Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Gold, Paul / Holsboer, Florian / Korth, Carsten / Li, Jay-Shake / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John


IMPACT FACTOR 2018: 2.157
5-year IMPACT FACTOR: 2.935

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 0.980
Source Normalized Impact per Paper (SNIP) 2017: 0.804

Online
ISSN
2191-0200
See all formats and pricing
More options …
Volume 28, Issue 3

Issues

Leptin and adiponectin: pathophysiological role and possible therapeutic target of inflammation in ischemic stroke

Jitender Gairolla
  • Department of Neurology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rupinder Kler
  • Department of Neurology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Manish Modi
  • Department of Neurology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dheeraj KhuranaORCID iD: http://orcid.org/0000-0003-1410-8939
Published Online: 2017-01-25 | DOI: https://doi.org/10.1515/revneuro-2016-0055

Abstract

Stroke is a multifactorial disease contributing to significant noncommunicable disease burden in developing countries. Risk of stroke is largely a consequence of morbidities of diabetes, obesity, hypertension, and heart diseases. Incidence of stroke is directly proportional to body mass index. Adipose tissue stores energy as well as acts as an active endocrine organ, which secretes numerous humoral factors. Adiponectin and leptin are the commonest adipocytokines and have been invariably linked to the development of coronary heart disease and may be involved in the underlying biological mechanism of stroke. Leptin and adiponectin mediate proatherogenic and antiatherogenic responses, respectively, and hence, determining the plasma or serum levels of leptin and adiponectin alone or in combination may act as a novel prognostic biomarker for inflammation and atherosclerosis in stroke. This review addresses leptin- and adiponectin-mediated inflammatory mechanism in ischemic stroke and their potential as therapeutic targets.

Keywords: adiponectin; adipose tissue; atherosclerosis; ischemic stroke; leptin

References

  • Adya, R., Tan, B. K., and Randeva H. S. (2015). Differential effects of leptin and adiponectin in endothelial angiogenesis. J Diabetes Res. 2015, 648239.Google Scholar

  • Ahima, R.S. and Osei, S.Y. (2004). Leptin signaling. Physiol. Behav. 81, 223–241.Google Scholar

  • Aleidi, S., Issa, A., Bustanji, H., Khalil M., and Bustanji Y. (2015). Adiponectin serum levels correlate with insulin resistance in type 2 diabetic patients. Saudi Pharm. J. 23, 250–256.Google Scholar

  • Aprahamian, T.R. and Sam, F. (2011). Adiponectin in cardiovascular inflammation and obesity. Int. J. Inflam. 2011, 376909.Google Scholar

  • Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., et al. (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem. Biophys. Res. Commun. 257, 79–83.Google Scholar

  • Bailleul, B., Akerblom, I., and Strosberg, A.D. (1997). The leptin receptor promoter controls expression of a second distinct protein. Nucleic Acids Res. 25, 2752–2758.Google Scholar

  • Bang, O.Y., Saver, J.L., Ovbiagele, B., Choi, Y.J., Yoon, S.R., and Lee, K.H. (2007). Adiponectin levels in patients with intracranial atherosclerosis. Neurology 22, 1931–1937.Google Scholar

  • Beltowski, J. (2006). Leptin and atherosclerosis. Atherosclerosis 189, 47–60.Google Scholar

  • Berg, A.H., Combs, T.P., Du, X., Brownlee, M., and Scherer, P.E. (2001). The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat. Med. 7, 947–953.Google Scholar

  • Berg, A.H., Combs, T.P., and Scherer, P.E. (2002). ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol. Metab. 13, 84–89.Google Scholar

  • Bidulescu, A., Liu, J., Chen, Z., Hickson, D.A., Musani, S.K., Samdarshi, T.E., Fox, E.R., Taylor, H.A., and Gibbons, G.H. (2013). Associations of adiponectin and leptin with incident coronary heart disease and ischemic stroke in African Americans: the Jackson Heart Study. Front. Public Health 1, 16.Google Scholar

  • Blumer, R.M., van Roomen, C.P., Meijer, A.J., Houben-Weerts, J.H., Sauerwein, H.P., and Dubbelhuis, P.F. (2008). Regulation of adiponectin secretion by insulin and amino acids in 3T3-L1 adipocytes. Metabolism 57, 1655–1662.Google Scholar

  • Bodary, P.F. and Eitzman, D.T. (2006). Adiponectin: vascular protection from the fat? Arterioscler. Thromb. Vasc. Biol. 26, 235–236.Google Scholar

  • Bodles, A.M., Banga, A., Rasouli, N., Ono, F., Kern, P.A., and Owens, R.J. (2006). Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes. Am. J. Physiol. Endocrinol. Metab. 291, E1100–E1105.Google Scholar

  • Bouloumie, A., Marumo, T., Lafontan, M., and Busse, R. (1999). Leptin induces oxidative stress in human endothelial cells. FASEB J. 13, 1231–1238.Google Scholar

  • Bouloumié, A., Curat, C.A., Sengenès, C., Lolmède, K., Alexandra M., and Busse, R. (2005). Role of Macrophage tissue infiltration in metabolic diseases. Curr. Opin. Clin. Nutr. Metab. Care 8, 347–54.Google Scholar

  • Buechler, C., Wanninger, J., and Neumeier, M. (2010). Adiponectin receptor binding proteins—recent advances in elucidating adiponectin signalling pathways. FEBS Lett. 584, 4280–4286.Google Scholar

  • Caselli, C., D’Amico, A., Cabiati, M., Prescimone, T., Del Ry, S., and Giannessi, D. (2014). Back to the heart: the protective role of adiponectin. Pharmacol. Res. 82, 9–20.Google Scholar

  • Chen, H., Montagnani, M., Funahashi, T., Shimomura, I., and Quon, M.J. (2003). Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J. Biol. Chem. 278, 45021–45026.Google Scholar

  • Chen, M.P., Tsai, J.C., Chung, F.M., Yang, S.S., Hsing, L.L., Shin, S.J., and Lee, Y.J. (2005). Hypoadiponectinemia is associated with ischemic cerebrovascular disease. Arterioscler. Thromb. Vasc. Biol. 25, 821–826.Google Scholar

  • Chen, K., Li, F., Li, J., Cai, H., Strom, S., Bisello, A., Kelley, D.E., Friedman-Einat, M., Skibinski, G.A., McCrory, M.A. (2006). Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat. Med. 12, 425–432.Google Scholar

  • Chen, B., Liao, W.Q., Xu, N., Xu., H., Wen, J.Y., Yu, C.A., Liu, X.Y., Li, C.L., Zhao, S.M., and Campbell, W. (2009). Adiponectin protects against cerebral ischemia-reperfusion injury through anti-inflammatory action. Brain Res. 1273, 129–137.Google Scholar

  • Cioffi, J.A., Shafer, A.W., Zupancic, T.J., Smith-Gbur, J., Mikhail, A., Platika, D., and Snodgrass, H.R. (1996). Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat. Med. 2, 585–589.Google Scholar

  • Clement, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.M., et al. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 392. 398–401.Google Scholar

  • Corsonello, A., Perticone, F., Malara, A., De Domenico, D., Loddo, S., Buemi, M., Ientile, R., and Corica, F. (2003). Leptin-dependent platelet aggregation in healthy, overweight and obese subjects. Int. J. Obes. Relat. Metab. Disord. 27, 566–573.Google Scholar

  • Deb, P., Sharma, S., and Hassan, K.M. (2010). Pathophysiologic mechanisms of acute ischemic stroke: an overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology 17, 197–218.Google Scholar

  • Dichgans, M. (2007). Genetics of ischaemic stroke. Lancet Neurol. 6, 149–161.Google Scholar

  • Fazeli, M., Zarkesh-Esfahani, H., Wu, Z., Maamra, M., Bidlingmaier, M., Pockley, A.G., Watson, P., Matarese, G., Strasburger, C.J., and Ross, R.J. (2006). Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation. J. Immunol. Methods 312, 190–200.Google Scholar

  • Feigin, V.L., Forouzanfar, M.H., Krishnamurthi, R., Mensah, G.A., Connor, M., Bennett, D.A., Moran, A.E., Sacco, R.L., Anderson, L., Truelsen, T., et al. (2014). Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study. Lancet 383, 245–254.Google Scholar

  • Fisman, E.Z. and Tenenbaum, A. (2014). Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc. Diabetol. 13, 103.Google Scholar

  • Friedman, J.M. (2009). Leptin at 14 y of age: an ongoing story. Am. J. Clin. Nutr. 89, 973S–979S.Google Scholar

  • Fruhbeck, G. (2006). Intracellular signalling pathways activated by leptin. Biochem. J. 393, 7–20.Google Scholar

  • Grunfeld, C., Zhao, C., Fuller, J., Pollack, A., Moser, A., Friedman, J., and. Feingold, K.R. (1996). Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J. Clin. Invest. 97, 2152–2157.Google Scholar

  • Gu, P. and Xu, A. (2013). Interplay between adipose tissue and blood vessels in obesity and vascular dysfunction. Rev. Endocr. Metab. Disord. 14, 49–58.Google Scholar

  • Hada, Y., Yamauchi, T., Waki, H., Tsuchida, A., Hara, K., Yago, H., Miyazaki, O., Ebinuma, H., and Kadowaki, T. (2007). Selective purification and characterization of adiponectin multimer species from human plasma. Biochem. Biophys. Res. Commun. 356, 487–493.Google Scholar

  • Hattori, Y., Nakano, Y., Hattori, S., Tomizawa, A., Inukai, K., and Kasai, K. (2008). High molecular weight adiponectin activates AMPK and suppresses cytokine-induced NF-kappaB activation in vascular endothelial cells. FEBS Lett. 582, 1719–1724.Google Scholar

  • Hribal, M.L., Fiorentino, T.V., and Sesti, G. (2014). Role of C reactive protein (CRP) in leptin resistance. Curr. Pharm. Des. 20, 609–615.Google Scholar

  • Hu, E., Liang, P., and Spiegelman, B.M. (1996). AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 271, 10697–10703.Google Scholar

  • Hukshorn, C.J. and Saris, W.H. (2004). Leptin and energy expenditure. Curr. Opin. Clin. Nutr. Metab. Care 7, 629–633.Google Scholar

  • Imagawa, K., Numata, Y., Katsuura, G., Sakaguchi, I., Morita, A., Kikuoka, S., Matumoto, Y., Tsuji, T., Tamaki, M., Sasakura, K., et al. (1998). Structure-function studies of human leptin. J. Biol. Chem. 273, 35245–35249.Google Scholar

  • Isse, N., Ogawa, Y., Tamura, N., Masuzaki, H., Mori, K., Okazaki, T., Satoh, N., Shigemoto, M., Yoshimasa, Y., Nishi S., et al. (1995). Structural organization and chromosomal assignment of the human obese gene. J. Biol. Chem. 270, 27728–27733.Google Scholar

  • Iwashima, Y., Katsuya, T., Ishikawa, K., Ouchi, N., Ohishi, M., Sugimoto, K., Fu, Y., Motone, M., Yamamoto, K., Matsuo, A., et al. (2004). Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 43, 1318–1323.Google Scholar

  • Jaleel, A., Aqil, S., Jaleel, S., and Jaleel, F. (2010). Adipocytokines in subjects with and without ischemic cerebrovascular disease. Acta Neurol. Belg. 110, 234–238.Google Scholar

  • Jin, R., Yang, G., and Li, G. (2010). Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J. Leukoc. Biol. 87, 779–789.Google Scholar

  • Juge-Aubry, C.E., Henrichot, E., and Meier, C.A. (2005). Adipose tissue: a regulator of inflammation. Best Pract. Res. Clin. Endocrinol. Metab. 19, 547–66.Google Scholar

  • Kadowaki, T. and Yamauchi, T. (2005). Adiponectin and adiponectin receptors. Endocr. Rev. 26, 439–451.Google Scholar

  • Kantorova, E., Chomova, M., Kurca, E., Sivak, S., Zelenak, K., Kucera, P., and Galajda, P. (2011). Leptin, adiponectin and ghrelin, new potential mediators of ischemic stroke. Neurol. Endocrinol. Lett. 32, 716–721.Google Scholar

  • Kantorová, E., Jesenská, Ľ., Čierny, D., Zeleňák, K., Sivák, S., Stančík, M., Galajda, P., Nosáľ, V., and Kurča, E. (2015). The intricate network of adipokines and stroke. Int. J. Endocrinol. 2015, 967698.Google Scholar

  • Kato, H., Kashiwagi, H., Shiraga, M., Tadokoro, S., Kamae, T., Ujiie, H., Honda, S., Miyata, S., Ijiri, Y., Yamamoto, J., et al. (2006). Adiponectin acts as an endogenous antithrombotic factor. Arterioscler. Thromb. Vasc. Biol. 26, 224–230.Google Scholar

  • Kershaw, E.E. and Flier, J.S. (2004). Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 89, 2548–2556.Google Scholar

  • Kielar, D., Clark, J.S., Ciechanowicz, A., Kurzawski, G., Sulikowski, T., and Naruszewicz, M. (1998). Leptin receptor isoforms expressed in human adipose tissue. Metabolism 47, 844–847.Google Scholar

  • Kim, B.J., Lee, S.H., Ryu, W.S., Kim, C.K., and Yoon, B.W. (2012). Adipocytokines and ischemic stroke: differential associations between stroke subtypes. J. Neurol. Sci. 312, 117–122.Google Scholar

  • Koh, K.K., Park., S.M., and Quon, M.J. (2008). Leptin and cardiovascular disease: response to therapeutic interventions. Circulation 117, 3238–3249.Google Scholar

  • Konstantinides, S., Schafer, K., Koschnick, S., and Loskutoff, D.J. (2001). Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J. Clin. Invest. 108, 1533–1540.Google Scholar

  • La Cava, A. and Matarese, G. (2004).The weight of leptin in immunity. Nat. Rev. Immunol. 4, 371–379.Google Scholar

  • Lago, F., Dieguez, C., Gómez-Reino, J., and Gualillo, O. (2007). Adipokines as emerging mediators of immune response and inflammation. Nat. Clin. Pract. Rheumatol. 3, 716–24.Google Scholar

  • Lakhan, S.E., Kirchgessner, A., and Hofer, M. (2009). Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J. Transl. Med. 7, 97.Google Scholar

  • Lam, Q.L. and Lu, L. (2007). Role of leptin in immunity. Cell. Mol. Immunol. 4, 1–13.Google Scholar

  • Lambertsen, K.L., Biber, K., and Finsen, B. (2012). Inflammatory cytokines in experimental and human stroke. J. Cereb. Blood. Flow. Metab. 32, 1677–1698.Google Scholar

  • Lee, C.H. and Hung, Y.J. (2015). Possible new therapeutic approach for obesity-related diseases: role of adiponectin receptor agonists. J. Diabetes Invest. 6, 264–66.Google Scholar

  • Lee, G.H., Proenca, R., Montez, J.M., Carroll, K.M., Darvishzadeh, J.G., Lee, J.I., and Friedman, J.M. (1996). Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632–635.Google Scholar

  • Libby, P. (2002). Inflammation in atherosclerosis. Nature 420, 868–74.Google Scholar

  • Liu, J. and Wang, L.N. (2014).Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack. Cochrane Database Syst. Rev. 1, CD010693.Google Scholar

  • Liu, J., Butler, K.R., Buxbaum, S.G., Sung, J.H., Campbell, B.W., and Taylor, H.A. (2010). Leptinemia and its association with stroke and coronary heart disease in the Jackson Heart Study. Clin. Endocrinol. (Oxf). 72, 32–37.Google Scholar

  • Lord, G.M., Matarese, G., Howard, J.K., Baker, R.J., Bloom, S.R., and Lechler, R.I. (1998). Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394, 897–901.Google Scholar

  • MacDougald, O.A. and Burant, C.F. (2007). The rapidly expanding family of adipokines. Cell Metab. 6, 159–161.Google Scholar

  • Margetic, S., Gazzola, C., Pegg, G.G., and Hill, R.A. (2002).Leptin: a review of its peripheral actions and interactions. Int. J. Obes. Relat. Metab. Disord. 26, 1407–1433.Google Scholar

  • Martin-Romero, C., Santos-Alvarez, J., Goberna, R., and Sanchez-Margalet, V. (2000). Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell. Immunol. 199, 15–24.Google Scholar

  • Matarese, G. (2000). Leptin and the immune system: how nutritional status influences the immune response. Eur. Cytokine Netw. 11, 7–14.Google Scholar

  • Matarese, G., Moschos, S., and Mantzoros, C.S. (2005). Leptin in Immunology. J. Immunol. 174, 3137–3142.Google Scholar

  • Matsubara, M., Maruoka, S., and Katayose, S. (2002). Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur. J. Endocrinol. 14, 173–180.Google Scholar

  • Matsumoto, M., Ishikawa, S., and Kajii, E. (2008). Association of adiponectin with cerebrovascular disease: a nested case-control study. Stroke 39, 323–328.Google Scholar

  • Mertens, I., Ballaux, D., Funahashi, T., Matsuzawa, Y., Van der Planken, M., Verrijken, A., Ruige, J.B., and Van Gaal, L.F. (2005). Inverse relationship between plasminogen activator inhibitor-I activity and adiponectin in overweight and obese women. Interrelationship with visceral adipose tissue, insulin resistance, HDL-chol and inflammation. Thromb. Haemost. 94, 1190–1195.Google Scholar

  • Nakamura, Y., Ueshima, H., Okuda, N., Miura, K., Kita, Y., Okamura, T., Okayama, A., Choudhury, S.R., Rodriguez, B., Masaki, K.H., et al. (2013). Relation of serum leptin and adiponectin level to serum c-reactive protein: the INTERLIPID Study. Int. J. Vasc. Med. 2013, 601364.Google Scholar

  • Nakata, M., Yada, T., Soejima, N., and Maruyama, I. (1999). Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes 48, 426–429.Google Scholar

  • Nakatsuji, H., Kobayashi, H., Kishida, K., Nakagawa, T., Takahashi, S., Tanaka, H., Akamatsu, S., Funahashi, T., and Shimomura, I. (2013). Binding of adiponectin and C1q in human serum, and clinical significance of the measurement of C1q-adiponectin/total adiponectin ratio. Metabolism 62, 109–120.Google Scholar

  • Nishimura, M., Izumiya, Y., Higuchi, A., Shibata, R., Qiu, J., Kudo, C., Shin, H.K., Moskowitz, M.A., and Ouchi, N. (2008). Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase dependent mechanisms. Circulation 117, 216–223.Google Scholar

  • Norata, G.D., Raselli, S., Grigore, L., Garlaschelli, K., Dozio, E., Magni, P., and Catapano, A.L. (2007). Leptin:adiponectin ratio is an independent predictor of intima media thickness of the common carotid artery. Stroke 38, 2844–2846.Google Scholar

  • Ogawa, Y., Masuzaki, H., Isse, N., Okazaki, T., Mori, K., Shigemoto, M., Satoh, N., Tamura, N., Hosoda, K., and Yoshimasa, Y. (1995). Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats. J. Clin. Invest. 96, 1647–1652.Google Scholar

  • Ohashi, K., Ouchi, N., and Matsuzawa, Y. (2012). Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie 94, 2137–2142.Google Scholar

  • Okada-Iwabu, M., Yamauchi, T., Iwabu, M., Honma, T., Hamagami, K., Matsuda, K., Yamaguchi, M., Tanabe, H., Kimura-Someya, T., Shirouzu, M., et al. (2013). A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 503, 493–499.Google Scholar

  • Ouchi, N. and Walsh, K. (2007). Adiponectin as an anti-inflammatory factor. Clin. Chim. Acta 380, 24–30.Google Scholar

  • Ouchi, N., Kihara, S., Arita, Y., Maeda, K., Kuriyama, H., Okamoto, Y., Hotta, K., Nishida, M., Takahashi, M., Nakamura, T., et al. (1999). Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100, 2473–2476.Google Scholar

  • Ouchi, N., Kihara, S., Arita, Y., Nishida, M., Matsuyama, A., Okamoto, Y., Ishigami, M., Kuriyama, H., Kishida, K., Nishizawa, H., et al. (2001). Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 103, 1057–1063.Google Scholar

  • Ouchi, N., Kihara, S., Funahashi, T., Nakamura, T., Nishida, M., Kumada, M., Okamoto, Y., Ohashi, K., Nagaretani, H., Kishida, K., et al. (2003). Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 107, 671–674.Google Scholar

  • Ouedraogo, R., Wu, X., Xu, S.Q., Fuchsel, L., Motoshima, H., Mahadev, K., Hough, K., Scalia, R., and Goldstein, B.J. (2006). Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. Diabetes 55, 1840–1846.Google Scholar

  • Pajvani, U.B., Du, X., Combs, T.P., Berg, A.H., Rajala, M.W., Schulthess, T., Engel, J., Brownlee, M., and Scherer, P.E. (2003). Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. J. Biol. Chem. 278, 9073–9085.Google Scholar

  • Procaccini, C., Jirillo, E., and Matarese, G. (2012). Leptin as an immunomodulator. Mol. Aspects Med. 33, 35–45.Google Scholar

  • Prugger, C., Luc, G., Haas, B., Arveiler, D., Machez, E., Ferrieres, J., Ruidavets, J.B., Bingham, A., Montaye, M., Amouyel, P., et al. (2012). Adipocytokines and the risk of ischemic stroke: the PRIME Study. Ann. Neurol. 71, 478–486.Google Scholar

  • Rajpathak, S.N., Kaplan, R.C., Wassertheil-Smoller, S., Cushman, M., Rohan, T.E., McGinn, A.P., Wang, T., Strickler, H.D., Scherer, P.E., Mackey, R., et al. (2011). Resistin, but not adiponectin and leptin, is associated with the risk of ischemic stroke among postmenopausal women: results from the Women’s Health Initiative. Stroke 42, 1813–1820.Google Scholar

  • Romero, JR., Morris, J., and Pikula, A. (2008). Stroke prevention: modifying risk factors. Ther. Adv. Cardiovasc. Dis. 2, 287–303.Google Scholar

  • Romero-Corral, A., Sierra-Johnson, J., Lopez-Jimenez, F., Thomas, R.J., Singh, P., Hoffmann, M., Okcay, A., Korinek, J., Wolk, R., and Somers, V.K. (2008). Relationships between leptin and C-reactive protein with cardiovascular disease in the adult general population. Nat. Clin. Pract. Cardiovasc. Med. 5, 418–425.Google Scholar

  • Rosamond, W., Flegal, K., Furie, K., Go, A., Greenlund, K., Haase, N., Hailpern, S.M., Ho, M., Howard, V., Kissela, B., et al., American Heart Association Statistics and S. Stroke Statistics. (2008). Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117, e25–e146.Google Scholar

  • Saito, K., Tobe, T., Minoshima, S., Asakawa, S., Sumiya, J., Yoda, M., Nakano, Y., Shimizu, N., and Tomita, M. (1999). Organization of the gene for gelatin-binding protein (GBP28). Gene 229, 67–73.Google Scholar

  • Sanchez-Margalet, V., Martin-Romero, C., Santos-Alvarez, J., Goberna, R., Najib, S., and Gonzalez-Yanes, C. (2003). Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action. Clin. Exp. Immunol. 133, 11–19.Google Scholar

  • Saxena, N.K., Sharma, D., Ding, X., Lin, S., Marra, F., Merlin, D., and Anania, F.A. (2007). Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res. 67, 2497–2507.Google Scholar

  • Scherer, P.E., Williams, S., Fogliano, M., Baldini, G., and Lodish, H.F. (1995). A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. 270, 26746–26749.Google Scholar

  • Schneiderman, J., Schaefer, K., Kolodgie, F.D., Savion, N., Kotev-Emeth, S., Dardik, R., Simon, A.J., Halak, M., Pariente, C., Engelberg, I., et al. (2012). Leptin locally synthesized in carotid atherosclerotic plaques could be associated with lesion instability and cerebral emboli. J. Am. Heart. Assoc. 1, e001727.Google Scholar

  • Shamsuzzaman, A.S., Winnicki, M., Wolk, R., Svatikova, A., Phillips, B.G., Davison, D.E., Berger, P.B., and Somers, V.K. (2004). Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 109, 2181–2185.Google Scholar

  • Shapiro, L. and Scherer, P.E. (1998). The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr. Biol. 8, 335–338.Google Scholar

  • Shibata, R., Murohara, T., and Ouchi, N. (2012). Protective role of adiponectin in cardiovascular disease. Curr. Med. Chem. 19, 5459–5466.Google Scholar

  • Shimada, K., Miyazaki, T., and Daida, H. (2004).Adiponectin and atherosclerotic disease. Clin. Chim. Acta 344, 1–12.Google Scholar

  • Siitonen, N., Pulkkinen, L., Lindstrom, J., Kolehmainen, M., Eriksson, J.G., Venojarvi, M., Ilanne-Parikka, P., Keinanen-Kiukaanniemi, S., Tuomilehto, J., and Uusitupa, M. (2011). Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study. BMC Med. Genet. 12, 5.Google Scholar

  • Singh, P., Hoffmann, M., Wolk, R., Shamsuzzaman, A.S., and Somers, V.K. (2007). Leptin induces C-reactive protein expression in vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol. 27, e302–e307.Google Scholar

  • Soderberg, S., Ahren, B., Stegmayr, B., Johnson, O., Wiklund, P.G., Weinehall, L., Hallmans, G., and Olsson, T. (1999). Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke 30, 328–337.Google Scholar

  • Soderberg, S., Stegmayr, B., Ahlbeck-Glader, C., Slunga-Birgander, L., Ahren, B., and Olsson, T. (2003). High leptin levels are associated with stroke. Cerebrovasc. Dis. 15, 63–69.Google Scholar

  • Soderberg, S., Stegmayr, B., Stenlund, H., Sjostrom, L.G., Agren, A., Johansson, L., Weinehall, L., and Olsson, T. (2004). Leptin, but not adiponectin, predicts stroke in males. J. Intern. Med. 256, 128–136.Google Scholar

  • Stott, D.J., Welsh, P., Rumley, A., Robertson, M., Ford, I., Sattar, N., Westendorp, R.G., Jukema, J.W., Cobbe, S.M., and Lowe, G.D. (2009). Adipocytokines and risk of stroke in older people: a nested case-control study. Int. J. Epidemiol. 38, 253–261.Google Scholar

  • Stumvoll, M., Tschritter, O., Fritsche, A., Staiger, H., Renn, W., Weisser, M., Machicao, F., and Haring, H. (2002). Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 51, 37–41.Google Scholar

  • Suk, S.H., Sacco, R.L., Boden-Albala, B., Cheun, J.F., Pittman, J.G., Elkind, M.S., Paik, M.C., and S. Northern Manhattan Stroke. (2003). Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study. Stroke 34, 1586–1592.Google Scholar

  • Sweeney, G. (2010). Cardiovascular effects of leptin. Nat. Rev. Cardiol. 7, 22–29.Google Scholar

  • Takahashi, M., Arita, Y., Yamagata, K., Matsukawa, Y., Okutomi, K., Horie, M., Shimomura, I., Hotta, K., Kuriyama, H., Kihara, S., et al. (2000). Genomic structure and mutations in adipose-specific gene, adiponectin. Int. J. Obes. Relat. Metab. Disord. 24, 861–868.Google Scholar

  • Tartaglia, L.A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G.J., Campfield, L.A., Clark, F.T., Deeds, J., et al. (1995). Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 1263–1271.Google Scholar

  • Tian, L., Luo, N., Klein, R.L., Chung, B.H., Garvey, W.T., and Fu, Y. (2009). Adiponectin reduces lipid accumulation in macrophage foam cells. Atherosclerosis 202, 152–161.Google Scholar

  • Vaisse, C., Halaas, J.L., Horvath, C.M., Darnell, J.E., Jr., Stoffel, M., and Friedman, J.M. (1996). Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat. Genet. 14, 95–97.Google Scholar

  • Van Gaal, L.F., Mertens, I.L., and De Block, C.E. (2006). Mechanisms linking obesity with cardiovascular disease. Nature 444, 875–880.Google Scholar

  • Wannamethee, S.G., Shaper, A.G., Whincup, P.H., Lennon, L., and Sattar, N. (2013). Adiposity, adipokines, and risk of incident stroke in older men. Stroke 44, 3–8.Google Scholar

  • Wong, G.W., Wang, J., Hug, C., Tsao, T.S., and Lodish, H.F. (2004). A family of Acrp30/adiponectin structural and functional paralogs. Proc. Natl. Acad. Sci. USA 101, 10302–10307.Google Scholar

  • Wozniak, S.E., Gee, L.L., Wachtel, M.S., and Frezza, E.E. (2009). Adipose tissue: the new endocrine organ? A review article. Digest. Dis. Sci. 54, 1847–1856.Google Scholar

  • Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001). The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7, 941–946.Google Scholar

  • Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002). Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 8, 1288–1295.Google Scholar

  • Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., et al. (2003). Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423, 762–769.Google Scholar

  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J.M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.Google Scholar

  • Zhu, W., Cheng, K.K., Vanhoutte, P.M., Lam, K.S., and Xu, A. (2008). Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin. Sci. (Lond). 114, 361–374.Google Scholar

About the article

Jitender Gairolla

Jitender Gairolla is pursuing his PhD in the Department of Neurology, PGIMER, Chandigarh, India and his research work is focused on genetic variation analysis of adipokine genes in ischemic stroke patients with extracranial and intracranial atherosclerotic disease. His other areas of interest are biomarker and antiplatelet drug discovery in the field of stroke.

Rupinder Kler

Rupinder Kler received her PhD in basic medical sciences from Panjab University. Currently working as research consultant in Department of Neurology, PGIMER Chandigarh, India. Her areas of interest are pharmacogenomics and stem cell therapy for neurological disorders.

Manish Modi

Manish Modi is currently working as Additional Professor in the Department of Neurology, Post graduate Institute of Medical Education & Research, Chandigarh, India. His areas of interest are Tropical Neurology, especially CNS infections and has many original research papers in Tuberculous meningitis, Neurocysticercosis, Japanese encephalitis, HIV, etc.

Dheeraj Khurana

Dheeraj Khurana is in charge of the stroke program and Professor of Neurology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. His areas of interest are acute stroke management, thrombolysis and intracranial atherosclerotic disease. He has been actively involved in research on carotid atherosclerotic disease, antiplatelet resistance and intracerebral hemorrhages. Currently he is the President of the Indian stroke association and vice president of World NCD federation.


Received: 2016-09-02

Accepted: 2016-11-30

Published Online: 2017-01-25

Published in Print: 2017-04-01


Conflict of interest statement: None of the authors declare any conflict of interest.


Citation Information: Reviews in the Neurosciences, Volume 28, Issue 3, Pages 295–306, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2016-0055.

Export Citation

©2017 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Chi-Hung Liu, Tsong-Hai Lee, Yu-Sheng Lin, Pi-Shan Sung, Yi-Chia Wei, and Yan-Rong Li
Cardiovascular Diabetology, 2020, Volume 19, Number 1
[2]
Hanlai Zhang, Yanwei Xing, Jingling Chang, Liqin Wang, Na An, Chao Tian, Mengchen Yuan, Xinyu Yang, Hongcai Shang, Ying Gao, and Yonghong Gao
Frontiers in Pharmacology, 2019, Volume 10
[3]
Zengliang Wang, Bo Li, Yongxin Wang, Aisha Maimaitili, Hu Qin, Geng Dangmurenjiafu, and Shuo Wang
Cardiovascular Diabetology, 2019, Volume 18, Number 1
[4]
Xiaobo Hu, Cong Hu, Caiping Zhang, Min Zhang, Shiyin Long, and Zhaohui Cao
International braz j urol, 2019, Volume 45, Number 2, Page 220
[5]
Giancarlo Ceccarelli, Claudia Pinacchio, Letizia Santinelli, Paolo Emilio Adami, Cristian Borrazzo, Eugenio Nelson Cavallari, Annamaria Vullo, Giuseppe Pietro Innocenti, Ivano Mezzaroma, Claudio Maria Mastroianni, and Gabriella d’Ettorre
AIDS and Behavior, 2019
[6]
Nevin Ilhan, Solmaz Susam, Omer Canpolat, and Oktay Belhan
British Journal of Neurosurgery, 2019, Page 1
[7]
Guoyi Liu, Minna Dong, Shu Ma, Liyan Fu, Yun Xiao, Lianmei Zhong, and Jia Geng
Neurological Research, 2018, Page 1
[8]
Yan-yan Zhu, Jian-long Zhang, Li Liu, Yingbo Han, Xiaomin Ge, and Shuai Zhao
Bioscience Reports, 2018, Volume 38, Number 5, Page BSR20180786
[9]
Amparo Luque-Sierra, Leticia Alvarez-Amor, Robert Kleemann, Franz Martín, and Lourdes M. Varela
Molecular Nutrition & Food Research, 2018, Page 1800295
[10]
Niki Katsiki, Dimitri P Mikhailidis, and Maciej Banach
Acta Pharmacologica Sinica, 2018
[11]
Niki Katsiki, Christos Mantzoros, and Dimitri P. Mikhailidis
Current Opinion in Lipidology, 2017, Volume 28, Number 4, Page 347

Comments (0)

Please log in or register to comment.
Log in