Molecular cloning of the myo-inositol oxygenase gene from the kidney of baboons

Abstract. The enzyme myo-Inositol oxygenase (MIOX) is also termed ALDRL6. It is a kidney‑specific member of the aldo‑keto reductase family. MIOX catalyzes the first reaction involved in the myo‑inositol metabolism signaling pathway and is fully expressed in mammalian tissues. MIOX catalyzes the oxidative cleavage of myo‑Inositol and its epimer, D-chiro-Inositol to D-glucuronate. The dioxygen-dependent cleavage of the C6 and C1 bond in myo‑Inositol is achieved by utilizing the Fe2+/Fe3+ binuclear iron center of MIOX. This enzyme has also been implicated in the complications of diabetes, including diabetic nephropathy. The MIOX gene was amplified with reverse transcription‑polymerase chain reaction from baboon tissue samples, and the product was cloned and sequenced. MIOX expression in the baboon kidney is described in the present study. The percentages of nucleotide and amino acid similarities between baboons and humans were 95 and 96%, respectively. The MIOX protein of the baboon may be structurally identical to that of humans. Furthermore, the evolutionary changes, which have affected these sequences, have resulted from purifying forces. Key words: animal models, gene expression, kidney, myo-inositol oxygenase, Old World monke

Mediterranean-like mix of fatty acids induces cellular protection on lipid-overloaded hepatocytes from western diet fed mice

Introduction and objective. Non-alcoholic fatty liver disease remains as one of the main liver disorders worldwide. It is widely accepted that is the kind of lipid, rather than the amount deposited in the cells that determines cell damage. Cholesterol and saturated free fatty acids are deleterious lipids when accumulated but, in contrast, there are some valuable lipids that could counteract those with harmful properties. Much of this knowledge arises from studies using a single fatty acid, but the effects of a combination of fatty acids, as obtained by diet has been poorly addressed. In the present work, we were focused to figure out the cellular effect of two different mixes of fatty acids, one with high proportion of saturated fatty acids, and another one with high proportion of unsaturated fatty acids (Mediterranean-like) in a cellular model of steatosis. Material and methods. Primary mouse hepatocytes from animals fed with a western diet (high fat and carbohydrates diet), were treated with both mixes of fatty acids for 24 h. Results. Our data clearly show that only the high unsaturated fatty acid mix induced a decrease in triglycerides (47.5%) and cholesterol (59%) content in steatotic hepatocytes mediating cellular protection associated to the decrement of ROS and oxidative damage. The mixture of high saturated fatty acids exhibited no effects, preserving high levels of cholesterol and triglycerides and oxidative damage. In conclusion, our results show that Mediterranean-like mix of fatty acids exerts cellular protection in steatosis by decreasing triglycerides, cholesterol, ROS content and oxidative damage

Heritability estimates (h2) for the severity of GERD symptoms, metabolic syndrome components and inflammation components.

<p>Heritability estimates (h2) for the severity of GERD symptoms, metabolic syndrome components and inflammation components.</p

Heritability and genetic correlation between GERD symptoms severity, metabolic syndrome, and inflammation markers in families living in Mexico City

<div><p>Objective</p><p>The aim of this study was to estimate the heritability (h²) and genetic correlation (ρG) between GERD symptoms severity, metabolic syndrome components, and inflammation markers in Mexican families.</p><p>Methods</p><p>Cross-sectional study which included 32 extended families resident in Mexico City. GERD symptoms severity was assessed by the ReQuest in Practice questionnaire. Heritability and genetic correlation were determined using the Sequential Oligogenic Linkage Analysis Routines software.</p><p>Results</p><p>585 subjects were included, the mean age was 42 (±16.7) years, 57% were women. The heritability of the severity of some GERD symptoms was h² = 0.27, 0.27, 0.37, and 0.34 (p-value <1.0x10^-5) for acidity complaints, lower abdominal complaints, sleep disturbances, and total ReQuest score, respectively. Heritability of metabolic syndrome components ranged from 0.40 for fasting plasma glucose to 0.61 for body mass index and diabetes mellitus. The heritability for fibrinogen and C-reactive protein was 0.64 and 0.38, respectively. Statistically significant genetic correlations were found between acidity complaints and fasting plasma glucose (ρG = 0.40); sleep disturbances and fasting plasma glucose (ρG = 0.36); acidity complaints and diabetes mellitus (ρG = 0.49) and between total ReQuest score and fasting plasma glucose (ρG = 0.43). The rest of metabolic syndrome components did not correlate with GERD symptoms.</p><p>Conclusion</p><p>Genetic factors substantially explain the phenotypic variance of the severity of some GERD symptoms, metabolic syndrome components and inflammation markers. Observed genetic correlations suggest that these phenotypes share common genes. These findings suggest conducting further investigation, as the determination of a linkage analysis in order to identify regions of susceptibility for developing of GERD and metabolic syndrome.</p></div

Genetic correlation^a between severity of GERD symptoms, inflammation components and metabolic syndrome components.

<p>Genetic correlation<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178815#t004fn002" target="_blank">^a</a> between severity of GERD symptoms, inflammation components and metabolic syndrome components.</p

Description of general data, severity of GERD symptoms, metabolic syndrome components and inflammation components by sex.

<p>Description of general data, severity of GERD symptoms, metabolic syndrome components and inflammation components by sex.</p

Heritability estimates (h2) for the severity of GERD symptoms, metabolic syndrome components and inflammation components.

<p>Heritability estimates (h2) for the severity of GERD symptoms, metabolic syndrome components and inflammation components.</p

Results of factor analysis, variance components and heritability estimation.

<p>Results of factor analysis, variance components and heritability estimation.</p

GDF11 restricts aberrant lipogenesis and changes in mitochondrial structure and function in human hepatocellular carcinoma cells

Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain stemness features. Recently, it has been reported that GDF11 exerts tumor‐suppressive properties in hepatocellular carcinoma cells, decreasing clonogenicity, proliferation, spheroid formation, and cellular function, all associated with a decrement in stemness features, resulting in mesenchymal to epithelial transition and loss of aggressiveness. The aim of the present work was to investigate the mechanism associated with the tumor‐suppressive properties displayed by GDF11 in liver cancer cells. Hepatocellular carcinoma‐derived cell lines were exposed to GDF11 (50 ng/ml), RNA‐seq analysis in Huh7 cell line revealed that GDF11 exerted profound transcriptomic impact, which involved regulation of cholesterol metabolic process, steroid metabolic process as well as key signaling pathways, resembling endoplasmic reticulum‐related functions. Cholesterol and triglycerides determination in Huh7 and Hep3B cells treated with GDF11 exhibited a significant decrement in the content of these lipids. The mTOR signaling pathway was downregulated, and this was associated with a reduction in key proteins involved in the mevalonate pathway. In addition, real‐time metabolism assessed by Seahorse technology showed abridged glycolysis as well as glycolytic capacity, closely related to an impaired oxygen consumption rate and decrement in adenosine triphosphate production. Finally, transmission electron microscopy revealed mitochondrial abnormalities, such as cristae disarrangement, consistent with metabolic changes. Results provide evidence that GDF11 impairs cancer cell metabolism targeting lipid homeostasis, glycolysis, and mitochondria function and morphology.This study was partially funded by a grant from the Consejo Nacionalde Ciencia y Tecnología (CONACYT): CB252942, Fronteras de laCiencia1320, Apoyo al Fortalecimiento y Desarrollo de la Infra-estructura 2013205941 and 2017280788, and Universidad Autonoma Metropolitana. We thank the confocal core unit of the Universidad Autonoma Metropolitana Iztapalapa. SH, MGR, ASN arescholarship holders from Conacyt. We acknowledge the support fromgrants: PID2019111669RB, and SAF201785877R from PlanNacional de IþD, Spain, and by the CIBEREHD; the center grantP50AA011999 Southern California Research Center for ALPD andCirrhosis funded by the National Institute on Alcohol Abuse andAlcoholism/National Institutes of Health (NIH); as well as supportfrom AGAUR of the Generalitat de Catalunya SGR20171112,European Cooperation in Science & Technology (COST) ACTIONCA17112 Prospective European DrugInduced Liver Injury Network,and the Fundación BBVA. RED Nacional 2018102799Tdeenfermedades metabólicas y Cáncer y Proyecto 201916/31 DeFundacion Marató TV3Peer reviewe