Nicotine, Metabolism and Body Weight

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1. The Papers
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The Papers (22)

Newest first. Study types on this page — Human trial: 2 · Review: 2 · Animal study: 18. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Nicotinic Signaling Stimulates Glucagon Secretion in Mouse and Human Pancreatic α-Cells

Animal study, 2025. Researchers looked at how nicotine acts on hormone-making cells in the pancreas, using pancreatic islets taken from mice and from human donors and studied in the lab. Nicotine quickly raised calcium levels in alpha cells, which make the hormone glucagon, but not in the insulin-making beta cells. The calcium rise was 2.8-fold and appeared in more than 70% of alpha cells, and in mouse islets glucagon release went up 2.5-fold. The authors conclude that steady nicotine stimulation is likely to lower insulin sensitivity by increasing glucagon release.

Hamilton A, Zhang Q, Gao R et al. (2025). Nicotinic Signaling Stimulates Glucagon Secretion in Mouse and Human Pancreatic α-Cells. Diabetes. — PubMed PMID: 39475504 · doi:10.2337/db23-0809

Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity

Animal study, 2023. This study in aging male mice looked at how low-dose nicotine affects NAD+, a molecule that cells use to make energy and that declines with age. The researchers found that nicotine restored the activity of an enzyme called NAMPT, which raised NAD+ production, and that this happened without going through nicotinic receptors. In these mice, nicotine also reduced the overactive sugar use seen in aging brains and bodies, encouraged new nerve cell growth, reduced brain inflammation, protected organs from oxidative stress and telomere shortening, and slowed age-related decline in memory and thinking. These results come from mice only, not from people.

Yang L, Shen J, Liu C et al. (2023). Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nat Commun. — PubMed PMID: 36797299 · doi:10.1038/s41467-023-36543-8

The emergence of insulin resistance following a chronic high-fat diet regimen coincides with an increase in the reinforcing effects of nicotine in a sex-dependent manner

Animal study, 2021. This study was done only in rats, not people. Female and male rats ate a high-fat diet or a regular diet for 8 weeks, and some were also given a drug that causes insulin resistance. Then they could give themselves nicotine through an intravenous line. The high-fat diet on its own did not change insulin resistance or how much nicotine the rats took. Insulin resistance was stronger in males than in females, but females with insulin resistance took more nicotine than males did. Withdrawal signs were similar in all groups. The authors suggest that females with conditions that disrupt insulin signaling, such as diabetes, may be more vulnerable to nicotine use.

Cruz B, Ortegon S, Giner P et al. (2021). The emergence of insulin resistance following a chronic high-fat diet regimen coincides with an increase in the reinforcing effects of nicotine in a sex-dependent manner. Neuropharmacology. — PubMed PMID: 34571112 · doi:10.1016/j.neuropharm.2021.108787

Prenatal Nicotine Exposure Induces Low Birthweight and Hyperinsulinemia in Male Rats

Animal study, 2021. This study was done in rats, not people. Researchers gave nicotine to pregnant rats and found that their pups were born lighter and stayed smaller at weaning than pups from untreated mothers. When the offspring were later fed a high-fat diet, their blood sugar was the same as in the control rats, but insulin levels rose only in the males from nicotine-treated mothers, and those males also had fewer insulin receptors in the liver. The authors conclude that nicotine exposure before birth led to high insulin levels in male rats given a high-fat diet, and that fewer insulin receptors in the liver may help explain it.

Nemoto T, Ando H, Nagao M et al. (2021). Prenatal Nicotine Exposure Induces Low Birthweight and Hyperinsulinemia in Male Rats. Front Endocrinol (Lausanne). — PubMed PMID: 34177815 · doi:10.3389/fendo.2021.694336

Maternal nicotine exposure impairs brown adipose tissue via AMPK-SIRT1-PGC-1α signals in male offspring

Animal study, 2021. Researchers gave pregnant rats nicotine injections (1.0 mg/kg twice a day) during pregnancy and nursing. They then looked at brown fat, the kind of fat that burns energy, in the male offspring, and they also tested nicotine on lab-grown brown fat cells. At 26 weeks the nicotine-exposed male offspring had brown fat cells that looked more like white fat cells and had abnormal mitochondria, along with lower activity of genes and signals involved in burning energy (UCP1 and the AMPK-SIRT1-PGC-1α pathway). These changes were not seen at 4 weeks. Nicotine at 50 μM had similar effects in the cells. The authors suggest this damage to brown fat may be one way nicotine exposure before birth leads to obesity in male offspring, but these results come only from rats and cells.

Li GL, Ping J, Chen HJ et al. (2021). Maternal nicotine exposure impairs brown adipose tissue via AMPK-SIRT1-PGC-1α signals in male offspring. Life Sci. — PubMed PMID: 33130079 · doi:10.1016/j.lfs.2020.118695

Insulin restores the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats

Animal study, 2021. This study in rats looked at whether insulin changes how nicotine affects the brain's reward pathway in diabetes. Diabetes was induced with a drug that lowers insulin, and some of the diabetic rats were given insulin pellets that brought their blood sugar back to normal. In normal rats, nicotine raised dopamine and acetylcholine in a reward area of the brain. In diabetic rats, nicotine did not raise dopamine and raised acetylcholine less, which went along with higher GABA and lower glutamate levels. Insulin brought nicotine's effects in the diabetic rats back to normal, and because this was done only in rats, it has not been shown in people.

Cruz B, Carcoba LM, Flores RJ et al. (2021). Insulin restores the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats. J Neurochem. — PubMed PMID: 32562571 · doi:10.1111/jnc.15104

Attenuated Tregs increase susceptibility to type 1 diabetes in prenatal nicotine exposed female offspring mice

Animal study, 2019. This study in mice looked at whether nicotine given to mothers during pregnancy raises the risk of type 1 diabetes in their female offspring. Compared with controls, the exposed offspring weighed less and had higher blood sugar from day 21 to day 42 after birth. By day 42 they also had raised levels of an autoantibody used to detect type 1 diabetes, along with smaller insulin-producing islet areas and fewer beta cells in the pancreas. They also had fewer regulatory T cells, a type of immune cell that helps prevent the immune system from attacking the body, and the authors suggest this drop may explain the diabetes-like changes. These findings come only from mice.

Zhao WH, Wen X, Qu W et al. (2019). Attenuated Tregs increase susceptibility to type 1 diabetes in prenatal nicotine exposed female offspring mice. Toxicol Lett. — PubMed PMID: 31442585 · doi:10.1016/j.toxlet.2019.08.016

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

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

Nicotine enhances modulation of food-cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex

Human trial, 2015. In a randomized crossover trial, 26 healthy normal-weight adults who had never smoked chewed either a 2 mg nicotine gum or a placebo gum. Researchers then used brain scans to measure how strongly their brains reacted to pictures of food, both after an overnight fast and after a sugar drink, and they measured the appetite hormones ghrelin and leptin in the blood. After the sugar drink, nicotine strengthened the link between these hormones and the brain's response to food pictures, especially in a front part of the brain involved in judging value (the ventromedial prefrontal cortex) and in the amygdala. The authors conclude that nicotine may boost the effect of these hormone signals on the brain, which might reduce appetite and could be one way nicotine lowers food intake.

Kroemer NB, Wuttig F, Bidlingmaier M et al. (2015). Nicotine enhances modulation of food-cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex. Addict Biol. — PubMed PMID: 25060944 · doi:10.1111/adb.12167

Molecules and circuits involved in nicotine addiction: The many faces of smoking

Review, 2014. This review looks at what is known about how nicotine acts on nicotine receptors in different brain circuits to drive tobacco addiction, drawing on drug, genetic, nerve-signalling and behaviour studies. The authors note that people say they smoke for many reasons, including to control anxiety, low mood or appetite, and that exposure to tobacco smoke during development makes adult smoking more likely. They describe how this research has already helped design a quit-smoking medicine, and suggest that finding what these different nicotine-driven behaviours have in common in the brain could guide new treatments to help people stop smoking.

Picciotto MR, Mineur YS (2014). Molecules and circuits involved in nicotine addiction: The many faces of smoking. Neuropharmacology. — PubMed PMID: 23632083 · doi:10.1016/j.neuropharm.2013.04.028

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

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

Effects of calcium channel blockers on nicotine-induced hyperglycemia in the rat

Animal study, 2001. This study tested in fasted, anesthetized male rats whether two blood pressure drugs that block calcium channels, nifedipine and verapamil, change the rise in blood sugar that nicotine causes. Nifedipine (0.05 to 0.20 mg/kg) reduced the nicotine-induced rise in blood sugar, and higher doses reduced it more. Lower doses of verapamil had no effect, while higher doses reduced the rise but did not abolish it, and neither drug changed baseline blood sugar at any dose used. The authors suggest the drugs work by blocking some of the processes through which nicotine raises blood sugar; these results come from rats only.

Alada AR (2001). Effects of calcium channel blockers on nicotine-induced hyperglycemia in the rat. Afr J Med Med Sci. — PubMed PMID: 14510152

Nicotine up-regulates expression of orexin and its receptors in rat brain

Animal study, 2000. Researchers gave rats nicotine for 14 days at doses the authors say are comparable to what an average smoker takes in, and looked at orexins, brain chemicals that can make animals want to eat. In the nicotine-treated rats, the genetic messages for orexin and its two receptors in the hypothalamus, the brain's appetite-control area, were 20-50% higher than in rats given a salt-water solution. Orexin A and orexin B levels rose 45-54% in one region of the hypothalamus, and orexin B rose 83% in a second region. The nicotine-treated rats also ate less and weighed less. These results are from rats only.

Kane JK, Parker SL, Matta SG et al. (2000). Nicotine up-regulates expression of orexin and its receptors in rat brain. Endocrinology. — PubMed PMID: 11014216 · doi:10.1210/endo.141.10.7707

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

Effects of nicotine on local cerebral glucose utilization in the rat

Animal study, 1988. Researchers gave rats injections of nicotine at four doses (0.1 to 1.75 mg/kg) and mapped how fast different brain areas used glucose, the brain's main fuel. Nicotine raised glucose use mainly in brain areas known to have nicotine binding sites, with increases of 100% or more in some regions such as the medial habenula and superior colliculus, and smaller increases in many others. The strongest effect in most areas came with 0.3 mg/kg given 2 minutes beforehand, and a drug that blocks nicotinic receptors (mecamylamine) cancelled the effect. This was a study in rats only; the authors conclude that nicotine acting on its receptors is linked to brain energy use in regions that may underlie its behavioral and physiological effects.

London ED, Connolly RJ, Szikszay M et al. (1988). Effects of nicotine on local cerebral glucose utilization in the rat. J Neurosci. — PubMed PMID: 3193185 · doi:10.1523/JNEUROSCI.08-10-03920.1988

Effect of cigarette smoking on the blood glucose level in normals and diabetics

Human trial, 1980. Researchers measured blood sugar in 50 people who smoked, 26 with diabetes and 24 without, before and 15, 30 and 60 minutes after they smoked two cigarettes. Blood sugar rose in both groups, and it rose more in the people with diabetes. In 16 people the test was repeated, and a second dose of nicotine raised blood sugar even higher. Blood sugar did not rise after nicotine-free cigarettes, or after cigarettes smoked without inhaling, and the authors think the rise comes from nicotine releasing stress hormones such as adrenaline-type hormones, growth hormone and cortisol.

Bornemisza P, Suciu I (1980). Effect of cigarette smoking on the blood glucose level in normals and diabetics. Med Interne. — PubMed PMID: 7455580

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PubMed Topic Searches

1. PubMed: Metabolism and Weight and nicotine (the search this page is built from)

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Connections

• Nicotine: The Research
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Brain and Memory
• Mood and Mental Health
• Inflammation and Immunity
• Cancer Research
• Heart and Blood Vessels
• Addiction and Withdrawal
• Patches, Gum and Delivery
• Toxicity and Safety

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