• Horwitz, Barbara A (PI)

Project: Research project

Project Details


Obesity when viewed in the broadest sense is a disorder of energy balance.
There is evidence that in a number of genetic models of obesity,
thermogenesis is defective and the major site of this defect is brown
adipose tissue. The bulk of this evidence comes from animals where the
obesity is already established. What is not known is whether thermogenic
alterations occur early enough to significantly contribute to the ontogeny
of obesity. In this proposal we will evaluate this problem in the
genetically obese Zucker rat. In addition, we will examine 3 genetically
lean strains of rats that achieve different degrees of obesity as adults
after overfeeding during weaning as well as after weaning. The intent is
to determine if thermogenic alterations are associated with the development
of different degrees of obesity. We are asking 4 specific questions: 1)
How early are alterations in thermogenesis manifested in the genetically
obese and genetically lean overfed animals? 2) Does overfeeding during
suckling affect postweaning thermogenic responses to palatable diets and do
these responses vary depending on the strain of rats? 3) Do the initial
thermogenic alterations reflect alterations at the target tissues effecting
nonshivering thermogenesis? 4) Do alterations in thermogenic capacity of
brown adipose tissue occur concurrently with the rats' altered response to
norepinephrine? These questions will be answered using a variety of
techniques including measurements of whole animal thermogenesis and
composition, morphological examination of brown and white adipose tissue
(cell size and number), biochemical analyses including measurements of
lipogenesis, cytochrome c and activities of citrate synthase,
beta-hydroxyacyl CoA dehydrogenase and lipoprotein lipase. The data will
provide basic information about thermogenesis in neonates and how this is
altered in obesity. Furthermore, this study will indicate the degree to
which thermogenic alterations contribute to the early development of
obesity. Of practical significance are preliminary observations by a
number of investigators that thermogenesis and brown adipose tissue may be
impaired in obese adult humans. Our basic findings should help to evaluate
and target treatment aimed at modifying this defect.
Effective start/end date4/1/843/31/87


  • National Institutes of Health


  • Medicine(all)


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