TitleCaloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats.
Publication TypeJournal Article
Year of Publication2021
AuthorsTurner, RT, Wong, CP, Fosse, KM, Branscum, AJ, Iwaniec, UT
JournalInt J Mol Sci
Date Published06/2021
KeywordsAdipokines, Adiponectin, Adipose Tissue, White, Adiposity, Animals, Biomarkers, Body Weight, Bone Marrow, Caloric Restriction, Dependovirus, Energy Intake, Energy Metabolism, Female, Gene Expression, Genetic Therapy, Genetic Vectors, Hypothalamus, Leptin, Rats, Transgenes

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 ( = 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-), and maintained on standard rat chow for 18 weeks. A second group ( = 15) was calorically-restricted to match the weight of the rAAV- 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 mRNA expression than rAAV- 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.

Alternate JournalInt J Mol Sci
PubMed ID34202651
PubMed Central IDPMC8269114
Grant ListAR 060913 / NH / NIH HHS / United States
W81XWH-04-1-0701 / / U.S. Department of Defense /