Appetite Regulation in Older-Aged Obese Individuals



 DESCRIPTION (provided by applicant): There is good evidence that the regulation of energy intake (EI) changes with aging. The "anorexia of aging" has been described and is associated with reduced hunger and reward-related eating and thus with reduced EI and ultimately weight loss. Paradoxically, however, obesity rates are increasing in older individuals, and within this rapidly growing segment of our population, the problem of obesity and excess adiposity has become particularly widespread. While changes in energy expenditure and lean body mass are thought to be important mediators of body weight regulation or "dysregulation" in older individuals, there is also good evidence that aging is associated with not only reduced appetite and motivation to eat but also with impaired ability to accurately regulate EI and thus adapt to energy imbalance. The mechanisms, though, for these findings have not been well elucidated, and it is unclear whether the mechanisms responsible for the development and/or maintenance of obesity are impacted by age. Because of the high prevalence of obesity in older-aged individuals and the number of unanswered questions and controversies, it is critical to determine the mechanisms for the development and/or persistence of obesity in this population and whether the mechanisms are different from younger adults. Furthermore, better understanding EI regulation in older individuals is also critical if we are to properly manage this growing population. The overall goal of this pilot project are to begin to examine age- and obesity-related differences in the regulatio of EI. Specifically, we propose to examine: 1) the neuronal response to salient visual food cues and during an impulsivity task using functional magnetic resonance imaging (fMRI); 2) appetite-related ratings and peptides; 3) eating-related behaviors; and 4) ad libitum EI. These assessments will be performed in older obese (OOb) as compared to older normal weight (ONW) and younger-aged obese (YOb) individuals. We hypothesize that measures of EI regulation will favor increased EI in OOb as compared to ONW as evidenced by: 1) increased neuronal responses to salient food cues in brain regions encoding reward, motivation and attention, and to an impulsivity task; 2) differences in measures of appetite (↑hunger, ↓satiet) and appetite-related peptides (↓leptin, ↑ghrelin, ↓PYY/GLP-1); 3) increased ratings of eating related behaviors; and 4) increased ad libitum EI. We also hypothesize that measures of EI regulation will favor decreased EI in OOb as compared to YOb as evidenced by: 1) decreased neuronal responses to salient food cues in brain regions encoding reward, motivation and attention, and to an impulsivity task; 2) differences in measures of appetite (↓hunger, ↑satiet) and appetite-related peptides (↑leptin, ↓ghrelin, ↑PYY/GLP-1); 3) decreased ratings of eating related behaviors; and 4) decreased ad libitum EI. More than 35% of Veterans in primary care are obese and this percentage is likely even higher among older Veterans. The knowledge generated by this project is expected to guide therapeutic weight loss strategies in the VHA and will advance GRECC research on Consequences and Treatments of Obesity in Older Adults.