Factors early in life associated with hepatic steatosis

Abstract

BACKGROUND The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) mirrors the obesity epidemic. NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis, fibrosis and cirrhosis and/or hepatocellular carcinoma. Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity. AIM To review the early developmental factors associated with NAFLD. METHODS Databases MEDLINE via PubMed, and EMBASE and Reference Citation Analysis were searched and relevant publications up to April 30, 2021 were assessed. Original research studies that included risk factors associated with early development of NAFLD in human subjects were included. These factors include: Maternal factors, intrauterine and prenatal factors, post-natal factors, genetic and ethnic predisposition, childhood and adolescence environmental factors. Studies were excluded if they were review articles or animal studies, case reports or conference abstracts, or if NAFLD was not clearly defined and assessed radiologically. RESULTS Of 1530 citations identified by electronic search, 420 duplicates were removed. Of the 1110 citations screened from title and abstract, 80 articles were included in the final analysis. Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) were associated with increased risk of NAFLD. Familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD. Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD. Studies relating to socioeconomic factors and its association with NAFLD reported confounding results. CONCLUSION Maternal metabolic dysfunction during pregnancy, being exclusively breastfed for a longer time postnatally, diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.

Postnatal Consumption of Black Bean Powder Protects against Obesity and Dyslipidemia in Male Adult Rat Offspring from Obese Pregnancies

“…In addition to the accumulation of liver fat, MASLD is further associated with disturbances in cholesterol metabolism [42][43][44], including increased cholesterol deposition [45] and synthesis [46,47], and the altered expression of cholesterol regulatory genes [48,49]. Although obesity and insulin resistance are closely linked to the pathophysiology of MASLD [50], recent work suggests that there may be a potential programming influence of maternal obesity that predisposes offspring to dysregulated hepatic fat metabolism and MASLD development [5,51,52]. Similarly, we observed that HC/CON offspring had a ~29% increase in liver TG concentration compared with offspring from CON/CON mothers.…”

Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity

“…Interestingly, maternal supplementation with one-carbon corrects these outcomes [32]. A meta-analysis of datasets also shows that maternal metabolic dysfunction and diet during pregnancy are early developmental factors associated with offspring NAFLD [33]. Taken together, these findings indicate that maternal nutrition programs the pathogenesis of NAFLD in the early life of offspring.…”

Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases

“…MBOAT7 functions to remodel phosphatidyl inositol with arachidonic acid and is primarily expressed in the liver ( 13 – 15 ). The rs641738 mutation (C > T), increases the risk of developing not only MAFLD, but an entire spectrum of liver diseases (NASH, cirrhosis, and hepatocellular carcinoma) ( 16 , 17 ).…”