RESUMO
Alarcón-Yaquetto, Dulce E., Lidia Caballero, and Gustavo F. Gonzales. Association between plasma N-acylethanolamides and high hemoglobin concentration in Southern Peruvian highlanders. High Alt Med Biol 18:322-329, 2017.-High-altitude (HA) hypoxia is a stressful condition endured by organisms through different mechanisms. Failing to adapt to chronic HA exposure leads to a disease called chronic mountain sickness (CMS) characterized by excessive erythrocytosis (hemoglobin [Hb] ≥19 g/dL for women and ≥21 g/dL for men). Genes encoding for peroxisome proliferator-activated receptor (PPAR) subunits α and γ have been proposed as candidate genes for HA adaptation. N-acylethanolamides (NAEs) are endogenous fatty acid substances that bind to PPAR-α and -γ. NAEs are also able to modulate the endocannabinoid system, a signaling pathway activated in physiological stressful conditions. In the frame of a metabolomic study, we measured plasma levels of four NAEs: palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoyl ethanolamide (SEA), and linoleoyl ethanolamide (LEA) in natives from Puno (3830 m), a city located in the Peruvian Southern Andes, and Lima (150 m). All NAEs were significantly higher in the HA population (p < 0.001, q < 0.001). Subjects with higher NAE values were those with higher Hb concentration and lower pulse oxygen saturation. However, there was no association between NAEs and CMS score. Our results suggest that PEA and OEA could be involved in physiological regulation following long-term HA exposure.
Assuntos
Altitude , Ácidos Graxos/sangue , Hemoglobinas/metabolismo , Hipóxia/sangue , Adulto , Doença da Altitude/sangue , Amidas , Doença Crônica , Endocanabinoides/sangue , Etanolaminas/sangue , Feminino , Humanos , Indígenas Sul-Americanos , Ácidos Linoleicos/sangue , Masculino , Ácidos Oleicos/sangue , Oxigênio/sangue , Ácidos Palmíticos/sangue , Peru , Alcamidas Poli-Insaturadas/sangue , Ácidos Esteáricos/sangueRESUMO
The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N-oleoylethanolamide and N-palmitoylethanolamide) were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 ± 1.8 to 35.9 ± 5.5 kg/m2 (mean ± 1 SD) and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR), adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity.
Assuntos
Amidoidrolases/genética , Endocanabinoides/sangue , Obesidade/etnologia , Obesidade/genética , Polimorfismo Genético , Adiponectina/sangue , Adulto , Amidas , Antropometria , Ácidos Araquidônicos/sangue , Pressão Sanguínea , Índice de Massa Corporal , Brasil , Etanolaminas/sangue , Etnicidade , Feminino , Genótipo , Glicerídeos/sangue , Homeostase , Homozigoto , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Ácidos Oleicos/sangue , Ácidos Palmíticos/sangue , Fenótipo , Alcamidas Poli-Insaturadas/sangue , Prevalência , Fatores de RiscoRESUMO
Lipid emulsion (LE) containing medium/ω-6 long chain triglyceride-based emulsion (MCT/ω-6 LCT LE) has been recommended in the place of ω-6 LCT-based emulsion to prevent impairment of immune function. The impact of MCT/ω-6 LCT LE on lymphocyte and neutrophil death and expression of genes related to inflammation was investigated. Seven volunteers were recruited and infusion of MCT/ω-6 LCT LE was performed for 6 h. Four volunteers received saline and no change was found. Blood samples were collected before, immediately afterwards and 18 h after LE infusion. Lymphocytes and neutrophils were studied immediately after isolation and after 24 and 48 h in culture. The following determinations were carried out: plasma-free fatty acids, triacylglycerol and cholesterol concentrations, plasma fatty acid composition, neutral lipid accumulation in lymphocytes and neutrophils, signs of lymphocyte and neutrophil death and lymphocyte expression of genes related to inflammation. MCT/ω-6 LCT LE induced lymphocyte and neutrophil death. The mechanism for MCT/ω-6 LCT LE-dependent induction of leucocyte death may involve changes in neutral lipid content and modulation of expression of genes related to cell death, proteolysis, cell signalling, inflammatory response, oxidative stress and transcription.
Assuntos
Emulsões Gordurosas Intravenosas/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Triglicerídeos/farmacologia , Adulto , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colesterol/sangue , Fragmentação do DNA , Ácidos Decanoicos/sangue , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Emulsões Gordurosas Intravenosas/química , Emulsões Gordurosas Intravenosas/metabolismo , Ácidos Graxos não Esterificados/análise , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos Ômega-6/sangue , Ácidos Graxos Ômega-6/química , Ácidos Graxos Ômega-6/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Humanos , Contagem de Leucócitos , Leucócitos/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Necrose/induzido quimicamente , Necrose/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Ácidos Palmíticos/sangue , Ácidos Esteáricos/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triglicerídeos/sangue , Triglicerídeos/química , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Adulto JovemRESUMO
Ionized calcium was determined in vitro in human serum in relation to increased concentrations (0.32 to 10 mM) of free fatty acids. Serum iCa levels varied inversely and linearly with increasing FFA concentrations. It is suggested that the formation of Ca-FFA complexes at clinically attainable levels of FFA decreases iCa and that elevated serum FFA levels may be a factor in the development of hypocalcemia.