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Bariatric Surgery

Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes

International Journal of Obesity volume 44, pages 178–185 (2020)Cite this article

Subjects

Abstract

Background/Objectives

Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB).

Subjects/Methods

Fifty-five subjects (all female) including lean controls (CT; n = 13), ND (n = 28), and T2D (n = 14) completed at least one study visit. Subjects underwent anthropometrics and a multi-echo MRI sequence to measure mean bilateral T2 relaxation time in the mediobasal hypothalamus (MBH) and two reference regions (amygdala and putamen). The obese groups underwent RYGB and were re-evaluated 9 months later. Analyses were by linear mixed models.

Results

Analyses of T2 relaxation time at baseline showed a group by region interaction only in the MBH (P < 0.0001). T2D had longer T2 relaxation times compared to either CT or ND groups. To examine the effects of RYGB on hypothalamic gliosis a three-way (group by region by time) mixed effects model adjusted for age was executed. Group by region (P < 0.0001) and region by time (P = 0.0005) interactions were significant. There was a reduction in MBH relaxation time by RYGB, and, although the T2D group still had higher T2 relaxation time overall compared to the ND group, the T2D group had significantly lower T2 relaxation time after surgery and the ND group showed a trend. The degree of reduction in MBH T2 relaxation time by RYGB was unrelated to clinical outcomes.

Conclusion

T2 relaxation times, a marker of hypothalamic gliosis, are higher in obese women with T2D and are reduced by RYGB-induced weight loss.

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References

  1. Morton GJ, Meek TH, Schwartz MW. Neurobiology of food intake in health and disease. Nat Rev Neurosci. 2014;15:367–78.

    Article  CAS  Google Scholar 

  2. Velloso LA, Schwartz MW. Altered hypothalamic function in diet-induced obesity. Int J Obes. 2011;35:1455–65.

    Article  CAS  Google Scholar 

  3. van de Sande-Lee S, Velloso LA. Hypothalamic dysfunction in obesity. Arq Bras Endocrinol Metabol. 2012;56:341–50.

    Article  Google Scholar 

  4. Moraes JC, Coope A, Morari J, Cintra DE, Roman EA, Pauli JR, et al. High-fat diet induces apoptosis of hypothalamic neurons. PLoS ONE. 2009;4:e5045.

    Article  Google Scholar 

  5. Morari J, Anhe GF, Nascimento LF, de Moura RF, Razolli D, Solon C, et al. Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity. Diabetes. 2014;63:3770–84.

    Article  CAS  Google Scholar 

  6. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122:153–62.

    Article  CAS  Google Scholar 

  7. Valdearcos M, Robblee MM, Benjamin DI, Nomura DK, Xu AW, Koliwad SK. Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep. 2014;9:2124–38.

    Article  CAS  Google Scholar 

  8. Matsuda M, Liu Y, Mahankali S, Pu Y, Mahankali A, Wang J, et al. Altered hypothalamic function in response to glucose ingestion in obese humans. Diabetes. 1999;48:1801–6.

    Article  CAS  Google Scholar 

  9. Vidarsdottir S, Smeets PA, Eichelsheim DL, van Osch MJ, Viergever MA, Romijn JA, et al. Glucose ingestion fails to inhibit hypothalamic neuronal activity in patients with type 2 diabetes. Diabetes. 2007;56:2547–50.

    Article  CAS  Google Scholar 

  10. van de Sande-Lee S, Pereira FR, Cintra DE, Fernandes PT, Cardoso AR, Garlipp CR, et al. Partial reversibility of hypothalamic dysfunction and changes in brain activity after body mass reduction in obese subjects. Diabetes. 2011;60:1699–704.

    Article  Google Scholar 

  11. Rachid B, van de Sande-Lee S, Rodovalho S, Folli F, Beltramini GC, Morari J, et al. Distinct regulation of hypothalamic and brown/beige adipose tissue activities in human obesity. Int J Obes. 2015;39:1515–22.

    Article  CAS  Google Scholar 

  12. Kreutzer C, Peters S, Schulte DM, Fangmann D, Turk K, Wolff S, et al. Hypothalamic inflammation in human obesity is mediated by environmental and genetic factors. Diabetes. 2017;66:2407–15.

    Article  CAS  Google Scholar 

  13. Berkseth KE, Guyenet SJ, Melhorn SJ, Lee D, Thaler JP, Schur EA, et al. Hypothalamic gliosis associated with high-fat diet feeding is reversible in mice: a combined immunohistochemical and magnetic resonance imaging study. Endocrinology. 2014;155:2858–67.

    Article  Google Scholar 

  14. Samocha-Bonet D, Dixit VD, Kahn CR, Leibel RL, Lin X, Nieuwdorp M, et al. Metabolically healthy and unhealthy obese—the 2013 Stock Conference report. Obes Rev. 2014;15:697–708.

    Article  CAS  Google Scholar 

  15. Souza GF, Solon C, Nascimento LF, De-Lima-Junior JC, Nogueira G, Moura R, et al. Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity. Sci Rep. 2016;6:29290.

    Article  CAS  Google Scholar 

  16. Schur EA, Melhorn SJ, Oh SK, Lacy JM, Berkseth KE, Guyenet SJ, et al. Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans. Obesity. 2015;23:2142–8.

    Article  CAS  Google Scholar 

  17. Lee D, Thaler JP, Berkseth KE, Melhorn SJ, Schwartz MW, Schur EA. Longer T(2) relaxation time is a marker of hypothalamic gliosis in mice with diet-induced obesity. Am J Physiol Endocrinol Metab. 2013;304:E1245–50.

    Article  CAS  Google Scholar 

  18. Hasan KM, Walimuni IS, Abid H, Frye RE, Ewing-Cobbs L, Wolinsky JS, et al. Multimodal quantitative magnetic resonance imaging of thalamic development and aging across the human lifespan: implications to neurodegeneration in multiple sclerosis. J Neurosci. 2011;31:16826–32.

    Article  CAS  Google Scholar 

  19. Tuulari JJ, Karlsson HK, Antikainen O, Hirvonen J, Pham T, Salminen P, et al. Bariatric surgery induces white and grey matter density recovery in the morbidly obese: a voxel-based morphometric study. Hum Brain Mapp. 2016;37:3745–56.

    Article  Google Scholar 

  20. Polimeni JR, Wald LL. Magnetic resonance Imaging technology-bridging the gap between noninvasive human imaging and optical microscopy. Curr Opin Neurobiol. 2018;50:250–60.

    Article  CAS  Google Scholar 

  21. Akassoglou K, Merlini M, Rafalski VA, Real R, Liang L, Jin Y, et al. In vivo imaging of CNS injury and disease. J Neurosci. 2017;37:10808–16.

    Article  CAS  Google Scholar 

  22. Patriarca L, Magerowski G, Alonso-Alonso M. Functional neuroimaging in obesity. Curr Opin Endocrinol Diabetes Obes. 2017;24:260–5.

    Article  Google Scholar 

  23. Ogawa S, Lee TM, Nayak AS, Glynn P. Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Magn Reson Med. 1990;14:68–78.

    Article  CAS  Google Scholar 

  24. Cornier MA, Salzberg AK, Endly DC, Bessesen DH, Rojas DC, Tregellas JR. The effects of overfeeding on the neuronal response to visual food cues in thin and reduced-obese individuals. PLoS ONE. 2009;4:e6310.

    Article  Google Scholar 

  25. Fletcher PC, Napolitano A, Skeggs A, Miller SR, Delafont B, Cambridge VC, et al. Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatum. J Neurosci. 2010;30:14346–55.

    Article  CAS  Google Scholar 

  26. HFA Zoon, de Bruijn SEM, Jager G, PAM Smeets, de Graaf C, Janssen IMC, et al. Altered neural inhibition responses to food cues after Roux-en-Y Gastric bypass. Biol Psychol. 2018;137:34–41.

    Article  Google Scholar 

  27. Dallaire-Theroux C, Callahan BL, Potvin O, Saikali S, Duchesne S. Radiological-pathological correlation in Alzheimer's disease: systematic review of antemortem magnetic resonance imaging findings. J Alzheimers Dis. 2017;57:575–601.

    Article  Google Scholar 

  28. Berkseth KE, Rubinow KB, Melhorn SJ, Webb MF, BDLM Rosalynn, Marck BT, et al. Hypothalamic gliosis by MRI and visceral fat mass negatively correlate with plasma testosterone concentrations in healthy Men. Obesity. 2018;26:1898–904.

    Article  CAS  Google Scholar 

  29. Puig J, Blasco G, Daunis IEJ, Molina X, Xifra G, Ricart W, et al. Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects. J Clin Endocrinol Metab. 2015;100:E276–81.

    Article  CAS  Google Scholar 

  30. Lips MA, Wijngaarden MA, van der Grond J, van Buchem MA, de Groot GH, Rombouts SA, et al. Resting-state functional connectivity of brain regions involved in cognitive control, motivation, and reward is enhanced in obese females. Am J Clin Nutr. 2014;100:524–31.

    Article  CAS  Google Scholar 

  31. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–95.

    Article  CAS  Google Scholar 

  32. Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement. Am J Clin Nutr. 1992;55(Suppl 2):615S–9S. https://doi.org/10.1093/ajcn/55.2.615s. (Abstract).

  33. de Carvalho CP, Marin DM, de Souza AL, Pareja JC, Chaim EA, de Barros Mazon S, et al. GLP-1 and adiponectin: effect of weight loss after dietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucose metabolism. Obes Surg. 2009;19:313–20.

    Article  Google Scholar 

  34. Diabetes A. 2. Classification and diagnosis of diabetes. Diabetes Care. 2017;40(Suppl 1):S11–24. American

    Google Scholar 

  35. Abel TW, Rance NE. Stereologic study of the hypothalamic infundibular nucleus in young and older women. J Comp Neurol. 2000;424:679–88.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank ER, GF, and LS for technical assistance. This work was supported by funding provided by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, grants from the Trust in Science Initiative from Glaxo-Smithkline, UK, and the National Institutes of Health (DK089036, DK098466; EAS). The Laboratories of Cell Signaling and Experimental Endocrinology belong to the Obesity and Comorbidities Research Center and the National Institute of Science and Technology—Diabetes and Obesity.

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Authors and Affiliations

  1. Laboratory of Cell Signaling, Department of Internal Medicine, University of Campinas, Campinas, Brazil

    Simone van de Sande-Lee, Briana Rachid, Sylka Rodovalho, José C. De-Lima-Junior & Licio A. Velloso

  2. Department of Medicine, Division of General Internal Medicine, University of Washington, Seattle, WA, USA

    Susan J. Melhorn & Ellen A. Schur

  3. Neuroimaging Laboratory, Department of Neurology, University of Campinas, Campinas, Brazil

    Brunno M. Campos, Tatiane Pedro & Fernando Cendes

  4. Neurophysics Group, Institute of Physics Gleb Wataghin, University of Campinas, Campinas, Brazil

    Guilherme C. Beltramini

  5. Department of Surgery, University of Campinas, Campinas, Brazil

    Eliton A. Chaim & Jose C. Pareja

  6. Department of Radiology, University of Washington, Seattle, WA, USA

    Kenneth R. Maravilla

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  1. Simone van de Sande-Lee
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van de Sande-Lee, S., Melhorn, S.J., Rachid, B. et al. Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes. Int J Obes 44, 178–185 (2020). https://doi.org/10.1038/s41366-019-0399-8

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