Obesity affects an estimated 25-35% of the U.S. population. Obese individuals are at greater risk for diabetes, heart disease and other complications making the prevention of this disease an important goal. We have developed a dietary obesity model in which factors leading to obesity susceptibility can be separated from factors conferring resistance to obesity. The work proposed will determine whether the growth hormone (GH) axis is involved either with the development of diet-induced obesity or resistance to obesity as exemplified by this model. The overall objective of this proposal is to determine whether differences in GH secretion or responsiveness alter susceptibility to diet--induced obesity using a rat model of diet-induced obesity.
Specific aim I will determine if circulating GH concentrations or provoked GH secretion are predictive measures of susceptibility to obesity. If so, direct manipulation of GH status will be conducted to demonstrate cause and effect. In parallel studies we will determine whether obesity-resistant and susceptible populations differ with regard to energy expenditure.
Specific aim II will focus on tissue responsiveness to GH as a factor in diet-induced obesity. We will determine if the lipolytic response to GH differs in obesity susceptible and resistant populations before they become obese. This involves the use of in vivo microdialysis which will enable us to obtain measures of lipolysis in awake animals under normal physiological conditions. Circulating factors that can alter the lipolytic response in response in obese and lean animals will be present under these conditions, which cannot be duplicated in vitro. The specificity of lipolytic response to GH as a predictive index will be assessed if differences are found by the use of other lipolytic agents in vivo if a divergent response to lipolysis does not exist prior to feeding the obesity-producing diet, change in adipose lipolysis will be evaluated over the course of dietary treatment by in vivo ultrafiltration. The effect of fat saturation will also be examined.
Specific aim III will complement the in vivo experiments by investigating lipolysis in adipose cells obtained from diet induced obese and lean rats in vitro. The effects of GH binding proteins on hormone-stimulated lipolysis will also be assessed.
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