Long-duration leptin transgene expression in dorsal vagal complex does not alter bone parameters in female Sprague Dawley rats
Leptin, a hormone produced by fat cells, plays an important role in regulating energy balance and body weight. It acts on various targets, including specific regions of the brain such as the hypothalamus and the dorsal vagal complex (DVC).
Previous studies have shown that leptin is also required for normal bone growth and turnover. Leptin deficiency leads to impaired bone development, while providing leptin to leptin-deficient mice can restore their skeletal abnormalities.
However, the role of leptin in regulating bone metabolism in individuals with normal leptin levels is less clear.
College of Health researcher(s)
Highlights
- Leptin is important for energy balance and bone maturation.
- The dorsal vagal complex (DVC) plays a role in integrating leptin signaling.
- Increased leptin gene expression in the DVC had no effect on bone in rats.
Abstract
The hypothalamus and dorsal vagal complex (DVC) are both important for integration of signals that regulate energy balance. Increased leptin transgene expression in either the hypothalamus or DVC of female rats was shown to decrease white adipose tissue and circulating levels of leptin and adiponectin. However, in contrast to hypothalamus, leptin transgene expression in the DVC had no effect on food intake, circulating insulin, ghrelin and glucose, nor on thermogenic energy expenditure. These findings imply different roles for hypothalamus and DVC in leptin signaling. Leptin signaling is required for normal bone accrual and turnover. Leptin transgene expression in the hypothalamus normalized the skeletal phenotype of leptin-deficient ob/ob mice but had no long-duration (≥10 weeks) effects on the skeleton of leptin-replete rats. The goal of this investigation was to determine the long-duration effects of leptin transgene expression in the DVC on the skeleton of leptin-replete rats. To accomplish this goal, we analyzed bone from three-month-old female rats that were microinjected with recombinant adeno-associated virus encoding either rat leptin (rAAV-Leptin, n = 6) or green fluorescent protein (rAAV-GFP, control, n = 5) gene. Representative bones from the appendicular (femur) and axial (3rd lumbar vertebra) skeleton were evaluated following 10 weeks of treatment. Selectively increasing leptin transgene expression in the DVC had no effect on femur cortical or cancellous bone microarchitecture. Additionally, increasing leptin transgene expression had no effect on vertebral osteoblast-lined or osteoclast-lined bone perimeter or marrow adiposity. Taken together, the findings suggest that activation of leptin receptors in the DVC has minimal specific effects on the skeleton of leptin-replete female rats.