scholarly journals PO-289 Lipidomic analysis of blood serum from prepubertal boys with different BMI

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Yuping Cao ◽  
Yi Yan ◽  
Minhao Xie
Keyword(s):  
Lipid Metabolism ◽  
Sex Hormones ◽  
Bone Growth ◽  
Metabolic Diseases ◽  
Bone Age ◽  
Liquid System ◽  
Lipid Species ◽  
Shbg Level ◽  
Prepubertal Boys ◽  
Lipid Metabolites

Objective Childhood obesity is a worldwide health problem which may causes metabolic diseases such as hyperglycemia, hyperlipidemia, hypertension and hyperuricemia. It is well know that lipid metabolites regulate fatty acid and glucose homeostasis. Lipidomics is the comprehensive analysis of lipid metabolites which include their quantitation and metabolic pathways. The intention of this study is to identify the circulating lipid species which are altered in obese prepubertal boys. Methods A total number of 72 boys aged 10.28 ±0.69 years old were included into this study, and divided into normal(NC), overweight(OW) and obese group(OB). The degree of maturation of all boys were measured by bone age and sex hormones. Then we measured the form indexes, blood lipids, blood glucose level to identify the current state of all boys. Serum indexes were detected by CLIA and ELISA methods. A lipidomic method was established by using a Waters Acquity UPLCI-Class liquid system combined with Waters Xevo G2-SQ-TOF mass spectrometry system. The identification and analysis of lipid metabolites were complished by using MassLynx 4.1, Progenesis QI software and LipidMaps database. Statistical analyzes were performed using SPSS22.0 software. Results (1)The waist-to-hip ratio, bone age and HDL-c levels ware significant lower in OW and OB groups. The TG level was significant higner in OB group. The DHEA and SHBG levels was significant higner in OW and OB groups and the other sex hormones are not . (2) In this study, 153 most significant different lipid metabolites were founded, incluing 3 diacylglycerol, 32 triglyceride, 1 Phosphatidyl cholines, 1 Phosphatidylinositol, 3 Sphingomyelin, 1 Ceramide which significant higher in OW&OB group; 4 diacylglycerol, 17 Phosphatidic acid, 32 Phosphatidyl cholines, 4 Phosphatidylinositol, 13 Phosphatidylserine, 18 Phosphatidyl ethanolamine, 3 Phosphoglycerides, 13 Sphingomyelin and 6 Ceramide which significant lower in OW&OB group. Among all this metabolites, 8 lipids (fold change ≥5) were founded as the significant biomarkers related prepubertal obesity , including 1 Phosphatidyl cholines, 1 phosphatidylserine, 2 sphingomyelin and 4 Triglyceride. What’s more, the level of SM(d16:1/24:0) and TG(15:0/17:1/20:3) which measured by UPLC-QTOF/MS are highly positive correlated with the level of serum SHBG; PC(18:0/0:0) and TG(16:1/18:0/20:3) are highly negtive correlated with serum SHBG. Conclusions Overweight and obese prepubertal boys showed disorder in lipid metabolism and bone growth. The lipidomic results showed lower SHBG level is related with the disorder of lipid metabolism. We suggest that further studies on these metabolites could help us gain a better understanding of the relationship between obesity and growth disorder.

Prenatal programming of hepatic lipid metabolism: Sex, hormones and lifelong health

2020 ◽  
Author(s):  
Katarzyna Siemienowicz ◽  
Panagiotis Filis ◽  
Chiara Talia ◽  
Jennifer Thomas ◽  
Paul Fowler ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Sex Hormones ◽  
Prenatal Programming ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

scholarly journals How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?

2021 ◽  
Vol 15 (1) ◽  
pp. 21-35
Author(s):  
Yana Geng ◽  
Klaas Nico Faber ◽  
Vincent E. de Meijer ◽  
Hans Blokzijl ◽  
Han Moshage
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Lipid Uptake ◽  
Cellular Mechanisms ◽  
Alcoholic Fatty Liver ◽  
Lipid Species ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the liver which is not due to alcohol use, has emerged as one of the major health problems around the world. The dysregulated lipid metabolism creates a lipotoxic environment which promotes the development of NAFLD, especially the progression from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on the mechanisms of lipid accumulation in the liver, with an emphasis on the metabolic fate of free fatty acids (FFAs) in NAFLD and presents an update on the relevant cellular processes/mechanisms that are involved in lipotoxicity. The changes in the levels of various lipid species that result from the imbalance between lipolysis/lipid uptake/lipogenesis and lipid oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial dysfunction, lysosomal dysfunction, JNK activation, secretion of extracellular vesicles (EVs) and aggravate (or be exacerbated by) hypoxia which ultimately lead to cell death. The aim of this review is to provide an overview of how abnormal lipid metabolism leads to lipotoxicity and the cellular mechanisms of lipotoxicity in the context of NAFLD.

scholarly journals OP0013 SEX DIFFERENCES IN AUTOIMMUNE DISEASE SUSCEPTIBILITY; A MULTI-OMIC APPROACH

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 8.1-8
Author(s):  
G. Robinson ◽  
K. Waddington ◽  
J. Peng ◽  
A. Radziszewska ◽  
H. Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
Lipid Metabolism ◽  
Sex Hormones ◽  
Cell Function ◽  
Immune Cell ◽  
Density Lipoprotein ◽  
Hormone Treatment ◽  
Immune Cell Function ◽  
Immune Cell Subsets ◽  
Males And Females

Background:Males and females have altered immune responses resulting in variation in autoimmune and cardiovascular disease risk (CVR). Recently, these differences have played a role in the inflammatory response to COVID-19. Sex differences exist in the frequency and activity of immune-cell subsets but mechanisms underlying sexual dimorphism remain unknown. Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder that commonly emerges during puberty, has a strong female prevalence (female:male ratio, 4.5:1) and results in an increased CVR. JSLE is characterised by chronic inflammation and dyslipidaemia, where cardiovascular disease is a leading cause of mortality for patients. Our previous work identified a link between immune cell function and lipid metabolism in adult-onset SLE. We hypothesised that sex hormones could influence both lipid metabolism and immune cell function and this could determine sex-specific susceptibility to JSLE and associated CVR.Objectives:We investigated the role of sex hormones in modifying systemic lipid metabolism and inflammation.Methods:Nuclear magnetic resonance spectroscopy based serum metabolomics measuring over 130 lipoproteins (14-subsets with lipid compositions), flow cytometry measuring immune-cells, and RNA-sequencing were used to assess the metabolic and immune profile in young, pre/post-pubertal males (n=10/17) and females (n=10/23) and in individuals with gender-dysphoria (GD) under cross-hormone treatment (trans-male/female, n=26/25). This analysis was also performed on a cohort of post-pubertal male (n=12) and female (n=23) JSLE patients. Data was analysed by logistic regression, balanced random forest machine learning (BRF-ML), differential gene expression (DEG) and pathway analysis.Results:Post-pubertal males had significantly reduced cardio-protective high-density lipoprotein (HDL) subsets (p<0.0001) and increased cardio-pathogenic very-low-density lipoprotein subsets (p<0.0001) compared to females. These differences were not observed pre-puberty and were reversed significantly by cross-hormone treatment in GD individuals, suggesting that sex hormones regulate lipid metabolism in-vivo.BRF-ML (28 immune-cell subsets) identified an increased frequency of anti-inflammatory regulatory T-cells (Tregs) in post-pubertal males compared to females (p=0.0097). These Tregs were also more suppressive in males compared to females. Differences in Treg frequency were seen pre-puberty and were not altered by sex hormone treatment in GD individuals. However, Treg DEGs and functional transcriptomic pathways altered between post-pubertal males and females, including those involved in inflammatory signalling, overlapped with those altered by hormones in GD, suggesting hormones may also drive Treg functional changes. In addition, HDL metabolites modified by hormones showed differential associations with Treg phenotypes between post-pubertal males and females.Strikingly, sex differences in lipoproteins and Tregs were lost in JSLE, suggesting hormone signalling could be dysregulated in the pathogenesis of autoimmunity and could increase CVR for patients.Conclusion:Sex hormones drive altered lipoprotein metabolism and functional transcriptomic pathways in Tregs. Males have a lipoprotein profile associated with increased CVR, but a more anti-inflammatory immune profile compared to females. Together, this could explain sex differences in inflammatory disease susceptibilities and inform future sex-specific therapeutic strategies for the management of both JSLE and CVR.Acknowledgements:Lupus UKRosetrees TrustVersus ArthritisNIHR UCLH Biomedical Research CentreDisclosure of Interests:None declared

scholarly journals Intelligent Bone Age Assessment: An Automated System to Detect a Bone Growth Problem Using Convolutional Neural Networks with Attention Mechanism

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 765
Author(s):  
Mohd Asyraf Zulkifley ◽  
Nur Ayuni Mohamed ◽  
Siti Raihanah Abdani ◽  
Nor Azwan Mohamed Kamari ◽  
Asraf Mohamed Moubark ◽  
...  
Keyword(s):  
Bone Growth ◽  
Bone Age ◽  
Attention Mechanism ◽  
Assessment System ◽  
Dominant Hand ◽  
Age Assessment ◽  
Image Normalization ◽  
X Ray ◽  
Bone Age Assessment ◽  
Skeletal Bone

Skeletal bone age assessment using X-ray images is a standard clinical procedure to detect any anomaly in bone growth among kids and babies. The assessed bone age indicates the actual level of growth, whereby a large discrepancy between the assessed and chronological age might point to a growth disorder. Hence, skeletal bone age assessment is used to screen the possibility of growth abnormalities, genetic problems, and endocrine disorders. Usually, the manual screening is assessed through X-ray images of the non-dominant hand using the Greulich–Pyle (GP) or Tanner–Whitehouse (TW) approach. The GP uses a standard hand atlas, which will be the reference point to predict the bone age of a patient, while the TW uses a scoring mechanism to assess the bone age using several regions of interest information. However, both approaches are heavily dependent on individual domain knowledge and expertise, which is prone to high bias in inter and intra-observer results. Hence, an automated bone age assessment system, which is referred to as Attention-Xception Network (AXNet) is proposed to automatically predict the bone age accurately. The proposed AXNet consists of two parts, which are image normalization and bone age regression modules. The image normalization module will transform each X-ray image into a standardized form so that the regressor network can be trained using better input images. This module will first extract the hand region from the background, which is then rotated to an upright position using the angle calculated from the four key-points of interest. Then, the masked and rotated hand image will be aligned such that it will be positioned in the middle of the image. Both of the masked and rotated images will be obtained through existing state-of-the-art deep learning methods. The last module will then predict the bone age through the Attention-Xception network that incorporates multiple layers of spatial-attention mechanism to emphasize the important features for more accurate bone age prediction. From the experimental results, the proposed AXNet achieves the lowest mean absolute error and mean squared error of 7.699 months and 108.869 months2, respectively. Therefore, the proposed AXNet has demonstrated its potential for practical clinical use with an error of less than one year to assist the experts or radiologists in evaluating the bone age objectively.

scholarly journals Lipid Remodeling Confers Osmotic Stress Tolerance to Embryogenic Cells during Cryopreservation

2021 ◽  
Vol 22 (4) ◽  
pp. 2174
Author(s):  
Liang Lin ◽  
Junchao Ma ◽  
Qin Ai ◽  
Hugh W. Pritchard ◽  
Weiqi Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Technology Development ◽  
Membrane Lipids ◽  
Species Conservation ◽  
Membrane Lipid ◽  
Cell Integrity ◽  
Embryogenic Cells ◽  
Osmotic Stress Tolerance ◽  
Lipid Species ◽  
Magnolia Officinalis

Plant species conservation through cryopreservation using plant vitrification solutions (PVS) is based in empiricism and the mechanisms that confer cell integrity are not well understood. Using ESI-MS/MS analysis and quantification, we generated 12 comparative lipidomics datasets for membranes of embryogenic cells (ECs) of Magnolia officinalis during cryogenic treatments. Each step of the complex PVS-based cryoprotocol had a profoundly different impact on membrane lipid composition. Loading treatment (osmoprotection) remodeled the cell membrane by lipid turnover, between increased phosphatidic acid (PA) and phosphatidylglycerol (PG) and decreased phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The PA increase likely serves as an intermediate for adjustments in lipid metabolism to desiccation stress. Following PVS treatment, lipid levels increased, including PC and PE, and this effectively counteracted the potential for massive loss of lipid species when cryopreservation was implemented in the absence of cryoprotection. The present detailed cryobiotechnology findings suggest that the remodeling of membrane lipids and attenuation of lipid degradation are critical for the successful use of PVS. As lipid metabolism and composition varies with species, these new insights provide a framework for technology development for the preservation of other species at increasing risk of extinction.

scholarly journals Mutations of uncertain significance in heterozygous variants as a possible cause of severe short stature: a case report

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Nami Mohammadian Khonsari ◽  
Sahar Mohammad Poor Nami ◽  
Benyamin Hakak-Zargar ◽  
Tessa Voth
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Hormone Receptors ◽  
Bone Growth ◽  
Synergistic Effects ◽  
Signs And Symptoms ◽  
Bone Age ◽  
Pathogenic Mutation ◽  
Paracrine Factors ◽  
Severe Short Stature

Abstract Background Linear bone growth is achieved by the division of chondrocytes at the growth plate and is regulated by endocrine and paracrine factors such as growth hormone. Mutations that negatively affect chondrogenesis can be a contributor to short stature. One such mutation can occur in the ACAN gene, causing short stature and advanced bone age. Similarly, mutations in growth hormone receptors (GHR) can lead to Laron syndrome (LS), one of the several disorders that are collectively called growth hormone insensitivity syndrome (GHI). Another example is Floating-Harbor syndrome (FHS), a rare autosomal dominant due to mutations in the SRCAP gene that can also result in short stature. Case presentation We report the case of a 6-year-old female with concomitant mutations in the three genes mentioned above. The mutations reported here were found on genetic studies and are usually benign, causing a variant of undetermined significance. However, our patient’s phenotype could only be explained by the compounded effects of pathogenic mutations of these genes. Some of the same mutations were also found in the patient’s father and her paternal grandfather. Both also presented with short stature, though not to the same degree as our patient. While these mutations are often reported to be insignificant, they gave rise to severe short stature and a specific phenotype in the patient when presented together. We think that even though the GHI spectrum is inherited through an autosomal recessive pattern, the sum of these heterozygous mutations resulted in severe short stature despite the limited GHI seen in our patient, the father, and the grandfather, through a rare ACAN and SRCAP mutation that, to our knowledge, has not been previously reported as a pathogenic mutation in the literature. Conclusion We investigated the possible synergistic effects of these variations on exacerbation or masking of the signs and symptoms of GHI with the hope of providing a better understanding of these genes and their function through our rare case.

scholarly journals The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Metabolic Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Lei Zhang ◽  
Qun Wang ◽  
Wen Liu ◽  
Fangyan Liu ◽  
Ailing Ji ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Nuclear Receptor ◽  
Metabolic Diseases ◽  
Early Response ◽  
Orphan Receptor ◽  
Special Focus ◽  
Orphan Nuclear Receptor ◽  
Physiological Functions ◽  
The Impact

Orphan nuclear receptor 4A1 (NR4A1) is a transcriptional factor of the nuclear orphan receptor (NR4A) superfamily that has sparked interest across different research fields in recent years. Several studies have demonstrated that ligand-independent NR4A1 is an immediate-early response gene and the protein product is rapidly induced by a variety of stimuli. Hyperfunction or dysfunction of NR4A1 is implicated in various metabolic processes, including carbohydrate metabolism, lipid metabolism, and energy balance, in major metabolic tissues, such as liver, skeletal muscle, pancreatic tissues, and adipose tissues. No endogenous ligands for NR4A1 have been identified, but numerous compounds that bind and activate or inactivate nuclear NR4A1 or induce cytoplasmic localization of NR4A1 have been identified. This review summarizes recent advances in our understanding of the molecular biology and physiological functions of NR4A1. And we focus on the physiological functions of NR4A1 receptor to the development of the metabolic diseases, with a special focus on the impact on carbohydrate and lipid metabolism in skeletal muscle, liver, adipose tissue, and islet.

scholarly journals Hepatocyte-specific Sirt6 deficiency impairs ketogenesis

2018 ◽  
Vol 294 (5) ◽  
pp. 1579-1589 ◽  
Author(s):  
Lei Chen ◽  
Qinhui Liu ◽  
Qin Tang ◽  
Jiangying Kuang ◽  
Hong Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Gene Promoter ◽  
Camp Response Element Binding ◽  
Hepatic Lipid Metabolism ◽  
Camp Response Element ◽  
Hepatic Lipid ◽  
Element Binding Protein ◽  
Regulate Lipid Metabolism

Sirt6 is an NADH (NAD+)-dependent deacetylase with a critical role in hepatic lipid metabolism. Ketogenesis is controlled by a signaling network of hepatic lipid metabolism. However, how Sirt6 functions in ketogenesis remains unclear. Here, we demonstrated that Sirt6 functions as a mediator of ketogenesis in response to a fasting and ketogenic diet (KD). The KD-fed hepatocyte-specific Sirt6 deficiency (HKO) mice exhibited impaired ketogenesis, which was due to enhanced Fsp27 (fat-specific induction of protein 27), a protein known to regulate lipid metabolism. In contrast, overexpression of Sirt6 in mouse primary hepatocytes promoted ketogenesis. Mechanistically, Sirt6 repressed Fsp27β expression by interacting with Crebh (cAMP response element–binding protein H) and preventing its recruitment to the Fsp27β gene promoter. The KD-fed HKO mice also showed exacerbated hepatic steatosis and inflammation. Finally, Fsp27 silencing rescued hypoketonemia and other metabolic phenotypes in KD-fed HKO mice. Our data suggest that the Sirt6–Crebh–Fsp27 axis is pivotal for hepatic lipid metabolism and inflammation. Sirt6 may be a pharmacological target to remedy metabolic diseases.

scholarly journals Homozygous SHBG Variant (rs6258) Linked to Gonadotropin-Independent Precocious Puberty in a Young Girl

2021 ◽  
Author(s):  
Victoria C Andriessen ◽  
Marissa Lightbourne ◽  
Chelsi Flippo ◽  
Fabio R Faucz ◽  
Angela Delaney ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Bone Age ◽  
Serum Levels ◽  
Young Girl ◽  
Sex Hormone Binding Globulin ◽  
Polycystic Ovaries ◽  
Shbg Level ◽  
History Of ◽  
Laboratory Investigations ◽  
Peripheral Precocious Puberty

Abstract Sex hormone-binding globulin (SHBG) in the blood is a major determinant of bioactivity for key sex steroids such as testosterone and estradiol. Low serum levels of SHBG have been associated with obesity, polycystic ovaries and metabolic syndrome, and other states associated with hyperandrogenemia. A 9-year, 6-month-old girl presented with a history of peripheral precocious puberty and aggressive behavior. The patient’s SHBG level was remarkably low for her age, at less than 5 nmol/L [reference range for a girl with a bone age of 10 years, 73 nmol/L (SEM= 10)](1). Upon genetic and protein analysis, the patient was found to have a homozygous missense potentially pathogenic variant in the SHBG gene (c.554 C&gt;T, p.P185L); her parents were asymptomatic heterozygote carriers. Laboratory investigations supported the possible involvement of this genetic alteration in the patient’s phenotype. Various analyses of this variant support its pathogenicity, although the exact mechanism remains unclear. In conclusion, we present a genetic SHBG variant in the homozygote state that may have been associated with gonadotropin-independent precocious puberty in a young girl.

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