Skip to main content

Advertisement

SpringerLink
Log in

ICH3, a selective alpha7 nicotinic acetylcholine receptor agonist, modulates adipocyte inflammation associated with obesity

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

The alpha7 nicotinic acetylcholine receptor (α7nAChR), involved in the modulation of inflammation and insulin sensitivity, is downregulated in white adipose tissue (WAT) of obese patients. This study aims to test the ability of a selective synthetic α7nAChR agonist, the spirocyclic Δ2-isoxazoline derivative (R)-(−)-ICH3 (ICH3), to counteract acute inflammation and obesity-associated modifications in WAT.

Methods

We employed the LPS-septic shock murine model, human primary adipocytes and diet-induced obese (DIO) mice. Inflammatory factor expression was assessed by ELISA and quantitative real-time PCR. Flow cytometry was employed to define WAT inflammatory infiltrate. Insulin signaling was monitored by quantification of AKT phosphorylation.

Results

In the septic shock model, ICH3 revealed antipyretic action and reduced the surge of circulating cytokines. In vitro, ICH3 stimulation (10 µM) preserved viability of human adipocytes, decreased IL-6 mRNA (P < 0.05) and blunted LPS-induced peak of TNFα (P < 0.05) and IL-6 (P < 0.01). Chronic administration of ICH3 to DIO mice was associated with lower numbers of CD8+ T cells (P < 0.05) and to changed WAT expression of inflammatory factors (Hp, P < 0.05; CD301/MGL1, P < 0.01; Arg-1, P < 0.05). As compared to untreated, ICH3 DIO mice exhibited improved insulin signaling in the skeletal muscle (P < 0.01) mirrored by an improved response to glucose load (ipGTT: P < 0.05 at 120 min).

Conclusions

We proved that ICH3 is an anti-inflammatory drug, able to reduce inflammatory cytokines in human adipocytes and to blunt the effects of obesity on WAT inflammatory profile, on glucose tolerance and on tissue insulin sensitivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Beckmann J, Lips KS (2013) The non-neuronal cholinergic system in health and disease. Pharmacology 92(5–6):286–302. https://doi.org/10.1159/000355835

    Article  CAS  PubMed  Google Scholar 

  2. de Jonge WJ, Ulloa L (2007) The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 151(7):915–929. https://doi.org/10.1038/sj.bjp.0707264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sharma G, Vijayaraghavan S (2008) Nicotinic receptors containing the alpha7 subunit: a model for rational drug design. Curr Med Chem 15(28):2921–2932

    Article  CAS  Google Scholar 

  4. Tracey KJ (2007) Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Investig 117(2):289–296. https://doi.org/10.1172/JCI30555

    Article  CAS  PubMed  Google Scholar 

  5. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421(6921):384–388. https://doi.org/10.1038/nature01339

    Article  CAS  PubMed  Google Scholar 

  6. Bray GA (2006) Obesity: the disease. J Med Chem 49(14):4001–4007. https://doi.org/10.1021/jm0680124

    Article  CAS  PubMed  Google Scholar 

  7. Chiellini C, Santini F, Marsili A, Berti P, Bertacca A, Pelosini C, Scartabelli G, Pardini E, Lopez-Soriano J, Centoni R, Ciccarone AM, Benzi L, Vitti P, Del Prato S, Pinchera A, Maffei M (2004) Serum haptoglobin: a novel marker of adiposity in humans. J Clin Endocrinol Metab 89(6):2678–2683. https://doi.org/10.1210/jc.2003-031965

    Article  CAS  PubMed  Google Scholar 

  8. Giovannini S, Onder G, Liperoti R, Russo A, Carter C, Capoluongo E, Pahor M, Bernabei R, Landi F (2011) Interleukin-6, C-reactive protein, and tumor necrosis factor-alpha as predictors of mortality in frail, community-living elderly individuals. J Am Geriatr Soc 59(9):1679–1685. https://doi.org/10.1111/j.1532-5415.2011.03570.x

    Article  PubMed  PubMed Central  Google Scholar 

  9. Maffei M, Barone I, Scabia G, Santini F (2016) The multifaceted haptoglobin in the context of adipose tissue and metabolism. Endocr Rev 37(4):403–416. https://doi.org/10.1210/er.2016-1009

    Article  CAS  PubMed  Google Scholar 

  10. Cancello R, Zulian A, Maestrini S, Mencarelli M, Della Barba A, Invitti C, Liuzzi A, Di Blasio AM (2012) The nicotinic acetylcholine receptor alpha7 in subcutaneous mature adipocytes: downregulation in human obesity and modulation by diet-induced weight loss. Int J Obes (Lond) 36(12):1552–1557. https://doi.org/10.1038/ijo.2011.275

    Article  CAS  Google Scholar 

  11. Dallanoce C, Frigerio F, Martelli G, Grazioso G, Matera C, Pome DY, Pucci L, Clementi F, Gotti C, De Amici M (2010) Novel tricyclic Delta(2)-isoxazoline and 3-oxo-2-methyl-isoxazolidine derivatives: synthesis and binding affinity at neuronal nicotinic acetylcholine receptor subtypes. Bioorg Med Chem 18(12):4498–4508. https://doi.org/10.1016/j.bmc.2010.04.065

    Article  CAS  PubMed  Google Scholar 

  12. Dallanoce C, Matera C, Pucci L, Gotti C, Clementi F, Amici MD, Micheli CD (2012) Synthesis and binding affinity at alpha4beta2 and alpha7 nicotinic acetylcholine receptors of new analogs of epibatidine and epiboxidine containing the 7-azabicyclo[2.2.1]hept-2-ene ring system. Bioorg Med Chem Lett 22(2):829–832. doi: 10.1016/j.bmcl.2011.12.052

  13. Grazioso G, Pome DY, Matera C, Frigerio F, Pucci L, Gotti C, Dallanoce C, De Amici M (2009) Design of novel alpha7-subtype-preferring nicotinic acetylcholine receptor agonists: application of docking and MM-PBSA computational approaches, synthetic and pharmacological studies. Bioorg Med Chem Lett 19(22):6353–6357. https://doi.org/10.1016/j.bmcl.2009.09.073

    Article  CAS  PubMed  Google Scholar 

  14. Matera C, Quadri M, Sciaccaluga M, Pome DY, Fasoli F, De Amici M, Fucile S, Gotti C, Dallanoce C, Grazioso G (2016) Modification of the anabaseine pyridine nucleus allows achieving binding and functional selectivity for the alpha3beta4 nicotinic acetylcholine receptor subtype. Eur J Med Chem 108:392–405. https://doi.org/10.1016/j.ejmech.2015.11.045

    Article  CAS  PubMed  Google Scholar 

  15. Quadri M, Matera C, Silnovic A, Pismataro MC, Horenstein NA, Stokes C, Papke RL, Dallanoce C (2017) Identification of alpha7 nicotinic acetylcholine receptor silent agonists based on the spirocyclic quinuclidine-delta(2)-isoxazoline scaffold: synthesis and electrophysiological evaluation. ChemMedChem 12(16):1335–1348. https://doi.org/10.1002/cmdc.201700162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dallanoce C, Magrone P, Matera C, Frigerio F, Grazioso G, De Amici M, Fucile S, Piccari V, Frydenvang K, Pucci L, Gotti C, Clementi F, De Micheli C (2011) Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2-isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors. ChemMedChem 6(5):889–903. https://doi.org/10.1002/cmdc.201000514

    Article  CAS  PubMed  Google Scholar 

  17. Matera C, Dondio G, Braida D, Ponzoni L, De Amici M, Sala M, Dallanoce C (2018) In vivo and in vitro ADMET profiling and in vivo pharmacodynamic investigations of a selective alpha7 nicotinic acetylcholine receptor agonist with a spirocyclic Delta(2)-isoxazoline molecular skeleton. Eur J Pharmacol 820:265–273. https://doi.org/10.1016/j.ejphar.2017.12.047

    Article  CAS  PubMed  Google Scholar 

  18. Di Cesare ML, Pacini A, Matera C, Zanardelli M, Mello T, De Amici M, Dallanoce C, Ghelardini C (2014) Involvement of alpha7 nAChR subtype in rat oxaliplatin-induced neuropathy: effects of selective activation. Neuropharmacology 79:37–48. https://doi.org/10.1016/j.neuropharm.2013.10.034

    Article  CAS  Google Scholar 

  19. Cerri C, Genovesi S, Allegra M, Pistillo F, Puntener U, Guglielmotti A, Perry VH, Bozzi Y, Caleo M (2016) The chemokine CCL2 mediates the seizure-enhancing effects of systemic inflammation. J Neurosci 36(13):3777–3788. https://doi.org/10.1523/JNEUROSCI.0451-15.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hagberg CE, Li Q, Kutschke M, Bhowmick D, Kiss E, Shabalina IG, Harms MJ, Shilkova O, Kozina V, Nedergaard J, Boucher J, Thorell A, Spalding KL (2018) Flow cytometry of mouse and human adipocytes for the analysis of browning and cellular heterogeneity. Cell Rep 24(10):2746–2756 e2745. doi: 10.1016/j.celrep.2018.08.006

  21. Berger S, Ceccarini G, Scabia G, Barone I, Pelosini C, Ferrari F, Magno S, Dattilo A, Chiovato L, Vitti P, Santini F, Maffei M (2017) Lipodystrophy and obesity are associated with decreased number of T cells with regulatory function and pro-inflammatory macrophage phenotype. Int J Obes (Lond) 41(11):1676–1684. https://doi.org/10.1038/ijo.2017.163

    Article  CAS  Google Scholar 

  22. Lisi S, Gamucci O, Vottari T, Scabia G, Funicello M, Marchi M, Galli G, Arisi I, Brandi R, D'Onofrio M, Pinchera A, Santini F, Maffei M (2011) Obesity-associated hepatosteatosis and impairment of glucose homeostasis are attenuated by haptoglobin deficiency. Diabetes 60(10):2496–2505. https://doi.org/10.2337/db10-1536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lawrence CB, Brough D, Knight EM (2012) Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide. Dis Models Mech 5(5):649–659. https://doi.org/10.1242/dmm.009068

    Article  CAS  Google Scholar 

  24. Chatzigeorgiou A, Karalis KP, Bornstein SR, Chavakis T (2012) Lymphocytes in obesity-related adipose tissue inflammation. Diabetologia 55(10):2583–2592. https://doi.org/10.1007/s00125-012-2607-0

    Article  CAS  PubMed  Google Scholar 

  25. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15(8):914–920. https://doi.org/10.1038/nm.1964

    Article  CAS  Google Scholar 

  26. Travers RL, Motta AC, Betts JA, Bouloumie A, Thompson D (2015) The impact of adiposity on adipose tissue-resident lymphocyte activation in humans. Int J Obes (Lond) 39(5):762–769. https://doi.org/10.1038/ijo.2014.195

    Article  CAS  Google Scholar 

  27. Marrero MB, Lucas R, Salet C, Hauser TA, Mazurov A, Lippiello PM, Bencherif M (2010) An alpha7 nicotinic acetylcholine receptor-selective agonist reduces weight gain and metabolic changes in a mouse model of diabetes. J Pharmacol Exp Therap 332(1):173–180. https://doi.org/10.1124/jpet.109.154633

    Article  CAS  Google Scholar 

  28. McFadden KL, Cornier MA, Tregellas JR (2014) The role of alpha-7 nicotinic receptors in food intake behaviors. Front Psychol 5:553. https://doi.org/10.3389/fpsyg.2014.00553

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mirrasekhian E, Nilsson JLA, Shionoya K, Blomgren A, Zygmunt PM, Engblom D, Hogestatt ED, Blomqvist A (2018) The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1-mediated hypothermia and is associated with prostaglandin inhibition in the brain. FASEB J 32(10):5751–5759. https://doi.org/10.1096/fj.201800272R

    Article  CAS  PubMed  Google Scholar 

  30. Pinheiro NM, Santana FP, Almeida RR, Guerreiro M, Martins MA, Caperuto LC, Camara NO, Wensing LA, Prado VF, Tiberio IF, Prado MA, Prado CM (2017) Acute lung injury is reduced by the alpha7nAChR agonist PNU-282987 through changes in the macrophage profile. FASEB J 31(1):320–332. https://doi.org/10.1096/fj.201600431R

    Article  CAS  PubMed  Google Scholar 

  31. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405(6785):458–462. https://doi.org/10.1038/35013070

    Article  CAS  PubMed  Google Scholar 

  32. Saeed RW, Varma S, Peng-Nemeroff T, Sherry B, Balakhaneh D, Huston J, Tracey KJ, Al-Abed Y, Metz CN (2005) Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med 201(7):1113–1123. https://doi.org/10.1084/jem.20040463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hajer GR, van Haeften TW, Visseren FL (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29(24):2959–2971. https://doi.org/10.1093/eurheartj/ehn387

    Article  CAS  PubMed  Google Scholar 

  34. Rodriguez-Hernandez H, Simental-Mendia LE, Rodriguez-Ramirez G, Reyes-Romero MA (2013) Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. Int J Endocrinol 2013:678159. https://doi.org/10.1155/2013/678159

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ubags ND, Stapleton RD, Vernooy JH, Burg E, Bement J, Hayes CM, Ventrone S, Zabeau L, Tavernier J, Poynter ME, Parsons PE, Dixon AE, Wargo MJ, Littenberg B, Wouters EF, Suratt BT (2016) Hyperleptinemia is associated with impaired pulmonary host defense. JCI Insight 1(8). doi: 10.1172/jci.insight.82101

  36. Huang CJ, Stewart JK, Shibata Y, Slusher AL, Acevedo EO (2015) Lipopolysaccharide-binding protein and leptin are associated with stress-induced interleukin-6 cytokine expression ex vivo in obesity. Psychophysiology 52(5):687–694. https://doi.org/10.1111/psyp.12387

    Article  PubMed  Google Scholar 

  37. Harris RB, Mitchell TD, Yan X, Simpson JS, Redmann SM Jr (2001) Metabolic responses to leptin in obese db/db mice are strain dependent. Am J Physiol Regul Integr Comp Physiol 281(1):R115–132. https://doi.org/10.1152/ajpregu.2001.281.1.R115

    Article  CAS  PubMed  Google Scholar 

  38. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91

    Article  CAS  Google Scholar 

  39. Sharma K, McCue P, Dunn SR (2003) Diabetic kidney disease in the db/db mouse. Am J Physiol Renal Physiol 284(6):F1138–1144. https://doi.org/10.1152/ajprenal.00315.2002

    Article  CAS  PubMed  Google Scholar 

  40. Aydin S, Aksoy A, Aydin S, Kalayci M, Yilmaz M, Kuloglu T, Citil C, Catak Z (2014) Today's and yesterday's of pathophysiology: biochemistry of metabolic syndrome and animal models. Nutrition 30(1):1–9. https://doi.org/10.1016/j.nut.2013.05.013

    Article  CAS  PubMed  Google Scholar 

  41. Panchal SK, Brown L (2011) Rodent models for metabolic syndrome research. J Biomed Biotechnol 2011:351982. https://doi.org/10.1155/2011/351982

    Article  PubMed  Google Scholar 

  42. Masoodi M, Kuda O, Rossmeisl M, Flachs P (1851) Kopecky J (2015) Lipid signaling in adipose tissue: connecting inflammation and metabolism. Biochem Biophys Acta 4:503–518. https://doi.org/10.1016/j.bbalip.2014.09.023

    Article  CAS  Google Scholar 

  43. Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol 28:445–489. https://doi.org/10.1146/annurev-immunol-030409-101212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. do Nascimento CO, Hunter L, Trayhurn P (2004) Regulation of haptoglobin gene expression in 3T3-L1 adipocytes by cytokines, catecholamines, and PPARgamma. Biochem Biophys Res Commun 313(3):702–708. https://doi.org/10.1016/j.bbrc.2003.12.008

    Article  CAS  PubMed  Google Scholar 

  45. Maffei M, Funicello M, Vottari T, Gamucci O, Costa M, Lisi S, Viegi A, Ciampi O, Bardi G, Vitti P, Pinchera A, Santini F (2009) The obesity and inflammatory marker haptoglobin attracts monocytes via interaction with chemokine (C-C motif) receptor 2 (CCR2). BMC Biol 7:87. https://doi.org/10.1186/1741-7007-7-87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lamacchia C, Palmer G, Bischoff L, Rodriguez E, Talabot-Ayer D, Gabay C (2010) Distinct roles of hepatocyte- and myeloid cell-derived IL-1 receptor antagonist during endotoxemia and sterile inflammation in mice. J Immunol 185(4):2516–2524. https://doi.org/10.4049/jimmunol.1000872

    Article  CAS  PubMed  Google Scholar 

  47. Lee YS, Li P, Huh JY, Hwang IJ, Lu M, Kim JI, Ham M, Talukdar S, Chen A, Lu WJ, Bandyopadhyay GK, Schwendener R, Olefsky J, Kim JB (2011) Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance. Diabetes 60(10):2474–2483. https://doi.org/10.2337/db11-0194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chung JH, Moon J, Lee YS, Chung HK, Lee SM, Shin MJ (2014) Arginase inhibition restores endothelial function in diet-induced obesity. Biochem Biophys Res Commun 451(2):179–183. https://doi.org/10.1016/j.bbrc.2014.07.083

    Article  CAS  PubMed  Google Scholar 

  49. Hu H, Moon J, Chung JH, Kim OY, Yu R, Shin MJ (2015) Arginase inhibition ameliorates adipose tissue inflammation in mice with diet-induced obesity. Biochem Biophys Res Commun 464(3):840–847. https://doi.org/10.1016/j.bbrc.2015.07.048

    Article  CAS  PubMed  Google Scholar 

  50. Moon J, Do HJ, Cho Y, Shin MJ (2014) Arginase inhibition ameliorates hepatic metabolic abnormalities in obese mice. PLoS ONE 9(7):e103048. https://doi.org/10.1371/journal.pone.0103048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Westcott DJ, Delproposto JB, Geletka LM, Wang T, Singer K, Saltiel AR, Lumeng CN (2009) MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206(13):3143–3156. https://doi.org/10.1084/jem.20091333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research has received funding from the European Community's Seventh Framework Programme [FP7/2007–2013] under Grant agreement no. 291778 (DTI-IMPORT).

Author information

Author notes

  1. G. Scabia, R. Cancello and C. Dallanoce have contributed equally to this work.

Authors and Affiliations

  1. CNR Institute of Clinical Physiology, Pisa, Italy

    G. Scabia & M. Maffei

  2. Obesity and Lipodystrophy Center at Endocrinology Unit, University Hospital of Pisa, Pisa, Italy

    G. Scabia, S. Berger, A. Dattilo, I. Barone, G. Ceccarini, F. Santini & M. Maffei

  3. Laboratorio di Ricerche Sull’Obesità, Istituto Auxologico Italiano, IRCCS, Milan, Italy

    R. Cancello & A. Zulian

  4. Department of Pharmaceuticals Sciences, University of Milano, Milan, Italy

    C. Dallanoce, C. Matera & M. De Amici

  5. Dulbecco Telethon Institute, Pisa, Italy

    S. Berger

  6. Life Science Institute, Scuola Superiore Sant’Anna, Pisa, Italy

    A. Dattilo

  7. Laboratorio di Ricerche di Biologia Molecolare, Istituto Auxologico Italiano, IRCCS, Milan, Italy

    A. M. Di Blasio

Authors
  1. G. Scabia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Cancello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Dallanoce
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Matera
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Dattilo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Zulian
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. I. Barone
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. Ceccarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F. Santini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M. De Amici
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A. M. Di Blasio
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M. Maffei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GS, RC, SB, AD, AZ, IB, and GC performed the experiments in vitro and in vivo; CD and CM synthesized the compound, GS, SB, and FS analyzed the data, GS, RC, SB, MDA, ADB, and MM conceived the experimental design. GS, RC, and MM wrote the paper.

Corresponding authors

Correspondence to A. M. Di Blasio or M. Maffei.

Ethics declarations

Conflict of interest

The authors have nothing to disclose.

Ethical approval

This study was approved by the Ethical Committee of IRCCS-Istituto Auxologico Italiano, and signed informed consent was obtained for adipose tissue sampling during surgery. All animal care protocols and procedures were approved by the Italian Ministry of Health (protocol 108/2015-PR) and all experiments performed in accordance with relevant guidelines and regulations.

Informed consent

All participants provided their informed consent prior to their participation.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 32 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scabia, G., Cancello, R., Dallanoce, C. et al. ICH3, a selective alpha7 nicotinic acetylcholine receptor agonist, modulates adipocyte inflammation associated with obesity. J Endocrinol Invest 43, 983–993 (2020). https://doi.org/10.1007/s40618-020-01182-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-020-01182-z

Keywords

Search

Navigation