Dieting is a common but often ineffective long-term strategy for preventing
weight gain. Similar to humans, adult rats exhibit progressive
weight gain. The
adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with
leptin resistance. Here, we compared the effects of increasing
leptin levels in the hypothalamus using gene therapy with conventional
caloric restriction on
weight gain, food consumption, serum
leptin and
adiponectin levels, white adipose tissue, marrow adipose tissue, and bone in nine-month-old female Sprague-Dawley rats. Rats (n = 16) were implanted with a
cannula in the 3rd ventricle of the hypothalamus and injected with a recombinant adeno-associated virus, encoding the rat gene for
leptin (rAAV-Lep), and maintained on standard rat chow for 18 weeks. A second group (n = 15) was calorically-restricted to match the weight of the rAAV-Lep group. Both approaches prevented
weight gain, and no differences in bone were detected. However, calorically-restricted rats consumed 15% less food and had lower brown adipose tissue Ucp-1
mRNA expression than rAAV-Lep rats. Additionally, calorically-restricted rats had higher abdominal white adipose tissue mass, higher serum
leptin and
adiponectin levels, and higher marrow adiposity.
Caloric restriction and hypothalamic
leptin gene therapy, while equally effective in preventing
weight gain, differ in their effects on energy intake, energy expenditure,
adipokine levels, and body composition.