Increased hypothalamic 5-HT2A receptor gene expression and effects of pharmacologic 5-HT2A receptor inactivation in obese Ay mice

Nov 14, 2006Biochemical and biophysical research communications

Higher levels of serotonin receptor gene in the brain's appetite center and effects of blocking this receptor in obese Ay mice

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Abstract

Systemic administration of sarpogrelate, a 5-HT2A receptor antagonist, suppressed appetite and increased specific receptor gene expression.

Sarpogrelate may inhibit overfeeding and body weight gain in obese A(y) mice.
Obesity is associated with increased hypothalamic 5-HT2A receptor gene expression in A(y) mice compared to wild-type mice.
Sarpogrelate did not increase plasma levels of adiponectin in the studied mice.
Increased expression of gene markers related to appetite control was observed with sarpogrelate treatment.

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Serotonin (5-hydroxytryptamine; 5-HT) 2A receptors contribute to the effects of 5-HT on platelet aggregation and vascular smooth muscle cell proliferation, and are reportedly involved in decreases in plasma levels of adiponectin, an adipokine, in diabetic subjects. Here, we report that systemic administration of sarpogrelate, a 5-HT2A receptor antagonist, suppressed appetite and increased hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript, corticotropin releasing hormone, 5-HT2C, and 5-HT1B receptor gene expression. A(y) mice, which have ectopic expression of the agouti protein, significantly increased hypothalamic 5-HT2A receptor gene expression in association with obesity compared with wild-type mice matched for age. Systemic administration of sarpogrelate suppressed overfeeding, body weight gain, and hyperglycemia in obese A(y) mice, whereas it did not increase plasma adiponectin levels. These results suggest that obesity increases hypothalamic 5-HT2A receptor gene expression, and pharmacologic inactivation of 5-HT2A receptors inhibits overfeeding and obesity in A(y) mice, but did not increase plasma adiponectin levels.

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Increased hypothalamic 5-HT2A receptor gene expression and effects of pharmacologic 5-HT2A receptor inactivation in obese Ay mice

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