Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life

Table 1

A summary of human and animal studies related to the developmental programming of NAFLD.

Early life insults	Species	Offspring NAFLD	Influence on offspring adiposity	References
Maternal obesogenic environment
Increased maternal BMI	Human	Increased neonatal hepatic lipid content	Independent of neonatal subcutaneous fat	[28, 29]
Maternal chronic HF diet consumption	NHP	Fetal hepatic steatosis persisting to juvenile age	No increase in body weight or body fat	[30]
Maternal chronic HF diet consumption	Mouse	Hepatic steatosis in offspring with postweaning chow diet; NASH in offspring with postweaning HF diet	Increase in fat accumulation, with highest increase in offspring with postweaning HF diet	[31]
Maternal HF diet	Mouse; rat	NASH in offspring with postweaning HF diet [33, 38, 57]; hepatic steatosis in offspring with postweaning chow diet [86]	Increased adiposity	[33, 38, 57, 86]
Maternal obesogenic diet (mixed source)	Mouse; rat	NASH in offspring with postweaning obesogenic diet [32, 34–37]; increased hepatic lipid accumulation at early age with postnatal chow diet [69]	Increased body weight/adiposity [32, 34–37]; no changes in body weight or adiposity [69]	[32, 34–37, 69]
HF diet induced maternal insulin resistance	NHP	NAFLD in offspring with postweaning chow diet	No obesity present	[40]
Intergenerational HF diet	Mice	Progressive exacerbation of NAFLD	Progressively increased adiposity	[41]
Growth restriction/maternal UN
Low birth weight	Human	Increased plasma ALT and GCT at 60–79 years	Adjusted for waist-to-hip ratio	[42]
Small for gestational age	Human	Independently associated with NAFLD	After correction for BMI	[43]
Accelerated weight gain in the first 3 months of infancy	Human	Increased risk for NAFLD in early adulthood	After correction for adult weight score	[44]
Lean in early life and subsequently obese	Human	Increased risk for NAFLD	Adjusted for adult BMI	[45]
Maternal low protein diet	Rat	Hepatic steatosis	Without a parallel increase in adiposity	[46, 47]
Maternal global nutrient restriction	Sheep	Hepatic lipid accumulation in aged offspring	Offspring are lean	[48]
Maternal undernutrition	Rat	Fetal hepatic fat deposition at embryonic day 20	Prior to the development of offspring adiposity	[49]
Prenatal hypoxia induced IUGR	Rat	Hepatic steatosis in offspring with hypoxia challenge at age of 6 months	No change in body weight	[50]
Vitamin B12 and folate deficiency induced IUGR	Rat	Hepatic steatosis at weaning	Significantly decreased body weight	[51]