Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Cardiometabolic Risk Factors in Adolescence: A Cross-Sectional Study of 1874 General Population Adolescents

Lawlor, Debbie A.; Callaway, Mark; Macdonald‐Wallis, Corrie; Anderson, Emma L; Fraser, Abigail; Howe, Laura D; Day, Chris; Sattar, Naveed

doi:10.1210/jc.2013-3612

Cited by 68 publications

(85 citation statements)

References 26 publications

(38 reference statements)

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“…We were unable to examine change in other measures of adiposity (such as DXA determined total (or trunkcal) fat mass or waist circumference) with liver outcomes in this study as these measurements were not undertaken in infancy and early childhood in ALSPAC. However, our earlier publication shows the relationships of BMI, DXA determined total and trunkcal fat mass with hepatic outcomes are similar [42]. In this study we used AUDIT to assess alcohol consumption in all participants.…”

Section: Discussionmentioning

confidence: 86%

Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: The ALSPAC study

Anderson

Howe

Fraser

et al. 2014

Journal of Hepatology

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114

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Background & AimsAdiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment.MethodsIndividual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0–3 months, 3 months–1 y, 1–3 y, 3–7 y, and 7–10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y.ResultsBirth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1–3 y, 3–7 y, and 7–10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness.ConclusionsGreater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness.

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Section: Discussionmentioning

confidence: 86%

Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: The ALSPAC study

Anderson

Howe

Fraser

et al. 2014

Journal of Hepatology

Self Cite

114

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“…17 More recently, it was reported that the prevalence of NAFLD in healthy European adolescents was estimated to be 2.5% based upon evaluation with ultrasound. 18 Multicenter population studies in Europe estimated a higher prevalence of NAFLD based upon ultrasound evaluation in adults than that observed in children (Spain: 33.4% men and 20.3% women; Italy: 33% in men and 20% in women). 19,20 It is important to acknowledge that there are limitations of both ALT and ultrasound which can both underdiagnose NAFLD because of inadequate sensitivity for detecting NAFLD and over diagnose NAFLD because abnormal findings are not specific for NAFLD.…”

Section: Epidemiologymentioning

confidence: 97%

Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease

et al. 2016

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Nonalcoholic fatty liver disease (NAFLD) is one of the main chronic non-communicable diseases in westernized societies; its worldwide prevalence has doubled during the last 20 years. NAFLD has serious health implications not only for adults, but also for children. However, pediatric NAFLD is not only an important global problem in itself, but it is likely to be associated with increases in comorbidities such as metabolic syndrome and cardiovascular diseases. There are several differences between NAFLD in children and adults and it is not clear whether the disease observed in children is the initial phase of a process that progresses with age. The increasing prevalence of pediatric NAFLD has serious implications for the future adult population requiring appropriate action. Studies of NAFLD progression, pathogenesis, and management should evaluate disease phenotypes in children and follow these over patient lifetimes. We review the similarities and differences of NAFLD between children and adults.

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“…Nonalcoholic fatty liver disease (NAFLD) has been rapidly emerging among children and adolescents and is now the most common cause of chronic liver disease in the developed world [2,15,26]. Adolescents with NAFLD also tend to be more insulin resistant and dyslipidemic, but the extent to which these associations are independent of total body fatness is not clearly understood [1,5,27].…”

Section: Introductionmentioning

confidence: 99%

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Chen

Zhou

et al. 2015

J Physiol Biochem

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Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease among children and adolescents in the developed world. Betaine, as a methyl donor, recently has been demonstrated to exert its hepatoprotective effects through rectifying the genomic DNA hypomethylation state. However, whether betaine supplementation affects N6-methyladenosine (m(6)A) mRNA methylation in NAFLD is still unknown. We conducted the current study to investigate the effects of betaine supplementation during adolescence on high-fat diet-induced pathological changes in liver of mice, and we further identified the effects of betaine supplementation on expression of the fat mass and obesity-associated gene (FTO) and hepatic m(6)A mRNA methylation. Our results showed that betaine supplementation across adolescence significantly alleviated high-fat-induced impairment of liver function and morphology as well as ectopic fat accumulation. Surprisingly, no significant effects on serum TG and NEFA level, as well as fat mass, were observed in mice supplemented with betaine. We also found that high-fat diet upregulated ACC1 and FAS gene expression and downregulated HSL and ATGL gene expression. However, these alterations were rectified by betaine supplementation. Moreover, an m(6)A hypomethylation state and increased FTO expression were detected in mice fed with high-fat diet, while betaine supplementation prevented these changes. Our results suggested that betaine supplementation during adolescence could protect mice from high-fat-induced NAFLD by decreasing de novo lipogenesis and increasing lipolysis. Furthermore, a novel FTO-dependent function of m(6)A may involve in the hepatoprotective effects of betaine.

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Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Cardiometabolic Risk Factors in Adolescence: A Cross-Sectional Study of 1874 General Population Adolescents

Cited by 68 publications

References 26 publications

Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: The ALSPAC study

Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: The ALSPAC study

Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

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