PMID- 20029382 OWN - NLM STAT- MEDLINE DCOM- 20101103 LR - 20220318 IS - 1476-5497 (Electronic) IS - 0307-0565 (Linking) VI - 34 IP - 3 DP - 2010 Mar TI - A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia. PG - 537-46 LID - 10.1038/ijo.2009.257 [doi] AB - OBJECTIVES: The mechanisms for how saturated fat and sugar-based beverages contribute to human obesity are poorly understood. This paper describes a series of experiments developed to examine the response of hypothalamic neuropeptides to diets rich in sugar and fat, using three different diets: a high-fat high-sugar (HFHS) choice diet with access to chow, saturated fat and a 30% sugar solution; a high-fat (HF) choice diet with access to chow and saturated fat; or to a high-sugar (HS) choice diet with access to chow and a sugar solution. METHOD: We first studied caloric intake, body weight gain, hormonal alterations and hypothalamic neuropeptide expression when male Wistar rats were subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week. Next, we studied caloric intake and body weight gain when rats were subjected to the choice diets for 5 weeks. Finally, we measured neuropeptide expression in hepatic vagotomized rats subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week. RESULTS: In rats on an HF choice diet, plasma leptin concentrations and proopiomelanocortin (POMC) mRNA increased and neuropeptide Y (NPY) mRNA decreased. Rats on an HFHS choice diet showed identical plasma leptin concentrations as rats on an HF choice diet. However, NPY mRNA increased and POMC mRNA decreased. An HS choice diet for 1 week did not alter hypothalamic neuropeptide expression or plasma leptin concentrations. As hormonal changes did not explain the differences in hypothalamic neuropeptide expression between rats on the choice diets, we addressed whether neuronal feedback signals mediated the hypothalamic neuropeptide response. The POMC mRNA response to different diets depended on an intact innervation of liver and upper intestinal tract. CONCLUSION: Our data suggest that the specific combination of saturated fat and a 30% sugar solution results in hyperphagia-induced obesity and alters hypothalamic neuropeptide expression, and that the response of the melanocortin system is mediated by the hepatic vagus. FAU - la Fleur, S E AU - la Fleur SE AD - Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands. s.e.lafleur@amc.uva.nl FAU - van Rozen, A J AU - van Rozen AJ FAU - Luijendijk, M C M AU - Luijendijk MC FAU - Groeneweg, F AU - Groeneweg F FAU - Adan, R A H AU - Adan RA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091222 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 0 (Dietary Fats) RN - 0 (Dietary Sucrose) RN - 0 (Leptin) RN - 0 (Neuropeptide Y) RN - 66796-54-1 (Pro-Opiomelanocortin) SB - IM MH - Animals MH - Body Weight/physiology MH - Dietary Fats/administration & dosage/*adverse effects MH - Dietary Sucrose/administration & dosage/*adverse effects MH - Energy Intake/physiology MH - Gene Expression MH - Hyperphagia/blood/*complications/physiopathology MH - Leptin/blood MH - Liver/innervation MH - Male MH - Neuropeptide Y/*blood MH - Obesity/blood/*etiology/physiopathology MH - Pro-Opiomelanocortin/blood MH - Rats MH - Rats, Wistar EDAT- 2009/12/24 06:00 MHDA- 2010/11/04 06:00 CRDT- 2009/12/24 06:00 PHST- 2009/12/24 06:00 [entrez] PHST- 2009/12/24 06:00 [pubmed] PHST- 2010/11/04 06:00 [medline] AID - ijo2009257 [pii] AID - 10.1038/ijo.2009.257 [doi] PST - ppublish SO - Int J Obes (Lond). 2010 Mar;34(3):537-46. doi: 10.1038/ijo.2009.257. Epub 2009 Dec 22.