RESUMO
There are major variations in the susceptibility to weight gain among individuals under similar external influences (decreased physical activity and excessive calorie intake), depending on the genetic background. In the present study, we performed a microarray analysis and real-time PCR validations in order to find out differential gene expression in subcutaneous abdominal adipose tissue from two groups of subjects that despite living in similar environmental conditions such as a habitual high-fat dietary intake (energy as fat >40%) and similar moderate physical activity, some of them were successfully "resistant" (lean) to weight gain, while others were "susceptible" to fat deposition (obese). The classification of up- and downregulated genes into different categories, together with the analysis of the altered biochemical pathways, revealed a coordinated downregulation of catabolic pathways operating in the mitochondria: fatty acid ß oxidation (P = 0.008), tricarboxylic acid cycle (P = 0.001), and electron transport chain (P = 0.012). At the same time, glucose metabolism (P = 0.010) and fatty acid biosynthesis (P = 0.011) pathways were also downregulated in obese compared to lean subjects. In conclusion, our data showed an orchestrated downregulation of nuclear-encoded mitochondrial gene expression. These genes are involved in cellular respiration and oxidative metabolic pathways and could play a role in the susceptibility to weight gain in some individuals.
Assuntos
Tecido Adiposo/metabolismo , Ácidos Graxos/biossíntese , Regulação da Expressão Gênica/genética , Mitocôndrias/metabolismo , Obesidade/genética , Análise Serial de Proteínas/normas , Magreza/genética , 3-Hidroxiacil-CoA Desidrogenases/genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Acil-CoA Desidrogenases/genética , Acil-CoA Desidrogenases/metabolismo , Adulto , Ciclo do Ácido Cítrico/genética , Gorduras na Dieta/administração & dosagem , Regulação para Baixo , Transporte de Elétrons/genética , Flavoproteínas Transferidoras de Elétrons/genética , Flavoproteínas Transferidoras de Elétrons/metabolismo , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Predisposição Genética para Doença/genética , Humanos , Proteínas Ferro-Enxofre/genética , Proteínas Ferro-Enxofre/metabolismo , Masculino , Mitocôndrias/genética , Oxirredução , Fosforilação Oxidativa , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Reação em Cadeia da Polimerase/normas , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismoRESUMO
OBJECTIVE: The aim of the present study was to investigate the relationship between the differential expression of genes related to lipid metabolism in subcutaneous adipose tissue and metabolic syndrome features in lean and obese subjects with habitual high fat intake. METHODS: Microarray and RT-PCR analysis were used to analyze and validate differential gene expression in subcutaneous abdominal adipose tissue samples from lean and obese phenotype subjects. RESULTS: Several genes and transcripts involved in lipolysis were down-regulated, such as AKAP1, PRKAR2B, Gi and CIDEA, whereas NPY1R and CES1 were up-regulated, when comparing obese to lean subjects. Similarly, transcripts associated with cholesterol and lipoprotein metabolism showed a differential expression, with APOE and ABCA being decreased and VLDLR being increased in obese versus lean subjects. In addition, positive correlations were found between different markers of the metabolic syndrome and CES1 and NPY1R mRNA expressions, while APOE showed an inverse association with some of them. CONCLUSION: Different expression patterns in transcripts encoding for proteins involved in lipolysis and lipoprotein metabolism were found between lean and obese subjects. Moreover, the dysregulation of genes such as CES1 and APOE seems to be associated with some physiopathological markers of insulin resistance and cardiovascular risk factors in obesity.
Assuntos
Gordura Abdominal/enzimologia , Apolipoproteínas E/genética , Hidrolases de Éster Carboxílico/genética , Doenças Cardiovasculares/genética , Metabolismo dos Lipídeos/genética , Obesidade/genética , Gordura Abdominal/fisiopatologia , Adulto , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Casos e Controles , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Resistência à Insulina/genética , Obesidade/enzimologia , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de Risco , Fatores de Risco , Espanha , Adulto JovemRESUMO
Aquaporin 7 (AQP7) is an aquaglyceroprotein responsible for the secretion and uptake of glycerol from the adipocyte. The modulation of the expression of this membrane transport protein might play an important role in the susceptibility to the development of obesity. The aim of the present study was to compare the AQP7 gene expression in subcutaneous abdominal fat in lean vs. obese high fat intakers with a similar daily physical activity pattern. Twelve young men, 6 lean (BMI=23.2+/-0.4kg/m(2)) and 6 obese (35.0+/-1.1kg/m(2)) with a similar habitual dietary intake of fat (45.5+/-2.5 vs. 43.5+/-1.7% daily energy from fat for lean and obese, respectively) and physical activity (16.0+/-5.7 vs. 17.2+/-5.1 METsh/week for lean and obese, respectively), were recruited. Subcutaneous abdominal fat biopsies were obtained and total RNA was extracted and purified. Pools of RNA from lean and obese individuals were probed into Affymetrix GeneChip Human U133A. The microarray analysis revealed that AQP7 gene was down-regulated in obese compared to lean subjects. The results of the microarray analysis were confirmed by real-time PCR studies. In summary, our data show that the AQP7 gene is differentially expressed in adipose tissue of lean and obese individuals. The down-regulation of the AQP7 gene could be implicated in the susceptibility to obesity by reducing glycerol release and promoting the accumulation of lipids in the adipose tissue.