Nicotine, BAT thermogenesis, UCPs

Nicotine uncouples the mitochondria via UCP1 (uncoupling protein 1, or thermogenin). It upregulates BAT thermogensis (brown adipose tissue) and increases in BAT thermogenesis is associated with increased longevity. I could see nicotine, aside from butter, promoting longevity. 

Mattson, M. P. (2010). Perspective: Does brown fat protect against diseases of aging? Ageing research reviews, 9(1), 69–76. doi:10.1016/j.arr.2009.11.004

The most commonly studied laboratory rodents possess a specialized form of fat called brown adipose tissue (BAT) that generates heat to help maintain body temperature in cold environments. In humans, BAT is abundant during embryonic and early postnatal development, but is absent or present in relatively small amounts in adults where it is located in paracervical and supraclavicular regions. BAT cells can “burn” fatty acid energy substrates to generate heat because they possess large numbers of mitochondria in which oxidative phosphorylation is uncoupled from ATP production as a result of a transmembrane proton leak mediated by uncoupling protein 1 (UCP1). Studies of rodents in which BAT levels are either increased or decreased have revealed a role for BAT in protection against diet-induced obesity. Data suggest that individuals with low levels of BAT are prone to obesity, insulin resistance and cardiovascular disease, whereas those with higher levels of BAT maintain lower body weights and exhibit superior health as they age. BAT levels decrease during aging, and dietary energy restriction increases BAT activity and protects multiple organ systems including the nervous system against age-related dysfunction and degeneration. Future studies in which the effects of specific manipulations of BAT levels and thermogenic activity on disease processes in animal models (diabetes, cardiovascular disease, cancers, neurodegenerative diseases) are determined will establish if and how BAT affects the development and progression of age-related diseases. Data from animal studies suggest that BAT and mitochondrial uncoupling can be targeted for interventions to prevent and treat obesity and age-related diseases. Examples include: diet and lifestyle changes; specific regimens of mild intermittent stress; drugs that stimulate BAT formation and activity; induction of brown adipose cell progenitors in muscle and other tissues; and transplantation of brown adipose cells.

Yoshida, T., Yoshioka, K., Hiraoka, N., & Kondo, M. (1990). Effect of nicotine on norepinephrine turnover and thermogenesis in brown adipose tissue and metabolic rate in MSG obese mice. Journal of nutritional science and vitaminology, 36(2), 123–30. Retrieved from

To clarify whether nicotine stimulates the sympathetic nervous system (SNS) and thermogenesis in brown adipose tissue (BAT) and whether it promotes the resting metabolic rate (RMR), with resulting mitigation of obesity, we measured norepinephrine (NE) turnover (an indicator of SNS activity), guanosine-5’-diphosphate (GDP) binding (a thermogenic indicator), oxygen consumption in BAT, and RMR in monosodium-L-glutamate (MSG) obese and saline control mice after 2 weeks treatment with nicotine. Nicotine significantly increased NE turnover, GDP binding, oxygen consumption in BAT, and RMR, and significantly reduced body weight in MSG obese mice as well as in control mice without affecting food intake. These results suggest that nicotine stimulates NE turnover and thermogenesis in BAT, and promotes RMR, all of which contribute to the mitigation of obesity.

Romestaing, C., Piquet, M.-A., Bedu, E., Rouleau, V., Dautresme, M., Hourmand-Ollivier, I., … Sibille, B. (2007). Long term highly saturated fat diet does not induce NASH in Wistar rats. Nutrition & metabolism, 4, 4. doi:10.1186/1743-7075-4-4 

BACKGROUND: Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. METHODS: 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. RESULTS: MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25-28% vs standard). CONCLUSION: Long term high saturated fat feeding led to increased “peripheral” fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH.

Di Paola, M., & Lorusso, M. (2006). Interaction of free fatty acids with mitochondria: coupling, uncoupling and permeability transition. Biochimica et biophysica acta, 1757(9-10), 1330–7. doi:10.1016/j.bbabio.2006.03.024 

Long chain free fatty acids (FFA) exert, according to their actual concentration, different effects on the energy conserving system of mitochondria. Sub-micromolar concentrations of arachidonic acid (AA) rescue DeltapH-dependent depression of the proton pumping activity of the bc1 complex. This effect appears to be due to a direct interaction of AA with the proton-input mouth of the pump. At micromolar concentrations FFA increase the proton conductance of the inner membrane acting as protonophores. FFA can act as natural uncouplers, causing a mild uncoupling, which prevents reactive oxygen species production in the respiratory resting state. When Ca(2+)-loaded mitochondria are exposed to micromolar concentrations of FFA, the permeability of the inner membrane increases, resulting in matrix swelling, rupture of the outer membrane and release of intermembrane pro-apoptotic proteins. The characteristics of AA-induced swelling appear markedly different in mitochondria isolated from heart or liver. While in the latter it presents the canonical features of the classical permeability transition (PT), in heart mitochondria substantial differences are observed concerning CsA sensitivity, DeltaPsi dependence, reversibility by BSA and specificity for the activating divalent cation. In heart mitochondria, the AA-dependent increase of the inner membrane permeability is affected by ANT ligands such as adenine nucleotides and atractyloside. AA apparently causes a Ca2+-mediated conversion of ANT from a translocator to a channel system. Upon diamide treatment of heart mitochondria, the Ca2+/AA-induced CsA insensitive channel is converted into the classical PT pore. The relevance of these observations in terms of tissue-specific components of the putative PTP and heart ischemic and post-ischemic process is discussed.

1 Comment Nicotine, BAT thermogenesis, UCPs

  1. Matt

    Bodyfat as it relates to longevity is interesting. The longest lived mammal, the bowhead whale, also has the most blubber of any whale, making it the heaviest whale relative to size. Same goes for the kakapo, the longest lived bird, which is the only land bird that can store body fat for energy, making it the heaviest parrot.

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