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Am J Physiol Regul Integr Comp Physiol 289: R156-R163, 2005. First published March 17, 2005; doi:10.1152/ajpregu.00774.2004
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Effects of high-fat diets with different carbohydrate-to-protein ratios on energy homeostasis in rats with impaired brain melanocortin receptor activity

C. Morens, M. Keijzer, K. de Vries, A. Scheurink, and G. van Dijk

Department of Animal Physiology, Unit Neuroendocrinology, University of Groningen, Haren, The Netherlands

Submitted 12 November 2004 ; accepted in final form 3 March 2005

Changes in dietary macronutrient composition and/or central nervous system neuronal activity can underlie obesity and disturbed fuel homeostasis. We examined whether switching rats from a diet with high carbohydrate content (HC; i.e., regular chow) to diets with either high fat (HF) or high fat/high protein content at the expense of carbohydrates (LC-HF-HP) causes differential effects on body weight and glucose homeostasis that depend on the integrity of brain melanocortin (MC) signaling. In vehicle-treated rats, switching from HC to either HF or LC-HF-HP feeding caused similar reductions in food intake without alterations in body weight. A reduced caloric intake (–16% in HF and LC-HF-HP groups) required to maintain or increase body weight underlay these effects. Chronic third cerebroventricular infusion of the MC receptor antagonist SHU9119 (0.5 nmol/day) produced obesity and hyperphagia with an increased food efficiency again observed during HF (+19%) and LC-HF-HP (+33%) feeding. In this case, however, HF feeding exaggerated SHU9119-induced hyperphagia and weight gain relative to HC and LC-HF-HP feeding. Relative to vehicle-treated controls, SHU9119 treatment increased plasma insulin (2.8–4 fold), leptin (7.7–15 fold), and adiponectin levels (2.4–3.7 fold), but diet effects were only observed on plasma adiponectin (HC and LC-HF-HP<HF). Finally, SHU9119-treated LC-HF-HP-fed rats were less glucose tolerant than others. Relatively low plasma adiponectin levels likely contributed to this effect. Thus HF feeding amplifies obesity induced by impaired MC signaling, provided that the carbohydrate-to-protein (C/P) ratio is high enough. Reduction of the C/P ratio within a HF diet ameliorates hyperphagia and obesity in rats with impaired MC signaling but aggravates associated disturbances in fuel homeostasis.

melanocortins; ketogenic diet; SHU9119; glucose tolerance



Address for reprint requests and other correspondence: G. van Dijk, Dept. of Animal Physiology, Unit Neuroendocrinology, Univ. of Groningen, PO Box 14, 9750 AA Haren, The Netherlands (E-mail: gertjan.van.dijk{at}rug.nl)




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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. Morens, V. Sirot, A. J. W. Scheurink, and G. van Dijk
Low-carbohydrate diets affect energy balance and fuel homeostasis differentially in lean and obese rats
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1622 - R1629.
[Abstract] [Full Text] [PDF]




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