# Novel Plant Alkaloids for the Treatment of Obesity

> **NIH VA IK2** · MINNEAPOLIS VA  MEDICAL CENTER · 2021 · —

## Abstract

The goal of this proposal is to investigate the changes in the behavioral and metabolic phenotypes and
neural correlates of obesity following the administration of two minor tobacco alkaloids as a novel approach to
the prevention and treatment of obesity. The prevalence of overweight/obesity has increased to epidemic
proportions and Veterans are more likely to become overweight. There are currently five FDA approved drugs
on the market for the treatment of obesity, but their effects have been modest and their side effects
undesirable. There is a crucial need to develop more effective pharmacotherapies to treat obesity in order to
reduce morbidity/mortality of Veterans. Nicotine, the primary psychoactive and addictive component in
cigarettes, has been shown to cause weight loss, and nicotine abstinence causes weight gain in human and
animal studies. Cigarette smoking is undeniably unhealthy and the benefits of quitting smoking outweigh any
positive effects smoking has on body weight. Even so, the ability of cigarette smoking to produce sustained
weight loss and reduced food intake suggests that investigating the underlying mechanisms and studying
similarly acting compounds may lead to novel anti-obesity drugs. In light of their similarities to nicotine, minor
tobacco alkaloids (MTAs) are prime candidates for treating obesity. They are found in tobacco products at very
low doses and act at nicotinic acetylcholine receptor subtypes, which are widely distributed throughout the
brain and modulate the release of many neurotransmitters and neuropeptides involved in obesity. Specifically,
nAChRs are located within the arcuate nucleus (AN), which plays a critical role in the drive to eat and within
the ventral tegmental area (VTA) and nucleus accumbens (NAcc), which are involved in reward. However, few
studies have actually examined MTAs and nAChR effects on ingestive behaviors. Considering the well-known
ability of nicotine to affect ingestive behaviors, the lack of research on the minor tobacco alkaloid effects on
food intake and weight gain represents a significant gap in the literature.
Aim 1 will assess the extent to which the MTAs produce alterations in obesity phenotypes without
affecting general malaise, anxiety or stress. Following peripheral administration of two minor tobacco
alkaloids, nornicotine and anatabine, changes in food intake, body weight, energy expenditure, adiposity, and
physical activity will be measured. To ensure that changes in these variables aren't due to the presence of
malaise, anxiety, or stress, the MTAs will be evaluated with conditioned taste aversion and open field testing,
and plasma corticosterone levels will be measured. Aim 2 will elucidate the neural mechanisms underlying
the effects of the MTAs on obesity phenotypes by evaluating changes in neuronal activation following
injections of the MTAs, specifically by quantifying cFos positive neurons within the AN, VTA, and NAcc, regions
of the brain important for food i...

## Key facts

- **NIH application ID:** 10265383
- **Project number:** 5IK2BX003838-04
- **Recipient organization:** MINNEAPOLIS VA  MEDICAL CENTER
- **Principal Investigator:** Patricia Elizabeth Bunney
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265383

## Citation

> US National Institutes of Health, RePORTER application 10265383, Novel Plant Alkaloids for the Treatment of Obesity (5IK2BX003838-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10265383. Licensed CC0.

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