The DOI matches its Crossref record; 111 of the 122 references it cites were found in a registry or an index, and 11 are not checked yet; none of the 103 sources its claims cite is checked for support yet.
Cigarette Smoking and Brain Regulation of Energy Homeostasis
Open accessAbstract
Cigarette smoking is an addictive behavior, and is the primary cause of cardiovascular and pulmonary disease, and cancer (among other diseases). Cigarette smoke contains thousands of components that may affect caloric intake and energy expenditure, although nicotine is the major addictive substance present, and has the best described actions. Nicotine exposure from cigarette smoke can change brain feeding regulation to reduce appetite via both energy homeostatic and reward mechanisms, causing a negative energy state which is characterized by reduced energy intake and increased energy expenditure that are linked to low body weight. These findings have led to the public perception that smoking is associated with weight loss. However, its effects at reducing abdominal fat mass (a predisposing factor for glucose intolerance and insulin resistance) are marginal, and its promotion of lean body mass loss in animal studies suggests a limited potential for treatment in obesity. Smoking during pregnancy puts pressure on the mother's metabolic system and is a significant contributor to adverse pregnancy outcomes. Smoking is a predictor of future risk for respiratory dysfunction, social behavioral problems, cardiovascular disease, obesity, and type-2 diabetes. Catch-up growth is normally observed in children exposed to intrauterine smoke, which has been linked to subsequent childhood obesity. Nicotine can have a profound impact on the developing fetal brain, via its ability to rapidly and fully pass the placenta. In animal studies this has been linked with abnormal hypothalamic gene expression of appetite regulators such as downregulation of NPY and POMC in the arcuate nucleus of the hypothalamus. Maternal smoking or nicotine replacement leads to unhealthy eating habits (such as junk food addiction) and other behavioral disorders in the offspring.
Checked 2026-11-13 · 11 references not checked yet
Overview
CoChat Summary
TL;DR
This narrative review argues that cigarette smoke/nicotine reduces appetite and body weight via hypothalamic energy-homeostatic and reward pathways, but has marginal effects on abdominal fat and may promote lean mass loss. It also reviews evidence that maternal smoking/nicotine exposure programs offspring for metabolic and behavioral disorders, while cautioning that nicotine’s fat-loss effects are unconfirmed in well-controlled human studies.
Key findings
- Smoking induces a negative energy state with reduced energy intake and body weight across species; >75% of former smokers gain weight after cessation, and globally there are >1 billion smokers with ∼6 million smoking-related deaths per year, projected to rise to ∼10 million per year in less than 40 years.
- In smoke-exposed mice, hypothalamic NPY was significantly suppressed compared with pair-fed animals, while UCP1 and UCP3 mRNA increased, suggesting increased energy expenditure despite reduced intake; nicotine-treated mice also showed increased CART and POMC-derived α-MSH with suppressed NPY and AgRP.
- Fat loss after smoke exposure occurred only with a low-fat balanced diet; with a high-fat cafeteria diet, smoke exposure failed to cause fat loss and lean body mass loss became prominent, with smoke-exposed mice consuming twice the recommended daily energy requirement.
- Maternal smoking is reported in ∼25–29% of pregnant women; fetal nicotine concentrations reach ∼115% of maternal levels, primate newborns from nicotine-treated mothers show ∼50% lower serum leptin, and intrauterine nicotine exposure downregulates NPY and POMC in the arcuate nucleus.
Methods
- Design: narrative review synthesizing animal and human studies on cigarette smoking/nicotine, brain regulation of energy homeostasis, and maternal smoking effects on offspring.
- Data/sample: cited literature including rodent, primate, and human observational/clinical studies; no new primary data are presented.
- Main analysis: qualitative synthesis of neurophysiological mechanisms and metabolic outcomes; no systematic review or meta-analysis is described.
Limitations
- Stated in the paper: the fat loss associated with nicotine has not been confirmed in human subjects under well-controlled experimental conditions; there is no direct data to support the hypothesis that NPY/POMC rebound causes later hyperphagia and obesity; and the impact of maternal smoking on offspring brain energy homeostatic pathways requires further study.
- Evident from the text: as a narrative review, it relies on selected cited studies rather than a systematic search, and several conclusions are explicitly speculative (“we speculate,” “can be suggested”).
- Evident from the text: many mechanistic conclusions derive from animal models, with limited well-controlled human intervention data.
Model-written summary. Check it against the paper before relying on it.
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Verification
Claims the paper makes
0 Valid · 0 Not valid · 61 Not checked · 11 Own results and interpretations
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In a rodent model, we have shown that the reduction in fat mass after cigarette smoke exposure occurred only if the mice consumed a low-fat balanced diet.”
§ Cigarette Smoking and Brain Regulation of Energy Homeostasis > Cigarette Smoking and Adiposity
boostedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, this weight loss was accompanied by lean body mass wasting, including that associated with some major organs such as liver, kidney, and skeletal muscle (Chen et al., 2005, 2006, 2008).”
§ Cigarette Smoking and Brain Regulation of Energy Homeostasis > Cigarette Smoking and Adiposity
What the sources say
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Smoking induces a negative energy state, characterized by reduced energy intake and body weight, which has been well documented across species (Perkins, 1992; Strauss and Mir, 2001; Bellinger et al., 2003; Fulkerson and French, 2003; Chen et al., 2006, 2007, 2008).”
§ Cigarette Smoking and Brain Regulation of Energy Homeostasis > Cigarette Smoking and Weight Control
What the sources say
- Not matchedcites Perkins, 1992
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked yetcites Strauss and Mir, 2001 source
- Not matchedcites Bellinger et al., 2003
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“The lowered body weight has been shown to be independent of diet type, with a similar proportion of weight loss displayed in mice consuming a diet with either low or high-fat concentrations after 7 weeks of cigarette smoke exposure (Chen et al., 2007).”
§ Cigarette Smoking and Brain Regulation of Energy Homeostasis > Cigarette Smoking and Weight Control
What the sources say
- Not checked yetcites Chen et al., 2007 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“with >75% of former smokers gaining weight after cessation (Williamson et al., 1991; Leischow et al., 1992).”
§ Cigarette Smoking and Brain Regulation of Energy Homeostasis > Cigarette Smoking and Weight Control
What the sources say
- Not checked yetcites Williamson et al., 1991 source
- Not matchedcites Leischow et al., 1992
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
38 more claims
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- It may state two separate claims as one. 26
- Probably not a substantial claim. 3
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,528
Brown Adipose Tissue: Function and Physiological Significance
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WHO Report on the Global Tobacco Epidemic, 2019
Alebshehy, R. (2019) · Cited by 1,331
NEUROPEPTIDE Y AND HUMAN PANCREATIC POLYPEPTIDE STIMULATE FEEDING BEHAVIOR IN RATS
Clark, J. T., Kalra, P. S., Crowley, W. R., & Kalra, S. P. (1984) · Endocrinology · doi:10.1210/endo-115-1-427 · Cited by 1,276
Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding
Bouret, S. G., Draper, S. J., & Simerly, R. B. (2004) · Science · doi:10.1126/science.1095004 · Cited by 1,247
Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons
Hahn, T. M., Breininger, J. F., Baskin, D. G., & Schwartz, M. W. (1998) · Nature Neuroscience · doi:10.1038/1082 · Cited by 1,164
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1995) · Nature · doi:10.1038/374479a0 · Cited by 1,125
Research works printed but not linked: 2
- Argyropoulos G. Harper M. E. (2002). Uncoupling proteins and thermoregulation. J. Appl. Physiol. 92, 2187– 2198 11960973
- Contal M. Masson G. Boyer C. Cazevielle C. Mares P. (2005). Neonatal consequences of maternal smoking during pregnancy. J. Gynecol. Obstet. Biol. Reprod. 34 3S215– S222 15980791
Cited by
Chan, Y. L., Saad, S., Pollock, C. A., Oliver, B. G. G., Al‐Odat, I., Zaky, A. A., Jones, N. M., & Chen, H. (2016) · Scientific Reports · doi:10.1038/srep25881 · Cited by 94
Self-citationEarly life factors and type 2 diabetes mellitus
Jiang, X., Ma, H., Wang, Y., & Liu, Y. (2013) · Journal of Diabetes Research · doi:10.1155/2013/485082 · Cited by 92
“have indicated that nicotine may also downregulate gene expression of appetite regulators neuropeptide Y and proopiomelanocortin in the arcuate nucleus of the hypothalamus in fetal brain, which may consequently lead to unhealthy eating habits in the offspring and predispose high risk of obesity or diabetes [54].”
BackgroundChao, A. M., White, M. A., Grilo, C. M., & Sinha, R. (2016) · Eating Behaviors · doi:10.1016/j.eatbeh.2016.12.009 · Cited by 76
Li, G., Saad, S., Oliver, B. G. G., & Chen, H. (2018) · Toxics · doi:10.3390/toxics6030043 · Cited by 67
Self-citationWang, Y., Gao, X., Pedram, P., Shahidi, M., Jian-ling, D., Yi, Y., Gulliver, W. P. F., Zhang, H., & Sun, G. (2016) · Nutrients · doi:10.3390/nu8010024 · Cited by 65
Metadata
- Authors
- Chen, H., Saad, S., Sandow, S. L., & Bertrand, P. P.
- Affiliations
- University of Technology Sydney (AU)
- The University of Sydney (AU)
- UNSW Sydney (AU)
- Corresponding author
- Chen, Hui
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2012
- Volume
- 3
- Pages
- 147-147
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC3404499
- OpenAlex
- W1999975239
- Semantic Scholar
- 428c037acf4097ce1971475f44c25a65232c8dfd
- Cited by
- 69
- References
- 111
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 10 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 8 · 2013: 9
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- USC Research Bank (University of the Sunshine Coast) (submittedVersion, cc-by)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion)
- UTS ePRESS (University of Technology Sydney) (submittedVersion)
- OPUS - Open Publications of UTS Scholars (University of Technology Sydney) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- cigarette smoking, nicotine, energy homeostasis, appetite regulation, feeding behavior, energy expenditure, obesity, type 2 diabetes, insulin resistance, pregnancy, fetal brain development, placental transfer, hypothalamus, arcuate nucleus, neuropeptide Y, proopiomelanocortin, catch-up growth, childhood obesity, nicotine replacement therapy
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
