Obesity induced by a high-fat diet downregulates apolipoprotein A-IV gene expression in rat hypothalamus.
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.
Liu
Min
M
The Obesity Research Center, Department of Pathology and Laboratory Medicine, University of Cincinnati Medical College, Ohio 45267, USA. lium@uc.edu
Shen
Ling
L
Liu
Yin
Y
Woods
Stephen C
SC
Seeley
Randy J
RJ
D'Alessio
David
D
Tso
Patrick
P
D000222:Adaptation, Physiological; D000818:Animals; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D001823:Body Composition; D004041:Dietary Fats / Q000008:administration & dosage*; D015536:Down-Regulation; D002149:Energy Intake / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans
D001054:Apolipoproteins A; D004041:Dietary Fats; D012333:RNA, Messenger; C022205:apolipoprotein A-IV