, Volume 63, Issue 3, pp 520–530 | Cite as

Maternal cinnamon intake during lactation led to visceral obesity and hepatic metabolic dysfunction in the adult male offspring

  • Jessika Geisebel Oliveira Neto
  • Thais Bento-Bernardes
  • Carmen Cabanelas Pazos-Moura
  • Karen Jesus OliveiraEmail author
Original Article



Studies with foods, known to promote health benefits in addition to the nutritive value, show that their consumption by pregnant and/or lactating females could induce negative outcomes to the offspring. It is well characterized that cinnamon intake promotes benefits to energy homeostasis. The present study aimed to analyze the effects of the consumption of an aqueous extract of cinnamon by lactating female rats on the endocrine-metabolic outcomes in the adult offspring.


Lactating dams (Wistar rats) were supplemented with cinnamon aqueous extract (400 mg/kg body weight/day) for the entire lactating period. The male adult offspring were evaluated at 180 days old (CinLac).


The offspring presented visceral obesity (P = 0.001), hyperleptinemia (P = 0.002), and hyperinsulinemia (P = 0.016). In the liver, CinLac exhibited reduced p-IRβ (P = 0.018) suggesting insulin resistance. However, phosphorylation of IRS1 (P = 0.041) and AKT (P = 0.050) were increased. JAK2 (P = 0.030) and p-STAT3 (P = 0.015) expressions were higher, suggesting that the activation of IRS1/AKT in the CinLac group could have resulted from the increased activation of leptin signaling. Although we observed no changes in the gluconeogenic pathway, the CinLac group exhibited lower hepatic glycogen content (P = 0.005) accompanied by increased p-GSK3β (P = 0.011). In addition, the CinLac group showed increased hepatic triacylglycerol content (P = 0.049) and a mild steatosis (P = 0.001), accompanied by reduced PPARα mRNA expression (P = 0.005).


We conclude that maternal intake of aqueous extract of cinnamon induces long-term molecular, metabolic, and hormonal changes in the adult progeny, including visceral obesity, higher lipid accumulation, and lower glycogen content in the liver.


Lactation Metabolic programming Cinnamon Liver Insulin Leptin 




This study was funded by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ; K.J.O., grant number 102.982) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). J.G.O.N. was recipient of a FAPERJ fellowship. T.B.B. was recipient of a CAPES fellowship.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Animal use and experimental procedures were approved by Ethics Committee on Animal Use of Fluminense Federal University under number 0120/11, and complied with the ethical guidelines of the Brazilian Society of Laboratory Animal Science.

Supplementary material

12020_2018_1775_MOESM1_ESM.docx (14 kb)
Supplementary material


  1. 1.
    D.J. Barker, The developmental origins of adult disease. J. Am. Coll. Nutr. 23, 588S–595S (2004)CrossRefPubMedGoogle Scholar
  2. 2.
    B. Hanley, J. Dijane, M. Fewtrell, A. Grynberg, S. Hummel, C. Junien, B. Koletzko, S. Lewis, H. Renz, M. Symonds, M. Gros, L. Harthoorn, K. Mace, F. Samuels, E.M. van Der, Beek, Metabolic imprinting, programming and epigenetics—a review of present priorities and future opportunities. Br. J. Nutr. 104, S1 (2010)CrossRefPubMedGoogle Scholar
  3. 3.
    M. Rolland-Cachera, M. Akrout, S. Péneau, Nutrient intakes in early life and risk of obesity. Int. J. Environ. Res. Public Health 13, 564 (2016)CrossRefPubMedCentralGoogle Scholar
  4. 4.
    M. Desai, J.K. Jellyman, M.G. Ross, Epigenomics, gestational programming and risk of metabolic syndrome. Int. J. Obes. 39, 633 (2015)CrossRefGoogle Scholar
  5. 5.
    K.M. Kolasa, G. Firnhaber, K. Haven, Diet for a healthy lactating woman. Clin. Obstet. Gynecol. 58, 893 (2015)CrossRefPubMedGoogle Scholar
  6. 6.
    E. Sosa-Castillo, M. Rodríguez-Cruz, C. Moltó-Puigmartí, Genomics of lactation: role of nutrigenomics and nutrigenetics in the fatty acid composition of human milk. Br. J. Nutr. 118, 161 (2017)CrossRefPubMedGoogle Scholar
  7. 7.
    O. Ballard, A.L. Morrow, Human milk composition. Pediatr. Clin. North Am. 60, 49 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    M. Champ, C. Hoebler, Functional food for pregnant, lactating women and in perinatal nutrition: a role for dietary fibres. Curr. Opin. Clin. Nutr. Metab. Care 12, 565 (2009)CrossRefPubMedGoogle Scholar
  9. 9.
    G. Pang, J. Xie, Q. Chen, Z. Hu, How functional foods play critical roles in human health. Food Sci. Hum. Wellness 1, 26 (2012)CrossRefGoogle Scholar
  10. 10.
    S. Li, I.M.Y. Tse, E.T.S. Li, J. Maternal green tea extract supplementation to rats fed a high-fat diet ameliorates insulin resistance in adult male offspring. Nutr. Biochem. 23, 1655 (2012)CrossRefGoogle Scholar
  11. 11.
    M.S. Figueiredo, M.C. da Fonseca Passos, I.H. Trevenzoli, A.A. Troina, A.S. Carlos, C.C. Alves Nascimento-Saba, M.C. Fraga, A.C. Manhães, E. de Oliveira, P.C. Lisboa, E.G. de Moura, Adipocyte morphology and leptin signaling in rat offspring from mothers supplemented with flaxseed during lactation. Nutrition 28, 307 (2012)CrossRefPubMedGoogle Scholar
  12. 12.
    P.V. Rao, S.H. Gan, Cinnamon: a multifaceted medicial plant. Evid. Based Complement. Alternat. Med 2014, 1–12 (2014)CrossRefGoogle Scholar
  13. 13.
    P. B. Wilson, A population-representative analysis of dietary supplementation among Americans with diabetes mellitus. J. Diabetes (2018).
  14. 14.
    T. Sartorius, A. Peter, N. Schulz, A. Drescher, I. Bergheim, J. Machann, F. Schick, D. Siegel-Axel, A. Schürmann, C. Weigert, H.-U. Häring, A.M. Hennige, Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity. PLoS One 9, e92358 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    R.W. Allen, E. Schwartzman, W.L. Baker, C.I. Coleman, O.J. Phung, Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann. Fam. Med. 11, 452 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    K. Couturier, C. Batandier, M. Awada, I. Hininger-Favier, F. Canini, R.A. Anderson, X. Leverve, A.M. Roussel, Cinnamon improves insulin sensitivity and alters the body composition in an animal model of the metabolic syndrome. Arch. Biochem. Biophys. 501, 158 (2010)CrossRefPubMedGoogle Scholar
  17. 17.
    A. Khan, M. Safdar, M.M. Ali Khan, K.N. Khattak, R.A. Anderson, Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 26, 3215 (2003)CrossRefPubMedGoogle Scholar
  18. 18.
    T.N. Ziegenfuss, J.E. Hofheins, R.W. Mendel, J. Landis, R.A. Anderson, Effects of a water-soluble cinnamon extract on body composition and features of the metabolic syndrome in pre-diabetic men and women. J. Int. Soc. Sports Nutr. 3, 45 (2006)CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    B.P. Lopes, T.G. Gaique, L.L. Souza, G.S.M. Paula, G.E.G. Kluck, G.C. Atella, A.C.C. Gomes, N.K. Simas, R.M. Kuster, T.M. Ortiga-Carvalho, C.C. Pazos-Moura, K.J. Oliveira, Cinnamon extract improves the body composition and attenuates lipogenic processes in the liver and adipose tissue of rats. Food Funct. 6, 3257 (2015)CrossRefPubMedGoogle Scholar
  20. 20.
    P. Ranasinghe, R. Jayawardana, P. Galappaththy, G.R. Constantine, N. de Vas Gunawardana, P. Katulanda, Efficacy and safety of ‘true’ cinnamon ( Cinnamomum zeylanicum ) as a pharmaceutical agent in diabetes: a systematic review and meta-analysis: efficacy and safety of ‘true’ cinnamon in diabetes. Diabet. Med. 29, 1480 (2012)CrossRefPubMedGoogle Scholar
  21. 21.
    B. Qin, M. Nagasaki, M. Ren, G. Bajotto, Y. Oshida, Y. Sato, Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats. Diabetes Res. Clin. Pract. 62, 139 (2003)CrossRefPubMedGoogle Scholar
  22. 22.
    Y. Shen, M. Fukushima, Y. Ito, E. Muraki, T. Hosono, T. Seki, T. Ariga, Verification of the antidiabetic effects of cinnamon (Cinnamomum zeylanicum) using insulin-uncontrolled type 1 diabetic rats and cultured adipocytes. Biosci. Biotechnol. Biochem. 74, 2418 (2010)CrossRefPubMedGoogle Scholar
  23. 23.
    T. Bento-Bernardes, F.P. Toste, C.C. Pazos-Moura, K.J. Oliveira, Maternal cinnamon extract intake during lactation leads to sex-specific endocrine modifications in rat offspring. J. Sci. Food Agric. 97, 3855 (2017)CrossRefPubMedGoogle Scholar
  24. 24.
    J.M. del Bas, A. Crescenti, A. Arola-Arnal, G. Oms-Oliu, L. Arola, A. Caimari, Intake of grape procyanidins during gestation and lactation impairs reverse cholesterol transport and increases atherogenic risk indexes in adult offspring. J. Nutr. Biochem. 26, 1670 (2015)CrossRefPubMedGoogle Scholar
  25. 25.
    K.L. Fischbeck, K.M. Rasmussen, Effect of repeated reproductive cycles on maternal nutritional status, lactational performance and litter growth in ad libitum-fed and chronically food-restricted rats. J. Nutr 117, 1967 (1987)CrossRefPubMedGoogle Scholar
  26. 26.
    X. Sheng, Y. Zhang, Z. Gong, C. Huang, Y.Q. Zang, Improved insulin resistance and lipid metabolism by cinnamon extract through activation of peroxisome proliferator-activated receptors. PPAR Res. 2008, 1 (2008)CrossRefGoogle Scholar
  27. 27.
    S. Reagan-Shaw, M. Nihal, N. Ahmad, Dose translation from animal to human studies revisited. FASEB J. 22, 659 (2008)CrossRefPubMedGoogle Scholar
  28. 28.
    J. Hlebowicz, G. Darwiche, O. Björgell, L.-O. Almér, Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects. Am. J. Clin. Nutr. 85, 1552–6 (2007)CrossRefPubMedGoogle Scholar
  29. 29.
    A. Mann, A. Thompson, N. Robbins, A.L. Blomkalns, Localization, identification, and excision of murine adipose depots. J. Vis. Exp 94, e52174 (2014)Google Scholar
  30. 30.
    T.G. Gaique, B.P. Lopes, L.L. Souza, G.S.M. Paula, C.C. Pazos-Moura, K.J. Oliveira, Cinnamon intake reduces serum T3 level and modulates tissue-specific expression of thyroid hormone receptor and target genes in rats: Cinnamon and thyroid function. J. Sci. Food Agric. 96, 2889 (2016)CrossRefPubMedGoogle Scholar
  31. 31.
    A. Helal, D. Tagliazucchi, E. Verzelloni, A. Conte, Bioaccessibility of polyphenols and cinnamaldehyde in cinnamon beverages subjected to in vitro gastro-pancreatic digestion. J. Funct. Foods 7, 506 (2014)CrossRefGoogle Scholar
  32. 32.
    G. Casimiro-Lopes, S. Alves, V. Salerno, M. Passos, P. Lisboa, E. Moura, Maximum acute exercise tolerancein hyperthyroid and hypothyroid rats subjected to forced swimming. Horm. Metab. Res. 40, 276 (2008)CrossRefPubMedGoogle Scholar
  33. 33.
    E.D.C. Frantz, R.F. Medeiros, I.G. Giori, J.B.S. Lima, T. Bento-Bernardes, T.G. Gaique, C. Fernandes-Santos, T. Fernandes, E.M. Oliveira, C.P. Vieira, C.A. Conte-Junior, K.J. Oliveira, A.C.L. Nobrega, Exercise training modulates the hepatic renin-angiotensin system in fructose-fed rats: exercise training modulates hepatic renin-angiotensin system. Exp. Physiol. 102, 1208 (2017)CrossRefPubMedGoogle Scholar
  34. 34.
    M. Catta-Preta, L.S. Mendonca, J. Fraulob-Aquino, M.B. Aguila, C.A. Mandarim-de-Lacerda, A critical analysis of three quantitative methods of assessment of hepatic steatosis in liver biopsies. Virchows. Arch. 459, 477 (2011)CrossRefPubMedGoogle Scholar
  35. 35.
    S. Sam, Differential effect of subcutaneous abdominal and visceral adipose tissue on cardiometabolic risk. Horm. Mol. Biol. Clin. Investig. 33, (2018).
  36. 36.
    S.A. Polyzos, J. Kountouras, C.S. Mantzoros, Leptin in nonalcoholic fatty liver disease: a narrative review. Metabolism 64, 60 (2015)CrossRefPubMedGoogle Scholar
  37. 37.
    S. Fruhwürth, H. Vogel, A. Schürmann, K.J. Williams, Novel insights into how overnutrition disrupts the hypothalamic actions of leptin. Front. Endocrinol. 9, (2018).
  38. 38.
    R.A. DeFronzo, D. Tripathy, Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32, S157 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    K. Nowotny, T. Jung, A. Höhn, D. Weber, T. Grune, Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules 5, 194 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    M. Li, B. Chang, Z. Zhen, P.-J. Qin, W.-K. Liu, X.-L. Tong, Hepatic PTP1B expression involvement in the effects of Chinese medicine formula Xiao-Gao-Jiang-Zhuo using an obese rat model. Am. J. Chin. Med. 39, 301 (2011)CrossRefPubMedGoogle Scholar
  41. 41.
    R.H. Hassan, Defect of insulin signal in peripheral tissues: Important role of ceramide. World J. Diabetes 5, 244 (2014)CrossRefGoogle Scholar
  42. 42.
    S. Bhattacharyya, L. Feferman, J.K. Tobacman, Carrageenan inhibits insulin signaling through GRB10-mediated decrease in Tyr(P)-IRS1 and through inflammation-induced increase in Ser(P) 307 -IRS1. J. Biol. Chem. 290, 10764 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    K. Ikejima, K. Okumura, T. Lang, H. Honda, W. Abe, S. Yamashina, N. Enomoto, Y. Takei, N. Sato, The role of leptin in progression of non-alcoholic fatty liver disease. Hepatol. Res. 33, 151 (2005)CrossRefPubMedGoogle Scholar
  44. 44.
    S.M. Schultze, J. Jensen, B.A. Hemmings, O. Tschopp, M. Niessen, Promiscuous affairs of PKB/AKT isoforms in metabolism. Arch. Physiol. Biochem. 117, 70 (2011)CrossRefPubMedGoogle Scholar
  45. 45.
    F.K. Huynh, U.H. Neumann, Y. Wang, B. Rodrigues, T.J. Kieffer, S.D. Covey, A role for hepatic leptin signaling in lipid metabolism via altered very low density lipoprotein composition and liver lipase activity in mice. Hepatology 57, 543 (2013)CrossRefPubMedGoogle Scholar
  46. 46.
    J.B.C. Carvalheira, E.B. Ribeiro, F. Folli, L.A. Velloso, M.J.A. Saad, Interaction between leptin and insulin signaling pathways differentially affects JAK-STAT and PI 3-kinase-mediated signaling in rat liver. Biol. Chem 384, 151 (2003)CrossRefPubMedGoogle Scholar
  47. 47.
    J.Y. Jun, Z. Ma, R. Pyla, L. Segar, Leptin treatment inhibits the progression of atherosclerosis by attenuating hypercholesterolemia in type 1 diabetic Ins2+/Akita:apoE−/− mice. Atherosclerosis 225, 341 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    J.G. Jones, Hepatic glucose and lipid metabolism. Diabetologia 59, 1098 (2016)CrossRefPubMedGoogle Scholar
  49. 49.
    C.C. Greenberg, M.J. Jurczak, A.M. Danos, M.J. Brady, Glycogen branches out: new perspectives on the role of glycogen metabolism in the integration of metabolic pathways. Am. J. Physiol. -Endocrinol. Metab. 291, E1 (2006)CrossRefPubMedGoogle Scholar
  50. 50.
    M. Wang, L. Chen, G.O. Clark, Y. Lee, R.D. Stevens, O.R. Ilkayeva, B.R. Wenner, J.R. Bain, M.J. Charron, C.B. Newgard, R.H. Unger, Leptin therapy in insulin-deficient type I diabetes. Proc. Natl. Acad. Sci. 107, 4813 (2010)CrossRefPubMedGoogle Scholar
  51. 51.
    L. Rossetti, D. Massillon, N. Barzilai, P. Vuguin, W. Chen, M. Hawkins, J. Wu, J. Wang, Effects of leptin on hepatic gluconeogenesis and in vivo insulin action. Biol. Chem. 272, 27758 (1997)CrossRefGoogle Scholar
  52. 52.
    S. Kamohara, R. Burcelin, J.L. Halaas, J.M. Friedman, M.J. Charron, Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389, 374 (1997)CrossRefPubMedGoogle Scholar
  53. 53.
    H.C. Denroche, F.K. Huynh, T.J. Kieffer, The role of leptin in glucose homeostasis: Leptin and glucose homeostasis. J. Diabetes Investig. 3, 115 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    J.M. Irimia, C.M. Meyer, C.L. Peper, L. Zhai, C.B. Bock, S.F. Previs, O.P. McGuinness, A. DePaoli-Roach, P.J.Roach, Impaired glucose tolerance and predisposition to the fasted state in liver glycogen synthase knock-out mice. J. Biol. Chem. 285, 12851 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    H.M. Al-Dayyat, Y.M. Rayyan, R.F. Tayyem, Non-alcoholic fatty liver disease and associated dietary and lifestyle risk factors. Diabetes Metab. Syndr. Clin. Res. Rev 12, 569 (2018)CrossRefGoogle Scholar
  56. 56.
    P.-T. Xu, Z. Song, W.-C. Zhang, B. Jiao, Z.-B. Yu, Impaired translocation of GLUT4 results in insulin resistance of atrophic soleus muscle. Biomed. Res. Int. 2015, 1 (2015)Google Scholar
  57. 57.
    T. Kisseleva, S. Bhattacharya, J. Braunstein, C. Schindler, Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285, 1 (2002)CrossRefPubMedGoogle Scholar
  58. 58.
    W. Zhang, M. Niu, K. Yan, X. Zhai, Q. Zhou, L. Zhang, Y. Zhou, Stat3 pathway correlates with the roles of leptin in mouse liver fibrosis and sterol regulatory element binding protein-1c expression of rat hepatic stellate cells. Int. J. Biochem. Cell Biol. 45, 736 (2013)CrossRefPubMedGoogle Scholar
  59. 59.
    L. Zhang, H. Song, Y. Ge, G. Ji, Z. Yao, Temporal relationship between diet-induced steatosis and onset of insulin/leptin resistance in male Wistar rats. PLoS One 10, e0117008 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    D.G. Mashek, Hepatic fatty acid trafficking: multiple forks in the road. Adv. Nutr. 4, 697 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    C.P. Dias-Rocha, M.M. Almeida, E.M. Santana, J.C.B. Costa, J.G. Franco, C.C. Pazos-Moura, I.H. Trevenzoli, Maternal high-fat diet induces sex-specific endocannabinoid system changes in newborn rats and programs adiposity, energy expenditure and food preference in adulthood. J. Nutr. Biochem. 51, 56–68 (2018)CrossRefPubMedGoogle Scholar
  62. 62.
    V.S.T. Rodrigues, E.G. Moura, D.N. Bernardino, J.C. Carvalho, P.N. Soares, T.C. Peixoto, N. Peixoto-Silva, E. Oliveira, P.C. Lisboa, Supplementation of suckling rats with cow’s milk induces hyperphagia and higher visceral adiposity in females at adulthood, but not in males. J. Nutr. Biochem. 55, 89–103 (2018)CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jessika Geisebel Oliveira Neto
    • 1
  • Thais Bento-Bernardes
    • 2
  • Carmen Cabanelas Pazos-Moura
    • 2
  • Karen Jesus Oliveira
    • 1
    Email author
  1. 1.Departamento de Fisiologia e FarmacologiaUniversidade Federal FluminenseNiteróiBrazil
  2. 2.Instituto de Biofísica Carlos Chagas FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil

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