humans. As consequence, energy metabolism imbalance has been commonly associated to several mental disorders, including depression. Here, by employing a metabolomic approach, we aimed to establish if differences in energy metabolite concentration may underlie the vulnerability and resilience in an animal model of mood disorder named chronic mild stress (CMS) paradigm. In addition, we have investigated the possibility that modulation of metabolite concentration may represent a pharmacological target for depression by testing whether repeated treatment with the antidepressant venlafaxine may normalize the pathological phenotype by acting at metabolic level. The analyses were conducted in the ventral hippocampus (vHip) for its key role in the modulation of anhedonia, a core symptom of patients affected by depression. Interestingly, we showed that a shift from glycolysis to beta oxidation seems to be responsible for the vulnerability to chronic stress and that vHip metabolism contributes to the ability of the antidepressant venlafaxine to normalize the pathological phenotype, as shown by the reversal of the changes observed in specific metabolites. These findings may provide novel perspectives on metabolic changes that could serve as diagnostic markers and preventive strategies for the early detection and treatment of depression as well as for the identification of potential drug targets.

Shengxian decoction protects against chronic heart failure in a rat model via energy regulation mechanisms

BackgroundChronic heart failure (CHF) is actually a disease caused by an imbalanced energy metabolism between myocardial energy demand and supply, ultimately resulting in abnormal myocardial cell structure and function. Energy metabolism imbalance plays an important role in the pathological process of chronic heart failure (CHF). Improving myocardial energy metabolism is a new strategy for the treatment of CHF. Shengxian decoction (SXT), a well-known traditional Chinese medicine (TCM) formula, has good therapeutic effects on the cardiovascular system. However, the effects of SXT on the energy metabolism of CHF is unclear. In this study, we probed the regulating effects of SXT on energy metabolism in CHF rats using various research methods.MethodsHigh-performance liquid chromatography (HPLC) analysis was used to perform quality control of SXT preparations. Then, SD rats were randomly assigned into 6 groups: sham, model, positive control (trimetazidine) and high-, middle-, and low-dose SXT groups. Specific reagent kits were used to detect the expression levels of ALT and AST in rats’ serum. Echocardiography was used to evaluate cardiac function. H&E, Masson and TUNEL staining were performed to examine myocardial structure and myocardial apoptosis. Colorimetry was used to determine myocardial ATP levels in experimental rats. Transmission electron microscopy was used to observe the ultrastructure of myocardial mitochondria. ELISA was used to estimate CK, cTnI, and NT-proBNP levels, and LA、FFA、MDA、SOD levels. Finally, Western blotting was used to examine the protein expression of CPT-1, GLUT4, AMPK, p-AMPK, PGC-1α, NRF1, mtTFA and ATP5D in the myocardium.ResultsHPLC showed that our SXT preparation method was feasible. The results of ALT and AST tests indicate that SXT has no side effect on the liver function of rats. Treatment with SXT improved cardiac function and ventricular remodelling and inhibited cardiomyocyte apoptosis and oxidative stress levels induced by CHF. Moreover, CHF caused decrease ATP synthesis, which was accompanied by a reduction in ATP 5D protein levels, damage to mitochondrial structure, abnormal glucose and lipid metabolism, and changes in the expression of PGC-1α related signal pathway proteins, all of which were significantly alleviated by treatment with SXT.ConclusionSXT reverses CHF-induced cardiac dysfunction and maintains the integrity of myocardial structure by regulating energy metabolism. The beneficial effect of SXT on energy metabolism may be related to regulating the expression of the PGC-1α signalling pathway.

The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level.

Type 2 diabetes mellitus (T2DM) is a chronic endocrine metabolic disease caused by insulin dysregulation. Studies have shown that aging-related oxidative stress (as "oxidative aging") play a critical role in the onset and progression of T2DM, by leading to an energy metabolism imbalance. However, the precise mechanisms through which oxidative aging lead to T2DM are yet to be fully comprehended. Thus, it is urgent to integrate the underlying mechanisms between oxidative aging and T2DM, where meaningful prediction models based on relative profiles are needed. First, machine learning was used to build the aging model and disease model. Next, an integrated oxidative aging model was employed to identify crucial oxidative aging risk factors. Finally, a series of bioinformatic analyses (including network, enrichment, sensitivity, and pan-cancer analyses) were used to explore potential mechanisms underlying oxidative aging and T2DM. The study revealed a close relationship between oxidative aging and T2DM. Our results indicate that nutritional metabolism, inflammation response, mitochondrial function, and protein homeostasis are key factors involved in the interplay between oxidative aging and T2DM, even indicating key indices across different cancer types. Therefore, various risk factors in T2DM were integrated, and the theories of oxi-inflamm-aging and cellular senescence were also confirmed. In sum, our study successfully integrated the underlying mechanisms linking oxidative aging and T2DM through a series of computational methodologies.

Effects of Long-Term Cold Stress on Growth Performance, Behavior, Physiological Parameters, and Energy Metabolism in Growing Beef Cattle.

This study aimed to evaluate the effects of a long-term cold environment on growth performance, physiological behavior, biochemical blood indexes, and hormone levels in Simmental cattle. Thirty Simmental crossbred bulls (weight = 350 ± 17 kg, 13-14 months old) were selected for two trials at autumn suitable temperatures (A-ST) and winter cold temperatures (W-CT) (15 cattle per season). The results showed that compared with the A-ST group, dry matter intake (p < 0.05) and feed:gain (p < 0.01) of the W-CT group increased, while body weight (p < 0.01) and average daily gain (p < 0.01) significantly decreased. Long-term cold stress also increased lying time (p < 0.01), feeding time (p < 0.05), and pulse rate (p < 0.01) in the W-CT group, while the rumen volatile fatty acids content (p < 0.01) and apparent digestibility of nutrients (p < 0.05) were significantly decreased. In terms of blood indicators, long-term cold stress increased the concentrations of glucose, glucose metabolic enzymes, glucocorticoids, triiodothyronine, and tetraiodothyronine in the plasma of the W-CT group (p < 0.05), but the levels of triglycerides, β-hydroxybutyrate, propionate, insulin, and growth hormone were decreased (p < 0.01). In summary, long-term cold stress may inhibit the digestive function of Simmental cattle and enhance the body's energy metabolism and stress hormone imbalance, ultimately damaging the normal growth and development of the body.

Phyllanthus emblica L. extract alleviates leptin resistance and lipid accumulation by inhibiting methylglyoxal production

Increasing leptin resistance and methylglyoxal (MG) levels have been observed in patients with obesity, which is characterized by an imbalance in energy metabolism and abnormal fat accumulation. MG is highly reactive and easily glycates proteins, impairing their physiological functions in cells. Whether MG glycates leptin and results in leptin resistance are untested. Therefore, we hypothesized that MG might directly affect leptin structure and activity or indirectly affect leptin gene and receptor expression, thereby triggering leptin resistance. The fruit of Indian gooseberry (Phyllanthus emblica L.) is rich in phenolic compounds (β-glucogallin, gallic acid, and ellagic acid) and can trap MG. This study aimed to evaluate the effect of a water extract from Indian gooseberry fruit (WEIG) on MG-induced leptin resistance in HepG2 cells. Protein cross-linking and carbonyl content measurement results showed that leptin resistance was induced by MG glycation but improved by WEIG treatment. Moreover, WEIG and its phenolic compounds (gallic acid and ellagic acid) significantly increased the mRNA expression of leptin receptors (Ob-Rb and HuB219.1), and this was accompanied by the suppression of SOCS3 and lipogenesis-associated signaling cascade (SREBP-1/ACC/FAS) gene expression and the activation of the JAK2/STAT3/AMPK/PPAR-α/CPT-1 pathway in human HepG2 liver cells exposed to free fatty acid. In conclusion, WEIG (150 μg/mL) dramatically alleviated leptin resistance and lipid accumulation by MG trapping and inhibiting MG-leptin glycation, indicating that MG is a risk factor for leptin resistance that WEIG can suppress. This finding will increase the application potential of P. emblica L. in anti-obesity functional food industrial development.

Emerging role of substance and energy metabolism associated with neuroendocrine regulation in tumor cells.

Cancer is the second most common cause of mortality in the world. One of the unresolved difficult pathological mechanism issues in malignant tumors is the imbalance of substance and energy metabolism of tumor cells. Cells maintain life through energy metabolism, and normal cells provide energy through mitochondrial oxidative phosphorylation to generate ATP, while tumor cells demonstrate different energy metabolism. Neuroendocrine control is crucial for tumor cells' consumption of nutrients and energy. As a result, better combinatorial therapeutic approaches will be made possible by knowing the neuroendocrine regulating mechanism of how the neuroendocrine system can fuel cellular metabolism. Here, the basics of metabolic remodeling in tumor cells for nutrients and metabolites are presented, showing how the neuroendocrine system regulates substance and energy metabolic pathways to satisfy tumor cell proliferation and survival requirements. In this context, targeting neuroendocrine regulatory pathways in tumor cell metabolism can beneficially enhance or temper tumor cell metabolism and serve as promising alternatives to available treatments.