Hepatic Physiology Lab

Hepatic Physiology Lab

The liver’s primary role is to filter and process nutrients coming from the digestive tract, therefore early diet has the potential to shape hepatic metabolism functionality 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 have increased hepatic cholesterol synthesis rates in formula fed infants as compared to those receiving breast milk, 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 between breast feeding and formula feeding is unknown nor is it known if these differences influence physiological development of cholesterol homeostasis.

To address this knowledge deficiency, the ACNC developed a piglet model of formula and breast milk 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, thus to offset this loss, the liver increases receptor mediated cholesterol uptake from the serum, thereby lowering circulating concentrations.  Cyp7a1 is highly regulated through positive and negative 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.

Group Members

Kelly Mercer, Ph.D.; Director of the ACNC Metabolomics Core and Hepatic Physiology Lab

Haixia Lin, Ph.D.