BACKGROUND Growing evidence supports a genetic link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Interesting data demonstrated that both the major NAFLD risk polymorphisms such as the I148M polymorphism in the patatin like phospholipase containing domain 3 ( PNPLA3 ) and the E167K allele in the transmembrane 6 superfamily member 2 gene ( TM6SF2 ) affect renal function. Recently the hydroxysteroid 17-beta dehydrogenase 13 ( HSD17B13 ) gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology. In particular, it has been showed the protective effect of the rs72613567:TA variant of this gene against liver damage both in adults and children. AIM To investigate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate (eGFR) in obese children. METHODS We enrolled 684 obese children (mean age 10.56 ± 2.94 years; mean BMI-SDS 2.98 ± 0.78) consecutively attending our Obesity Clinic. All the patients underwent a careful clinical assessment and a comprehensive biochemical evaluation. To detect hepatic steatosis, a liver ultrasound was performed. NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase (ALT) levels > 40 IU/L. The study population was divided on the basis of the NAFLD presence. Genotyping for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also made. RESULTS Patients carrying the HSD17B13 rare A allele showed higher eGFR levels compared with homozygous patients both among subjects with and without NAFLD. A general linear model confirmed a direct and significant association of eGFR values with HSD17B13 genotype independently of PNPLA3 and TM6SF2 polymorphisms both in patients with and without NAFLD. A comparison of regression line confirmed the influence of HSD17B13 genotype on the relationship between eGFR and age both among patients with and without NAFLD. H omozygous patients for HSD17B13 genotype with NAFLD showed a significantly higher decline of eGFR with the increase of the age compared with the patients with NAFLD carrying the HSD17B13 rare A allele ( P value for intercepts = 0.005; P value for slopes = 0.94). The same effect was observed among patients without NAFLD ( P value for intercepts = 0.0012; P value for slopes...
Due its close relationship with obesity, nonalcoholic fatty liver disease (NAFLD) has become a major worldwide health issue even in childhood. The most accepted pathophysiological hypothesis is represented by the “multiple hits” theory, in which both hepatic intracellular lipid accumulation and insulin resistance mainly contribute to liver injury through several factors. Among these, lipotoxicity has gained particular attention. In this view, the pathogenic role of different lipid classes in NAFLD ( e.g., sphingolipids, fatty acids, ceramides, etc. ) has been highlighted in recent lipidomics studies. Although there is some contrast between plasma and liver findings, lipidomic profile in the NAFLD context provides novel insights by expanding knowledge in the intricate field of NAFLD pathophysiology as well as by suggesting innovative therapeutic approaches in order to improve both NAFLD prevention and treatment strategies. Selective changes of distinct lipid species might be an attractive therapeutic target for treating NAFLD. Herein the most recent evidence in this attractive field has been summarized to provide a comprehensive overview of the lipidomic scenario in paediatric NAFLD.
Parallel to the dramatic rise of pediatric obesity, estimates reported an increased prevalence of type 2 diabetes (T2D) already in childhood. The close relationship between obesity and T2D in children is mainly sustained by insulin resistance (IR). In addition, the cardiometabolic burden of T2D including nonalcoholic fatty liver disease, cardiovascular disease and metabolic syndrome is also strictly related to IR. Although T2D pathophysiology has been largely studied in an attempt to improve therapeutic options, molecular mechanisms are still not fully elucidated. In this perspective, omics approaches (including lipidomics, metabolomics, proteomics and metagenomics) are providing the most attractive therapeutic options for T2D. In particular, distinct both lipids and metabolites are emerging as potential therapeutic tools. Of note, among lipid classes, the pathogenic role of ceramides in T2D context has been supported by several data. Thus, selective changes of ceramides expression might represent innovative therapeutic strategies for T2D treatment. More, distinct metabolomics pathways have been also found to be associated with higher T2D risk, by providing novel potential T2D biomarkers. Taken together, omics data are responsible for the expanding knowledge of T2D pathophysiology, by providing novel insights to improve therapeutic strategies for this tangled disease. We aimed to summarize the most recent evidence in the intriguing field of the omics approaches in T2D both in adults and children.
Renal diseases in childhood form a spectrum of different conditions with potential long-term consequences. Given that, a great effort has been made by researchers to identify candidate biomarkers that are able to influence diagnosis and prognosis, in particular by using omics techniques (e.g., metabolomics, lipidomics, genomics, and transcriptomics). Over the past decades, metabolomics has added a promising number of ‘new’ biomarkers to the ‘old’ group through better physiopathological knowledge, paving the way for insightful perspectives on the management of different renal diseases. We aimed to summarize the most recent omics evidence in the main renal pediatric diseases (including acute renal injury, kidney transplantation, chronic kidney disease, renal dysplasia, vesicoureteral reflux, and lithiasis) in this narrative review.
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