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High fat diet altered the mechanism of energy homeostasis induced by nicotine and withdrawal in C57BL/6 mice

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Molecules and Cells

Abstract

Nicotine treatment has known to produce an inverse relationship between body weight and food intake in rodents. Present study determined the effect of repeated treatment with nicotine and withdrawal in control and obese mice, on: (1) body weight, caloric intake and energy expenditure; (2) hypothalamic neuropeptides mRNA expression; and (3) serum leptin. 21-week-old C57BL/6 mice (n = 65) received nicotine (3.0 mg/kg/day; 2 weeks) and saline (1 ml/kg/day; 2 weeks) subcutaneously. Animals were given either a normal-fat (10% kcal from fat, NF) or a high-fat diet (45% kcal from fat, HF) from the 12th week to 25th week. While, nicotine treatment for 14 days induced an increase in hypothalamic agouti-related protein, cocaine- and amphetamine- regulated transcript, pro-opiomelanocortin mRNA expressions, nicotine also produced a reducing effect in body weight gain and leptin concentration in NF mice. High-fat diet induced obese mice showed a blunted hypothalamic and leptin response to nicotine. Remarkable weight loss in obese mice was mediated not just by decreasing caloric intake, but also by increasing total energy expenditure (EE). During nicotine withdrawal period, weight gain occurred in NF and HF groups, which was ascribed to a decrease in EE rather than changes in caloric intake. Hypothalamic AgRP might play a role for maintaining energy balance under the nicotine-induced negative energy status.

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References

  • Ahima, R.S., Saper, C.B., Flier, J.S., and Elmquist, J.K. (2000). Leptin regulation of neuroendocrine systems. Front. Neuroendocrinol. 21, 263–307.

    Article  CAS  PubMed  Google Scholar 

  • An, S., Han, J.I., Kim, M.J., Park, J.S., Han, J.M., Baek, N.I., Chung, H.G., Choi, M.S., Lee, K.T., and Jeong, T.S. (2010). Ethanolic extracts of Brassica campestris spp. rapa roots prevent high-fat diet-induced obesity via beta(3)-adrenergic regulation of white adipocyte lipolytic activity. J. Med. Food 13, 1–9.

    Article  Google Scholar 

  • Andersson, K., and Arner, P. (2001). Systemic nicotine stimulates human adipose tissue lipolysis through local cholinergic and catecholaminergic receptors. Int. J. Obes. Relat. Metab. Disord. 25, 1225–1232.

    Article  CAS  PubMed  Google Scholar 

  • Anubhuti and Arora, S. (2008). Leptin and its metabolic interactions: an update. Diabetes Obes. Metab. 10, 973–993.

    Article  CAS  PubMed  Google Scholar 

  • Bellinger, L., Cepeda-Benito, A., and Wellman, P.J. (2003). Meal patterns in male rats during and after intermittent nicotine administration. Pharmacol. Biochem. Behav. 74, 495–504.

    Article  CAS  PubMed  Google Scholar 

  • Bellinger, L.L., Wellman, P.J., Harris, R.B., Kelso, E.W., and Kramer, P.R. (2010). The effects of chronic nicotine on meal patterns, food intake, metabolism and body weight of male rats. Pharmacol. Biochem. Behav. 95, 92–99.

    Article  CAS  PubMed  Google Scholar 

  • Bishop, C., Parker, G.C., and Coscina, D.V. (2004). Systemic nicotine alters whole-body fat utilization in female rats. Physiol. Behav. 80, 563–567.

    Article  CAS  PubMed  Google Scholar 

  • Brees, D.J., Elwell, M.R., Tingley, F.D., 3rd, Sands, S.B., Jakowski, A.B., Shen, A.C., Cai, J.H., and Finkelstein, M.B. (2008). Pharmacological effects of nicotine on norepinephrine metabolism in rat brown adipose tissue: relevance to nicotinic therapies for smoking cessation. Toxicol. Pathol. 36, 568–575.

    Article  CAS  PubMed  Google Scholar 

  • Cano, P., Cardinali, D.P., Spinedi, E., and Esquifino, A.I. (2008). Effect of aging on 24-hour pattern of stress hormones and leptin in rats. Life Sci. 83, 142–148.

    Article  CAS  PubMed  Google Scholar 

  • Cano, P., Cardinali, D.P., Rios-Lugo, M.J., Fernandez-Mateos, M.P., Reyes Toso, C.F., and Esquifino, A.I. (2009). Effect of a high-fat diet on 24-hour pattern of circulating adipocytokines in rats. Obesity (Silver Spring). 17, 1866–1871.

    Article  CAS  Google Scholar 

  • Chen, Y., Hu, C., Hsu, C.K., Zhang, Q., Bi, C., Asnicar, M., Hsiung, H.M., Fox, N., Slieker, L.J., Yang, D.D., et al. (2002). Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology 143, 2469–2477.

    Article  CAS  PubMed  Google Scholar 

  • Collins, S., Kuhn, C.M., Petro, A.E., Swick, A.G., Chrunyk, B.A., and Surwit, R.S. (1996). Role of leptin in fat regulation. Nature 380, 677.

    Article  CAS  PubMed  Google Scholar 

  • Collins, S., Daniel, K.W., and Rohlfs, E.M. (1999). Depressed expression of adipocyte beta-adrenergic receptors is a common feature of congenital and diet-induced obesity in rodents. Int. J. Obes. Relat. Metab. Disord. 23, 669–677.

    Article  CAS  PubMed  Google Scholar 

  • Commins, S.P., Watson, P.M., Levin, N., Beiler, R.J., and Gettys, T.W. (2000). Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue via different beta-adrenoceptor subtypes. J. Biol. Chem. 275, 33059–33067.

    Article  CAS  PubMed  Google Scholar 

  • Considine, R.V., and Caro, J.F. (1997). Leptin and the regulation of body weight. Int. J. Biochem. Cell. Biol. 29, 1255–1272.

    Article  CAS  PubMed  Google Scholar 

  • Enriori, P.J., Evans, A.E., Sinnayah, P., and Cowley, M.A. (2006). Leptin resistance and obesity. Obesity 14, 254S–258S.

    Article  CAS  PubMed  Google Scholar 

  • Fornari, A., Pedrazzi, P., Lippi, G., Picciotto, M.R., Zoli, M., and Zini, I. (2007). Nicotine withdrawal increases body weight, neuropeptide Y and Agouti-related protein expression in the hypothalamus and decreases uncoupling protein-3 expression in the brown adipose tissue in high-fat fed mice. Neurosci. Lett. 411, 72–76.

    Article  CAS  PubMed  Google Scholar 

  • Frankish, H.M., Dryden, S., Wang, Q., Bing, C., MacFarlane, I.A., and Williams, G. (1995). Nicotine administration reduces neuropeptide Y and neuropeptide Y mRNA concentrations in the rat hypothalamus: NPY may mediate nicotine’s effects on energy balance. Brain Res. 694, 139–146.

    Article  CAS  PubMed  Google Scholar 

  • Fruhbeck, G., Aguado, M., and Martinez, J.A. (1997). In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin. Biochem. Biophys. Res. Commun. 240, 590–594.

    Article  CAS  PubMed  Google Scholar 

  • Gaidhu, M.P., Anthony, N.M., Patel, P., Hawke, T.J., and Ceddia, R.B. (2010). Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK. Am. J. Physiol. Cell Physiol. 298, C961–C971.

    Article  CAS  PubMed  Google Scholar 

  • Handjieva-Darlenska, T., and Boyadjieva, N. (2009). The effect of high-fat diet on plasma ghrelin and leptin levels in rats. J. Physiol. Biochem. 65, 157–164.

    Article  CAS  PubMed  Google Scholar 

  • Hardie, L.J., Rayner, D.V., Holmes, S., and Trayhurn, P. (1996). Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochem. Biophys. Res. Commun. 223, 660–665.

    Article  CAS  PubMed  Google Scholar 

  • Henry, B.A., and Clarke, I.J. (2008). Adipose tissue hormones and the regulation of food intake. J. Neuroendocrinol. 20, 842–849.

    Article  CAS  PubMed  Google Scholar 

  • Hewson, A.K., Tung, L.Y., Connell, D.W., Tookman, L., and Dickson, S.L. (2002). The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic. Diabetes 51, 3412–3419.

    Article  CAS  PubMed  Google Scholar 

  • Hu, C.C., Qing, K., and Chen, Y. (2004). Diet-induced changes in stearoyl-CoA desaturase 1 expression in obesiyt-prone and — resistant mice. Obes. Res. 12, 1264–1270.

    Article  CAS  PubMed  Google Scholar 

  • Ilnytska, O., and Argyropoulos, G. (2008). The role of the Agouti-Related Protein in energy balance regulation. Cell Mol. Life Sci. 65, 2721–2731.

    Article  CAS  PubMed  Google Scholar 

  • Jessen, A.B., Toubro, S., and Astrup, A. (2003). Effect of chewing gum containing nicotine and caffeine on energy expenditure and substrate utilization in men. Am. J. Clin. Nutr. 77, 1442–1447.

    CAS  PubMed  Google Scholar 

  • Jo, Y.H., Talmage, D.A., and Role, L.W. (2002). Nicotinic receptormediated effects on appetite and food intake. J. Neurobiol. 53, 618–632.

    Article  CAS  PubMed  Google Scholar 

  • John, U., Hanke, M., Rumpf, H.J., and Thyrian, J.R. (2005). Smoking status, cigarettes per day, and their relationship to overweight and obesity among former and current smokers in a national adult general population sample. Int. J. Obes. 29, 1289–1294.

    Article  CAS  Google Scholar 

  • Kirshenbaum, A.P., Brown, S.J., Hughes, D.M., and Doughty, A.H. (2008). Differential-reinforcement-of-low-rate-schedule performance and nicotine administration: a systematic investigation of dose, dose-regimen, and schedule requirement. Behav. Pharmacol. 19, 683–697.

    Article  CAS  PubMed  Google Scholar 

  • Kramer, P.R., Kramer, S.F., Marr, K., Guan, G., Wellman, P.J., and Bellinger, L.L. (2007). Nicotine administration effects on feeding and cocaine-amphetamine-regulated transcript (CART) expression in the hypothalamus. Regul. Pept. 138, 66–73.

    Article  CAS  PubMed  Google Scholar 

  • Lage, R., Gonzalez, C.R., Dieguez, C., and Lopez, M. (2007). Nicotine treatment regulates neuropeptide S system expression in the rat brain. Neurotoxicology 28, 1129–1135.

    Article  CAS  PubMed  Google Scholar 

  • Levine, M.D., Perkins, K.A., and Marcus, M.D. (2001). The characteristics of women smokers concerned about postcessation weight gain. Addict. Behav. 26, 749–756.

    Article  CAS  PubMed  Google Scholar 

  • Li, M.D., and Kane, J.K. (2003). Effect of nicotine on the expression of leptin and forebrain leptin receptors in the rat. Brain Res. 991, 222–231.

    Article  CAS  PubMed  Google Scholar 

  • Li, H., Matheny, M., and Scarpace, P.J. (1997). beta 3-Adrenergicmediated suppression of leptin gene expression in rats. Am. J. Physiol. 272, E1031–1036.

    CAS  PubMed  Google Scholar 

  • Li, M.D., Kane, J.K., Parker, S.L., McAllen, K., Matta, S.G., and Sharp, B.M. (2000). Nicotine administration enhances NPY expression in the rat hypothalamus. Brain Res. 867, 157–164.

    Article  CAS  PubMed  Google Scholar 

  • Lindqvist, A., de la Cour, C.D., Stegmark, A., Hakanson, R., and Erlanson-Albertsson, C. (2005). Overeating of palatable food is associated with blunted leptin and ghrelin responses. Regul. Pept. 130, 123–132.

    Article  CAS  PubMed  Google Scholar 

  • Lollmann, B., Gruninger, S., Stricker-Krongrad, A., and Chiesi, M. (1997). Detection and quantification of the leptin receptor splice variants Ob-Ra, b, and, e in different mouse tissues. Biochem. Biophys. Res. Commun. 238, 648–652.

    Article  CAS  PubMed  Google Scholar 

  • Lupien, J.R., and Bray, G.A. (1988). Nicotine increases thermogenesis in brown adipose tissue in rats. Pharmacol. Biochem. Behav. 29, 33–37.

    Article  CAS  PubMed  Google Scholar 

  • Mark, A.L., Rahmouni, K., Correia, M., and Haynes, W.G. (2003). A leptin-sympathetic-leptin feedback loop: potential implications for regulation of arterial pressure and body fat. Acta. Physiol. Scand. 177, 345–349.

    Article  CAS  PubMed  Google Scholar 

  • Masuo, K., Katsuya, T., Kawaguchi, H., Fu, Y., Rakugi, H., Ogihara, T., and Tuck, M.L. (2006). Beta2-adrenoceptor polymorphisms relate to obesity through blunted leptin-mediated sympathetic activation. Am. J. Hypertens. 19, 1084–1091.

    Article  CAS  PubMed  Google Scholar 

  • Masuo, K., Straznicky, N.E., Lambert, G.W., Katsuya, T., Sugimoto, K., Rakugi, H., Socratous, F., Hastings, J., Lambert, E.A., Ogihara, T., et al. (2008). Leptin-receptor polymorphisms relate to obesity through blunted leptin-mediated sympathetic nerve activation in a Caucasian male population. Hypertens. Res. 31, 1093–1100.

    Article  CAS  PubMed  Google Scholar 

  • Mitchell, S.E., Nogueiras, R., Morris, A., Tovar, S., Grant, C., Cruickshank, M., Rayner, D.V., Dieguez, C., and Williams, L.M. (2009). Leptin receptor gene expression and number in the brain are regulated by leptin level and nutritional status. J. Physiol. 587, 3573–3585.

    Article  CAS  PubMed  Google Scholar 

  • Morris, D.L., and Rui, L. (2009). Recent advances in understanding leptin signaling and leptin resistance. Am. J. Physiol. Endocrinol. Metab. 297, E1247–1259.

    Article  CAS  PubMed  Google Scholar 

  • Nakhate, K.T., Dandekar, M.P., Kokare, D.M., and Subhedar, N.K. (2009). Involvement of neuropeptide Y Y(1) receptors in the acute, chronic and withdrawal effects of nicotine on feeding and body weight in rats. Eur. J. Pharmacol. 609, 78–87.

    Article  CAS  PubMed  Google Scholar 

  • O’Doherty, R.M., and Nguyen, L. (2004). Blunted fasting-induced decreases in plasma and CSF leptin concentrations in obese rats: the role of increased leptin secretion. Int. J. Obes. Relat. Metab. Disord. 28, 173–175.

    Article  PubMed  Google Scholar 

  • Oswal, A., and Yeo, G. (2009). Leptin and the control of body weight: a review of Its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity. Obesity 18, 221–229.

    Article  PubMed  Google Scholar 

  • Palou, M., Sanchez, J., Rodriguez, A.M., Priego, T., Pico, C., and Palou, A. (2009). Induction of NPY/AgRP orexigenic peptide expression in rat hypothalamus is an early event in fasting: relationship with circulating leptin, insulin and glucose. Cell Physiol. Biochem. 23, 115–124.

    Article  CAS  PubMed  Google Scholar 

  • Paxinos, G., and Franklin, K. (2001). The mouse brain in stereotaxic coordinates, (San Diego, USA: Academic Press).

    Google Scholar 

  • Perello, M., Chacon, F., Cardinali, D.P., Esquifino, A.I., and Spinedi, E. (2006). Effect of social isolation on 24-h pattern of stress hormones and leptin in rats. Life Sci. 78, 1857–1862.

    Article  CAS  PubMed  Google Scholar 

  • Reseland, J.E., Mundal, H.H., Hollung, K., Haugen, F., Zahid, N., Anderssen, S.A., and Drevon, C.A. (2005). Cigarette smoking may reduce plasma leptin concentration via catecholamines. Prostaglandins Leukot. Essent. Fatty Acids 73, 43–49.

    Article  CAS  Google Scholar 

  • Ricci, M.R., Lee, M.J., Russell, C.D., Wang, Y., Sullivan, S., Schneider, S.H., Brolin, R.E., and Fried, S.K. (2005). Isoproterenol decreases leptin release from rat and human adipose tissue through posttranscriptional mechanisms. Am. J. Physiol. Endocrinol. Metab. 288, E798–804.

    Article  CAS  PubMed  Google Scholar 

  • Rowell, P.P., and Li, M. (1997). Dose-response relationship for nicotine-induced up-regulation of rat brain nicotinic receptors. J. Neurochem. 68, 1982–1989.

    Article  CAS  PubMed  Google Scholar 

  • Sahu, A., Nguyen, L., and O’Doherty, R.M. (2002). Nutritional regulation of hypothalamic leptin receptor gene expression is defective in diet-induced obesity. J. Neuroendocrinol. 14, 887–893.

    Article  CAS  PubMed  Google Scholar 

  • Sakane, N., Yoshida, T., Umekawa, T., Kogure, A., Kondo, M., Nakamura, Y., Sasaki, Y., Asano, A., and Saito, M. (1998). Acute and chronic regulation of ob mRNA levels by beta3-adrenoceptor agonists in obese Yellow KK mice. Endocr. J. 45, 647–651.

    CAS  PubMed  Google Scholar 

  • Sanigorski, A., Fahey, R., Cameron-Smith, D., and Collier, G.R. (2002). Nicotine treatment decreases food intake and body weight via a leptin-independent pathway in Psammomys obesus. Diabetes Obes. Metab. 4, 346–350.

    Article  CAS  PubMed  Google Scholar 

  • Scarpace, P.J., and Matheny, M. (1998). Leptin induction of UCP1 gene expression is dependent on sympathetic innervation. Am. J. Physiol. 275, E259–264.

    CAS  PubMed  Google Scholar 

  • Scarpace, P.J., Matheny, M., Moore, R.L., and Kumar, M.V. (2000). Modulation of uncoupling protein 2 and uncoupling protein 3: regulation by denervation, leptin and retinoic acid treatment. J. Endocrinol. 164, 331–337.

    Article  CAS  PubMed  Google Scholar 

  • Sellayah, D., Sek, K., Anthony, F.W., Hanson, M.A., and Cagampang, F.R. (2008). Sensitivity of housekeeping genes in the hypothalamus to mismatch in diets between pre- and postnatal periods in mice. Neurosci. Lett. 447, 54–57.

    Article  CAS  PubMed  Google Scholar 

  • Shi, H., Akunuru, S., Bierman, J.C., Hodge, K.M., Mitchell, M.C., Foster, M.T., Seeley, R.J., and Reizes, O. (2009). Diet-induced obese mice are leptin insufficient after weight reduction. Obesity 17, 1702–1709.

    Article  CAS  PubMed  Google Scholar 

  • Shiraev, T., Chen, H., and Morris, M.J. (2009). Differential effects of restricted versus unlimited high-fat feeding in rats on fat mass, plasma hormones and brain appetite regulators. J. Neuroendocrinol. 21, 602–609.

    Article  CAS  PubMed  Google Scholar 

  • Strauss, R.S., and Mir, H.M. (2001). Smoking and weight loss attempts in overweight and normal-weight adolescents. Int. J. Obes. Relat. Metab. Disord. 25, 1381–1385.

    Article  CAS  PubMed  Google Scholar 

  • Stutz, A.M., Morrison, C.D., and Argyropoulos, G. (2005). The agouti-related protein and its role in energy homeostasis. Peptides 26, 1771–1781.

    Article  PubMed  Google Scholar 

  • Vogler, O., Lopez-Bellan, A., Alemany, R., Tofe, S., Gonzalez, M., Quevedo, J., Pereg, V., Barcelo, F., and Escriba, P.V. (2008). Structure-effect relation of C18 long-chain fatty acids in the reduction of body weight in rats. Int. J. Obes. (Lond). 32, 464–473.

    Article  CAS  Google Scholar 

  • Wager-Srdar, S.A., Levine, A.S., Morley, J.E., Hoidal, J.R., and Niewoehner, D.E. (1984). Effects of cigarette smoke and nicotine on feeding and energy. Physiol. Behav. 32, 389–395.

    Article  CAS  PubMed  Google Scholar 

  • Walker, J.F., and Kane, C.J. (2002). Effects of body mass on nicotine-induced thermogenesis and catecholamine release in male smokers. Sheng Li. Xue. Bao. 54, 405–410.

    CAS  PubMed  Google Scholar 

  • Walker, J.F., Collins, L.C., Rowell, P.P., Goldsmith, L.J., Moffatt, R.J., and Stamford, B.A. (1999). The effect of smoking on energy expenditure and plasma catecholamine and nicotine levels during light physical activity. Nicotine Tob. Res. 1, 365–370.

    Article  CAS  PubMed  Google Scholar 

  • Wang, M.Y., Lee, Y., and Unger, R.H. (1999). Novel form of lipolysis induced by leptin. J. Biol. Chem. 274, 17541–17544.

    Article  CAS  PubMed  Google Scholar 

  • Weir, J.B. (1949). New methods for calculating metabolic rate with special reference to protein metabolism. J. Physiol. 109, 1–9.

    PubMed  Google Scholar 

  • Wellman, P.J., Bellinger, L.L., Cepeda-Benito, A., Susabda, A., Ho, D.H., and Davis, K.W. (2005). Meal patterns and body weight after nicotine in male rats as a function of chow or high-fat diet. Pharmacol. Biochem. Behav. 82, 627–634.

    Article  CAS  PubMed  Google Scholar 

  • Yoshida, T., Yoshioka, K., Hiraoka, N., and Kondo, M. (1990). Effect of nicotine on norepinephrine turnover and thermogenesis in brown adipose tissue and metabolic rate in MSG obese mice. J. Nutr. Sci. Vitaminol. 36, 123–130.

    CAS  PubMed  Google Scholar 

  • Zhang, Y., Matheny, M., Zolotukhin, S., Tumer, N., and Scarpace, P.J. (2002). Regulation of adiponectin and leptin gene expression in white and brown adipose tissues: influence of beta3-adrenergic agonists, retinoic acid, leptin and fasting. Biochim. Biophys. Acta 1584, 115–122.

    CAS  PubMed  Google Scholar 

  • Ziotopoulou, M., Mantzoros, C.S., Hileman, S.M., and Flier, J.S. (2000). Differential expression of hypothalamic neuropeptides in the early phase of diet-induced obesity in mice. Am. J. Physiol. Endocrinol. Metab. 279, E838–845.

    CAS  PubMed  Google Scholar 

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Hur, YN., Hong, GH., Choi, SH. et al. High fat diet altered the mechanism of energy homeostasis induced by nicotine and withdrawal in C57BL/6 mice. Mol Cells 30, 219–226 (2010). https://doi.org/10.1007/s10059-010-0110-3

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