Apo AIV-Induced Satiety and HF Diet-Induced Obesity

University Of Cincinnati, Cincinnati OH

Investigators

Linked publications & trials

Abstract

During the current funding cycle, we made significant progress and made several key observations. First, we[unreadable] demonstrated that apo AIV is synthesized in the arcuate nucleus of the hypothalamus where adiposity signals[unreadable] act to influence energy homeostasis. Also, the administration of exogenous apo AIV either peripherally or[unreadable] centrally into the brain reduces food intake and body weight, and the administration of apo AIV antibodies[unreadable] centrally increases food intake. Second, obese rats maintained on a high fat saturated diet (HF-SAT, butter[unreadable] fat) have greatly reduced hypothalamic apo AIV gene and protein expression. Third. HF-SAT obese rats also[unreadable] have an attenuated intestinal and hypothalamic apo AIV gene and protein response to fasting and lipid[unreadable] feeding when compared to rats maintained on a low-fat (LF-SAT) diet or chow. Finally, we found that[unreadable] apo AIV knockout (KO) mice are more susceptible to high-fat (HF) diet-induced obesity. These observations[unreadable] imply that normal apo AIV activity is necessary to prevent obesity. Preliminary evidence from our Animal[unreadable] Core suggest that rats maintained on a diet matched in total fat but using olive oil (rich in oleic acid, a monounsaturated[unreadable] fat, abbreviated as HF-MONO) had less obesity than those on the HF-SAT diet. Furthermore,[unreadable] unlike the HF-SAT fed rats, the HF-MONO rats did not have reduced hypothalamic apo ATV gene expression.[unreadable] We hypothesize that apo AIV protects the animal against obesity caused by the chronic[unreadable] feeding of a HF-SAT diet and that the type of fatty acid in the diet regulates hypothalamic[unreadable] apo AIV gene and protein expression (saturated FA apo AIV expression while oleic acid is[unreadable] neutral). To test these hypotheses, we have proposed 4 specific aims. SPECIFIC AIM 1.2. (Project i,[unreadable] Specific Aim i) We will determine the role of intestinal apo AIV and hypothalamic apo AIV in diet-induced[unreadable] obesity caused by maintenance on a HF-SAT or a HF-MONO diet. SPECIFIC AIM 1.2. We will[unreadable] determine the interaction of apo AIV and CCKonfood intake and whether this interaction is influenced by[unreadable] maintenance on HF-SAT or HF-MONO. SPECIFIC AIM 1.3. We will test the hypothesis that gut peptides[unreadable] are differentially modified by dietary fats. SPECIFIC AIM 1.4. This specific aim utilizes the apo AIV[unreadable] knockout (KO) mouse as a tool to complement the other specific aims and to specifically address the question[unreadable] of whether apo AIV protects the animal against diet-induced obesity.[unreadable]