Attenuated growth during early postnatal life protects offspring from obesity and a fatty liver.

Abstract

Early life nutrition significantly impacts adult metabolic health, particularly protein supply during pregnancy and lactation, affecting susceptibility to metabolic syndromes like obesity, type II diabetes, fatty liver, and cardiovascular disease. This thesis used a mouse model of delayed postnatal growth to evaluate the impact of early nutrition on adult metabolic health. Programmed mice nursed by a casein-deficient mother only grow to 50% of their body weight by the end of lactation. During adolescence, the programmed mice reach about 80% of the weight of control animals but then retain that lower weight throughout life. The reduced postnatal growth results in a partial resistance to high-fat diet-induced obesity and full protection against fatty liver. Chapter 3 found that programmed mice increased the expression of energy expenditure markers Dio2 and PGC1a in brown adipose tissue at a conventional house temperature of 20 °C. They also showed increased UCP1 expression and adiponectin expression. In a second experiment, at a thermal house temperature of 30 °C, PGC1a expression increased in brown adipose tissue, subcutaneous white adipose tissue, and epididymal white adipose tissue. Ucp1 gene expression was also increased in BAT and sWAT, with a reduction in response to a high-fat diet. Programed mice showed increased adiponectin expression and decreased leptin expression. chapter 4 found that a microarray study found that early nutrition significantly impacted the expression of FGF21, Elovl5, Insig2, and Erg1 in programmed mice, which is associated with lipid metabolism and metabolic health. This difference was observed in programmed mice compared to wild-type mice. Quantitative PCR confirmed the findings, suggesting protection against obesity and fatty liver. In chapter 5 found that in vitro experiments using HepG2 liver cells demonstrated that the casein amino acid composition enhances lipid storage in liver cells compared to other amino acid compositions such as soy, microalgae, and cell culture medium.