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Objective: Intermittent (INT) access to a high-fat diet (HFD) can induce excessive-intake phenotypes in rodents. This study hypothesized that impaired satiation responses contribute to elevated intake in an INT-HFD access model. Methods: First, this study characterized the intake and meal patterns of female rats that were subjected to an INT HFD in which a 45% HFD was presented for 20 hours every fourth day. To examine nutrient-induced satiation, rats received intragastric infusions of saline or Ensure Plus prior to darkness-onset food access. A similar design was used to examine sensitivity to the satiating effect of amylin. This study then examined whether an INT HFD influences amylin-induced c-Fos in feeding-relevant brain areas. Results: Upon INT HFD access, rats consumed meals of larger size. The anorexic response to intragastric Ensure infusion and exogenous amylin treatment was blunted in INT rats on both chow-only and INT-HFD days of the diet regimen, compared with chow-maintained and continuous-HFD rats. An INT HFD did not influence amylin-induced c-Fos in the area postrema, nucleus of the solitary tract, and lateral parabrachial nucleus. Conclusions: Impaired satiation responses, mediated in part by reduced sensitivity to amylin, may explain the elevated intake observed upon INT HFD access and may play a role in disorders of INT overconsumption, including binge eating.Obesity (2020) 28, 942-952.

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