Regulation Of Energy Metabolism Research Articles

Estrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System.

The orphan nuclear receptor ERRα is the most extensively researched member of the estrogen-related receptor family and holds a pivotal role in various functions associated with energy metabolism, especially in tissues characterized by high energy requirements, such as the heart, skeletal muscle, adipose tissue, kidney, and brain. Abscisic acid (ABA), traditionally acknowledged as a plant stress hormone, is detected and actively functions in organisms beyond the land plant kingdom, encompassing cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. Its ancient, cross-kingdom role enables ABA and its signaling pathway to regulate cell responses to environmental stimuli in various organisms, such as marine sponges, higher plants, and humans. Recent advancements in understanding the physiological function of ABA and its mammalian receptors in governing energy metabolism and mitochondrial function in myocytes, adipocytes, and neuronal cells suggest potential therapeutic applications for ABA in pre-diabetes, diabetes, and cardio-/neuroprotection. The ABA/LANCL1-2 hormone/receptor system emerges as a novel regulator of ERRα expression levels and transcriptional activity, mediated through the AMPK/SIRT1/PGC-1α axis. There exists a reciprocal feed-forward transcriptional relationship between the LANCL proteins and transcriptional coactivators ERRα/PGC-1α, which may be leveraged using natural or synthetic LANCL agonists to enhance mitochondrial function across various clinical contexts.

Irisin attenuates ventilator-induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK.

Mechanical ventilation (MV) is an essential life-saving technique, but prolonged MV can cause significant diaphragmatic dysfunction due to atrophy and decreased contractility of the diaphragm fibres, called ventilator-induced diaphragmatic dysfunction (VIDD). It is not clear about the mechanism of occurrence and prevention measures of VIDD. Irisin is a newly discovered muscle factor that regulates energy metabolism. Studies have shown that irisin can exhibit protective effects by downregulating endoplasmic reticulum (ER) stress in a variety of diseases; whether irisin plays a protective role in VIDD has not been reported. Sprague-Dawley rats were mechanically ventilated to construct a VIDD model, and intervention was performed by intravenous administration of irisin. Diaphragm contractility, degree of atrophy, cross-sectional areas (CSAs), ER stress markers, AMPK protein expression, oxidative stress indicators and apoptotic cell levels were measured at the end of the experiment.Our findings showed that as the duration of ventilation increased, the more severe the VIDD was, the degree of ER stress increased, and the expression of irisin decreased.ER stress may be one of the causes of VIDD. Intervention with irisin ameliorated VIDD by reducing the degree of ER stress, attenuating oxidative stress, and decreasing the apoptotic index. MV decreases the expression of phosphorylated AMPK in the diaphragm, whereas the use of irisin increases the expression of phosphorylated AMPK. Irisin may exert its protective effect by activating the phosphorylated AMPK pathway.

Interplay of human gastrointestinal microbiota metabolites: Short-chain fatty acids and their correlation with Parkinson's disease.

Short-chain fatty acids (SCFAs) are, the metabolic byproducts of intestinal microbiota that, are generated through anaerobic fermentation of undigested dietary fibers. SCFAs play a pivotal role in numerous physiological functions within the human body, including maintaining intestinal mucosal health, modulating immune functions, and regulating energy metabolism. In recent years, extensive research evidence has indicated that SCFAs are significantly involved in the onset and progression of Parkinson disease (PD). However, the precise mechanisms remain elusive. This review comprehensively summarizes the progress in understanding how SCFAs impact PD pathogenesis and the underlying mechanisms. Primarily, we delve into the synthesis, metabolism, and signal transduction of SCFAs within the human body. Subsequently, an analysis of SCFA levels in patients with PD is presented. Furthermore, we expound upon the mechanisms through which SCFAs induce inflammatory responses, oxidative stress, abnormal aggregation of alpha-synuclein, and the intricacies of the gut-brain axis. Finally, we provide a critical analysis and explore the potential therapeutic role of SCFAs as promising targets for treating PD.

Ginsenoside Rh2 shifts tumor metabolism from aerobic glycolysis to oxidative phosphorylation through regulating the HIF1-α/PDK4 axis in non-small cell lung cancer

BackgroundGinsenoside Rh2 (G-Rh2), a steroidal compound extracted from roots of ginseng, has been extensively studied in tumor therapy. However, its specific regulatory mechanism in non-small cell lung cancer (NSCLC) is not well understood. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in various malignant tumors. We investigated the impact of G-Rh2 on the malignant progression of NSCLC and how it regulated PDK4 to influence tumor aerobic glycolysis and mitochondrial function.MethodWe examined the inhibitory effect of G-Rh2 on NSCLC through I proliferation assay, migration assay and flow cytometry in vitro. Subsequently, we verified the ability of G-Rh2 to inhibit tumor growth and metastasis by constructing subcutaneous tumor and metastasis models in nude mice. Proteomics analysis was conducted to analyze the action pathways of G-Rh2. Additionally, we assessed glycolysis and mitochondrial function using seahorse, PET-CT, Western blot, and RT-qPCR.ResultTreatment with G-Rh2 significantly inhibited tumor proliferation and migration ability both in vitro and in vivo. Furthermore, G-Rh2 inhibited the tumor’s aerobic glycolytic capacity, including glucose uptake and lactate production, through the HIF1-α/PDK4 pathway. Overexpression of PDK4 demonstrated that G-Rh2 targeted the inhibition of PDK4 expression, thereby restoring mitochondrial function, promoting reactive oxygen species (ROS) accumulation, and inducing apoptosis. When combined with sodium dichloroacetate, a PDK inhibitor, it complemented the inhibitory capacity of PDKs, acting synergistically as a detoxifier.ConclusionG-Rh2 could target and down-regulate the expression of HIF-1α, resulting in decreased expression of glycolytic enzymes and inhibition of aerobic glycolysis in tumors. Additionally, by directly targeting mitochondrial PDK, it elevated mitochondrial oxidative phosphorylation and enhanced ROS accumulation, thereby promoting tumor cells to undergo normal apoptotic processes.

Study on the estradiol degradation gene expression and resistance mechanism of Rhodococcus R-001 under low-temperature stress

Estradiol (E2), an endocrine disruptor, acts by mimicking or interfering with the normal physiological functions of natural hormones within organisms, leading to issues such as endocrine system disruption. Notably, seasonal fluctuations in environmental temperature may influence the degradation speed of estradiol (E2) in the natural environment, intensifying its potential health and ecological risks. Therefore, this study aims to explore how bacteria can degrade E2 under low-temperature conditions, unveiling their resistance mechanisms, with the goal of developing new strategies to mitigate the threat of E2 to health and ecological safety. In this paper, we found that Rhodococcus equi DSSKP-R-001 (R-001) can efficiently degrade E2 at 30 °C and 10 °C. Six genes in R-001 were shown to be involved in E2 degradation by heterologous expression at 30 °C. Among them, 17β-HSD, KstD2, and KstD3, were also involved in E2 degradation at 10 °C; KstD was not previously known to degrade E2. RNA-seq was used to characterize differentially expressed genes (DEGs) to explore the stress response of R-001 to low-temperature environments to elucidate the strain's adaptation mechanism. At the low temperature, R-001 cells changed from a round spherical shape to a long rod or irregular shape with elevated unsaturated fatty acids and were consistent with the corresponding genetic changes. Many differentially expressed genes linked to the cold stress response were observed. R-001 was found to upregulate genes encoding cold shock proteins, fatty acid metabolism proteins, the ABC transport system, DNA damage repair, energy metabolism and transcriptional regulators. In this study, we demonstrated six E2 degradation genes in R-001 and found for the first time that E2 degradation genes have different expression characteristics at 30 °C and 10 °C. Linking R-001 to cold acclimation provides new insights and a mechanistic basis for the simultaneous degradation of E2 under cold stress in Rhodococcus adaptation.

In vivo evidence of sea buckthorn relieving oxidative stress and improving immune performance of common carp (Cyprinus carpio L.).

Sea buckthorn has the functions of antioxidation, antitumor, anti-inflammation and regulating energy metabolism. In order to investigate the effects of sea buckthorn powder and sea buckthorn flavonoids on the antioxidant properties, immune function and muscle fatty acid composition of common carp, an oral feeding experiment was carried out. The administration of glucose significantly reduced the levels of glutathione and the activity of total antioxidant capacity enzyme in serum and hepatopancreas, while concurrently upregulating the level of malondialdehyde (MDA)(P < 0.05). Conversely, oral intake of sea buckthorn powder and flavonoids increased antioxidant enzyme activity and decreased MDA levels. In terms of antioxidant molecular indicators, sea buckthorn powder and sea buckthorn flavonoids significantly increased the mRNA levels of nuclear factor NF-E2-related factor (nrf2) in the hepatopancreas and muscle. Meanwhile, mRNA expression levels of downstream antioxidant-related genes (gr, cat, gpx, and sod) regulated by Nrf2 were also upregulated. In the immune aspects, the mRNA expression levels of proinflammatory cytokines, such as interleukin-6 (il-6), interleukin-1β (il-1β) and nuclear factor-κB (nf-κb), were reduced but the expressions of anti-inflammatory cytokines, such as growth factor-β (tgf-β) and interleukin-10 (il-10), were enhanced in the head kidney and spleen tissues after oral administration with sea buckthorn. In terms of muscle fatty acid composition, the ratio of n-3 polyunsaturated fatty acid (PUFA)/n-6 PUFA was notably higher after administering sea buckthorn flavonoids than that of the glucose group (P < 0.05). This study demonstrated that oral administration of sea buckthorn powder and sea buckthorn flavonoids significantly enhanced the antioxidant capacity and immune response and improved the muscle fatty acid compositions in common carp, and also mitigated the adverse effects of glucose treatment to a certain extent. © 2024 Society of Chemical Industry.

Prolyl isomerase Pin1 in skeletal muscles contributes to systemic energy metabolism and exercise capacity through regulating SERCA activity

The skeletal muscle is a pivotal organ involved in the regulation of both energy metabolism and exercise capacity. There is no doubt that exercise contributes to a healthy life through the consumption of excessive energy or the release of myokines. Skeletal muscles exhibit insulin sensitivity and can rapidly uptake blood glucose. In addition, they can undergo non-shivering thermogenesis through actions of both the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) and small peptide, sarcolipin, resulting in systemic energy metabolism. Accordingly, the maintenance of skeletal muscles is important for both metabolism and exercise. Prolyl isomerase Pin1 is an enzyme that converts the cis-trans form of proline residues and controls substrate function. We have previously reported that Pin1 plays important roles in insulin release, thermogenesis, and lipolysis. However, the roles of Pin1 in skeletal muscles remains unknown. To clarify this issue, we generated skeletal muscle-specific Pin1 knockout mice.Pin1 deficiency had no effects on muscle weights, morphology and ratio of fiber types. However, they showed exacerbated obesity or insulin resistance when fed with a high-fat diet. They also showed a lower ability to exercise than wild type mice did. We also found that Pin1 interacted with SERCA and elevated its activity, resulting in the upregulation of oxygen consumption. Overall, our study reveals that Pin1 in skeletal muscles contributes to both systemic energy metabolism and exercise capacity.

Independent organelle and organelle-organelle interactions: essential mechanisms for malignant gynecological cancer cell survival.

Different eukaryotic cell organelles (e.g., mitochondria, endoplasmic reticulum, lysosome) are involved in various cancer processes, by dominating specific cellular activities. Organelles cooperate, such as through contact points, in complex biological activities that help the cell regulate energy metabolism, signal transduction, and membrane dynamics, which influence survival process. Herein, we review the current studies of mechanisms by which mitochondria, endoplasmic reticulum, and lysosome are related to the three major malignant gynecological cancers, and their possible therapeutic interventions and drug targets. We also discuss the similarities and differences of independent organelle and organelle-organelle interactions, and their applications to the respective gynecological cancers; mitochondrial dynamics and energy metabolism, endoplasmic reticulum dysfunction, lysosomal regulation and autophagy, organelle interactions, and organelle regulatory mechanisms of cell death play crucial roles in cancer tumorigenesis, progression, and response to therapy. Finally, we discuss the value of organelle research, its current problems, and its future directions.

AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation.

Zinc-alpha2-glycoprotein (AZGP1) has been implicated in peripheral metabolism; however, its role in regulating energy metabolism in the brain, particularly in POMC neurons, remains unknown. Here, we show that AZGP1 in POMC neurons plays a crucial role in controlling whole-body metabolism. POMC neuron-specific overexpression of Azgp1 under high-fat diet conditions reduces energy intake, raises energy expenditure, elevates peripheral tissue leptin and insulin sensitivity, alleviates liver steatosis, and promotes adipose tissue browning. Conversely, mice with inducible deletion of Azgp1 in POMC neurons exhibit the opposite metabolic phenotypes, showing increased susceptibility to diet-induced obesity. Notably, an increase in AZGP1 signaling in the hypothalamus elevates STAT3 phosphorylation and increases POMC neuron excitability. Mechanistically, AZGP1 enhances leptin-JAK2-STAT3 signaling by interacting with acylglycerol kinase (AGK) to block its ubiquitination degradation. Collectively, these results suggest that AZGP1 plays a crucial role in regulating energy homeostasis and glucose/lipid metabolism by acting on hypothalamic POMC neurons.

Ingredients in Rhus chinensis Mill. fruits oil relieve fatigue by reducing oxidative damage and regulating energy metabolism and gut microbiota

Fatigue is an intricate physiological phenomenon, causing serious secondary concerns and bioregulation disorders. The objective of this research was to look into the anti-fatigue effect and potential mechanisms of natural ingredients in methanol extract of edible oil from Rhus chinensis Mill. fruits (PMRO). Results showed that a total of 18 fatty acids and 9 anacardic acids were identified by GC-MS and UHPLC-ESI-HCES/MS in PMRO. PMRO significantly increased the weight-bearing swimming time. Further investigations showed that PMRO significantly improved physiological indexes related to fatigue and regulated the oxidative stress (Keap1/Nrf2) and energy metabolism (AMPK/PGC-1α)-related proteins expression to exert anti-fatigue effects. The 16S rRNA sequence analysis indicated that a potential role of PMRO in modulating the abundance of gut bacteria and influencing the short-chain fatty acids content, thereby exerting an anti-fatigue effect. Therefore, the natural ingredients in PMRO may hold promise as a dietary supplement capable of delaying body fatigue.

Anthocyanins prevent the development and progression of urethane-induced lung cancer by regulating energy metabolism in mice.

Anthocyanin (ACN) is a natural antioxidant with multiple biological activities, and the aim of this study was to evaluate the protective effect of ACN on the development and progression of lung cancer and to further explore its possible mechanism of action. In vivo, we fed C57BL/6J mice a 0.5%ACN diet or a control diet to observe their effects on the development and progression of urethane-induced lung cancer. In vitro, multiple lung cancer cell lines were used to investigate the effects of C3G on cell viability. The results showed a reduction in lung tumor burden and downregulation of oxidative phosphorylation and fatty acid degradation pathways in lung tissue of urethane-administrated ACN-fed mice compared with control diet-fed mice. In vitro, cyanidin-3-O-glucoside chloride (C3G) intervention treatment significantly inhibited proliferation and apoptosis of A549 cells. This process is likely due to the modulation of AMPK/mTOR signaling pathway by C3G to regulate cellular fatty acid metabolism and reduce intracellular lipid accumulation which affects the growth of lung cancer cells. These results suggest that ACN can inhibit the development and progression of urethane-induced lung tumors and alter the lipid metabolism of tumors in C57BL/6J mice.

The Water Extract of Rhubarb Prevents Ischemic Stroke by Regulating Gut Bacteria and Metabolic Pathways.

Rhubarb (RR), Chinese name Dahuang, is commonly used in the treatment of ischemic stroke (IS). However, its potential mechanism is not fully elucidated. This study intended to verify the effect of RR on IS and investigate the possible mechanism of RR in preventing IS. IS in male rats was induced by embolic middle cerebral artery occlusion (MCAO) surgery, and drug administration was applied half an hour before surgery. RR dramatically decreased the neurological deficit scores, the cerebral infarct volume, and the cerebral edema rate, and improved the regional cerebral blood flow (rCBF) and histopathological changes in the brain of MCAO rats. The 16S rRNA analysis showed the harmful microbes such as Fournierella and Bilophila were decreased, and the beneficial microbes such as Enterorhabdus, Defluviitaleaceae, Christensenellaceae, and Lachnospira were significantly increased, after RR pretreatment. 1H-nuclear magnetic resonance (1H-NMR) was used to detect serum metabolomics, and RR treatment significantly changed the levels of metabolites such as isoleucine, valine, N6-acetyllysine, methionine, 3-aminoisobutyric acid, N, N-dimethylglycine, propylene glycol, trimethylamine N-oxide, myo-inositol, choline, betaine, lactate, glucose, and lipid, and the enrichment analysis of differential metabolites showed that RR may participate in the regulation of amino acid metabolism and energy metabolism. RR exerts the role of anti-IS via regulating gut bacteria and metabolic pathways.

The 26RFa (QRFP)/GPR103 Neuropeptidergic System: A Key Regulator of Energy and Glucose Metabolism.

Obesity and type 2 diabetes are strongly associated pathologies, currently considered as a worldwide epidemic problem. Understanding the mechanisms that drive the development of these diseases would enable to develop new therapeutic strategies for their prevention and treatment. Particularly, the role of the brain in energy and glucose homeostasis has been studied for 2 decades. In specific, the hypothalamus contains well-identified neural networks that regulate appetite and potentially also glucose homeostasis. A new concept has thus emerged, suggesting that obesity and diabetes could be due to a dysfunction of the same, still poorly understood, neural networks. The neuropeptide 26RFa (also termed QRFP) belongs to the family of RFamide regulatory peptides and has been identified as the endogenous ligand of the human G protein-coupled receptor GPR103 (QRFPR). The primary structure of 26RFa is strongly conserved during vertebrate evolution, suggesting its crucial roles in the control of vital functions. Indeed, the 26RFa/GPR103 peptidergic system is reported to be involved in the control of various neuroendocrine functions, notably the control of energy metabolism in which it plays an important role, both centrally and peripherally, since 26RFa regulates feeding behavior, thermogenesis and lipogenesis. Moreover, 26RFa is reported to control glucose homeostasis both peripherally, where it acts as an incretin, and centrally, where the 26RFa/GPR103 system relays insulin signaling in the brain to control glucose metabolism. This review gives a comprehensive overview of the role of the 26RFa/GPR103 system as a key player in the control of energy and glucose metabolism. In a pathophysiological context, this neuropeptidergic system represents a prime therapeutic target whose mechanisms are highly relevant to decipher.

Glucagon-like peptide (GLP)-1 regulation of lipid and lipoprotein metabolism

Abstract Metabolic health is highly dependent on intestinal and hepatic handling of dietary and endogenous lipids and lipoproteins. Disorders of lipid and lipoprotein metabolism are commonly observed in patients with insulin resistant states such as obesity, metabolic syndrome, and type 2 diabetes. Evidence from both animal models and human studies indicates that a major underlying factor in metabolic or diabetic dyslipidemia is the overproduction of hepatic and intestinal apolipoprotein (apo)B-containing lipoprotein particles. These particles are catabolized down into highly proatherogenic remnants, which can be taken up into the arterial intima and promote plaque development. Several gut-derived peptides have been identified as key regulators of energy metabolism; one such peptide is the incretin hormone glucagon-like peptide (GLP)-1. Our laboratory has previously demonstrated that GLP-1 can signal both centrally and peripherally to reduce postprandial and fasting lipoprotein secretion. Moreover, we have demonstrated that GLP-1 receptor (GLP-1R) agonists can ameliorate diet-induced dyslipidemia. Recently, we published evidence for a novel vagal neuroendocrine signalling pathway by which native GLP-1 may exert its anti-lipemic effects. Furthermore, we demonstrated a novel role for other gut-derived peptides in regulating intestinal lipoprotein production. Overall, ample evidence supports a key role for GLP-1R on the portal vein afferent neurons and nodose ganglion in modulating intestinal fat absorption and lipoprotein production and identifies other gut-derived peptides as novel regulators of postprandial lipemia. Insights from these data may support identification of potential drug targets and the development of new therapeutics targeting treatment of diabetic dyslipidemia.

The molecular mechanism of macrophage-adipocyte crosstalk in maintaining energy homeostasis.

Interactions between macrophages and adipocytes in adipose tissue are critical for the regulation of energy metabolism and obesity. Macrophage polarization induced by cold or other stimulations can drive metabolic reprogramming of adipocytes, browning, and thermogenesis. Accordingly, investigating the roles of macrophages and adipocytes in the maintenance of energy homeostasis is critical for the development of novel therapeutic approaches specifically targeting macrophages in metabolic disorders such as obesity. Current review outlines macrophage polarization not only regulates the release of central nervous system and inflammatory factors, but controls mitochondrial function, and other factor that induce metabolic reprogramming of adipocytes and maintain energy homeostasis. We also emphasized on how the adipocytes conversely motivate the polarization of macrophage. Exploring the interactions between adipocytes and macrophages may provide new therapeutic strategies for the management of obesity-related metabolic diseases.

Feedback regulation between AMPK and HIF-1α contributes to color stability via energy metabolism and mitochondrial efficiency regulation of yak meat

Despite the well-established individual roles of AMP-activated protein kinase (AMPK) and hypoxia-inducible factor-1α (HIF-1α) in sensing energy stress and/or hypoxia in postmortem muscle, a knowledge gap persists regarding their interplay and the consequent impact on the yak meat color stability. This study aimed to elucidate the AMPK–HIF–1α interaction and its consequential impact on mitochondrial functionality, energy metabolism, and ultimately, color attributes. Postmortem yak longissimus thoracis et lumborum (LTL) muscles were incubated with saline, AMPK inhibitor (Compound C), Compound C plus HIF-1α activator (DMOG), and Compound C plus HIF-1α inhibitor (YC-1) for 0, 6, 12, 24, 72, and 120 h, respectively. Results indicate that Compound C hindered the nuclear translocation of HIF-1α (P < 0.001), in turn, DMOG upregulated AMPK protein levels (P < 0.05) by a yet unknown mechanism. Mass spectrometry analysis identified seven AMPK-induced phosphorylation sites (Ser58, Thr63, Ser65, Tyr66, Thr677, Ser14, and Ser15) mapped onto three phosphopeptides on HIF-1α. Moreover, Compound C induced a significant reduction in energy metabolism levels, evidenced by decreased glycogen degradation, lactate accumulation, and pH decline (P < 0.05). Besides, Compound C promoted a consistently decreased mitochondrial protein yield, reduced NADH content, and OCR (P < 0.05). However, DMOG attenuated the effects of Compound C on mitochondrial efficiency, and interconversion of oxy-to deoxymyoglobin. Collectively, these findings establish the collaborative influence of AMPK and HIF-1α on postmortem energy metabolism, concurrently emphasizing their antagonistic effects on mitochondrial function.

Regulatory mechanisms of autophagy on DHA and carotenoid accumulation in Crypthecodinium sp. SUN

BackgroundAutophagy is a crucial process of cellular self-destruction and component reutilization that can affect the accumulation of total fatty acids (TFAs) and carotenoids in microalgae. The regulatory effects of autophagy process in a docosahexaenoic acid (DHA) and carotenoids simultaneously producing microalga, Crypthecodinium sp. SUN, has not been studied. Thus, the autophagy inhibitor (3-methyladenine (MA)) and activator (rapamycin) were used to regulate autophagy in Crypthecodinium sp. SUN.ResultsThe inhibition of autophagy by 3-MA was verified by transmission electron microscopy, with fewer autophagy vacuoles observed. Besides, 3-MA reduced the glucose absorption and intracellular acetyl-CoA level, which resulting in the decrease of TFA and DHA levels by 15.83 and 26.73% respectively; Surprisingly, 3-MA increased intracellular reactive oxygen species level but decreased the carotenoids level. Comparative transcriptome analysis showed that the downregulation of the glycolysis, pentose phosphate pathway and tricarboxylic acid cycle may underlie the decrease of acetyl-CoA, NADPH and ATP supply for fatty acid biosynthesis; the downregulation of PSY and HMGCR may underlie the decreased carotenoids level. In addition, the class I PI3K-AKT signaling pathway may be crucial for the regulation of carbon and energy metabolism. At last, rapamycin was used to activate autophagy, which significantly enhanced the cell growth and TFA level and eventually resulted in 1.70-fold increase in DHA content.ConclusionsOur findings indicate the mechanisms of autophagy in Crypthecodinium sp. SUN and highlight a way to manipulate cell metabolism by regulating autophagy. Overall, this study provides valuable insights to guide further research on autophagy-regulated TFA and carotenoids accumulation in Crypthecodinium sp. SUN.

Oxalic acid alleviates chilling injury and positively influences post-harvest parameters of sweet bell pepper by affecting glycine betaine accumulation, cells respiration rate and NADPH oxidase enzyme activity during cold storage

Bell pepper as tropical crop and warm-season vegetable is sensitive to cold storage under temperatures below 7.5 °C. The purposes of the current study were to investigate the influence of pre-harvest treatment of oxalic acid (OA 0, 1, 5, 10, and 15 mM) on some of most important morphological, physiological and bio-chemical characteristics of red bell pepper cv. "2090 Westland" at post-harvest stage, and assessment of mechanisms and enzymatic pathways of crop response to OA treatments. OA treatments greatly reduced the chilling index, and the positive effects of treatments enhanced by increasing the concentration of OA. The energy level (ATP content) of pepper fruits decreased with extending storage duration, but OA treatment maintained the ATP content of fruits. On 24 d of storage, the highest and lowest activity rate of NADPH oxidase enzyme was recorded in control and 10 mM-treated fruits. Extending storage duration led to a significant increase in cells respiration rate, but this increase was more pronounced in control. Oxalic acid as low-risk and environmentally friendly compound could be an appropriate choice to apply as pre-harvest treatment in order to extend shelf-life of bell pepper fruits during cold storage under 4 ºC. The most important mechanisms reaction of OA are enhancing of enzymatic and non-enzymatic antioxidant activities, increasing the accumulation rate of osmoprotectants and regulation of energy metabolism of cells. Pre-harvest treatment of OA 10 mM could be introduced as efficient technique to overcome adverse effects of chilling stress on post-harvest characteristics of bell pepper.

Review of Saponins in Treating Heart Failure

Traditional Chinese Medicine (TCM) has a long history and rich experience in treating Heart Failure (HF), with good clinical effect and little side effects. Saponins, as one of the active substances in TCM, have a variety of pharmacological activities, wide sources and low toxicity, and their functions can not be ignored. Further research on the role of saponins in the treatment of HF found that saponins have the advantages of multi-level, multi-target and multi-channel comprehensive regulation effects, which has important research and development value in the treatment of HF. Through the analysis and summary of the related literatures on the mechanism of treating HF with saponins, it is found that saponins can improve heart function mainly by inhibiting inflammatory reaction, regulating energy metabolism disorder, resisting myocardial ischemia, inhibiting myocardial apoptosis and other ways. The purpose of this paper is to further explore the mechanism of saponin in treating different HF, and to provide further ideas and references for the research and drug development and application of TCM in preventing and treating HF.

Regulation of energy metabolism through central GIPR signaling

In recent years, significant progress has been made to pharmacologically combat the obesity pandemic, particularly with regard to biochemically tailored drugs that simultaneously target the receptors for glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP). But while the pharmacological benefits of GLP-1 receptor (GLP-1R) agonism are widely acknowledged, the role of the GIP system in regulating systems metabolism remains controversial. When given in adjunct to GLP-1R agonism, both agonism and antagonism of the GIP receptor (GIPR) improves metabolic outcome in preclinical and clinical studies, and despite persistent concerns about its potential obesogenic nature, there is accumulating evidence indicating that GIP has beneficial metabolic effects via central GIPR agonism. Nonetheless, despite growing recognition of the GIP system as a valuable pharmacological target, there remains great uncertainty as to where and how GIP acts in the brain to regulate metabolism, and how GIPR agonism may differ from GIPR antagonism in control of energy metabolism. In this review we highlight current knowledge on the central action of GIP, and discuss open questions related to its multifaceted biology in the brain and the periphery.