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

Patricia E Grebenstein,Martha Grace,Catherine M Kotz,Paige Erickson

doi:10.3390/jcm11030481

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.

Highlights

Obesity is a leading cause of preventable death in the United States
The purpose of the present study was to examine the effects of nornicotine, anabasine, and anatabine on weight gain, food intake, and physical activity across seven consecutive days of administration, with nicotine included as a positive control
The present study examined the effects of one week-long administration of nornicotine, anatabine, and anabasine, alongside nicotine, on food intake, body weight, body composition, and physical activity

Summary

Introduction

Obesity is a leading cause of preventable death in the United States. It is characterized by an excess of adipose tissue and is positively correlated with the development of various diseases, including coronary heart disease, type II diabetes, stroke, cancer, and metabolic syndrome. There has been an increasing demand for more natural weight loss therapies [2], with over 30% of individuals attempting to jump start or increase their overall weight loss turning to non-prescription, over-the-counter supplement use [3] This rise in interest in complementary and alternative medicine stems largely from the dissatisfaction with current long-term pharmacotherapy success, negative side effects, and the desire for quick and easy results [3]. Within the last 40 years, the US Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA) have approved 9 anti-obesity drugs for long-term use [4] While these pharmacotherapies are successful in treating obesity in the short term, many of these marketed drugs have been associated with rebound weight gain, negative side effects ( related to cardiovascular health), and the potential for drug abuse [4]. The negative side effects associated with these compounds and individual variability in responsiveness to these drugs underscore the need for additional pharmacotherapies for obesity with more desirable side effect profiles

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