Reference intervals for preprandial and postprandial serum bile acid in adult rhesus macaques (Macaca mulatta).

Bile acids are amphiphilic organic acids (detergent-like compounds) that are synthesized exclusively in the liver and derived from cholesterol.5 Their principal functions are to improve intestinal fat assimilation and to eliminate bilirubin and cholesterol.5 Changes in bile acid metabolism and excretion are a reflection of liver dysfunction.3 Thus the measurement of total serum bile acid concentration (SBAC) is a sensitive and noninvasive method of identifying hepatic disease.3,5-7 The physiology of bile acid synthesis, metabolism, excretion, and enterohepatic circulation is complex and influenced by several factors. Bile salts are synthesized by hepatocytes using cholesterol as a precursor and producing the primary bile acids, cholic acid and chenodeoxylic acid.15 Secondary bile acids are formed by dehydroxylation during passage through the intestines. In rhesus macaques, the main secondary bile acid is deoxycholic acid. After synthesis, the bile acids are conjugated in the liver, preferentially with taurine, in rhesus macaques.28 This conjugation process improves their solubility in aqueous solution, where they aggregate to form micelles that can incorporate cholesterol and phospholipids.3 The bile acids then are transported across the hepatocyte membrane into the biliary canaliculi, through the biliary ducts, and are eventually stored in the gall bladder. When the gall bladder contracts, bile acids are released and pass through the common bile duct into the duodenum. Once the bile acids reach the small intestine, principally the ileum, they are actively transported into the portal circulation, circulated through the sinusoids, and are actively recaptured by the hepatocytes. The enterohepatic circulation of bile acids is 95% efficient.29 In the preprandial fasting state, bile acids are found in low concentration in the peripheral blood and are present due to the leakage of bile acids from the enterohepatic circulation. The SBAC is a measure of this spillover. After the ingestion of a meal, especially one high in fat, the gall bladder contracts. This contraction is mediated by cholecystokinin released in response to food, especially fat, in the upper gastrointestinal system. Subsequently, the concentration of bile acid in the portal vein increases, and this elevation is reflected in the peripheral blood as a postprandial increase in SBAC. In liver disease, the ability of hepatocytes to recapture bile acids may be decreased, resulting in high postprandial SBAC. An endogenous challenge to the enterohepatic circulation of bile acids is used clinically in small animal and human medicine to evaluate liver function. Preprandial fasting and 2-h postprandial SBAC are used for evaluation.7 Liver function can be evaluated by other methods as well.3,27 The median preprandial and postprandial values can be elevated significantly in dogs with several types of liver disease, including cirrhosis, chronic hepatitis, hepatic necrosis, cholestasis, neoplasia, and portosystemic vascular anomaly.6 Nonspecific clinical signs often are associated with liver disease (weight loss, lethargy, gastro-intestinal and neurologic abnormalities). SBAC values are especially useful in diagnosing hepatic dysfunction in these cases where there is no icterus and no abnormal (or only mildly increased) liver enzyme activity, such as can be seen with hepatoportal perfusion abnormalities or severely reduced hepatic mass.6,7 In conjunction with historic data, physical examination, and clinical pathology findings, preprandial and postprandial SBAC provide a convenient noninvasive test that has high sensitivity and variable specificity for hepatic disease in companion animals.7 Currently there are no normal reference intervals for preprandial and postprandial SBAC in rhesus macaques. The primary objective of this study was to establish 12-h fasting preprandial and 2-h postprandial SBAC reference intervals in healthy captive indoor-housed adult rhesus macaques (Macaca mulatta). We hypothesize that, as in companion animals, mean postprandial SBAC in rhesus macaques will be significantly higher than mean preprandial SBAC. In addition, a secondary objective was to compare the SBAC of rhesus macaques to defined SBAC references intervals reported for dogs, cats, and humans.