Anatabine, Nornicotine, and Anabasine Reduce Weight Gain and Body Fat through Decreases in Food Intake and Increases in Physical Activity

Abstract

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.

The chemotype core collection of genus Nicotiana

“…Other pyridine alkaloids produced by Nicotiana species, such as anatabine and anabasine, have recently been associated with beneficial medicinal properties for e.g. Alzheimer disease, chronic lymphocytic autoimmune (Hashimoto's) thyroiditis and obesity (Grebenstein et al., 2022; Schmeltz et al., 2014; Verma et al., 2015). The untargeted approach, used in the present study for volatile analysis, detected nicotine and four derived pyridine alkaloids: cotinine, nornicotine, myosmine and nicotyrine.…”

Integration of LC-MS-Based and GC-MS-Based Metabolic Profiling to Reveal the Effects of Domestication and Boiling on the Composition of Duck Egg Yolks

“…Dimethylethanolamine (N,N-dimethylethanolamine) is a colorless, volatile liquid with an unpleasant ammonia odor that may be associated with the heavy, earthy stench of wild duck eggs. Grebenstein et al (2022) showed that short-term daily administration of minor tobacco alkaloids (nornicotine, anatabine, and anabasine) produced a positive effect on weight loss by reducing body fat and food intake and increasing physical activity [ 58 ]. Linoleic acid is known to be an important fatty acid for both humans and animals.…”