Spontaneous obesity and increased bile saturation in the ground squirrel

Obesity is a well-known risk factor for developing cholesterol gallstones, but only indirect human studies are available. Presently available animal models of cholesterol gallstone disease do not become obese under normal conditions, while genetically obese or dietarily manipulated rats lack a gallbladder. The Richardson ground squirrel on a high-cholesterol diet develops impaired gallbladder contractility, excess cholesterol in its bile, and then cholesterol gallstones. To determine if ground squirrels would spontaneously become obese and serve as an appropriate model, animal weights were followed over several months while being maintained under a regulated laboratory environment. The five obese animals were twice the body weight of the five lean controls and also had a 20% rise in body fat. Plasma cholesterol levels were markedly increased and liver histology revealed mild microvesicular steatosis. Cholesterol saturation rose in the gallbladder bile of the obese group. This alteration was primarily due to a significant increase in phospholipid (33%) and cholesterol (86%) levels. Such a laboratory environment interrupts the natural annual rhythm of the ground squirrel and prevents hibernation. Animals continued to eat and develop severe obesity and abnormal gallbladder bile. These spontaneously obese animals provide an excellent means for examining altered hepatobiliary secretion and gallbladder motility relative to cholesterol gallstone disease.