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Am J Physiol Endocrinol Metab 287: E366-E370, 2004. First published April 13, 2004; doi:10.1152/ajpendo.00448.2003
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TRANSLATIONAL PHYSIOLOGY

Obesity induced by a high-fat diet downregulates apolipoprotein A-IV gene expression in rat hypothalamus

Min Liu,1,2 Ling Shen,2 Yin Liu,2 Stephen C. Woods,1,3 Randy J. Seeley,1,3 David D'Alessio,1,4 and Patrick Tso1,2

1The Obesity Research Center and Departments of 2Pathology and Laboratory Medicine, 3Psychiatry, and 4Medicine, University of Cincinnati Medical College, Cincinnati, Ohio 45267

Submitted 6 October 2003 ; accepted in final form 8 April 2004

Apolipoprotein A-IV (apo A-IV) is an anorectic protein produced in the intestine and brain that has been proposed as a satiety signal. To determine whether diet-induced obesity alters apo A-IV gene expression in the intestine and hypothalamus, rats were fed a high-fat (HF), low-fat (LF), or standard chow (CHOW) diet for 2, 4, 6, 8, or 10 wk. Rats fed the HF diet had significantly greater body weights than rats given the LF and CHOW diets. Intestinal and plasma apo A-IV levels were comparable across dietary groups and time. LF and CHOW rats had comparable hypothalamic apo A-IV mRNA across the course of the experiment. However, HF rats had a slow and progressive diminution in hypothalamic apo A-IV mRNA over time that became significantly lower than that of LF or CHOW rats by 10 wk. Intragastric infusion of lipid emulsion to animals that were fasted overnight significantly stimulated hypothalamic apo A-IV mRNA in LF and CHOW rats but had no effect in HF rats. These results demonstrate that chronic consumption of a HF diet significantly reduces apo A-IV mRNA levels and the response of apo A-IV gene expression to dietary lipids in the hypothalamus. This raises the possibility that dysregulation of hypothalamic apo A-IV could contribute to diet-induced obesity.

lipids; gene expression; hypothalamus; intestine


Address for reprint requests and other correspondence: M. Liu, Dept. of Pathology and Laboratory Medicine, Univ. of Cincinnati College of Medicine, Cincinnati, Ohio 45237-0507 (E-mail: lium{at}uc.edu).




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K. Gotoh, M. Liu, S. C. Benoit, D. J. Clegg, W. S. Davidson, D. D'Alessio, R. J. Seeley, P. Tso, and S. C. Woods
Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R202 - R207.
[Abstract] [Full Text] [PDF]


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