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To this end, we fed C57BL\/6J mice for 8 weeks with diets containing 10\u00a0% energy as fat (low-fat diet, LFD) or 45\u00a0% energy as fat (HFD) enriched with either 20\u00a0% energy as casein (LFD and HFD) or WPI (high-fat WPI). Metabolic parameters and the hypothalamic and epididymal adipose tissue expression of energy balance-related genes were investigated. The HFD increased fat mass and plasma leptin levels and decreased the dark-phase energy intake, meal number, RER, and metabolic (VO<jats:sub>2<\/jats:sub>and heat) and locomotor activities compared with the LFD. The HFD increased the hypothalamic tissue mRNA expression of the leptin receptor, insulin receptor (<jats:italic>INSR<\/jats:italic>) and carnitine palmitoyltransferase 1b (<jats:italic>CPT1b<\/jats:italic>). The HFD also reduced the adipose tissue mRNA expression of<jats:italic>GLUT4<\/jats:italic>and<jats:italic>INSR<\/jats:italic>. In contrast, WPI reduced fat mass, normalised dark-phase energy intake and increased meal size in HFD-fed mice. The dietary protein did not have an impact on plasma leptin, insulin, glucose or glucagon-like peptide 1 levels, but increased plasma TAG levels in HFD-fed mice. At a cellular level, WPI significantly reduced the HFD-associated increase in the hypothalamic tissue mRNA expression of the leptin receptor,<jats:italic>INSR<\/jats:italic>and<jats:italic>CPT1b<\/jats:italic>. Also, WPI prevented the HFD-induced reduction in the adipose tissue mRNA expression of<jats:italic>INSR<\/jats:italic>and<jats:italic>GLUT4<\/jats:italic>. In comparison with casein, the effects of WPI on energy intake and hypothalamic and adipose tissue gene expression may thus represent a state of reduced susceptibility to weight gain on a HFD.<\/jats:p>","DOI":"10.1017\/s0007114513001396","type":"journal-article","created":{"date-parts":[[2013,6,4]],"date-time":"2013-06-04T08:31:20Z","timestamp":1370334680000},"page":"2114-2126","source":"Crossref","is-referenced-by-count":33,"title":["Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes"],"prefix":"10.1017","volume":"110","author":[{"given":"Liam","family":"McAllan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deirdre","family":"Keane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harri\u00ebt","family":"Schellekens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen M.","family":"Roche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riitta","family":"Korpela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Cryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanishka N.","family":"Nilaweera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2013,6,4]]},"reference":[{"key":"S0007114513001396_ref44","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kve071"},{"key":"S0007114513001396_ref52","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.233288"},{"key":"S0007114513001396_ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2010.04.017"},{"key":"S0007114513001396_ref41","doi-asserted-by":"crossref","unstructured":"Westerterp KR (1993) Food quotient, respiratory quotient, and energy balance. 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