Cholesterol and bile acid synthesis during total parenteral nutrition with and without lipid emulsion in the rat

Abstract

The origin of excess plasma free cholesterol known to accumulate in plasma of patients or animals given total parenteral nutrition (TPN) with lipid emulsion was investigated. Rats were infused for 8 days with a specially formulated TPN solution plus either lipid emulsion (lipid-TPN) or an equicaloric volume of 25% dextrose (dextrose-TPN). Laboratory diet-fed controls were sham operated. Lipid-TPN suppressed hepatic HMG CoA reductase (HMG CoAR) activity but elevated cholesterol 7 alpha-hydroxylase (7 alpha-OH) activity. HMG CoAR activity, however, was increased in adipose tissue and skeletal muscle by lipid-TPN when compared to dextrose-TPN. Plasma lecithin/cholesterol acyl transfer activity was similar among all groups. It is suggested that in lipid-TPN excess plasma free cholesterol does not arise from decreased hepatic clearance or plasma esterification but may originate from extrahepatic tissue, possibly through leaching of membrane cholesterol by mesophase phospholipid present in the lipid emulsion. The changes in hepatic HMG CoAR and 7 alpha-OH activity imply that during lipid-TPN plasma free cholesterol is cleared by the liver and catabolized to bile acid.