Nicotine, Metabolism and Body Weight
Quitting nicotine is followed by weight gain often enough that it is one of the commonest reasons people relapse, and nicotine also changes insulin sensitivity and how the body stores fat. This page collects the published research on nicotine, appetite, body weight, insulin and blood sugar, each paper summarised in plain language with its PubMed record.
This collection is research only: papers found on PubMed, each described as its own abstract reports it. Cell and animal results are labelled as such, and harms are listed beside benefits. It is not medical advice.
Table of Contents
Research at a Glance
What kind of study each paper on this page is, and when the papers were published. Hover over a bar for its count.
The Papers (18)
Newest first. Study types on this page — Review: 5 · Animal study: 13. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.
A mouse model of weight gain after nicotine withdrawal
Animal study, 2022. Mice fed a high-fat diet were given nicotine for two weeks and then switched to a placebo for two weeks to mimic nicotine withdrawal. After nicotine stopped, the mice ate more food and gained significantly more weight than mice kept on nicotine, linked to higher levels of an appetite-stimulating brain signal (agouti-related peptide) in the hypothalamus; oxygen use (a measure of calorie burning) did not differ between groups. A diabetes drug (exendin-4) given to the withdrawn mice strongly reduced their food intake and weight gain, showing the effect could be blocked with medication in this mouse model.
Takeda K, Aotani D, Kuga Y et al. (2022). A mouse model of weight gain after nicotine withdrawal. Biochem Biophys Res Commun. — PubMed PMID: 34954521 · doi:10.1016/j.bbrc.2021.12.064
Nicotine' actions on energy balance: Friend or foe?
Review, 2021. This review looks at research on how nicotine affects body weight and energy balance in humans and rodents. The studies it covers report that nicotine reduces appetite, changes how much energy the body burns by acting on brown fat and on the 'browning' of white fat, and affects blood sugar control. The authors say many of these effects start in the brain's appetite-control centers, though nicotine also acts directly on fat tissue, the liver and the pancreas. Because few obesity treatments work well, the authors suggest that nicotine or the nicotinic receptors it acts on might be worth studying as a possible extra approach.
Seoane-Collazo P, Diéguez C, Nogueiras R et al. (2021). Nicotine' actions on energy balance: Friend or foe?. Pharmacol Ther. — PubMed PMID: 32987056 · doi:10.1016/j.pharmthera.2020.107693
Nicotine-mediated upregulation of microRNA-141 expression determines adipokine-intervened insulin resistance
Animal study, 2020. Researchers gave young (early adolescent) rats nicotine at four doses (0.5, 1.0, 3.0 and 6.0 mg/kg) for one month, then measured blood sugar, fat-tissue hormones, inflammation and a small regulatory RNA molecule called microRNA-141. At the higher doses, the rats had higher blood sugar, HbA1c, leptin, the inflammatory marker IL-6 and blood fats, and lower insulin, adiponectin and HDL cholesterol, along with poorer glucose tolerance. Higher nicotine doses also raised microRNA-141 levels, which the authors suggest could serve as a marker of insulin resistance and metabolic disturbance. These results are in rats only.
Faheem A, Rehman K, Jabeen K et al. (2020). Nicotine-mediated upregulation of microRNA-141 expression determines adipokine-intervened insulin resistance. Environ Toxicol Pharmacol. — PubMed PMID: 33002592 · doi:10.1016/j.etap.2020.103506
Central nicotine induces browning through hypothalamic κ opioid receptor
Animal study, 2019. This study looked at how nicotine acting on the brain affects body fat. The researchers found that nicotine turned white fat, which stores energy, into a more 'brown-like' fat that burns energy. This effect depended on a receptor called the kappa opioid receptor in one part of the brain, the lateral hypothalamic area. They also found that the white fat of people who smoke had higher levels of UCP1, a heat-producing protein, which matched their smoking status. The authors say this brain pathway could be a target against obesity in humans.
Seoane-Collazo P, Liñares-Pose L, Rial-Pensado E et al. (2019). Central nicotine induces browning through hypothalamic κ opioid receptor. Nat Commun. — PubMed PMID: 31492869 · doi:10.1038/s41467-019-12004-z
Nicotine induces insulin resistance via downregulation of Nrf2 in cardiomyocyte
Animal study, 2019. This study looked at how nicotine affects insulin response in heart muscle cells grown in the lab and in mice. In the heart cells, nicotine raised levels of reactive oxygen species (harmful oxygen-based molecules) and reduced the glucose the cells took up in response to insulin. It also lowered the activity of Nrf2, a protein that helps protect cells, and pretreatment with the antioxidant N-acetyl-L-cysteine reversed these effects. Mice given nicotine developed glucose intolerance and impaired insulin tolerance, with similar changes in their heart tissue; these results come only from cells and mice.
Li Z, Xu W, Su Y et al. (2019). Nicotine induces insulin resistance via downregulation of Nrf2 in cardiomyocyte. Mol Cell Endocrinol. — PubMed PMID: 31315024 · doi:10.1016/j.mce.2019.110507
Nicotine promotes the differentiation of C2C12 myoblasts and improves skeletal muscle regeneration in obese mice
Animal study, 2019. Researchers tested nicotine on immature mouse muscle cells (C2C12 cells) grown in the lab, and on obese mice whose leg muscles had been injured with a toxin. In the cells, nicotine helped them develop into mature muscle cells by raising the muscle-building factors MyoD and Myogenin. It did this through a cell signalling route called PI3K/Akt, and the effect disappeared when that route was blocked. In the obese mice, injured muscles injected with nicotine healed faster than muscles injected with salt water, but these results come only from cells and mice, not people.
He L, Tian X, Yan C et al. (2019). Nicotine promotes the differentiation of C2C12 myoblasts and improves skeletal muscle regeneration in obese mice. Biochem Biophys Res Commun. — PubMed PMID: 30833077 · doi:10.1016/j.bbrc.2019.02.137
Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis
Animal study, 2017. Researchers gave adult male mice either a normal diet or a high-fat diet for 16 weeks, along with twice-daily injections of nicotine or salt water. In mice on the high-fat diet, nicotine caused a large increase in the death of heart muscle cells. This was fully prevented by a drug that blocks nicotine's receptors. The cell death came with more oxidative stress, activation of a cell-death pathway, and switching off of an energy-sensing enzyme called AMPK. These results come from mice only.
Sinha-Hikim I, Friedman TC, Falz M et al. (2017). Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis. Cell Tissue Res. — PubMed PMID: 27917437 · doi:10.1007/s00441-016-2536-1
Could Vaping be a New Weapon in the Battle of the Bulge?
Review, 2017. This review article looks at whether vaping nicotine with e-cigarettes could help control appetite and body weight the way smoking does. The authors note that smoking limits weight gain through nicotine's effects on the brain and metabolism, but smoking also causes many illnesses and early death. They argue that the possible weight-control effect of vaping nicotine and flavors deserves study, and they suggest a first research agenda. The article reports no new experimental results in people or animals.
Glover M, Breier BH, Bauld L (2017). Could Vaping be a New Weapon in the Battle of the Bulge?. Nicotine Tob Res. — PubMed PMID: 27798086 · doi:10.1093/ntr/ntw278
Neonatal Nicotine Exposure Leads to Hypothalamic Gliosis in Adult Overweight Rats
Animal study, 2015. This rat study looked at what happens in adulthood to male offspring whose mothers were given nicotine through a small implanted pump for 14 days while nursing. Earlier work in this model had found that such offspring develop belly fat and resistance to the appetite hormone leptin. At about six months of age, these offspring had more activated support cells (astrocytes) in several appetite-control areas of the brain's hypothalamus, with increases ranging from 82% to 144%. They also had more immune cells (microglia) in one of these areas (68% more), and levels of the anti-inflammatory signal interleukin-10 were lower in belly fat (58% lower) and in blood (50% lower); these results are in rats only.
Younes-Rapozo V, Moura EG, Manhães AC et al. (2015). Neonatal Nicotine Exposure Leads to Hypothalamic Gliosis in Adult Overweight Rats. J Neuroendocrinol. — PubMed PMID: 26453898 · doi:10.1111/jne.12328
Nicotinic regulation of energy homeostasis
Review, 2012. This review article looks at how nicotine affects appetite, body weight and the body's energy use. The authors describe the brain and hormone systems that control hunger and metabolism, then identify which types of nicotinic receptors are found in those systems and could be the targets nicotine acts on. They also review what is known about how nicotine, and withdrawal from it, change eating and energy metabolism, and which cells in the brain and the rest of the body may be responsible. The abstract notes that nicotine's effect on appetite and weight is one reason smokers give for not quitting, and the main reason teenage girls start smoking.
Zoli M, Picciotto MR (2012). Nicotinic regulation of energy homeostasis. Nicotine Tob Res. — PubMed PMID: 22990212 · doi:10.1093/ntr/nts159
The endocrine effects of nicotine and cigarette smoke
Review, 2012. This review looks at research on how nicotine and tobacco smoking affect the body's hormone (endocrine) system, including blood sugar and blood fat control. It focuses on how smoking affects diabetes and obesity, and on what happens to these conditions when people stop smoking. The authors say smoking still affects about 20% of people and harms health. They suggest that understanding these hormone effects could lead to targeted treatments and better ways to help people quit smoking.
Tweed JO, Hsia SH, Lutfy K et al. (2012). The endocrine effects of nicotine and cigarette smoke. Trends Endocrinol Metab. — PubMed PMID: 22561025 · doi:10.1016/j.tem.2012.03.006
Developmental plasticity in adrenal function and leptin production primed by nicotine exposure during lactation: gender differences in rats
Animal study, 2011. This rat study looked at whether nicotine given to mothers while they were nursing changed adrenal gland function and leptin, a hormone made by fat tissue, in their offspring once the offspring were adults. As adults, males whose mothers received nicotine had 89% more catecholamines (adrenaline-type stress hormones) in the adrenal gland, 77% higher blood levels of the stress hormone corticosterone and 23% more leptin in belly fat. Females were affected differently: they had 46% less leptin in fat under the skin and 22% more in muscle, but normal blood leptin levels. The researchers concluded that nicotine exposure during nursing affected male and female rats differently, and these results come from animals only.
Pinheiro CR, Oliveira E, Trevenzoli IH et al. (2011). Developmental plasticity in adrenal function and leptin production primed by nicotine exposure during lactation: gender differences in rats. Horm Metab Res. — PubMed PMID: 21932173 · doi:10.1055/s-0031-1285909
Nicotine suppresses energy storage through activation of sympathetic outflow to brown adipose tissue via corticotropin-releasing factor type 1 receptor
Animal study, 2009. Researchers gave rats nicotine by injection (0.1 or 0.5 mg/kg) and measured how much noradrenaline was released in their brown fat. Brown fat burns energy to make heat, and noradrenaline is a chemical signal that switches it on. At the higher dose, nicotine clearly increased noradrenaline release in brown fat. A drug that blocks corticotropin-releasing factor type 1 receptors (part of the body's stress-signalling system) stopped this increase completely, but a drug that blocks the type 2 receptors did not. The authors conclude that nicotine may raise energy use by activating brown fat through these type 1 receptors. This was found only in rats.
Mano-Otagiri A, Iwasaki-Sekino A, Ohata H et al. (2009). Nicotine suppresses energy storage through activation of sympathetic outflow to brown adipose tissue via corticotropin-releasing factor type 1 receptor. Neurosci Lett. — PubMed PMID: 19429100 · doi:10.1016/j.neulet.2009.03.054
Nicotinic receptor-mediated effects on appetite and food intake
Review, 2002. This review looks at research on how nicotine affects appetite and eating. It explains that smoking goes along with eating less and weighing less, that nicotine is thought to be the main part of tobacco that suppresses appetite, and that people often gain a lot of weight after they stop smoking. The authors look at where in the body's network of feeding controls nicotine might act. They propose that the lateral hypothalamus, a brain area that helps drive hunger, is an especially important site for nicotine's appetite-suppressing effect. They also discuss how the brain's own acetylcholine signaling in this area may affect the drive to eat.
Jo YH, Talmage DA, Role LW (2002). Nicotinic receptor-mediated effects on appetite and food intake. J Neurobiol. — PubMed PMID: 12436425 · doi:10.1002/neu.10147
Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice
Animal study, 1999. Researchers gave obese mice nicotine for 6 months and compared them with obese mice injected with salt water. The nicotine-treated mice weighed less, had smaller fat deposits under the skin and around the kidneys, and ate less food. In these mice, a heat-producing protein called UCP1 appeared in their brown fat and also in their ordinary white fat, which contained many brown-fat-like cells. The authors concluded that this rise in UCP1, together with eating less, helped reduce obesity in these mice; this result comes from mice only.
Yoshida T, Sakane N, Umekawa T et al. (1999). Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice. Int J Obes Relat Metab Disord. — PubMed PMID: 10411229 · doi:10.1038/sj.ijo.0800870
Systemic nicotine administration suppresses food intake via reduced meal sizes in both male and female rats
Animal study, 1998. This study looked at how nicotine changes eating patterns in male and female rats, using small pumps under the skin that delivered nicotine continuously for seven days (6 mg/kg). Nicotine reduced how much food the rats ate in both sexes, and this happened because each meal was smaller, not because the rats ate fewer meals. In female rats, nicotine did not change the normal hormonal cycle or the cyclical pattern of eating. The authors concluded that nicotine suppresses appetite by making the animals feel full sooner, and that this effect is not related to sex hormones; these results are in rats only.
Bláha V, Yang ZJ, Meguid M et al. (1998). Systemic nicotine administration suppresses food intake via reduced meal sizes in both male and female rats. Acta Medica (Hradec Kralove). — PubMed PMID: 9951048
Alterations of lipolysis and lipoprotein lipase in chronically nicotine-treated rats
Animal study, 1996. This study looked at how nicotine affects fat storage. Rats received nicotine or salt water by infusion for one week, and researchers then examined their fat cells. Rats given nicotine gained 37% less weight and had 21% smaller fat pads. Their fat cells broke down fat 78% faster at rest, and an enzyme that helps fat tissue take up fat fell by 30%, while the same enzyme rose in the heart. The authors suggest that in rats, nicotine shifts fat away from storage in fat tissue and toward use by muscle.
Sztalryd C, Hamilton J, Horwitz BA et al. (1996). Alterations of lipolysis and lipoprotein lipase in chronically nicotine-treated rats. Am J Physiol. — PubMed PMID: 8779941 · doi:10.1152/ajpendo.1996.270.2.E215
Nicotine increases thermogenesis in brown adipose tissue in rats
Animal study, 1988. This study in rats tested whether nicotine raises heat production in brown fat, a type of fat tissue that burns energy to make heat, by switching on the nerves that supply it. Three hours after a single nicotine injection, two signs of brown-fat activity rose significantly: how quickly the nerve messenger norepinephrine was used up in the tissue, and how much of a molecule called GDP bound to the tissue's mitochondria. After 11 days of nicotine treatment, both signs stayed raised, but the rats' weight gain was no different from untreated rats. The authors say these results, found only in rats, fit the idea that some of nicotine's effects may come from increased heat production in brown fat.
Lupien JR, Bray GA (1988). Nicotine increases thermogenesis in brown adipose tissue in rats. Pharmacol Biochem Behav. — PubMed PMID: 3353430 · doi:10.1016/0091-3057(88)90269-9
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