Date of Award

Summer 2000

Document Type


Degree Name

Doctor of Philosophy (PhD)


Biological Sciences


Biomedical Sciences

Committee Director

Thomas J. Lauterio

Committee Member

Paul Aravich

Committee Member

Gerald Pepe

Committee Member

Russell Prewitt


Obesity is an increasingly common public health problem with approximately one-half of the American adult population overweight and one-quarter considered obese. This alarming trend has led researchers to determine potential causative factors of excess weight gain in humans. However, it is difficult to discern whether perturbations that result in obesity are the cause or simply the result of the obese state. Diet-induced obesity is one of the animal models that allow researchers to address temporal issues. Our laboratory utilizes a diet-induced obesity model in which Sprague-Dawley rats are placed on a purified moderately high fat diet and ultimately diverge into two distinct populations based on body weight gain. Approximately 50% of the rats gain more body weight and fat and are considered obesity-prone (OP), whereas the other half (obesity-resistant—OR) are similar in body composition to rats fed a low fat diet. Interestingly, rates of body weight gain and food consumption are greater for OP rats than OR rats during early phases of the dietary challenge, but not during later phases. Moreover, weight gain is associated with excess fat accretion in OP rats. These data led us to examine the potential causes of increased fat weight gain during the early phases. The major site of lipid storage is the adipose tissue. Two major processes occurring in adipocytes are lipolysis (lipid mobilization) and lipogenesis (lipid formation), which are controlled by different metabolic hormones. Potential differences in these processes or hormone sensitivity may predispose OP rats to develop obesity or protect OR rats from the obese state. In experiment 1, in vivo lipolysis was measured in outbred OP and OR rats prior to exposure to an obesity-inducing diet. In vitro lipolysis was assessed in various adipocytes from inbred OP and OR rats in experiment 2. Early effects of moderately high fat feeding on insulin-stimulated glucose uptake and metabolism and body composition were examined in another set of experiments. Results demonstrated that in vivo lipolytic responses were not a causative factor in excess body weight and fat accretion in OP rats. Next, in vitro responses to various lipolytic agents were reduced in visceral adipocytes of inbred OP rats, which were already fatter than inbred OR rats. In the last set of experiments, MHF-feeding reduced insulin-stimulated glucose uptake and metabolism in adipocytes vs. LF feeding. Epididymal fat cells of OP rats synthesized more fatty acids from glucose than those of OR rats after short-term exposures to the same MHF diet. It may be speculated that altered lipolysis is not a causative factor for excess adiposity in OP rats. Moreover, increased insulin responsiveness (via lipid synthesis) may promote excess fat accretion in OP rats. As obesity develops, adipocytes of OP rats may become less responsive to lipolytic agents, which may exacerbate visceral fatness.