Nutritional Approaches in Children with Overweight or Obesity and Hepatic Steatosis

Abstract

Childhood obesity is a global public health problem. Worldwide, 41 million children under 5 years and 340 million children and adolescents between 5 and 19 years are overweight. In addition, the recent COVID-19 epidemic has further amplified this social phenomenon. Obesity is a condition associated with various comorbidities, such as nonalcoholic fatty liver disease (NAFLD). The pathophysiology of NAFLD in obesity is intricate and involves the interaction and dysregulation of several mechanisms, such as insulin resistance, cytokine signaling, and alteration of the gut microbiota. NAFLD is defined as the presence of hepatic steatosis in more than 5% of hepatocytes, evaluated by histological analysis. It can evolve from hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver failure. Body weight reduction through lifestyle modification remains the first-line intervention for the management of pediatric NAFLD. Indeed, studies suggest that diets low in fat and sugar and conversely rich in dietary fibers promote the improvement of metabolic parameters. This review aims to evaluate the existing relationship between obesity and NAFLD in the pediatric population and to assess the dietary patterns and nutritional supplementations that can be recommended to prevent and manage obesity and its comorbidities.

Chronic pharmacologic manipulation of dopamine transmission ameliorates metabolic disturbance in syndrome caused by mutated trappc9

“…Genome-wide association studies link trappc9 to NAFLD (15), a common comorbidity of obesity (16)(17)(18). Liver enlargement is seen in trappc9 KO mice (24).…”

“…Loss-of-function mutations of the gene coding for the trafficking protein particle (TRAPP) complex subunit 9 (trappc9) cause an autosomal recessive syndrome with intellectual disability and malformations of various brain structures; over half of the cases exhibit obesity (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Genome-wide analyses detect differential methylation of the trappc9 gene in children with severe obesity as well as in women with a high body-mass index (12)(13)(14) and link trappc9 to non-alcoholic fatty liver disease (NAFLD) (15), the most common liver disease frequently associated with obesity (16)(17)(18). Consistent with a role for trappc9 in metabolic homeostasis, global metabolic changes are detected in cells from patients with trappc9 mutations (11).…”

Chronic pharmacologic manipulation of dopamine transmission ameliorates metabolic disturbance in Trappc9-linked brain developmental syndrome

“…Genome-wide association studies link trappc9 to NAFLD (15), a common comorbidity of obesity (16)(17)(18). Liver enlargement is seen in trappc9 KO mice (19).…”

“…Loss-of-function mutations of the gene coding for the trafficking protein particle (TRAPP) complex subunit 9 (trappc9) cause an autosomal recessive syndrome with intellectual disability and malformations of various brain structures; over half of the cases exhibit obesity (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Genome-wide analyses uncover differential methylation of the trappc9 gene in children with severe obesity as well as in women with a high body-mass index (12)(13)(14) and link trappc9 to non-alcoholic fatty liver disease (NAFLD) (15), the most common liver disease frequently associated with obesity (16)(17)(18). Consistent with a role for trappc9 in metabolism homeostasis, tracer metabolomics studies detect increased levels of dihydroxyacetone phosphate and glycerol-3-phosphate, precursors of triglyceride synthesis, and changes in levels of many other metabolites in skin fibroblasts from patients with the trappc9 syndrome (11).…”