Increased Leptin Expression in the Dorsal Vagal Complex Suppresses Adiposity without Affecting Energy Intake and Metabolic Hormones

OBJECTIVE: Increased leptin transgene expression locally in hypothalamic sites suppresses weight and energy intake, enhances thermogenic energy expenditure, and differentially modulates metabolic hormones for an extended period. We evaluated whether a similar localized expression of leptin transgene in the dorsal vagal complex (DVC) in the caudal brain stem that also displays the biologically relevant leptin receptor would reproduce these varied responses and thus demonstrate functional connectivity between the hypothalamus and DVC. RESEARCH METHODS AND PROCEDURES: Adult female rats were microinjected with a recombinant adeno-associated virus encoding either rat leptin or green fluorescent protein gene (control) in the DVC. Food intake and body weight were monitored weekly, and metabolic variables were analyzed at the end of 10 weeks. RESULTS AND DISCUSSION: Increased leptin transgene expression in the DVC suppressed the time-related increase in body weight accompanied by a transient decrease in food intake at week 1 post-injection and little effect on thermogenic energy expenditure. That suppression of weight was due to decreased adiposity is shown by the markedly suppressed white adipose tissue-derived hormones, leptin and adiponectin. Circulating concentrations of pancreatic insulin, gastric ghrelin, and glucose levels were unchanged. This segregation of the varied effects of leptin expression in hypothalamic sites vs. DVC endorses the view that among the various endocrine organs under sympathetic nervous system control, only those leptin-activated neural circuits in the hypothalamus that suppress weight and adiposity on a long-term basis transverse through DVC en route to white adipose tissue.