Acute hyperphagia on a high-fat diet: Relation to circulating triglycerides and orexigenic peptide.

Abstract

Animals and humans are known to overeat on highly palatable and energy dense high-fat foods. To investigate mechanisms that mediate this hyperphagia, an acute “preload-to-test meal” paradigm was used (based on Warwick, 2000), in which normal weight adult Sprague-Dawley rats were given a small high-fat (HF) or low-fat (LF) preload and then, after an intermeal interval (IMI), were allowed to freely consume a subsequent test meal for 30 min. Several experiments were performed to determine the robustness of the acute HF-induced hyperphagia and mechanisms that may underlie this phenomenon. In all tests, a HF preload of only 10–15 kcal, compared to an equicaloric LF preload, significantly stimulated food intake by 40–50% (4–6 kcal) in subsequent test meal. This effect occurred with HF and LF preloads that were liquid or solid, equal in energy density and palatability, ingested or injected, and followed after a 60- or 120-min IMI by a test meal with variable fat content. This robust hyperphagia after HF preload was invariably associated with a 2- to 3-fold increase in circulating levels of triglycerides, with no change in leptin or insulin. It was accompanied by increased expression of galanin in the paraventricular nucleus and orexin in the perifornical hypothalamus, peptides known to stimulate intake on a fat-rich diet. Repeated administration of HF compared to an equicaloric LF preload significantly increased 24-h food intake. These results define an acute paradigm for studying hyperphagia on HF diet under controlled conditions and suggest mechanisms that possibly mediate this phenomenon. Supported by MH43422.