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Cited by 40Regulation of Appetite and ObesitySmoking Behavior and CessationNicotinic Acetylcholine Receptors Study

Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake

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Calarco, Cali A, Picciotto, Marina R·2020·Nicotine & Tobacco Research
DOI 10.1093/ntr/ntz010PMC PMC7297099
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Abstract

Despite health risks associated with smoking, up to 20% of the US population persist in this behavior; many smoke to control body weight or appetite, and fear of post-cessation weight gain can motivate continued smoking. Nicotine and tobacco use is associated with lower body weight, and cessation yields an average weight gain of about 4 kg, which is thought to reflect a return to the body weight of a typical nonsmoker. Nicotine replacement therapies can delay this weight gain but do not prevent it altogether, and the underlying mechanism for how nicotine is able to reduce weight is not fully understood. In rodent models, nicotine reduces weight gain, reduces food consumption, and alters energy expenditure, but these effects vary with duration and route of nicotine administration. Nicotine, acting through nicotinic acetylcholine receptors (nAChRs), increases the firing rate of both orexigenic agouti-related peptide and anorexigenic proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (ARC). Manipulation of nAChR subunit expression within the ARC can block the ability of nicotine and the nicotinic agonist cytisine from decreasing food intake; however, it is unknown exactly how this reduces food intake. This review summarizes the clinical and preclinical work on nicotine, food intake, and weight gain, then explores the feeding circuitry of the ARC and how it is regulated by nicotine. Finally, we propose a novel hypothesis for how nicotine acts on this hypothalamic circuit to reduce food intake. Implications: This review provides a comprehensive and updated summary of the clinical and preclinical work examining nicotine and food intake, as well as a summary of recent work examining feeding circuits of the hypothalamus. Synthesis of these two topics has led to new understanding of how nAChR signaling regulates food intake circuits in the hypothalamus.

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  • At the circuit level, stimulation of nAChRs shifts the balance toward neuronal patterns that signal satiety.

    “showing that at the circuit level, stimulation of nAChRs shifts the balance toward neuronal patterns that signal satiety (Calarco and Picciotto 2020).”

    From Mechanisms of Nicotine Addiction (2021) · cites this paper as Calarco and Picciotto 2020

    The 'nAChR Signaling in the ARC' section reports that nicotine increases firing in POMC neurons, which are associated with reduced feeding. But it also increases firing in AgRP neurons, and the paper presents its explanation for reduced food intake as a hypothesis—not a demonstrated shift toward a satiety-associated neuronal pattern. The Figure 3 caption likewise describes both populations as activated by nicotine. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Calarco, C. A., & Picciotto, M. R.
Affiliations
Yale University (US)
Corresponding author
Picciotto, Marina R
ORCID
Venue
Nicotine & Tobacco Research
Publisher
Oxford University Press (OUP)
Published
2019-01-25
Volume
22
Issue
2
Pages
152-163
ISSN
  • 1462-2203 (ISSN-L)
  • 1469-994X
DOI
10.1093/ntr/ntz010
PMC
PMC7297099
OpenAlex
W2914543685
Cited by
40
References
12
Citations by year
2026: 7 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 1 · 2019: 3
FWCI
0.45
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Nicotine & Tobacco Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (DA037566, DA14241)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
nicotinic acetylcholine receptors, nicotine, dietary intake, hypothalamus, arcuate nucleus, post-cessation weight gain, nicotine replacement therapy, agouti-related protein, proopiomelanocortin, feeding circuits, energy expenditure, cytisine
MeSH terms
Tobacco Smoking, Animals, Eating, Humans, Hypothalamus, Nicotine, Receptors, Nicotinic, Signal Transduction, Smoking Cessation, Nicotinic Agonists, Tobacco Use Cessation Devices

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