| Description |
Mice homozygous for the obese spontaneous mutation, (Lepob
commonly referred to as ob or ob/ob) exhibit obesity
hyperphagia, a diabetes-like syndrome of hyperglycemia,
glucose intolerance, elevated plasma insulin, subfertility,
impaired wound healing, and an increase in hormone
production from both pituitary and adrenal glands. They are
also hypometabolic and hypothermic. The obesity is
characterized by an increase in both number and size of
adipocytes. Although hyperphagia contributes to the obesity,
homozygotes gain excess weight and deposit excess fat even
when restricted to a diet sufficient for normal weight
maintenance in lean mice. Hyperinsulinemia does not develop
until after the increase body weight and is probably the
result of it. Homozygotes do have an abnormally low
threshold for stimulation of pancreatic islet insulin
secretion even in very young preobese animals. As is the
case with mice carrying the diabetes mutation (Leprdb),
manifestation of the diabetic syndrome is strikingly
dependent on genetic background. Lepob homozygotes on the
BTBR background develop diabetes at six weeks (males), and
eight weeks (females). Hyperglycemia is severe and
progressive with a fasting plasma glucose of 400 mg/dl at 10
weeks (Stoehr et al., 2000). In contrast to homozygotes
onthe C57BL/6 background, BTBR homozygotes develop extreme
obesity (Stoehr et al., 2004) and progressive
hypertriglyceridemia (Lan et al., 2003). Hepatic lipogenesis
is not increased and homozygotes do not develop hepatic
steatosis (Lan et al., 2003) Males remain hyperinsulinemic
although insulin levels and islet mass are much reduced
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