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Hepatol Res. 2013 Oct;43(10):1105-14. doi: 10.1111/hepr.12062. Epub 2013 Feb 3.

Derangement of ghrelin secretion after long-term high-fat diet feeding in rats.

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Faculty of Pharmacy, Keio University, Tokyo, Japan.



Appetite control is an important goal for the management of non-alcoholic fatty liver disease, diabetes mellitus and obesity; however, little is known about how hormones concerning appetite regulation are affected by long-term consumption of a high-fat diet. We investigated the effect of high-fat diet on secretory regulation of ghrelin and leptin in rats.


Rats were fed a control or a high-fat diet for 18 weeks and then killed. Before being killed, a glucose tolerance test was performed. Weight, total calorie intake and blood glucose levels were measured, and the plasma levels of total and active ghrelin, and leptin were analyzed by enzyme-linked immunosorbent assay.


Body and fat weight and total calorie intake were significantly higher in the high-fat diet group than in the control, although blood glucose levels did not differ. Plasma leptin was significantly higher in the high-fat diet group, and a significant positive correlation was observed between bodyweight and leptin levels in both groups. The levels of active and total ghrelin were not significantly changed by high-fat diet, and active ghrelin levels in the control group significantly correlated negatively with bodyweight, while its correlation was lost in the high-fat diet group. The glucose tolerance test showed that ghrelin levels were significantly higher than those of controls even 60 min after glucose loading.


These results indicate that secretion of ghrelin, but not leptin, are deranged by consumption of a high-fat diet, and active ghrelin levels lose their correlation with bodyweight and food intake.


appetite; calorie; central obesity; leptin; non-alcoholic steatohepatitis

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