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Rapid onset of peripheral and central leptin resistance in rats offered chow, lard, and 30% sucrose solution
Author(s) -
Apolzan John W,
Harris Ruth BS
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.588.1
Subject(s) - leptin , peripheral , sucrose , medicine , endocrinology , chemistry , resistance (ecology) , food science , biology , obesity , ecology
Rats given free access to chow, 30% sucrose solution, and lard (choice) more than double their body fat mass within 3 weeks. In this study, we evaluated the development of leptin resistance in 36 ~300 g male Sprague Dawley rats. Energy intake of choice rats was 21% higher than for chow rats and was 33% chow, 25% liquid sucrose, and 42% lard. Leptin (2mg/kg, i.p.) inhibited food intake and body weight gain of both choice and chow rats after 2 and 4 days on diet. On day 8, however, the choice rats were leptin insensitive and by day 16 they were resistant, whereas chow fed rats remained leptin responsive. Fasting serum leptin was higher in choice than chow rats. On day 20, choice rats were switched back to a chow only diet and their ad libitum energy intake was 40% lower than chow rats for 4 days. Two days later, choice and chow rats fasting serum leptin was similar. Four days after switching back to chow, the choice rats were again leptin responsive. A 2 nd study found choice rats, but not chow fed rats, were centrally leptin resistant (1.5μg/2μl, 3 rd ventricle) after 16 days on diet. Thus, the choice diet rapidly induces peripheral and central leptin resistance. When lard and sucrose solution are no longer available, leptin sensitivity is quickly restored. The rapid onset and reversal of leptin responsiveness of rats fed choice diet suggests a direct effect of metabolism on signaling pathways, rather than resistance due to development of obesity. Support: NIH R01 DK 53903 Grant Funding Source : NIH R01 DK 53903