The liver is an essential regulator of energy metabolism, and its function can be disrupted by nutritional alterations. Since liver development continues during breastfeeding nutritional challenges during this period predispose patients to diseases throughout life. A maternal protein-restricted (PR) diet during lactation promotes reductions in the body weight, adiposity, and plasma glucose and insulin, leptin resistance and an increase in corticosterone and catecholamines in adult male rat offspring. Here, we investigated hepatic metabolism in the offspring (both sexes) of PR (8% protein diet during lactation) and control (23% protein diet) dams. Both male and female offspring were evaluated at 6 months of age. PR males had no liver steatosis and manifested a reduction in lipids in hepatocytes adjacent to the vasculature. These animals had lower levels of esterified cholesterol in hepatocytes, suggesting higher biliary excretion, unchanged glycolysis and gluconeogenesis, and lower contents of the markers of mitochondrial redox balance and endoplasmic reticulum (ER) stress response and estrogen receptor alpha. PR females showed normal hepatic morphology associated with higher uptake of cholesterol esters, normal glycolysis and gluconeogenesis, and lower ER stress parameters without changes in the key markers of the redox balance. Additionally, these animals had lower content of estrogen receptor alpha and higher content of androgen receptor. The maternal PR diet during lactation did not program hepatic lipid accumulation in the adult progeny. However, several repair homeostasis pathways were altered in males and females, possibly compromising maintenance of normal liver function.

Metabolic programming

lactation

maternal diet

protein restriction

liver

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