Negative Effect of Chronic High-fat Diet Consumption on Postprandial Plasma Peptide YY Levels



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Introduction: Peptide YY (PYY) is a satiety hormone that is released from the small intestine following consumption of nutrients such as carbohydrates, protein, and dietary fats. Chronic excess energy consumption leads to suppressed satiety signaling. Therefore, we hypothesized that chronic consumption of high amounts of dietary fat stimulates PYY release while promoting rate of fat absorption. Methods: In this study, male C57BL/6 mice (age 8 weeks) were given either chow or a high-fat diet (HF) ad libitum for twelve weeks (n = 6/group). Mice were weighed and their food intake was measured weekly. Mice were fasted and given a high-fat liquid meal challenge via oral gavage following the twelve-week trial. Postprandial tail vein blood was collected and PYY levels were measured by an ELISA assay. Mice were euthanized and tissues were collected for further analyses. Results: As predicted, HF-fed mice gained significantly more weight than standard chow-fed mice (38.3+/-1.8 vs. 29.8+/-1.6; p=0.0002). To our surprise, HF-fed mice displayed significantly reduced basal and postprandial plasma PYY compared with chow mice (2808.9 ±290.5 pg/ml and 3640.7 ±605.5 pg/ml, respectively). Intriguingly, HF-fed mice displayed elevated intestinal PYY expression. Conclusion: Our observations indicate that PYY levels are decreased in high-fat mice. Thus, this study provides evidence supporting the hypothesis that chronic high fat consumption promotes enhanced fat digestion and absorption, which ultimately leads to increased food intake and obesity.