Obesity is a leading cause of preventable death in the United States. Currently approved
pharmacotherapies for the treatment of
obesity are associated with rebound
weight gain, negative side effects, and the potential for abuse. There is a need for new treatments with fewer side effects. Minor tobacco
alkaloids (MTAs) are potential candidates for novel
obesity pharmacotherapies. These
alkaloids are structurally related to
nicotine, which can help reduce
body weight, but without the same addictive potential. The purpose of the current study was to examine the effects of three MTAs (
nornicotine,
anatabine, and
anabasine) and
nicotine on
weight gain, body composition, chow intake, and physical activity. We hypothesized that the MTAs and
nicotine would reduce
weight gain through reductions in chow intake and increases in physical activity. To test this, male Sprague Dawley rats were housed in metabolic phenotyping chambers. Following acclimation to these chambers and to (subcutaneous (sc))
injections of saline, animals received daily
injections (sc) of
nornicotine,
anabasine,
anatabine, or
nicotine for one week. Compared to saline-injected animals that gained
body weight and body fat during the treatment phase,
injections of
nornicotine and
anatabine prevented additional
weight gain, alongside reductions in body fat. Rats receiving
anabasine and
nicotine gained
body weight at a slower rate relative to rats receiving saline
injections, and body fat remained unchanged. All compounds reduced the intake of chow pellets.
Nornicotine and
nicotine produced consistent increases in physical activity 6 h post-injection, whereas
anabasine's and
anatabine's effects on physical activity were more transient. These results show that short-term, daily administration of
nornicotine,
anabasine, and
anatabine has positive effects on
weight loss, through reductions in body fat and food intake and increases in physical activity. Together, these findings suggest that MTAs are worthy of further investigations as anti-
obesity pharmacotherapies.