Two main categories of hormones influence food intake:

1. High-fat diet-induced obesity impairs the response to the satiety signal GLP-1Diana L. Williams, Psychology Department & Program in Neuroscience Introduction HF-maintained rats gained significantly more weight than LF-maintained rats, as expected. HF LF 8 weeks on a HF diet impairs rats’ ability to respond to Ex4, the potent GLP-1 receptor activator • Two main categories of hormones influence food intake: • Adiposity signals: secreted by fat cells in proportion to fat mass, provide feedback to brain about how much fat an individual is carrying • Satiety signals – secreted by the intestines in response to food entering the gastrointestinal tract, provide feedback to brain about how much and what kinds of foods are being absorbed at the moment • Adiposity and satiety signals interact to determine hunger and fullness at any given meal • If your body fat has recently decreased (e.g., dieting, famine), adiposity signals are low. This makes you less sensitive to satiety signals the next time you eat, so you require more food to feel full. • We have previously demonstrated interactions between the adiposity signal leptin and several different satiety signals, including one called Glucagon-like Peptide 1 (GLP-1). • Rats that have defective leptin receptors (i.e., they have leptin but cannot sense it) fail to reduce food intake when injected with GLP-1. * % of baseline food intake * • Rats were tested with both LF and HF food because HF food tastes better • Regardless of the food available during testing, HF-maintained rats failed to show the usual anorexic response to Ex4 Saline Saline GLP-1 Ex4 High-Fat Diet impairs the response to GLP-1 % of baseline food intake * • LF-maintained rats showed the expected anorexic response to GLP-1 when tested on the LF diet • However, when eating HF diet for the test, LF-maintained rats failed to respond to GLP-1 • HF-maintained rats did not respond to GLP-1 when tested on either food Conclusions • Hypothesis • A similar effect occurs in diet-induced obesity – weight gain caused by overeating on a high-fat diet • Diet-induced obesity is a state of leptin resistance: the individual’s fat cells are secreting a large amount of leptin, but leptin receptors do not signal properly • High-fat diet-induced obesity impairs rats’ sensitivity to GLP-1 • GLP-1 is less effective in lean animals eating a HF meal • This is a potential mechanism for overeating and maintenance of elevated body weight on high-fat diets Future directions • Is this effect actually due to leptin resistance? Could some other feature of high-fat diet impair the response to satiety signals? • What are the neural circuits that mediate this change in response to satiety signals? • Methods • Rats were maintained on either high, 60% fat (HF) or low, 13% fat (LF) diets for 8 weeks. N = 12/group • The anorexic response to intraperitoneal injection of GLP-1 (100 ug/kg) or Exendin-4 (Ex4, 1 ug/kg), a potent activator of GLP-1 receptors, was tested relative to saline injection after 8 weeks of maintenance on HF or LF diets Acknowledgements: Funded by NIH grant 4R00DK078779 & FYAP Technical assistance from Nicole Lilly & Nina Hyvarinen Contact information: williams@psy.fsu.edu or 850-645-8717