Hepatic Physiology Lab
The liver’s primary role is to filter and process nutrients coming from the digestive tract, and development of these processes during infancy and childhood could have lifelong impact on health. Early diet, in particular, has the potential to shape hepatic (liver) metabolism during development. Our lab is focused on understanding the immediate and long-term effects of different postnatal diets and dietary factors on hepatic nutrient metabolism and energy expenditure.
One well-defined nutritional difference between human breast milk and typical infant formulas is cholesterol content. Cholesterol concentrations are significantly lower in infant formulas. To compensate for the loss in dietary cholesterol, formula-fed infants seem to have increased hepatic cholesterol synthesis rates, yet formula-fed infants have lower serum LDL-cholesterol concentrations compared to their breastfed counterparts. The molecular basis for this apparent disparity in synthesis rates and serum cholesterol concentrations is unknown, and it is not clear if these differences influence physiological development of cholesterol homeostasis.
The ACNC developed a piglet model of formula and breastmilk feeding. In formula-fed piglets, we observed increased hepatic 7-a-hydroxylase (Cyp7a1) protein expression and activity. Cyp7a1 is responsible for converting cholesterol to bile acids; increased cholesterol metabolism to bile acids reduces hepatic cholesterol concentrations; to offset this loss, the liver increases receptor-mediated cholesterol uptake from the serum, thereby lowering circulating concentrations. Cyp7a1 is highly regulated through feedback mechanisms initiated by bile acid and cholesterol uptake in the small intestine. Current studies are underway to elucidate which of these feedback mechanisms are involved in upregulating Cyp7a1 activity.
Kelly Mercer, Ph.D.; Director of the ACNC Metabolomics Core and Hepatic Physiology Lab
Haixia Lin, Ph.D.