RESUMEN
BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. METHODS: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. RESULTS: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). CONCLUSIONS: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.
Asunto(s)
Alanina Transaminasa/sangre , Predisposición Genética a la Enfermedad , Enfermedades Inflamatorias del Intestino/complicaciones , Lipasa/genética , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico/enzimología , Enfermedad del Hígado Graso no Alcohólico/etiología , Alelos , Aspartato Aminotransferasas/sangre , Biomarcadores/análisis , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Genotipo , Heterocigoto , Humanos , Enfermedades Inflamatorias del Intestino/genética , Italia , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/patología , Reacción en Cadena de la Polimerasa , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: Low fat utilization is linked to weight gain and to the presence of certain atherosclerosis markers. It is not clear whether the presence of hyperlipidemia can further affect nutrients utilization. The main objective of this study was to investigate the fasting fuel utilization of obese subjects suffering from hypertriglyceridemia, and to compare it with that of individuals that are solely obese. METHOD: We recruited 20 obese individuals with hypertriglyceridemia and 20 matched individuals not affected by hypertriglyceridemia. The fuel utilization (respiratory quotient) was measured by respiratory gas exchange, by Indirect Calorimetry. RESULTS: There was a significant difference in fuel utilization and HDL-cholesterol between cases and controls (respiratory quotient 0.89 ± 0.07 vs. 0.84 ± 0.06; p = 0.020 respectively). The univariate and multivariate linear regression analysis confirmed that hypertrygliceridemia was positively correlated to the respiratory quotient (p = 0.035). CONCLUSION: obese subjects with hypertriglyceridemia had a higher respiratory quotient in comparison to unaffected subjects. This could suggest a limitation in the beta-oxidation mechanisms; this could actually imply that fatty acids may be redirected from oxidation to reesterification into triglycerides. The study could suggest the presence of different mechanisms unrelated to obesity and also a potential new therapeutic target for hypertriglyceridemia management.