Advances in pediatric non-alcoholic fatty liver disease: From genetics to lipidomics

Riccio, Simona; Melone, Rosa; Vitulano, Caterina; Guida, Pierfrancesco; Maddaluno, Ivan; Guarino, Stefano; Marzuillo, Pierluigi; Giudice, Emanuele Miraglia del; Sessa, Anna Di

doi:10.5409/wjcp.v11.i3.221

Cited by 7 publications

(6 citation statements)

References 149 publications

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“…As there is evidence that epigenetic changes can contribute to hyperuricemia, connecting both epigenetic and GM could reveal the roles played by uric acid in the increased serum uric acid levels 144 . Omics determinants as “multiple hits” theory are potential innovative markers especially for the NAFLD diagnosis and treatment.…”

Section: Discussionmentioning

confidence: 99%

The connection between epigenetics and gut microbiota‐current perspective

Yuan,

Tan,

Bajinka

et al. 2024

Cell Biochemistry & Function

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Both the epigenetic changes and gut microbiota (GM) have attracted a growing interest in establishing effective diagnostics and potential therapeutic strategies for a number of diseases. These disorders include metabolic, central nervous system‐related diseases, autoimmune, and gastrointestinal infections (GI). Despite the number of studies, there is no extensive review that connects the epigenetics modifications and GM as biomarkers that could confer effective diagnostics and confer treatment options. To this end, this review hopes to give detailed information on connecting the modifications in epigenetic and GM. An updated and detailed information on the connection between the epigenetics factors and GM that influence diseases are given. In addition, the review showed some associations between the epigenetics to the maternal GM and offspring health. Finally, the limitations of the concept and prospects into this new emerging discipline were also looked into. Although this review elucidated on the maternal diet and response to offspring health with respect to GM and epigenetic modifications, there still exist various limitations to this newly emerging discipline. In addition to integrating complementary multi‐omics data, longitudinal sampling will aid with the identification of functional mechanisms that may serve as therapeutic targets. To this end, this review gave a detailed perspective into harnessing disease diagnostics, prevention and treatment options through epigenetics and GM.

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Section: Discussionmentioning

confidence: 99%

The connection between epigenetics and gut microbiota‐current perspective

Yuan,

Tan,

Bajinka

et al. 2024

Cell Biochemistry & Function

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“…Glucokinase regulator protein (GCKR), known as glucokinase inhibitor, is responsible for adjusting glucose storage and disposal, as well as controlling de novo lipogenesis through regulating glucose flow into hepatocytes [ 81 ]. GCKR rs1260326 (P446L) is a missense variant that increases glucose uptake and DNL by reducing the ability of glucokinase inhibitory effect [ 82 ]. The GCKR rs1260326-T is associated with metabolism-related mechanisms, such as glycolysis, fatty acid circulation, and saturation.…”

Section: Metabolic-related Genes Influencing Nafldmentioning

confidence: 99%

Exploring the role of genetic variations in NAFLD: implications for disease pathogenesis and precision medicine approaches

Mahmoudi,

Tarzemani,

Aghajanzadeh

et al. 2024

Eur J Med Res

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Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases, affecting more than one-quarter of people worldwide. Hepatic steatosis can progress to more severe forms of NAFLD, including NASH and cirrhosis. It also may develop secondary diseases such as diabetes and cardiovascular disease. Genetic and environmental factors regulate NAFLD incidence and progression, making it a complex disease. The contribution of various environmental risk factors, such as type 2 diabetes, obesity, hyperlipidemia, diet, and sedentary lifestyle, to the exacerbation of liver injury is highly understood. Nevertheless, the underlying mechanisms of genetic variations in the NAFLD occurrence or its deterioration still need to be clarified. Hence, understanding the genetic susceptibility to NAFLD is essential for controlling the course of the disease. The current review discusses genetics’ role in the pathological pathways of NAFLD, including lipid and glucose metabolism, insulin resistance, cellular stresses, and immune responses. Additionally, it explains the role of the genetic components in the induction and progression of NAFLD in lean individuals. Finally, it highlights the utility of genetic knowledge in precision medicine for the early diagnosis and treatment of NAFLD patients.

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“…Presence of PPARGC1B c.988C>T and c.1166C>A variants was positively associated with higher insulin AUC [medians 308.4 (IQR 221.7-395.1) pmol/L vs. 214.0 (IQR 180.0-248.0) pmol/L in those without; p = 0.037] during OGTT. Presence of c.2718T>G among AA was associated with older age at the time of enrollment in the clinical protocol [medians 16.5 (IQR 14.6-18.5) years vs. 13…”

Section: Association Analyses Of High-frequency Variantsmentioning

confidence: 99%

“…The PNPLA3 I148M variant, common among Hispanic populations, is associated with two-fold higher hepatic fat content than non-carriers while the S453I variant, common in African Americans (AAs), is associated with decreased hepatic fat (12). Several other well-known variants in the genes transmembrane 6 superfamily member 2 (TM6SF2) (variant: E167K), glucokinase regulator (GCKR), membrane bound O-acyltransferase domain containing 7 gene-transmembrane channel-like 4 (MBOAT7-TMC4) (variant: rs641738), and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) (variant: rs72613567:TA), in addition to gut microbiota composition, contribute to NAFLD susceptibility in children (13). The etiology of NAFLD involves genetic and non-genetic factors, including oxidative stress; altered lipid metabolism, cytokines, and adipokines; and mitochondrial dysfunction that promotes inflammation, cell death, and fibrosis, that interact in parallel to increase NAFLD susceptibility (14).…”

Section: Introductionmentioning

confidence: 99%

High-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities

Bloyd,

Sinaii,

Faucz

et al. 2023

Front. Endocrinol.

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IntroductionPediatric obesity has steadily increased in recent decades. Large-scale genome-wide association studies (GWAS) conducted primarily in Eurocentric adult populations have identified approximately 100 loci that predispose to obesity and type II diabetes. GWAS in children and individuals of non-European descent, both disproportionately affected by obesity, are fewer. Rare syndromic and monogenic obesities account for only a small portion of childhood obesity, so understanding the role of other genetic variants and their combinations in heritable obesities is key to developing targeted and personalized therapies. Tight and responsive regulation of the cAMP-dependent protein kinase (PKA) signaling pathway is crucial to maintaining healthy energy metabolism, and mutations in PKA-linked genes represent the most common cause of monogenic obesity.MethodsFor this study, we performed targeted exome sequencing of 53 PKA signaling-related genes to identify variants in genomic DNA from a large, ethnically diverse cohort of obese or metabolically challenged youth.ResultsWe confirmed 49 high-frequency variants, including a novel variant in the PDE11A gene (c.152C>T). Several other variants were associated with metabolic characteristics within ethnic groups.DiscussionWe conclude that a PKA pathway-specific variant search led to the identification of several new genetic associations with obesity in an ethnically diverse population.

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Advances in pediatric non-alcoholic fatty liver disease: From genetics to lipidomics

Cited by 7 publications

References 149 publications

The connection between epigenetics and gut microbiota‐current perspective

The connection between epigenetics and gut microbiota‐current perspective

Exploring the role of genetic variations in NAFLD: implications for disease pathogenesis and precision medicine approaches

High-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities

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