Influence of dietary pattern, physical activity, and I148M PNPLA3 on steatosis severity in at-risk adolescents

Abstract

Evidence relating dietary patterns to obesity and related disorders such as non-alcoholic fatty liver disease (NAFLD) is limited in pediatric age. Aim of this study was to analyze the association between dietary patterns, obesity and development of severe steatosis and the metabolic syndrome in a series of children and adolescents referred for suspected NAFLD, and the interaction with the rs738409 I148M PNPLA3 polymorphism. Two hundred patients (112 females) had completed a food frequency and demographic questionnaire. Nearly 58 % were obese, and 32 % were overweight. Mild, moderate, and severe fatty liver was present in 60 (30 %), 87 (44 %), and 51 (26 %) participants, respectively. A great proportion of overweight/obese children and adolescents reported a correct dietary pattern. At multivariate ordinal regression analysis considering demographic, anthropometric, genetic, and behavioral determinants, the major determinant of steatosis severity was PNPLA3 I148M genotype (p \ 0.0001), followed by older age (p = 0.017), higher waist circumference (p = 0.016), and less time spent practising physical exercise (p = 0.034). Furthermore, there was a significant interaction between PNPLA3 I148M and intake of sweetened beverages (p = 0.033) and of vegetables (p = 0.038).In conclusion, although dietary pattern was reportedly correct in at-risk overweight adolescents with NAFLD, we report a novel interaction between PNPLA3 I148M and dietary components with the severity of steatosis.

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

“…For instance, Hispanic children who were homozygous for the patatin-like phospholipase domain-containing protein 3 ( PNPLA3 ) gene variant rs738409 were found to have a positive correlation between liver fat content and carbohydrate (r=0.38, p=0.02) and total sugar (r=0.33, p=0.04) intake (138). A similar correlation was made in Italian adolescents with the variant and liver fat content and SSB intake (139). Also of note in 18 adult NAFLD patients (matched for liver fat content), a 6 day low calorie, low carbohydrate diet revealed reductions in liver fat content, but was 2.5 fold greater in those who were PNPLA3 GG homozygotes (n=8) vs CC homozygotes (n=10) (140).…”

PNPLA3 gene in liver diseases

“…The PNPLA3 rs738409[G] variation displays a strong interaction with the environment. Indeed, as highlighted above, the increased susceptibility to liver damage observed with rs738409[G] occurs predominantly in the presence of a concomitant liver insult (e.g., obesity, alcohol consumption, viral infection) or in association with increased consumption of certain types of fatty acids [21,102,103]. Although rs738409[G] might not be directly associated with all these risk factors, such as every feature of the metabolic syndrome, these phenotypes may, in fact, trigger the impact of PNPLA3 on steatosis and fibrogenesis and the complex relationships among these factors should not be dissociated.…”

Physical activity and sedentary behavior can modulate the effect of the PNPLA3 variant on childhood NAFLD: a case-control study in a Chinese population

“…Santoro, et al [10] conducted a study in 127 children and adolescents (aged 14.7 ± 3.3 years old, of different ethnic backgrounds) and found that HFF was influenced by the interaction of SNP and omega-6/omega-3 PUFA ratio ( P  = 0.002). Furthermore, interactions between the PNPLA3 rs738409 polymorphism and the intake of sweetened beverage ( P  = 0.033) and vegetables ( P  = 0.038) on NAFLD were reported in a study consisting of 200 Italian obese children aged 10–13 years old by Nobili, et al [11]. Shen, et al [22] conducted the interaction analysis in 920 Hong Kong Chinese (251 had NAFLD) but observed no significant interaction between rs738409 and the dietary pattern including energy intake, carbohydrate consumption, fat consumption or dietary fiber intake.…”

“…Studies have indicated that the total carbohydrate (specifically sugar) [9], high omega-6/omega-3 polyunsaturated fatty acids (PUFA) ratio [10], high sweetened beverage intake and low vegetable intake [11] can influence the association between rs738409 and NAFLD. Davis, et al [9] reported in a study of 153 Hispanic children of 8–18 years old that hepatic fat fraction (HFF) was influenced by a significant interaction between rs738409 and carbohydrate (genotype × carbohydrate, P  = 0.04), specifically between genotype and total sugar intake (genotype × total sugar, P  = 0.01).…”

“…Previous studies have provided evidence of the main effect of the PNPLA3 rs738409 polymorphism on NAFLD [6–8], and also its interaction with behavioral risk factors including total carbohydrate (specifically sugar) [9], high omega-6/omega-3 polyunsaturated fatty acids (PUFA) ratio [10], high sweetened beverage intake and low vegetable intake [11]. Recent studies demonstrated that lacking of physical activity and having too much sedentary behavior are also risk factors of NAFLD [12, 13].…”