Energy Metabolism Disorder Research Articles

Safety of COVID-19 vaccines in children with inborn errors of metabolism in terms of developing metabolic decompensation.

AimThere are no recommended guidelines or clinical studies on safety of COVID‐19 vaccines in patients with inborn errors of metabolism (IEMs). Here, we aimed to examine the relationship between COVID‐19 vaccination and metabolic outcome in paediatric IEM patients.MethodsPatients with IEM between the ages of 12 and 18 were enrolled. Term metabolic decompensation was defined as acute disruption in metabolic homeostasis due to vaccination. Clinical and biochemical markers were compared between pre‐ and post‐vaccination periods.ResultsData from a total of 36 vaccination episodes in 18 patients were included. Thirteen patients had intoxication‐type metabolic disorders including organic acidemia (OA), urea cycle disorders (UCDs), maple syrup urine disease (MSUD) and phenylketonuria (PKU); 4 patients had energy metabolism disorders including fatty acid metabolism disorders and LIPIN 1 deficiency; and 1 patient had glycogen storage disorder (GSD) type 5. Seventeen patients received BNT162b2, and 1 received CoronaVac because of an underlying long QT syndrome. Fatty acid metabolism disorders, LIPIN 1 deficiency and GSD type 5 were included in the same group named ‘metabolic myopathies’. In two PKU patients, plasma phenylalanine level increased significantly within 24 h following the second dose of vaccination. None of the OA, UCD, MSUD and metabolic myopathy patients experienced acute metabolic attack and had emergency department admission due to metabolic decompensation within 1 month after vaccination.ConclusionsCOVID‐19 vaccines did not cause acute metabolic decompensation in a cohort of 18 children with IEM.

Atlas of metabolism reveals palmitic acid results in mitochondrial dysfunction and cell apoptosis by inhibiting fatty acid β-oxidation in Sertoli cells.

In recent years, the impact of lipotoxicity on male fertility has received extensive attention, especially on Sertoli cells (SCs). In SCs, energy metabolism is important as disorders of energy metabolism result in infertility eventually. However, the underlying mechanism of lipotoxicity on energy metabolism in SCs remains unknown. Advances in high-throughput metabolomics and lipidomics measurement platforms provide powerful tools to gain insights into complex biological systems. Here, we aimed to explore the potential molecular mechanisms of palmitic acid (PA) regulating energy metabolism in SCs based on metabolomics and lipidomics. The results showed that glucose metabolism-related metabolites were not significantly changed, which suggested that PA treatment had little effect on glucose metabolism and may not influence the normal energy supply from SCs to germ cells. However, fatty acid β-oxidation was inhibited according to accumulation of medium- and long-chain acylcarnitines in cells. In addition, the pool of amino acids and the levels of most individual amino acids involved in the tricarboxylic acid (TCA) cycle were not changed after PA treatment in SCs. Moreover, PA treatment of SCs significantly altered the lipidome, including significant decreases in cardiolipin and glycolipids as well as remarkable increases in ceramide and lysophospholipids, which indicated that mitochondrial function was affected and apoptosis was triggered. The increased apoptosis rate of SCs was verified by elevated protein expression levels of Cleaved Caspase-3 and Bax as well as decreased Bcl-2 protein expression level. Together, these findings indicated that PA may result in mitochondrial dysfunction and increased apoptosis by inhibiting fatty acid β-oxidation of SCs.

Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications.

Ischemic stroke caused by arterial occlusion is the most common type of stroke and is one of the leading causes of disability and death, with the incidence increasing each year. Fyn is a nonreceptor tyrosine kinase belonging to the Src family of kinases (SFKs), which is related to many normal and pathological processes of the nervous system, including neurodevelopment and disease progression. In recent years, more and more evidence suggests that Fyn may be closely related to cerebral ischemia-reperfusion, including energy metabolism disorders, excitatory neurotoxicity, intracellular calcium homeostasis, free radical production, and the activation of apoptotic genes. This paper reviews the role of Fyn in the pathological process of cerebral ischemia-reperfusion, including neuroexcitotoxicity and neuroinflammation, to explore how Fyn affects specific signal cascades and leads to cerebral ischemia-reperfusion injury. In addition, Fyn also promotes the production of superoxide and endogenous NO, so as to quickly react to produce peroxynitrite, which may also mediate cerebral ischemia-reperfusion injury, which is discussed in this paper. Finally, we revealed the treatment methods related to Fyn inhibitors and discussed its potential as a clinical treatment for ischemic stroke.

Insight into the Effects of High-Altitude Hypoxic Exposure on Learning and Memory.

The earth land area is heterogeneous in terms of elevation; about 45% of its land area belongs to higher elevation with altitude above 500 meters compared to sea level. In most cases, oxygen concentration decreases as altitude increases. Thus, high-altitude hypoxic stress is commonly faced by residents in areas with an average elevation exceeding 2500 meters and those who have just entered the plateau. High-altitude hypoxia significantly affects advanced neurobehaviors including learning and memory (L&M). Hippocampus, the integration center of L&M, could be the most crucial target affected by high-altitude hypoxia exposure. Based on these points, this review thoroughly discussed the relationship between high-altitude hypoxia and L&M impairment, in terms of hippocampal neuron apoptosis and dysfunction, neuronal oxidative stress disorder, neurotransmitters and related receptors, and nerve cell energy metabolism disorder, which is of great significance to find potential targets for medical intervention. Studies illustrate that the mechanism of L&M damaged by high-altitude hypoxia should be further investigated based on the entire review of issues related to this topic.

The synergistic compatibility mechanisms of fuzi against chronic heart failure in animals: A systematic review and meta-analysis.

Background: Fuzi’s compatibilities with other medicines are effective treatments for chronic heart failure. Pre-clinical animal experiments have indicated many possible synergistic compatibility mechanisms of it, but the results were not reliable and reproducible enough. Therefore, we performed this systematic review and meta-analysis of pre-clinical animal studies to integrate evidence, conducted both qualitative and quantitative evaluations of the compatibility and summarized potential synergistic mechanisms. Method: An exhaustive search was conducted for potentially relevant studies in nine online databases. The selection criteria were based on the Participants, Interventions, Control, Outcomes, and Study designs strategy. The SYRCLE risk of bias tool for animal trials was used to perform the methodological quality assessment. RevMan V.5.3 and STATA/SE 15.1 were used to perform the meta-analysis following the Cochrane Handbook for Systematic Reviews of Interventions. Result: 24 studies were included in the systematic review and meta-analysis. 12 outcomes were evaluated in the meta-analysis, including BNP, HR, HWI, ALD, LVEDP, LVSP, EF, FS, +dP/dtmax, −dP/dtmax, TNF-α and the activity of Na + -K + -ATPase. Subgroup analyses were performed depending on the modeling methods and duration. Conclusion: The synergistic Fuzi compatibility therapeutic effects against CHF animals were superior to those of Fuzi alone, as shown by improvements in cardiac function, resistance to ventricular remodeling and cardiac damage, regulation of myocardial energy metabolism disorder and RAAS, alleviation of inflammation, the metabolic process in vivo, and inhibition of cardiomyocyte apoptosis. Variations in CHF modeling methods and medication duration brought out possible model–effect and time-effect relationships.

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy.

Heart failure occurs because of various cardiovascular pathologies, such as coronary artery disease or cardiorenal syndrome, eventually reaching end-stage disease. Various factors contribute to cardiac structural or functional changes that result in systolic or diastolic dysfunction. Several studies have confirmed that the key factor in heart failure progression is myocardial cell death, and mitophagy is the major mechanism regulating myocardial cell death in heart failure. The clinical mechanisms of heart failure are well understood in practice. However, the essential role of mitophagic regulation in heart failure has only recently received widespread attention. Receptor-mediated mitophagy is involved in various mitochondrial processes like oxidative stress injury, energy metabolism disorders, and calcium homeostasis, which are also the main causes of heart failure. Understanding of the diverse regulatory mechanisms in mitophagy and the complexity of its pathophysiology in heart failure remains incomplete. Related studies have found that various natural medicinal plants and active ingredients, such as flavonoids and saponins, can regulate mitophagy to a certain extent, improve myocardial function, and protect myocardial cells. This review comprehensively covers the relevant mechanisms of different types of mitophagy in regulating heart failure pathology and controlling mitochondrial adaptability to stress injury. Further, it explores the relationship between mitophagy and cardiac ejection dysfunction. Natural medicinal plant-targeted regulation strategies and scientific evidence on mitophagy were provided to elucidate current and potential strategies to apply mitophagy-targeted therapy for heart failure.

Cardiac-specific overexpression of Claudin-5 exerts protection against myocardial ischemia and reperfusion injury

Claudin-5 has recently attracted increasing attention by its potential as a novel treatment target in the early stage of heart failure. However, whether Claudin-5 produces beneficial effects on myocardial ischemia and reperfusion (IR) injury has not been elucidated yet. In this study, we identified reduced levels of Claudin-5 in the hearts of mice subjected to acute myocardial IR injury and murine HL-1 cardiomyocytes subjected to hypoxia and reoxygenation (HR). We then constructed cardiac-specific Cldn5-overexpressing mice using an adeno-associated virus (AAV9) vector and demonstrated that Cldn5 overexpression ameliorated cardiac dysfunction and myocardial damage in mice subjected to myocardial IR injury. Moreover, Cldn5 overexpression attenuated myocardial oxidative stress (DHE and protein levels of Nrf2, HO-1, and NQO1), inflammatory response (levels of MPO, F4/80, Ly6C, and circulating inflammatory cells), mitochondrial dysfunction (protein levels of PGC-1α, NRF1, and TFAM), endoplasmic reticulum stress (protein levels of GRP78, ATF6, and CHOP and p-PERK), energy metabolism disorder (p-AMPK and ACC), and apoptosis (TUNEL assay and protein levels of Bax and Bcl2) in mice subjected to myocardial IR. Next, we generated Cldn5 knockdown cells by lentiviral shRNA and observed that Cldn5 knockdown inhibited cell viability and affected the expression or activation of these IR-related signalings in HL-1 cardiomyocytes subjected to HR. Mechanistically, SIRT1 was proved to be involved in regulating the expression of Claudin-5 by co-immunoprecipitation analysis and Sirt1 knockdown experiments. Our data demonstrated that targeting Claudin-5 may represent a promising approach for preventing and treating acute myocardial IR injury.

Investigating the Metabolic Level of Endogenous and Exogenous Substances on the Intervention of Traditional Chinese Medicine Fuzheng Yiliu Decoction in a Rat Orthotopic Liver Cancer Model.

BackgroundFuzheng Yiliu decoction (FZYLD), a Chinese formula consisting of four herbs, can be clinically used as an adjuvant therapy after surgery or palliative treatment for advanced liver cancer.MethodsThis study identified the endogenous and exogenous metabolites of FZYLD in rat serum to characterize the underlying mechanism of its antitumor activity, as well as relieving cancer-related weakness. An orthotopic transplantation rat model of HepG2 cells was established and administered with FZYLD by gastric perfusion for 14 days. Cardiopulmonary function and tail suspension test were used to evaluate the bodily weakness of hepatocellular carcinoma (HCC) rats. Tumor weight and size were measured to calculate inhibition ratios. Serum of different concentrations of FZYLD was used to culture the 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose-labeled HepG2 cells. IC50 value was measured using MTT assay. Endogenous and exogenous metabolites in rat serum were detected using nuclear magnetic resonance or LC-MS/MS spectroscopy.ResultsFZYLD improved cardiopulmonary function, decreased immobility time in tail suspension test, and yielded tumor inhibition ratios of up to 27%. Serum endogenous markers, such as lipoproteins (high- and low-density lipoproteins), glucose, and valine, and lactic acid metabolic disturbance were recovered, to some extent, in HCC rats. Exogenous metabolites, diosgenin, apigenin-7-O-acetyl-β-D-glucoside, calycosin-7-glucoside, calycosin, ganoderic-acid-A, formononetin, and methylnissolin, became detectable in the blood. FZYLD-containing serum substantially inhibited the proliferation of HepG2-cells. IC50 value was found to be 24.31%. Further, we confirmed that FZYLD could revert energy and lipid metabolism disorders and that its constituents could be bioactive components that induce apoptosis in cancer cells.ConclusionThe present study explained the mechanism of the effect of FZYLD on body empty, fatigue, and low immunity in patients with cancer, offering an efficient way for research of natural compounds in traditional Chinese medicine.

Epigenetic regulation in energy metabolism: Effects of physiological and dietary factors

Obesity represents a rapidly growing, major global health problem. A wide range of epigenetic regulatory mechanisms are associated with obesity-related metabolic changes. These mechanisms include (a) changes to epigenetic regulation of neuroendocrine regulators such as adipocytokines and hypothalamic neurons that affect food intake, as well as (b) modulation of epigenetic programs by nutrients and other dietary components, and by the gut microbiome metabolites of these dietary components. Herein, an analysis of such epigenetic regulation is presented, and examples are discussed in relation to energy metabolism, obesity, and related metabolic disorders. • Epigenetic regulatory mechanisms can influence obesity-related metabolic changes. • Adipocytokines and other neuroendocrine factors are subject to epigenetic regulation. • Nutrients and microbiome metabolites of dietary components can influence metabolism through epigenetic changes.

The Role of Fibroblast Growth Factor 21 as an Endocrine Regulator of Lipid Metabolism: From Progression to Pathophysiology and Physiology

Objective: The primary aim of this research was to study the molecular history of fibroblast growth factor 21 (FGF21) as well as its physiological and pathological functions. Study Design: Observational study Place and Duration: This study was carried out at Hayatabad Medical Complex from December 2021 to April 2022 Methods: There were 77 patients of non-alcoholic fatty disease had age 20-65 years were presented in this study. After obtaining informed written consent details demographics were recorded. Diseases of all the patients were recorded and their relation with the FGF21 levels was observed. SPSS 23.0 was used to analyze all data. Mean standard deviation was use for categorical variables. Results: There were 42 (54.5%) males and 35 (45.5%) females among all cases. Mean age of the patients was 40.11±8.74 years and had mean BMI 27.8±11.34 kg/m2. Majority of the patients 31 (40.3%) had diabetes mellitus, 24 (31.2%) cases had renal failure, 20 (25.97%) cases had cardiovascular disease, mitochondrial disease in 17 (22.1%) cases, energy metabolism disorder in 15 (19.5%), lipid metabolism disorder in 13 (16.9%) and frequency of stroke was 9 (11.7%). We found significantly increased volume of FGF21 among diabetic obese cases which were resistant to insulin with p value <0.005. Conclusion: Pathophysiological functions, potential risk factors, and diagnostic biomarkers for endocrine FGFs in adult metabolic and genetic diseases are all supported by the available evidence. Pharmaceutical research is being conducted on endocrine FGFs. These results provide insight on the pathological and physiological functions of endocrine FGFs and offer new insights into the diagnosis and treatment of metabolic disorders. Keywords: FGF21, Lipid Metabolism, Pathaphysiology, Outcomes

Effects of Sheep Bone Collagen Peptide on Liver Lipid Deposition in Ovariectomized Rats.

Liver can be directly involved in the synthesis and decomposition of fatty acids. Liver lipid deposition is one of the most common chronic liver diseases. Estrogen deficiency can cause lipid deposition and energy metabolism disorders in the liver. Sheep bone collagen peptide (SBCP) has been shown to have estrogen-like effects in previous studies. And SBCP has high bioavailability, safety and non-toxic side effects. This study aimed to investigate the effect of SBCP on liver lipid deposition (LLD) caused by estrogen deficiency. Female Wistar rats were treated as follows (n=10): sham group: underwent peri-ovary fat removal operations, ovariectomized rats (model group), ovariectomized rats receiving SBCP treatments: SBCP high dose group (SBCP-H), SBCP medium dose group (SBCP-M) and SBCP low dose group (SBCP-L). After 8 wk, the model group demonstrated severe LLD and liver pathological changes, with increased malondialdehyde (MDA) and free fatty acid (FFA) levels (p<0.05). Additionally, the total superoxide dismutase (T-SOD) activity (p<0.05), serum albumin-to-globulin (A/G) ratio (p<0.05), amount of butyric acid-producing bacteria and short-chain fatty acids (SCFAs) content decreased. SBCP intervention could inhibit the occurrence of LLD and alleviate the liver histopathological damage induced by estrogen deficiency by relieving oxidative stress, preventing the loss of butyric acid-producing bacteria, and decreasing the abundance of Lactobacillus reuteri in the gut. The results suggested that SBCP could improve the LLD indecued by estrogen deficiency.

COVID-19 in Unvaccinated patients with inherited metabolic disorders: A single center experience

Patients with certain inherited metabolic disorders (IMD) are at high risk for metabolic decompensation with exposure to infections. The COVID-19 pandemic has been particularly challenging for health care providers dealing with IMD patients, in view of its unpredictable consequences in these patients. There is limited data in literature on evaluating the impact and the outcome of COVID-19 infection in these patients. This cross-sectional retrospective study on a large cohort of unvaccinated IMD patients, reviewed the incidence of COVID-19 infection, disease manifestation and outcome during the pandemic between November 2019 and July 2021. In this cohort of 1058 patients, 11.7% (n = 124) were infected with COVID-19. Their median age was 16 years (age range 2–42); 57% (n = 71) were males. Post-exposure positive test was noted in 78% (n = 97) patients, while 19% (n = 24) had symptomatic diagnosis and three patients tested positive during pre-hospital visits screening. Most patients, 68.5% (n = 85) had mild COVID-19 related symptoms such as fever, cough, headache and diarrhea while 13.7% (n = 17) patients had no symptoms. Of twenty-two patients (17.7%) who required hospitalization, 16 were adults with various intoxication and energy metabolism disorders, who developed IMD related complications such as metabolic acidosis, hyperammonemia, acute pancreatitis, hypoglycemia, rhabdomyolysis and thrombosis. Ten patients needed intensive care management. The cohort death rate was 2.4% (3 patients).Overall, the clinical course of COVID-19 infection in these IMD patients was relatively mild except for patients with intoxication and energy metabolism disorders who had high risk of developing acute metabolic decompensation with severe complications.

Sodium houttuyfonate protects against cardiac injury by regulating cardiac energy metabolism in diabetic rats

Diabetic cardiomyopathy is a diabetic complication with complicated pathophysiological changes and pathogenesis and difficult treatment. Sodium houttuyfonate is the adduct of sodium bisulfite and houttuynin, the main volatile component in Houttuynia cordata Thunb, possesses a variety of activities including multiple interventions on inhibiting ventricular remodeling. The study aims to explore effect of sodium houttuyfonate on diabetic myocardial injury and its underlying mechanisms. The diabetes model was established by intraperitoneal injection of streptozotocin at a dose of 85 mg/kg. By intragastric administration for 26 days, sodium houttuyfonate (50 and 100 mg/kg/d) reversed the abnormal serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, improved the abnormal levels of serum aspartate aminotransferase and brain natriuretic peptide, reduced electrocardiogram P-R and QRS interval extension, accelerated the heart rate, decreased serum malondialdehyde content, up-regulated the myocardial energy metabolism including elevated the contents of ATP, ADP, total adenine nucleotides and phosphocreatine in myocardium, decreased AMP/ATP ratio, elevated myocardial Ca2+-Mg2+-ATPase activity, and down-regulated the mRNA expressions of AMP protein activation kinase α2 (AMPK-α2) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). In a conclusion, these results suggest that sodium houttuyfonate can improve cardiac energy metabolism disorder caused by diabetes by increasing cardiac Ca2+-Mg2+-ATPase activity and regulating AMPK signaling pathway, and then attenuates cardiac injury caused by hyperglycemia. In addition, sodium houttuyfonate also has the effects of anti-oxidation and improving abnormal levels of blood lipid.

Energy metabolism disorders and oxidative stress in the SH-SY5Y cells following PM2.5 air pollution exposure

Studies have shown that PM2.5 exposure can induce neuronal apoptosis and neurobehavioral changes in animal experiments due partly to the mitochondria-mediated oxidative damage. How does it affect the mitochondrial energy metabolism as well as the neuronal damage, however, remain unclear. This study aimed to investigate the molecular processes of energy metabolism and oxidative damage induced by ambient PM2.5 exposure in SH-SY5Y cells. SH-SY5Y cells were treated with PM2.5 to establish a cytotoxicity model. A Seahorse Extracellular Flux Analyzer (XFp) was performed to evaluate the cellular mitochondrial respiratory and glycolysis after exposure to PM2.5. The dose- and time-dependent effects of PM2.5 on oxidative damage and apoptosis were analyzed. To further explore the relationship among oxidative damage, energy metabolism and apoptosis, SH-SY5Y cells were co-cultured with BHA and PM2.5 for 24 h. The results demonstrated that the basic respiration and ATP production, the typical index of mitochondrial respiration as well as glycolysis, significantly reduced in SH-SY5Y cells with dose and time dependent. At the same time, the PM2.5 could significantly decrease the cell viability and Mn-SOD activity, and increase the ROS levels and apoptosis rate as the escalation of dose and the extension of time. Importantly, the application of BHA could synchronously recover the PM2.5 induced cell energy metabolism disorder, oxidative damage, and apoptosis. It seems that the abnormal cellular energy metabolism may be caused by oxidative damage following fine particles exposure, and further led to apoptosis.

Cardiotonic Pills® protects from myocardial fibrosis caused by in stent restenosis in miniature pigs

BackgroundStent implantation has been increasingly applied for the treatment of obstructive coronary artery disease, which, albeit effective, often harasses patients by in-stent restenosis (ISR). PurposeThe present study was to explore the role of compound Chinese medicine Cardiotonic Pills® (CP) in attenuating ISR-evoked myocardial injury and fibrosis. Study DesignChinese miniature pigs were used to establish ISR model by implanting obsolete degradable stents into coronary arteries. Quantitative coronary angiography (QCA) was performed to confirm the success of the model. MethodsCP was given at 0.2 g/kg daily for 30 days after ISR. On day 30 and 60 after stent implantation, the myocardial infarct and myocardial blood flow (MBF) were assessed. Myocardial histology was evaluated by hematoxylin-eosin and Masson's trichrome staining. The content of ATP, MPO, and the activity of mitochondrial respiratory chain complex Ⅳ were determined by ELISA. Western blot was performed to assess the expression of ATP5D and related signaling proteins, and the mediators of myocardial fibrosis. ResultsTreatment with CP diminished myocardial infarct size, retained myocardium structure, attenuated myocardial fibrosis, and restored MBF. CP ameliorated energy metabolism disorder, attenuated TGFβ1 up-regulation and reversed its downstream gene expression, such as Smad6 and Smad7, and inhibited the increased expression of MCP-1, PR S19, MMP-2 and MMP-9. ConclusionCP effectively protects myocardial structure and function from ISR challenge, possibly by regulating energy metabolism via inactivation of RhoA/ROCK signaling pathway and inhibition of monocyte chemotaxis and TGF β1/Smads signaling pathway.

Evaluation of clinical and electroencephalographic findings in patients with early childhood epilepsy and inborn errors of metabolism

Epilepsy is one of the leading chronic diseases of childhood, and an underlying IEM is an etiology that can easily be overlooked. The aim of this study was to determine the frequency of metabolic disease in patients diagnosed with epilepsy in the first two years of life, as well as to determine the clinical, radiological, and electroencephalographic (EEG) characteristics of the metabolic disease subtypes associated with epilepsy and evaluate treatment response in our study. The records of patients diagnosed with epilepsy before the age of 2years in our pediatric neurology clinic between 2014 and 2021 were reviewed retrospectively. Those diagnosed with an IEM and followed up in the pediatric neurology and pediatric metabolism departments of our hospital were included in the study. A total of 990 patients under the age of 2years were diagnosed with epilepsy in the pediatric neurology clinic of our hospital and 74 (7.5%) of them had IEM. Thirty-nine (52.7%) of the 74 patients were female. The median age at admission was 144days (min-max: 0-284). Of the 74 patients diagnosed with metabolic epilepsy, 38 patients were diagnosed with amino acid metabolism disorder, 17 with lysosomal storage disease, 9 with energy metabolism disorder, 5 with vitamin/cofactor/trace element metabolism disorders, 2 with fatty acid metabolism disorder, 2 with peroxisomal disease, and 1 with carbohydrate metabolism disorder. Epilepsy was refractory despite appropriate treatment in 39 patients (52.7%). Inborn errors of metabolism are a rare cause of epilepsy, in regions like our country with high rates of consanguineous marriage, IEM should be considered in patients presenting with seizures that do not respond to conventional antiepileptic treatments.

Level of Student Knowledge about Obesity in Adolescents at SMA Negeri 3 Mataram

Obesity is a complex disorder of appetite regulation and energy metabolism that is controlled by several specific biological factors. The prevalence of obesity in several Southeast Asian countries shows a high percentage. Indonesia ranks second after Singapore with the most significant number of obese adolescents, 12.2%, then Thailand (8%), Malaysia (6%) and Vietnam (4.6%) (Unicef, 2012). The emergence of nutritional problems in adolescents is basically due to wrong dietary behaviour, which is an imbalance between nutritional consumption and recommended nutritional adequacy. This research uses a descriptive-analytic design with a cross-sectional approach. The population was all students of class XI of SMA Negeri 3 Mataram, totalling 430 people. The sample was 86 people with simple random sampling technique. The variable used in this study is the level of student knowledge about obesity in adolescents. The data collection method uses a questionnaire that has tested for validity and reliability. Data analysis uses univariate analysis. The results showed that of the 86 respondents there were students with sufficient knowledge of 44 people (51.2%), most students aged 15-17 years were 74 people (86%), the majority of students were female, namely 57 people (66, 3%), and most students with average body mass index are 51 people (59.3%). Suggestion: students are expected to be able to increase their knowledge and control food intake both in the amount of food, type of food and frequency of meals to achieve the ideal BMI.

Transcriptome analysis of emamectin benzoate caused midgut damage by inducing oxidative stress, energy metabolism disorder and apoptosis in gypsy moth (Lymantria dispar).

Emamectin benzoate (EMB) is a semisynthetic bioinsecticide, which has been widely used in the control of forestry and agricultural pests. However, the mechanism of its toxic effects on the non-neural tissues has been rarely reported. Here, we explored the mechanism of the midgut damage induced by EMB in gypsy moth (Lymantria dispar) in order to better understand the toxicological mechanism of EMB. Our results confirmed that EMB caused damage to the midgut of gypsy moth by inducing apoptosis. Transcriptome showed that 1469, 650 and 950 genes were significantly differentially expressed in the midgut of gypsy moth after 24, 48 and 72 h of EMB exposure, and oxidative stress, energy metabolism disorder and apoptosis may be related to the toxic effects of EMB. The indicators related to oxidative stress, energy metabolism and apoptosis were further examined. The results showed that EMB could cause oxidative stress by increasing ROS level and inhibiting antioxidant enzymes (P < 0.05), such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), which in turn causes mitochondria injury. Subsequently, energy metabolism was inhibited by downregulating the activities and mRNA level of energy metabolism enzymes. Furthermore, the mitochondrial apoptosis pathway was activated, triggering apoptosis, and eventually causing midgut injury in gypsy moth. Our results indicated that EMB caused damage to midgut by inducing oxidative stress, energy metabolism disorder and apoptosis in gypsy moth. Our findings shed new light on the toxicological mechanism of EMB on non-neural tissues from oxidative stress, energy metabolism and apoptosis perspectives. © 2022 Society of Chemical Industry.

Palmitate Induces Mitochondrial Energy Metabolism Disorder and Cellular Damage via the PPAR Signaling Pathway in Diabetic Cardiomyopathy.

PurposeTo establish an in vitro lipotoxicity model with mouse cardiomyocytes (MCMs) and investigate the molecular mechanism of the peroxisome proliferator-activated receptors (PPAR) signaling on mitochondrial energy metabolism disorder and cellular injury in diabetic cardiomyopathy (DCM).MethodsGene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the differentially expressed genes (DEGs) of DCM. CCK-8 method was used to detect the proliferation inhibition effect of palmitate (PA) on MCMs. Oil red O staining and mRNA levels of CD36 were used to verify intracellular lipid accumulation. DCFH-DA method was used to determine the content of intracellular reactive oxygen species (ROS), and ATP levels were detected by the ATP Detection Kit. Transmission electron microscope (TEM) was used to observe the mitochondrial structure. Western blot was used to detect the expression levels of PPARα, PPARγ, P-mTOR, mTOR, PGC-1α, UCP2, and BNP. In addition, the expression of PPARγ was also detected by cellular immunofluorescence staining. BNP levels were detected by qRT-PCR and the ELISA Kit.ResultsKEGG pathway analysis combined with GO analysis has shown that PPAR signaling played a significant regulatory role in mitochondrial biogenesis and fatty acid metabolism in DCM. Then, MCMs stimulated with PA for 24 h were selected as an in vitro lipotoxicity model. PA decreased cell viability, cell membrane shrinkage, and lipid accumulation. Meanwhile, PA-induced increase in cellular ROS led to ATP generation reduction and mitochondrial damage. Furthermore, the expression levels of p-mTOR- PPARα/γ were decreased, and the expressions of PGC-1α and UCP2 were increased. The levels of BNP were elevated, demonstrating PA impaired cardiomyocytes.ConclusionMitochondrial energy metabolism obstacle and cell injury appeared in cardiac lipotoxicity of DCM, associated with lipid accumulation and increased ROS, indicating a crosstalk with the PPAR pathway mediated mechanism.

Adropin's Role in Energy Homeostasis and Metabolic Disorders.

Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by the Enho gene, plays a crucial role in energy homeostasis. The literature review indicates that adropin alleviates the degree of insulin resistance by reducing endogenous hepatic glucose production. Adropin improves glucose metabolism by enhancing glucose utilization in mice, including the sensitization of insulin signaling pathways such as Akt phosphorylation and the activation of the glucose transporter 4 receptor. Several studies have also demonstrated that adropin improves cardiac function, cardiac efficiency and coronary blood flow in mice. Adropin can also reduce the levels of serum triglycerides, total cholesterol and low-density lipoprotein cholesterol. In contrast, it increases the level of high-density lipoprotein cholesterol, often referred to as the beneficial cholesterol. Adropin inhibits inflammation by reducing the tissue level of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6. The protective effect of adropin on the vascular endothelium is through an increase in the expression of endothelial nitric oxide synthase. This article provides an overview of the existing literature about the role of adropin in different pathological conditions.