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1 Department of Nutrition, The University of Tennessee, Knoxville, TN, USA
* To whom correspondence should be addressed. E-mail: gtruett{at}utk.edu.
The onset of hyperphagia in the Zucker fatty (fa/fa) rat occurs on a single day in postnatal development and could be driven by an increase in insulin sensitivity. To test this hypothesis, we performed insulin tolerance tests at several points in development. In rapidly growing juvenile rats, fatties are as insulin sensitive as leans at 4 weeks of age, but become increasingly insulin resistant as they became obese. During the suckling to weaning transition, fatties are insulin resistant at 2 weeks of age, when they are exclusively suckling; they are also insulin resistant at 3 weeks of age, when they are suckling and consuming solid food, but not hyperphagic. By 4 weeks of age, when fatties are hyperphagic, fatties are as insulin sensitive as their lean littermates. These data indicate that fatties experience two phases of insulin resistance, punctuated by a brief period of insulin sensitivity that follows the onset of hyperphagia. To determine whether the increase in insulin sensitivity could be driving the onset of hyperphagia, insulin tolerance tests were performed from 21 to 27 days of age. Fatties and leans became increasingly insulin resistant from 21 days to 23 days of age, and then became as insulin sensitive as leans by 25 days of age. These data show that increased insulin resistance precedes the onset of hyperphagia and increased insulin sensitivity follows the onset of hyperphagia. This pattern suggests that developmental perturbations in insulin signaling are likely to be involved in the onset of hyperphagia.
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