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Effect of Leptin on Hypothalamic Gene Expression in Calorie-Restricted Rats

Department of Pathology & Gerontology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Japan.

Address correspondence to Isao Shimokawa, MD, PhD, Department of Pathology & Gerontology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan. E-mail: shimo{at}net.nagasaki-u.ac.jp

Diminished leptin signaling to the arcuate nucleus of hypothalamus (ARH) may induce calorie restriction (CR)–specific neuroendocrine and metabolic adaptation, which is potentially relevant to the effect of CR. The present study investigated whether restoration of leptin signaling to the ARH could reverse CR-induced alterations in neuropeptide gene expression in rats. Male F344 rats, fed ad libitum or a 30% CR diet from 6 weeks of age, received leptin or vehicle intracerebroventricularly for 14 days via osmotic mini-pumps implanted in the subcutis at 34 weeks of age. The messenger RNA levels were quantified by real-time reverse transcription–polymerase chain reaction using total RNA extracted from microdissected tissues containing the ARH. The results indicated that leptin administration reversed the upregulated expression of neuropeptide Y and agouti-related protein genes in CR rats, suggesting the possibility of a role for the leptin–ARH pathway in the effect of CR.