DEFICITS IN FEEDING AND VAGAL RESPONSES IN TWO RAT MODELS OF OBESITY
Open Access
- Author:
- Swartz, Timothy David
- Graduate Program:
- Physiology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- April 09, 2009
- Committee Members:
- Michael Thomas Green, Thesis Advisor/Co-Advisor
Mihai Covasa, Thesis Advisor/Co-Advisor - Keywords:
- obesity
CCK
satiation
fats - Abstract:
- Obesity is currently a global epidemic, while in the United States, approximately 33% of the population is obese. Consumption of a HF diet is linked both with overconsumption and obesity in humans and rodents. Cholecystokinin (CCK) a peptide hormone, secreted from the duodenum in response to intestinal fats and proteins, is partially responsible for meal termination. While a HF diet suppresses the satiating effects of CCK, fats also exert orosensory stimulating effects, which promotes further intake of both fats and other nutrients. Because obese individuals have increased preference for fats compared to lean individuals, it is possible that increased orosensory stimulation causes over consumption. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a model of obesity that lacks a functional CCK-1 receptor (CCK-1R). This rat is hyperphagic compared to Long-Evans Tokushima Otuska (LETO) lean controls. Therefore, in an attempt to elucidate the role of the orosensory component in hyperphagia in the OLETF.rat, we employed one bottle sham feeding tests. To examine the role of an energy deficit in preferences of fats, we subjected OLETF and LETO rats to non-deprivation, overnight deprivation, and two hour deprivation and tested their acceptance for fat. Additionally, to examine the interaction between both the oral and postoral properties of fats, we assessed acceptance and preference for fats using real feeding tests. We found that OLETF rats’ sham intake was significantly increased at higher oil concentrations during a fed state compared to LETO. Conversely the concentration curve was shifted left towards the lower concentrations after deprivation. Real feeding also resulted in increased oil intake at high oil concentrations compared to LETO. Together, these results suggest that OLETF rats have an increased oral avidity to fats compared to LETO. During deprived conditions, OLETF consumed more from low concentrations of oils. To examine bodyweight and adiposity as well as peripheral deficits in an established rodent model that becomes obese when fed a high-fat (HF), we measured 24-hour chow intake, body weight, and relative fat pad mass in dietary induced obese (DIO) and dietary induced obese resistant (DR) rats. Additionally, we studied the sensitivity of both DIO and DR to CCK at doses of 2.0, 4.0, and 8.0 μg/kg when fed chow over 60 minutes. Finally, to complement our behavioral experiment, we examined CCK-induced Fos-like immunoreactivity (Fos-Li) in the dorsal vagal complex (DVC) after pre-treatment with 4.0 and 8.0 μg/kg doses of CCK. We found that DIO rats ate more chow in 24 hours and weighed more than DR rats. However, epididymal and total relative fat pad mass was significantly lower in DIO rats compared to DR. Lastly, CCK significantly suppressed chow intake more and produced more Fos-Li in the DIO strain compared to DR at the 4.0 μg/kg dose, These results show that DIO rats are more sensitive to the satiating effects of CCK at 4.0 μg/kg that is most likely due to vagal mechanisms, such as an increase of CCK-1R.