Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Jan;93(1):265–272. doi: 10.1172/JCI116955

Effects of cigarette smoking and its cessation on lipid metabolism and energy expenditure in heavy smokers.

M K Hellerstein 1, N L Benowitz 1, R A Neese 1, J M Schwartz 1, R Hoh 1, P Jacob 3rd 1, J Hsieh 1, D Faix 1
PMCID: PMC293761  PMID: 8282797

Abstract

The relationship between thermogenic and potentially atherogenic effects of cigarette smoking (CS) and its cessation was investigated. Heavy smokers (n = 7, serum cotinine > 200 ng/ml, > 20 cigarettes/d) were maintained on isoenergetic, constant diets for 2 wk, 1 wk with and 1 wk without CS. Stable isotope infusions with indirect calorimetry were performed on day 7 of each phase, after an overnight fast. CS after overnight abstention increased resting energy expenditure by 5% (not significant vs. non-CS phase; P = 0.18). CS increased the flux of FFA by 77%, flux of glycerol by 82%, and serum FFA concentrations by 73% (P < 0.02 for each), but did not significantly affect fat oxidation. Hepatic reesterification of FFA increased more than threefold (P < 0.03) and adipocyte recycling increased nonsignificantly (P = 0.10). CS-induced lipid substrate cycles represented only 15% (estimated 11 kcal/d) of observed changes in energy expenditure. De novo hepatic lipogenesis was low (< 1-2 g/d) and unaffected by either acute CS or its chronic cessation. Hepatic glucose production was not affected by CS, despite increased serum glycerol and FFA fluxes. Cessation of CS caused no rebound effects on basal metabolic fluxes. In conclusion, a metabolic mechanism for the atherogenic effects of CS on serum lipids (increased hepatic reesterification of FFA) has been documented. Increased entry of FFA accounts for CS-induced increases in serum FFA concentrations. The thermogenic effect of CS is small or absent in heavy smokers while the potentially atherogenic effect is maintained, and cessation of CS does not induce a rebound lipogenic milieu that specifically favors accrual of body fat in the absence of increased food intake.

Full text

PDF
265

Images in this article

268Image
on p.268
268Image
on p.268
268Image
on p.268
268Image
on p.268
269Image
on p.269
269Image
on p.269
270Image
on p.270
270Image
on p.270

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benowitz N. L. Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addition. N Engl J Med. 1988 Nov 17;319(20):1318–1330. doi: 10.1056/NEJM198811173192005. [DOI] [PubMed] [Google Scholar]
  2. Billimoria J. D., Pozner H., Metselaar B., Best F. W., James D. C. Effect of cigarette smoking on lipids, lipoproteins, blood coagulation, fibrinolysis and cellular components of human blood. Atherosclerosis. 1975 Jan-Feb;21(1):61–76. doi: 10.1016/0021-9150(75)90094-5. [DOI] [PubMed] [Google Scholar]
  3. Bizzi A., Tacconi M. T., Medea A., Garattini S. Some aspects of the effect of nicotine on plasma FFA and tissue triglycerides. Pharmacology. 1972;7(4):216–224. doi: 10.1159/000136292. [DOI] [PubMed] [Google Scholar]
  4. CARLSON L. A., HAVEL R. J., EKELUND L. G., HOLMGREN A. EFFECT OF NICOTINIC ACID ON THE TURNOVER RATE AND OXIDATION OF THE FREE FATTY ACIDS OF PLASMA IN MAN DURING EXERCISE. Metabolism. 1963 Sep;12:837–845. [PubMed] [Google Scholar]
  5. CARLSON L. A., ORO L. The effect of nicotinic acid on the plasma free fatty acid; demonstration of a metabolic type of sympathicolysis. Acta Med Scand. 1962 Dec;172:641–645. doi: 10.1111/j.0954-6820.1962.tb07203.x. [DOI] [PubMed] [Google Scholar]
  6. Carney R. M., Goldberg A. P. Weight gain after cessation of cigarette smoking. A possible role for adipose-tissue lipoprotein lipase. N Engl J Med. 1984 Mar 8;310(10):614–616. doi: 10.1056/NEJM198403083101002. [DOI] [PubMed] [Google Scholar]
  7. Chajek-Shaul T., Berry E. M., Ziv E., Friedman G., Stein O., Scherer G., Stein Y. Smoking depresses adipose lipoprotein lipase response to oral glucose. Eur J Clin Invest. 1990 Jun;20(3):299–304. doi: 10.1111/j.1365-2362.1990.tb01859.x. [DOI] [PubMed] [Google Scholar]
  8. Comstock G. W., Stone R. W. Changes in body weight and subcutaneous fatness related to smoking habits. Arch Environ Health. 1972 Apr;24(4):271–276. doi: 10.1080/00039896.1972.10666082. [DOI] [PubMed] [Google Scholar]
  9. ELLIS S. The metabolic effects of epinephrine and related amines. Pharmacol Rev. 1956 Dec;8(4):485–565. [PubMed] [Google Scholar]
  10. Figge H. L., Figge J., Souney P. F., Mutnick A. H., Sacks F. Nicotinic acid: a review of its clinical use in the treatment of lipid disorders. Pharmacotherapy. 1988;8(5):287–294. doi: 10.1002/j.1875-9114.1988.tb04085.x. [DOI] [PubMed] [Google Scholar]
  11. Giaccari A., Rossetti L. Predominant role of gluconeogenesis in the hepatic glycogen repletion of diabetic rats. J Clin Invest. 1992 Jan;89(1):36–45. doi: 10.1172/JCI115583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Glauser S. C., Glauser E. M., Reidenberg M. M., Rusy B. F., Tallarida R. J. Metabolic changes associated with the cessation of cigarette smoking. Arch Environ Health. 1970 Mar;20(3):377–381. doi: 10.1080/00039896.1970.10665607. [DOI] [PubMed] [Google Scholar]
  13. Gordon T., Kannel W. B., Dawber T. R., McGee D. Changes associated with quitting cigarette smoking: the Framingham Study. Am Heart J. 1975 Sep;90(3):322–328. doi: 10.1016/0002-8703(75)90320-8. [DOI] [PubMed] [Google Scholar]
  14. HAVEL R. J., CARLSON L. A., EKELUND L. G., HOLMGREN A. STUDIES ON THE RELATION BETWEEN MOBILIZATION OF FREE FATTY ACIDS AND ENERGY METABOLISM IN MAN: EFFECTS OF NOREPINEPHRINE AND NICOTINIC ACID. Metabolism. 1964 Dec;13:1402–1412. doi: 10.1016/0026-0495(64)90034-4. [DOI] [PubMed] [Google Scholar]
  15. Hajek P., Jackson P., Belcher M. Long-term use of nicotine chewing gum. Occurrence, determinants, and effect on weight gain. JAMA. 1988 Sep 16;260(11):1593–1596. [PubMed] [Google Scholar]
  16. Hall S. M., Ginsberg D., Jones R. T. Smoking cessation and weight gain. J Consult Clin Psychol. 1986 Jun;54(3):342–346. doi: 10.1037//0022-006x.54.3.342. [DOI] [PubMed] [Google Scholar]
  17. Hellerstein M. K., Christiansen M., Kaempfer S., Kletke C., Wu K., Reid J. S., Mulligan K., Hellerstein N. S., Shackleton C. H. Measurement of de novo hepatic lipogenesis in humans using stable isotopes. J Clin Invest. 1991 May;87(5):1841–1852. doi: 10.1172/JCI115206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hellerstein M. K., Grunfeld C., Wu K., Christiansen M., Kaempfer S., Kletke C., Shackleton C. H. Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. J Clin Endocrinol Metab. 1993 Mar;76(3):559–565. doi: 10.1210/jcem.76.3.8445011. [DOI] [PubMed] [Google Scholar]
  19. Hellerstein M. K., Neese R. A. Mass isotopomer distribution analysis: a technique for measuring biosynthesis and turnover of polymers. Am J Physiol. 1992 Nov;263(5 Pt 1):E988–1001. doi: 10.1152/ajpendo.1992.263.5.E988. [DOI] [PubMed] [Google Scholar]
  20. Hellerstein M. K., Wu K., Kaempfer S., Kletke C., Shackleton C. H. Sampling the lipogenic hepatic acetyl-CoA pool in vivo in the rat. Comparison of xenobiotic probe to values predicted from isotopomeric distribution in circulating lipids and measurement of lipogenesis and acetyl-CoA dilution. J Biol Chem. 1991 Jun 15;266(17):10912–10919. [PubMed] [Google Scholar]
  21. Hofstetter A., Schutz Y., Jéquier E., Wahren J. Increased 24-hour energy expenditure in cigarette smokers. N Engl J Med. 1986 Jan 9;314(2):79–82. doi: 10.1056/NEJM198601093140204. [DOI] [PubMed] [Google Scholar]
  22. Ilebekk A., Miller N. E., Mjös O. D. Effects of nicotine and inhalation of cigarette smoke on total body oxygen consumption in dogs. Scand J Clin Lab Invest. 1975 Jan;35(1):67–72. doi: 10.1080/00365517509068007. [DOI] [PubMed] [Google Scholar]
  23. Jacob P., 3rd, Yu L., Wilson M., Benowitz N. L. Selected ion monitoring method for determination of nicotine, cotinine and deuterium-labeled analogs: absence of an isotope effect in the clearance of (S)-nicotine-3',3'-d2 in humans. Biol Mass Spectrom. 1991 May;20(5):247–252. doi: 10.1002/bms.1200200503. [DOI] [PubMed] [Google Scholar]
  24. Jacobs M. A., Knapp P. H., Anderson L. S., Karush N., Meissner R., Richman S. J. Relationship of oral frustration factors with heavy cigarette smoking in males. J Nerv Ment Dis. 1965 Aug;141(2):161–171. doi: 10.1097/00005053-196508000-00003. [DOI] [PubMed] [Google Scholar]
  25. KERSHBAUM A., KHORSANDIAN R., CAPLAN R. F., BELLET S., FEINBERG L. J. The role of catecholamines in the free fatty acid response to cigarette smoking. Circulation. 1963 Jul;28:52–57. doi: 10.1161/01.cir.28.1.52. [DOI] [PubMed] [Google Scholar]
  26. Klein S., Young V. R., Blackburn G. L., Bistrian B. R., Wolfe R. R. Palmitate and glycerol kinetics during brief starvation in normal weight young adult and elderly subjects. J Clin Invest. 1986 Oct;78(4):928–933. doi: 10.1172/JCI112682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mjøs O. D. Lipid effects of smoking. Am Heart J. 1988 Jan;115(1 Pt 2):272–275. doi: 10.1016/0002-8703(88)90649-7. [DOI] [PubMed] [Google Scholar]
  28. Muscat J. E., Harris R. E., Haley N. J., Wynder E. L. Cigarette smoking and plasma cholesterol. Am Heart J. 1991 Jan;121(1 Pt 1):141–147. doi: 10.1016/0002-8703(91)90967-m. [DOI] [PubMed] [Google Scholar]
  29. Park O. J., Cesar D., Faix D., Wu K., Shackleton C. H., Hellerstein M. K. Mechanisms of fructose-induced hypertriglyceridaemia in the rat. Activation of hepatic pyruvate dehydrogenase through inhibition of pyruvate dehydrogenase kinase. Biochem J. 1992 Mar 15;282(Pt 3):753–757. doi: 10.1042/bj2820753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Perkins K. A., Epstein L. H., Marks B. L., Stiller R. L., Jacob R. G. The effect of nicotine on energy expenditure during light physical activity. N Engl J Med. 1989 Apr 6;320(14):898–903. doi: 10.1056/NEJM198904063201404. [DOI] [PubMed] [Google Scholar]
  31. Perkins K. A., Epstein L. H., Stiller R. L., Sexton J. E., Fernstrom M. H., Jacob R. G., Solberg R. Metabolic effects of nicotine after consumption of a meal in smokers and nonsmokers. Am J Clin Nutr. 1990 Aug;52(2):228–233. doi: 10.1093/ajcn/52.2.228. [DOI] [PubMed] [Google Scholar]
  32. Pirie P. L., Murray D. M., Luepker R. V. Gender differences in cigarette smoking and quitting in a cohort of young adults. Am J Public Health. 1991 Mar;81(3):324–327. doi: 10.2105/ajph.81.3.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Randle P. J. Fuel selection in animals. Biochem Soc Trans. 1986 Oct;14(5):799–806. doi: 10.1042/bst0140799. [DOI] [PubMed] [Google Scholar]
  34. Reaven G. M., Chang H., Hoffman B. B. Additive hypoglycemic effects of drugs that modify free-fatty acid metabolism by different mechanisms in rats with streptozocin-induced diabetes. Diabetes. 1988 Jan;37(1):28–32. doi: 10.2337/diab.37.1.28. [DOI] [PubMed] [Google Scholar]
  35. Reaven G. M., Greenfield M. S. Diabetic hypertriglyceridemia: evidence for three clinical syndromes. Diabetes. 1981;30(Suppl 2):66–75. doi: 10.2337/diab.30.2.s66. [DOI] [PubMed] [Google Scholar]
  36. Rigotti N. A. Cigarette smoking and body weight. N Engl J Med. 1989 Apr 6;320(14):931–933. doi: 10.1056/NEJM198904063201409. [DOI] [PubMed] [Google Scholar]
  37. Rodin J. Weight change following smoking cessation: the role of food intake and exercise. Addict Behav. 1987;12(4):303–317. doi: 10.1016/0306-4603(87)90045-1. [DOI] [PubMed] [Google Scholar]
  38. STEINBERG D., NESTEL P. J., BUSKIRK E. R., THOMPSON R. H. CALORIGENIC EFFECT OF NOREPINEPHRINE CORRELATED WITH PLASMA FREE FATTY ACID TURNOVER AND OXIDATION. J Clin Invest. 1964 Feb;43:167–176. doi: 10.1172/JCI104901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schechter M. D., Cook P. G. Nicotine-induced weight loss in rats without an effect on appetite. Eur J Pharmacol. 1976 Jul;38(1):63–69. doi: 10.1016/0014-2999(76)90201-6. [DOI] [PubMed] [Google Scholar]
  40. Stamford B. A., Matter S., Fell R. D., Papanek P. Effects of smoking cessation on weight gain, metabolic rate, caloric consumption, and blood lipids. Am J Clin Nutr. 1986 Apr;43(4):486–494. doi: 10.1093/ajcn/43.4.486. [DOI] [PubMed] [Google Scholar]
  41. Stern M. P., Haffner S. M. Dyslipidemia in type II diabetes. Implications for therapeutic intervention. Diabetes Care. 1991 Dec;14(12):1144–1159. doi: 10.2337/diacare.14.12.1144. [DOI] [PubMed] [Google Scholar]
  42. Sutherland G., Stapleton J. A., Russell M. A., Jarvis M. J., Hajek P., Belcher M., Feyerabend C. Randomised controlled trial of nasal nicotine spray in smoking cessation. Lancet. 1992 Aug 8;340(8815):324–329. doi: 10.1016/0140-6736(92)91403-u. [DOI] [PubMed] [Google Scholar]
  43. WATTS D. T. The effect of nicotine and smoking on the secretion of epinephrine. Ann N Y Acad Sci. 1960 Sep;90:74–80. doi: 10.1111/j.1749-6632.1960.tb32619.x. [DOI] [PubMed] [Google Scholar]
  44. Wack J. T., Rodin J. Smoking and its effects on body weight and the systems of caloric regulation. Am J Clin Nutr. 1982 Feb;35(2):366–380. doi: 10.1093/ajcn/35.2.366. [DOI] [PubMed] [Google Scholar]
  45. Weekley C. K., 3rd, Klesges R. C., Reylea G. Smoking as a weight-control strategy and its relationship to smoking status. Addict Behav. 1992;17(3):259–271. doi: 10.1016/0306-4603(92)90031-p. [DOI] [PubMed] [Google Scholar]
  46. Williamson D. F., Madans J., Anda R. F., Kleinman J. C., Giovino G. A., Byers T. Smoking cessation and severity of weight gain in a national cohort. N Engl J Med. 1991 Mar 14;324(11):739–745. doi: 10.1056/NEJM199103143241106. [DOI] [PubMed] [Google Scholar]
  47. Wolfe R. R., Herndon D. N., Jahoor F., Miyoshi H., Wolfe M. Effect of severe burn injury on substrate cycling by glucose and fatty acids. N Engl J Med. 1987 Aug 13;317(7):403–408. doi: 10.1056/NEJM198708133170702. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES