Energy Metabolism Research Articles

Short-term continuous cropping leads to a decline in rhizosphere soil fertility by modulating the perilla root exudates

Continuous cropping obstacles are a prevalent issue in agricultural production worldwide. However, the key factors leading to these obstacles differ among various crops. This study utilized high-throughput sequencing and metabolomics to assess the community structure of microbes and the types and abundance of metabolites in rhizosphere soil after different continuous cropping years of Perilla frutescens L. Britt. (perilla). The results indicate that differential metabolites in soils of varying continuous cropping years are primarily associated with pathways for cellular lipid formation, oxidative stress responses, and energy metabolism. These findings suggest that the changes in soil composition over time are linked to specific biological processes related to lipid formation, oxidative stress, and energy metabolism. The relative abundance of beneficial bacteria in the soil, such as Sphingomonas, Gemmatimonas, and Blastococcus, decreased significantly (p < 0.05), while harmful fungi, such as Neocosmospora and Didymella, increased in response to the increase in continuous cropping years (p < 0.05). The symbiotic network between bacteria and fungi has become less dense and stable after continuous cropping. Enzymatic activities in rhizosphere soil decreased significantly (p < 0.05). Soil organic matter, total nitrogen, total phosphorus, total potassium, available phosphorus, and available potassium declined significantly (p < 0.05). Pearson correlation analysis identified 10 differential secondary metabolites that were closely related to the relative abundance of key microorganisms. Among them, cinnamic acid and flavonoid compounds are key factors leading to changes in microbial diversity, and they can regulate the microorganisms-soil- plants interactions. In summary, this study provides a novel scientific explanation for how continuous cropping can reduce soil fertility and a theoretical basis for subsequent cultivation strategies of perilla.

Antifatigue effect of okara protein hydrolysate supplementation during cycling exercise in men: a pre-post uncontrolled pilot study.

Prolonged exercise usually leads to exercise fatigue, which has a negative short-term impact on exercise performance and metabolic rate; thus, fatigue needs to be resolved. Okara is a protein-rich residue of soy processing. Enzyme hydrolysis is known to increase the content of branched-chain amino acids (BCAAs), which have been reported to confer benefits for exercise. The purpose of this study was to investigate the antifatigue effect of okara protein hydrolysate (OPH) on cycling exercise. A total of 16 male participants who habitually exercised (2 times or more per week and without participation in athletic contests) were instructed to receive 11.74 g of OPH once a day. They then completed two intense cycling exercise challenges before and after four weeks of supplementation. Exercise time and blood markers related to fatigue and energy metabolism were measured. The results showed that the time to exhaustion significantly increased after the treatment. The levels of lactate during exercise and at the end of exercise were significantly lower after treatment than before. Additionally, postexercise insulin sensitivity was increased after treatment. This study showed that OPH supplementation can promote endurance in exercise by decreasing the accumulation of fatigue-related metabolites during exercise and can promote energy recovery by increasing insulin function. These findings suggest that OPH has an antifatigue property.

Molecular pathways of osmoregulation in response to salinity stress in the gills of the scalloped spiny lobster (Panulirus homarus) within survival salinity

Scalloped spiny lobster (Panulirus homarus) aquaculture is the preferred strategy to resolve the conflict between supply and demand for lobster. Environmental conditions, such as salinity, are key to the success of lobster aquaculture. However, physiological responses of P. homarus to salinity stress have not been well studied. This study investigated the gill histology, osmoregulation and gill transcriptome of the early juvenile P. homarus (weight 19.04 ± 3.95 g) cultured at salinity 28 (control), 18, and 38 for 6 weeks. The results showed that the gill filaments of P. homarus exposed to low salinity showed severe separation of the cuticle and epithelial cells due to water absorption and swelling, as well as the dissolution and thinning of the cuticle and the rupture of the septum that separates the afferent and efferent channels. The serum osmolarity of P. homarus varied proportionately with external medium salinity and remained consistently above ambient osmolarity. The serum Na+, Cl−, K+, and Mg2+ concentrations P. homarus exhibited a pattern similar to that of serum osmolality, while the concentration of Ca2+ remained unaffected at salinity 18 but significantly increased at salinity 38. Gill Na+/K+-ATPase activity of P. homarus increased (p < 0.05) under the both salinity stress. Salinity 18 significantly increased Glutamate dehydrogenase (GDH) and Glutamicpyruvic transaminase (GPT) activity in the hepatopancreas of P. homarus (p < 0.05). According to transcriptome analysis, versus control group (salinity 28), 929 and 1095 differentially expressed genes (DEGs) were obtained in the gills of P. homarus at salinity 18 and 38, respectively, with these DEGs were mainly involved in energy metabolism, transmembrane transport and oxidative stress and substance metabolism. In addition, the expression patterns of 8 key DEGs mainly related to amino acid metabolism, transmembrane transport and oxidative stress were verified by quantitative real-time PCR (RT-qPCR). The present study suggests that salinity 18 has a greater impact on P. homarus than salinity 38, and P. homarus demonstrates effective osmoregulation and handle with salinity fluctuations (18 to 38) through physiological and functional adaptations. This study provides an improved understanding of the physiological response strategies of P. homarus facing salinity stress, which is crucial for optimizing aquaculture practices for this species.

NAD+ depletion is central to placental dysfunction in an inflammatory subclass of preeclampsia.

Preeclampsia (PE) is a hypertensive disorder of pregnancy and a major cause of maternal/perinatal adverse health outcomes with no effective therapeutic strategies. Our group previously identified distinct subclasses of PE, one of which exhibits heightened placental inflammation (inflammation-driven PE). In non-pregnant populations, chronic inflammation is associated with decreased levels of cellular NAD+, a vitamin B3 derivative involved in energy metabolism and mitochondrial function. Interestingly, specifically in placentas from women with inflammation-driven PE, we observed the increased activity of NAD+-consuming enzymes, decreased NAD+ content, decreased expression of mitochondrial proteins, and increased oxidative damage. HTR8 human trophoblasts likewise demonstrated increased NAD+-dependent ADP-ribosyltransferase (ART) activity, coupled with decreased mitochondrial respiration rates and invasive function under inflammatory conditions. Such adverse effects were attenuated by boosting cellular NAD+ levels with nicotinamide riboside (NR). Finally, in an LPS-induced rat model of inflammation-driven PE, NR administration (200 mg/kg/day) from gestational days 1-19 prevented maternal hypertension and fetal/placental growth restriction, improved placental mitochondrial function, and reduced inflammation and oxidative stress. This study demonstrates the critical role of NAD+ in maintaining placental function and identifies NAD+ boosting as a promising preventative strategy for PE.

An improved dynamic metabolic model for application to biota

Any major nuclear facility must ensure the conservation of biodiversity regarding radiation protection of biota. A special concern is for tritium (3H) and radiocarbon (14C) transfer in wild mammals, birds and reptiles. Hydrogen and carbon are the main components of biological tissues and enter the life cycle. The present study improves the scientific bases of a previous model, analyses the uncertainty of input parameters and tests the model for a larger range of mammals and birds. The biological and metabolic half-times for organically bound tritium (OBT) and 14C are linked with energy metabolism and recent results are revised in relation with metabolic scaling. A large data base regarding basal metabolic rate (BMR), field metabolic rate (FMR), and organ mass is used for input information of the present model, which considers brain as a separate compartment. Metabolic energy partition in organs of active animal is defined and the factors affecting the metabolic rate are analysed. Body and ambient temperature, diet and habitat, and phylogeny are important factors considered in animal adaptation to environment. The available experimental data for carbon turnover rates in animals are analysed and it is observed that the experimental conditions are not appropriate for wild animals. The link between 13,14C and 134,137Cs turnover rate is analysed and the present metabolic approach is successfully tested for mammals and reptiles. Considering animal adaptation and the large data base for 134,137Cs, the radiological impact of accidental releases of 3H and 14C on biota can be pursued in the future research.

TMT-based quantitative proteomics reveals the effects of electromagnetic field and freezing preservation techniques on mutton quality

This study investigated the effects of electromagnetic field preservation (EP) and freezing storage (FS) on the quality of northern Qianbei Ma mutton. Using tandem mass tagging (TMT)-labeled quantitative proteomics and bioinformatics, it was observed that EP more effectively inhibited pH increase and maintained a* and b* values compared to FS. Furthermore, the EP group was able to better maintain the water-holding capacity and tenderness of the mutton under prolonged storage. Proteomics analysis identified 397 differentially expressed proteins (DEPs) between the two storage methods at the same storage duration. GO and KEGG enrichment analyses indicated that proteins such as A0A452DSW4, A0A452E8M7, and D3JYV6 were involved in energy metabolism and redox processes, while A0A452EJ66, A0A452DSW4, and A0A452FJE8 played significant roles in protein binding. Overall, EP technology demonstrated superior benefits for maintaining mutton quality, suggesting a novel approach for mutton preservation.

Landscapes of maternal and neonatal gut microbiome and plasma metabolome signatures and their interaction in gestational diabetes mellitus

BackgroundGestational diabetes mellitus (GDM) is prevalent among pregnant individuals and is linked to increased risks for both mothers and foetuses. Although GDM is known to cause disruptions in gut microbiota and metabolites, their potential transmission to the foetus has not been fully explored. This study aimed to characterize the similarities in microbial and metabolic signatures between mothers with GDM and their neonates as well as the interactions between these signatures. MethodsThis study included 89 maternal-neonate pairs (44 in the GDM group and 45 in the normoglycaemic group). We utilized 16S rRNA gene sequencing and untargeted metabolomics to analyse the gut microbiota and plasma metabolomics of mothers and neonates. Integrative analyses were performed to elucidate the interactions between these omics. ResultsDistinct microbial and metabolic signatures were observed in GDM mothers and their neonates compared to those in the normoglycaemic group. Fourteen genera showed similar alterations across both groups. Metabolites linked to glucose, lipid, and energy metabolism were differentially influenced in GDM, with similar trends observed in both mothers and neonates in the GDM group. Network analysis indicated significant associations between Qipengyuania and metabolites related to bile acid metabolism in mothers and newborns. Furthermore, we observed a significant correlation between several genera and metabolites and clinical phenotypes in normoglycaemic mothers and newborns, but these correlations were disrupted in the GDM group. ConclusionOur findings suggest that GDM consistently affects both the microbiota and metabolome in mothers and neonates, thus elucidating the mechanism underlying metabolic transmission across generations. These insights contribute to knowledge regarding the multiomics interactions in GDM and underscore the need to further investigate the prenatal environmental impacts on offspring metabolism.

Nephropathy induced by cisplatin results from mitochondrial disruption, impaired energy metabolism, altered expression of renal transporters, and accumulation of urinary toxins

BackgroundThe administration of platinum-based drugs such as cisplatin and its derivatives, which are frequently used during clinical chemotherapy, is highly restricted due to the incidence of nephrotoxicity. The present study focused on investigating cisplatin-induced nephrotoxicity from the perspective of energy metabolism, renal transporter expression and urinary toxin accumulation. MethodsThis study investigated cisplatin's toxic effects, including nephrotoxicity, cardiotoxicity, hepatotoxicity, pulmonary toxicity, and splenotoxicity. We used transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to characterize the accumulation of cisplatin in the kidney and the structure of renal mitochondria. The production of reactive oxygen species (ROS) induced by cisplatin in renal tubular epithelial cells was evaluated by in vitro experiments, and apoptosis of renal tubular epithelial cells and alterations to the renal microvasculature were assessed. Metabolites associated with the glycolytic and tricarboxylic acid pathways were measured, and renal transporters expression, autophagy, and urinary toxins (UTs) accumulation were also assessed. ResultsOur results reveal that cisplatin-induced varying degrees of damage to the heart, liver, spleen, lungs, and kidneys, including inflammatory and fibrotic damage. Accumulation of cisplatin in renal mitochondria disrupted mitochondrial structure and mitochondrial function, as evidenced by decreased levels of glucose 6-phosphate and ribose 5-phosphate and elevated levels of isocitric acid. Cisplatin-induced accumulation of ROS in renal tubular epithelial cells led to apoptosis and, ultimately, constriction or loss of renal microvasculature. Furthermore, dysregulation of renal transporter expression, activation of autophagy and increased accumulation of UTs was observed. ConclusionAccumulation of cisplatin in the kidney led to damage to mitochondrial structure and function, apoptosis of renal tubular epithelial cells, constriction or loss of renal microvasculature, dysfunction of renal transporters, activation of autophagy, and accumulation of UTs.

Development and Validation of the Diagnostic Model of 7 Gene in Endometriosis.

To explore the diagnostic biomarkers for diagnosing endometriosis. Endometriosis is a benign, progressive, estrogen-dependent gynecological disorder that has highly variant prevalence. Therefore, it is essential to develop reliable diagnostic biomarkers for endometriosis diagnosis. To explore the diagnostic biomarkers for endometriosis diagnosis. Based on transcriptome data from GSE145701, we identified potential therapeutic targets through the intersection of endometriosis-related genes from weighted gene correlation network analysis (WGCNA) and differential expression analysis. Aprotein-protein interaction (PPI) was constructed. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed for functional enrichment analysis. The intersection of hub genes from topological analysis and module genes from module-based network analysis were selected as core targets, which were used for diagnostic model construction. Its robustness was validated using GSE7305 and GSE134056. Associations of core targets with immune characteristics and pathways were further evaluated. Molecular docking was employed to evaluate the docking affinity between core targets and drugs. Additionally, western blot and quantitative real-time polymerase chain reaction were also carried out to validate molecular docking results. A diagnostic model was constructed using 7 core targets, which had a high diagnostic ability for endometriosis. CTSK was positively correlated with immune scores, while CDH2 was negatively correlated with immune scores. CTSK, HGF, and EPCAM were positively correlated with energy metabolism and inflammation-related pathways, while RUNX2, FN1, NCAM1, and CDH2 were positively correlated with epithelial-to-mesenchymal transition (EMT) and unfolded protein response (UPR). Moreover, FN1 had good docking affinity with Elagolix, Esmya, and Proellex. NCAM1 might be a promising target modulated by Elagolix. In vitro experiment revealed that the expression of FN1 in human normal endometrial cell lines (hEEC) gradually decreased with the increase of Esmya concentration, indicating that FN1 was a target for Esmya. These results may facilitate the in-depth understanding of the development of endometriosis, and guide early diagnostic as well as clinical treatments for patients with endometriosis.

Multi-omics analyses of the mechanism for formation of key aroma-active compounds in blood orange wine fermented by Pichia kudriavzevii

Pichia kudriavzevii is an emerging non-Saccharomyces yeast recognized for its ability to enhance aroma quality in fermented foods, though the precise mechanisms underlying its effects remain poorly understood. This study delves into the influence of P. kudriavzevii BP15 on the formation of key aroma-active compounds (KAACs) and metabolic pathways during the fermentation of blood orange wine. By integrating multi-omics approaches, including volatilomics, genomics, and transcriptomics, this work systematically evaluated the profile of volatile organic compounds (VOCs), pinpointed the genes implicated in KAACs metabolism, and elucidated the biotransformation pathways of KAACs. The volatilomics results demonstrated that inoculation with P. kudriavzevii BP15 significantly improved the complexity and desirability of aroma by promoting the accumulation of diverse VOCs, particularly esters. The genomics analysis further revealed that a substantial portion of P. kudriavzevii BP15 genome was dedicated to carbohydrate, amino acid, and energy metabolisms. The transcriptomics data identified the high expression of multiple genes (e.g., ARO8, ACC1, ALD4, ILV5) during the early stages of fermentation by P. kudriavzevii BP15 that are integral to the biosynthesis of KAACs. These insights provide a deeper understanding of P. kudriavzevii BP15′s potential application in the production of high-quality blood orange wine, underscoring its role in enhancing the aroma profile through sophisticated metabolic interventions.

Carbohydrate storage in cells: a laboratory activity for the assessment of glycogen stores in biological tissues.

Carbohydrates and fats constitute our primary energy sources. The importance of each of these energy substrates varies across cell types and physiological conditions. For example, the brain normally relies almost exclusively on glucose oxidation, whereas skeletal muscle shifts from lipids toward higher carbohydrate oxidation rates as exercise intensity increases. Understanding how carbohydrates are stored in our cells and which tissues contain significant carbohydrate stores is crucial for health professionals, especially given the role of carbohydrate metabolism in various pathophysiological conditions. This laboratory activity uses a simple and low-cost iodine binding method to quantify glycogen in mouse skeletal muscle and liver samples. By integrating the results of this activity with literature data, students can determine overall glycogen storage in the human body. The primary goal of the activity is to enhance students' understanding of the importance and limitations of glycogen stores in energy metabolism.NEW & NOTEWORTHY Carbohydrates are one of the primary energy sources utilized by our cells. Liver and skeletal muscle glycogen, which are the main carbohydrate reserves in the body, play a central role in energy metabolism, especially during periods of fasting and exercise. In this laboratory activity, students measure glycogen levels in tissues to gain insights into how carbohydrates are stored in our cells and understand the role and limitations of liver and muscle carbohydrate stores.

Electroacupuncture combined with NSCs-Exo alters the response of hippocampal neurons in a chronic unpredictable mild stress paradigm in ovx rats

Electroacupuncture (EA) is a form of Traditional Chinese Medicine (TCM) that combines acupuncture with microcurrents mimicking the body's bioelectricity to prevent and treat diseases. Previous studies have demonstrated its antidepressant-like effects in chronic unpredictable mild stress (CUMS)-induced ovariectomy (OVX) rats. Neural stem cell-derived exosomes (NSCs-Exo) are heterogeneous and targeted, effectively promoting nerve regeneration and repairing neuronal damage, while potentially conveying the effects of EA. However, the precise mechanism remains unclear. In this study, perimenopausal depressive disorder (PDD) rat model were established using a two-step protocol CUMS + OVX. Treatment with EA combined with NSCs-Exo (EA-Exo) significantly improved depression-like behaviors in PDD rats, as indicated by increased sucrose intake in the Sucrose Preference Test (SPT), reduced immobility in the Forced Swimming Test (FST), and prolonged activity in the Out-of-Field Test (OFT). EA-Exo treatment improved depression-like behaviors by increasing serum levels of 5-hydroxytryptamine (5-HT) and decreasing immobility in the FST. It also alleviated OVX-CUMS-induced disturbances in energy metabolism, inflammation, and oxidative stress responses by enhancing serum levels of 5-HT, dopamine (DA), ATP, superoxide dismutase (SOD), and interleukin-10 (IL-10), while reducing cyclic AMP (cAMP), interleukin-6 (IL-6), reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, EA-Exo treatment reversed structural and functional impairments in hippocampal synapses and mitochondria. This was evidenced by reductions in hippocampal synaptic plasticity proteins PSD95, SYN, and GAP43, as well as decreased expression of energy metabolism pathway proteins AMPK, NRF1, PGC1α, and TFAM. These findings suggest that EA-Exo ameliorates depressive behavior in OVX-CUMS rats by modulating synaptic plasticity and activating the AMPK/NRF1/PGC1α/TFAM signaling pathway.

Influence of nano-encapsulated Yucca schidigera extract on ruminal anaerobic gases of methane, carbon monoxide, and hydrogen sulfide production of different carbohydrate-based diets

Saponins, the primary component of Yucca schidigera extract (YSE), are known to influence microbial activity in the rumen, which can affect various fermentation parameters. Moreover, encapsulating YSE with Chitosan (CS) at varying carbohydrate levels (CHO) adds another layer of complexity that can provide valuable insights into the use of additives in mitigating greenhouse gases. This study investigated the impact of both crude and encapsulated forms of YSE on the production of ruminal anaerobic gases in cattle fed different levels of CHO-based diets. Ruminal contents were obtained from four slaughtered, crossbreed bulls (Charollais × Limousin) with a live weight of 400 ± 25 kg. The experimental design followed a completely randomized factorial arrangement, with factors including CHO level (25%, 45%, and 55% DM), YSE forms (without extract, CS, crude, and nano-capsules), and dose of extract (0, 0.25, 0.5 and 1.0 mL/g of DM). Results showed that the type of extract significantly affected asymptotic total gas production, methane (CH4), Hydrogen sulfide (H2S), Carbon monoxide (CO), and dry matter digestibility. Nano-chitosan increased gas production and exhibited greater efficiency in reducing CH4 production by up to 61.36%. While crude YSE reduced CH4 production by 38%, nano-capsules increased production by 17.7% to 42.8%. Furthermore, a significant interaction effect among CHO levels, type of extract, and extract dose was observed, particularly impacting H2S and CH4 production after 48 hours of incubation, alongside an increase of about 25.3% in metabolizable energy compared to the control. The use of CS and YSE significantly (p <0.0001) improved the CH4 conversion efficiency by 71.3% and 23.4% respectively, and at some point, the encapsulation of YSE resulted in a significant reduction in efficiency by up to about 49.5%. The study concluded that both CS and YSE have the potential to enhance digestibility in cattle and reduce CH4 production and its conversion efficiency. However, encapsulating YSE with CS may reduce the efficiency of either compound in optimizing ruminal fermentation, unless other influencing factors are carefully considered. Therefore, the optimal efficacy of nano-encapsulated YSE depends on finding a balance between extract type, dosage, and dietary CHO level.

Abamectin inhibits energy metabolism by disturbing tricarboxylic acid (TCA) cycle in red swamp crayfish (Procambarus clarkii)

Abamectin inhibits energy metabolism by disturbing tricarboxylic acid (TCA) cycle in red swamp crayfish (Procambarus clarkii)

Combined effects of low pH stress and bacterial infection on the transcriptional changes of hemocytes in Chinese mitten crab Eriocheir sinensis

Water pH is a critical environmental factor for aquaculture. Acidification is a pressing environmental issue that poses significant threats to the aquaculture industry. Since the outbreaks of disease generally accompany with environmental stress, comparative transcriptome analyses were performed to investigate the combined effects of low pH stress and bacterial infection on the transcriptional changes of hemocytes in the economically important crab Eriocheir sinensis. The results revealed that the immune deficiency (IMD) pathway and prophenoloxidase (proPO) system was activated to defense against Vibro parahaemolyticus even when crabs were subjected to low pH stress, whereas low pH stress resulted in the disorder of Toll-like receptor (TLR) pathway upon V. parahaemolyticus infection. Moreover, low pH stress might weaken crabs′ defense against V. parahaemolyticus by inhibiting the up-regulation of crustin and suppressing the expression of lysozyme, and disturb the maintaining of protein homeostasis through the transcriptional decrement of a batch of heat shock proteins (HSPs). It is worth noting that both V. parahaemolyticus infection and low pH stress might suppress the energy metabolism in the hemocytes via inhibiting the expression of critical enzymes, dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex and fumarase, in the tricarboxylic acid (TCA) cycle. This study provides novel understandings concerning the transcriptional changes of hemocyte in E. sinensis subjected to a combination of low pH stress and V. parahaemolyticus infection as well as contribute to optimize the management strategies for the prevention and control of diseases in E. sinensis farming.

The role of microRNAs regulation of endoplasmic reticulum stress in ischemia-reperfusion injury: A review.

The endoplasmic reticulum (ER) is an important organelle in eukaryotic cells, responsible for a range of biological functions such as the secretion, modification and folding of proteins, maintaining Ca2+ homeostasis and the synthesis of steroids/lipids, secreted proteins and membrane proteins. When cells are affected by internal or external factors, including abnormal energy metabolism, disrupted Ca2+ balance, altered glycosylation, drug toxicity, and so on, the unfolded or misfolded proteins accumulate in the ER, leading to the unfolded protein response (UPR) and ER stress. The abnormal ER stress has been reported to be involved in various pathological processes. MicroRNAs (miRNAs) are non-coding RNAs with the length of approximately 19-25 nucleotides. They control the expression of multiple genes through posttranscriptional gene silencing in eukaryotes or some viruses. Increasing evidence indicates that miRNAs are involved in various cellular functions and biological processes, such as cell proliferation and differentiation, growth and development, and metabolic homeostasis. Hence, miRNAs participate in multiple pathological processes. Recently, many studies have shown that miRNAs play an important role by regulating ER stress in ischemia-reperfusion (I/R) injury, but the relevant mechanisms are not fully understood. In this review, we reviewed the current understanding of ER stress, as well as the biogenesis and function of miRNAs, and focused on the role of miRNAs regulation of ER stress in I/R injury, with the aim of providing new targets for the treatment of I/R injury.

Sheep skin collagen peptide exerts an anti-fatigue effect by improving energy metabolism via AMPK/PGC-1α axis and reducing oxidative damage via NRF2/HO-1 axis

Sheep skin collagen peptide exerts an anti-fatigue effect by improving energy metabolism via AMPK/PGC-1α axis and reducing oxidative damage via NRF2/HO-1 axis

Swertiamarin ameliorates type 2 diabetes by activating ADRB3/UCP1 thermogenic signals in adipose tissue

Background and purposeSwertiamarin (STM), a secoiridoid glycoside from Swertia chirayita (Roxb.) H. Karst, has been shown to decrease body weight, blood glucose, and blood lipids by inhibiting adipose tissue hypertrophy. However, the underlying mechanisms remain unclear. In particular, adipose thermogenesis is a novel avenue for exploring the pharmacological effects of STM. We aim to investigate the efficacy of STM on type 2 diabetes mellitus (T2DM), with a focus on underlying mechanisms, particularly the activation of ADRB3/UCP1 thermogenic signaling pathways. MethodsT2DM model was established by a high-fat diet (HFD) and streptozotocin (STZ) in C57BL/6J male mice. Mice were given to either 100 or 200 mg/kg/day of STM, or 200 mg/kg/day of metformin via intragastric administration for 7 weeks. In vitro, 3T3-L1 cells were differentiated into adipocytes. Molecular markers related to ADRB3-UCP1 signals, lipolysis, and mitochondrial function were detected. ResultsSTM-treated diabetic mice showed a reduction of body weight, fat mass, and blood glucose/lipids and an improvement in insulin sensitivity. Bioinformatics analysis indicated STM promoted lipid metabolism and mitochondrial function, features by closely associated with adipose thermogenesis. STM upregulated the lipolysis-related genes and p-HSL protein in inguinal subcutaneous white adipose tissue (igSWAT) and brown adipose tissue (BAT). STM-treated mice processed a more active energy metabolism. Additionally, the ADRB3-UCP1 signals, mitochondrial-related genes, and oxidative phosphorylation were improved in igSWAT and BAT. In vitro, we found STM interacted with ADRB3, increasing glucose uptake, glycerol release, ADRB3-UCP1 signals, p-HSL expression, mitochondrial content, oxidative phosphorylation complex expression with improved mitochondrial Δψm, as well as reduced lipid accumulation in adipocytes. All these effects were reversed upon ADRB3 inhibition. ConclusionThis study identifies a previously unknown role of STM activating ADRB3/UCP1 signals in adipose tissue, suggesting a potential strategy for treating T2DM.

Effects of saline-alkaline stress on metabolomics profiles, biochemical parameters, and liver histopathology in large yellow croaker (Larimichthys crocea)

China has several saline-alkaline bodies. Studies on the adaptation of fish in saline-alkaline conditions are important for the efficient utilization of such areas. In this study, we employed a comprehensive approach combining histopathological analysis, biochemical markers, and metabolomic profiling to examine the impact of saline-alkaline stress on the liver of the large yellow croaker (Larimichthys crocea). It was found that the survival rate of L. crocea in the saline-alkaline treated group (EX) was significantly higher than that of the control group (CK). Saline-alkaline stress could not influence the structure of the liver of L. crocea, and not change the levels of superoxide dismutase (SOD), catalase (CAT), alkaline phosphatase (ALP), acid phosphatase (ACP). In addition, we identified 5953 metabolites, and 312 differentially expressed metabolites (DEMs) showed significant differential expression between the CK and EX groups. In the positive ion mode, 216 DEMs were identified, including 120 up-regulated and 96 down-regulated DEMs, and in the negative ion mode, 178 DEMs were identified, including 131 up-regulated and 47 down-regulated DEMs. Pathway enrichment analysis revealed significant involvement in 58 metabolic pathways, primarily linked to energy metabolism. These included the metabolism of amino acid, carbohydrate, and lipid pathways, including cysteine and methionine metabolism, biosynthesis of valine, leucine, isoleucine, and ascorbate; aldarate metabolism; galactose metabolism; glycerophospholipid metabolism; and the biosynthesis of unsaturated fatty acids. Metabolomics revealed that increased synthesis of compounds, such as succinic acid, arachidonic acid, and L-gulonic acid in the liver of L.crocea, is associated with adaptation to saline-alkaline aquaculture conditions. The findings of this study indicated that the fish mitigate reactive oxygen species induced by hyperosmotic environments and improve cellular membrane fluidity and intercellular signal transduction through the metabolism of unsaturated fatty acids and carbohydrates, facilitating adaptation to saline-alkaline conditions.

Riboflavin kinase binds and activates inducible nitric oxide synthase to reprogram macrophage polarization

Riboflavin kinase (RFK) is essential in riboflavin metabolism, converting riboflavin to flavin mononucleotide (FMN), which is further processed to flavin adenine dinucleotide (FAD). While RFK enhances macrophage phagocytosis of Listeria monocytogenes, its role in macrophage polarization is not well understood. Our study reveals that RFK deficiency impairs M(IFN-γ) and promotes M(IL-4) polarization, both in vitro and in vivo. Mechanistically, RFK interacts with inducible nitric oxide (NO) synthase (iNOS), which requires FMN and FAD as cofactors for activation, leading to increased NO production that alters energy metabolism by inhibiting the tricarboxylic acid cycle and mitochondrial electron transport chain. Exogenous FAD reverses the metabolic and polarization changes caused by RFK deficiency. Furthermore, bone marrow adoptive transfer from high-riboflavin-fed mice into wild-type tumor-bearing mice reprograms tumor-associated macrophage polarization and inhibits tumor growth. These results suggest that targeting RFK-iNOS or modulating riboflavin metabolism could be potential therapies for macrophage-related immune diseases.