Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Animal Models

Hypothalamic neuronal cellular and subcellular abnormalities in experimental obesity

International Journal of Obesity volume 43, pages 2361–2369 (2019)Cite this article

Subjects

Abstract

The characterization of the hypothalamic neuronal network, that controls food intake and energy expenditure, has provided great advances in the understanding of the pathophysiology of obesity. Most of the advances in this field were obtained thanks to the development of a number of genetic and nongenetic animal models that, at least in part, overtook the anatomical constraints that impair the study of the human hypothalamus. Despite the undisputed differences between human and rodent physiology, most seminal studies undertaken in rodents that have unveiled details of the neural regulation of energy homeostasis were eventually confirmed in humans; thus, placing experimental studies in the forefront of obesity research. During the last 15 years, researchers have provided extensive experimental proof that supports the existence of hypothalamic dysfunction, which leads to a progressive whole-body positive energy balance, and thus, to obesity. Here, we review the experimental work that unveiled the mechanisms behind hypothalamic dysfunction in obesity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rossi MA, Stuber GD. Overlapping brain circuits for homeostatic and hedonic feeding. Cell Metabol. 2018;27:42–56.

    CAS  Google Scholar 

  2. Andermann ML, Lowell BB. Toward a wiring diagram understanding of appetite control. Neuron. 2017;95:757–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, et al. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology. 2005;146:4192–9.

    PubMed  Google Scholar 

  4. Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell. 2008;135:61–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE, et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci. 2009;29:359–70.

    CAS  PubMed  PubMed Central  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.

    CAS  PubMed  Google Scholar 

  7. Schneeberger M, Dietrich MO, Sebastian D, Imbernon M, Castano C, Garcia A, et al. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance. Cell. 2013;155:172–87.

    CAS  PubMed  Google Scholar 

  8. 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.

    CAS  PubMed  Google Scholar 

  9. Dietrich MO, Liu ZW, Horvath TL. Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity. Cell. 2013;155:188–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Valdearcos M, Douglass JD, Robblee MM, Dorfman MD, Stifler DR, Bennett ML, et al. Microglial inflammatory signaling orchestrates the hypothalamic immune response to dietary excess and mediates obesity susceptibility. Cell Metabol. 2017;26:185–97 e3.

    CAS  Google Scholar 

  11. Tsaousidou E, Paeger L, Belgardt BF, Pal M, Wunderlich CM, Bronneke H, et al. Distinct roles for JNK and IKK activation in agouti-related peptide neurons in the development of obesity and insulin resistance. Cell Rep. 2014;9:1495–506.

    CAS  PubMed  Google Scholar 

  12. Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metabol. 2009;9:35–51.

    CAS  Google Scholar 

  13. Ignacio-Souza LM, Bombassaro B, Pascoal LB, Portovedo MA, Razolli DS, Coope A, et al. Defective regulation of the ubiquitin/proteasome system in the hypothalamus of obese male mice. Endocrinology. 2014;155:2831–44.

    PubMed  Google Scholar 

  14. Carraro RS, Souza GF, Solon C, Razolli DS, Chausse B, Barbizan R, et al. Hypothalamic mitochondrial abnormalities occur downstream of inflammation in diet-induced obesity. Mol Cell Endocrinol. 2018;460:238–45.

    CAS  PubMed  Google Scholar 

  15. Yan J, Zhang H, Yin Y, Li J, Tang Y, Purkayastha S, et al. Obesity- and aging-induced excess of central transforming growth factor-beta potentiates diabetic development via an RNA stress response. Nat Med. 2014;20:1001–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 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.

    PubMed  PubMed Central  Google Scholar 

  17. Yi CX, Walter M, Gao Y, Pitra S, Legutko B, Kalin S, et al. TNFalpha drives mitochondrial stress in POMC neurons in obesity. Nat Commun. 2017;8:15143.

    PubMed  PubMed Central  Google Scholar 

  18. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.

    CAS  PubMed  Google Scholar 

  19. Mansour E, Pereira FG, Araujo EP, Amaral ME, Morari J, Ferraroni NR, et al. Leptin inhibits apoptosis in thymus through a janus kinase-2-independent, insulin receptor substrate-1/phosphatidylinositol-3 kinase-dependent pathway. Endocrinology. 2006;147:5470–9.

    CAS  PubMed  Google Scholar 

  20. Cioffi JA, Shafer AW, Zupancic TJ, Smith-Gbur J, Mikhail A, Platika D, et al. Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat Med. 1996;2:585–9.

    CAS  PubMed  Google Scholar 

  21. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897–901.

    CAS  PubMed  Google Scholar 

  22. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100:197–207.

    CAS  PubMed  Google Scholar 

  23. Donato J Jr., Cravo RM, Frazao R, Gautron L, Scott MM, et al. Leptin’s effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons. J Clin Invest. 2011;121:355–68.

    PubMed  Google Scholar 

  24. Farooqi S, O’Rahilly S. Genetics of obesity in humans. Endocr Rev. 2006;27:710–18.

    CAS  PubMed  Google Scholar 

  25. Balland E, Dam J, Langlet F, Caron E, Steculorum S, Messina A, et al. Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metabol. 2014;19:293–301.

    CAS  Google Scholar 

  26. Cui H, Lopez M, Rahmouni K. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat Rev Endocrinol. 2017;13:338–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature. 2003;421:856–9.

    CAS  PubMed  Google Scholar 

  28. Schwartz MW, Seeley RJ, Woods SC, Weigle DS, Campfield LA, Burn P, et al. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes. 1997;46:2119–23.

    CAS  PubMed  Google Scholar 

  29. Seeley RJ, Yagaloff KA, Fisher SL, Burn P, Thiele TE, van Dijk G, et al. Melanocortin receptors in leptin effects. Nature. 1997;390:349.

    CAS  PubMed  Google Scholar 

  30. Boston BA, Blaydon KM, Varnerin J, Cone RD. Independent and additive effects of central POMC and leptin pathways on murine obesity. Science. 1997;278:1641–4.

    CAS  PubMed  Google Scholar 

  31. Mizuno TM, Mobbs CV. Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology. 1999;140:814–7.

    CAS  PubMed  Google Scholar 

  32. Xu J, Bartolome CL, Low CS, Yi X, Chien CH, Wang P, et al. Genetic identification of leptin neural circuits in energy and glucose homeostases. Nature. 2018;556:505–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Balland E, Chen W, Dodd GT, Conductier G, Coppari R, Tiganis T, et al. Leptin signaling in the arcuate nucleus reduces insulin’s capacity to suppress hepatic glucose production in obese mice. Cell Rep. 2019;26:346–55 e3.

    CAS  PubMed  Google Scholar 

  34. Caron A, Dungan Lemko HM, Castorena CM, Fujikawa T, Lee S, Lord CC, et al. POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels. Elife. 2018;7:e33710. pii

    PubMed  PubMed Central  Google Scholar 

  35. Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978;272:827–9.

    CAS  PubMed  Google Scholar 

  36. Folli F, Ghidella S, Bonfanti L, Kahn CR, Merighi A. The early intracellular signaling pathway for the insulin/insulin-like growth factor receptor family in the mammalian central nervous system. Mol Neurobiol. 1996;13:155–83.

    CAS  PubMed  Google Scholar 

  37. Folli F, Bonfanti L, Renard E, Kahn CR, Merighi A. Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system. J Neurosci. 1994;14(11 Pt 1):6412–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Frank HJ, Pardridge WM, Morris WL, Rosenfeld RG, Choi TB. Binding and internalization of insulin and insulin-like growth factors by isolated brain microvessels. Diabetes. 1986;35:654–61.

    CAS  PubMed  Google Scholar 

  39. Biesecker KR, Srienc AI, Shimoda AM, Agarwal A, Bergles DE, Kofuji P, et al. Glial cell calcium signaling mediates capillary regulation of blood flow in the retina. J Neurosci. 2016;36:9435–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289:2122–5.

    CAS  PubMed  Google Scholar 

  41. Lien E, Means TK, Heine H, Yoshimura A, Kusumoto S, Fukase K, et al. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J Clin Invest. 2000;105:497–504.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Fioravante M, Bombassaro B, Ramalho AF, de Moura RF, Haddad-Tovolli R, Solon C, et al. Hypothalamic expression of the atypical chemokine receptor ACKR2 is involved in the systemic regulation of glucose tolerance. Biochim Biophys Acta Mol Basis Dis. 2019;1865:1126–37.

    CAS  PubMed  Google Scholar 

  43. Fioravante M, Bombassaro B, Ramalho AF, Dragano NR, Morari J, Solon C, et al. Inhibition of hypothalamic leukemia inhibitory factor exacerbates diet-induced obesity phenotype. J Neuroinflammation. 2017;14:178.

    PubMed  PubMed Central  Google Scholar 

  44. Benoit SC, Kemp CJ, Elias CF, Abplanalp W, Herman JP, Migrenne S, et al. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents. J Clin Investig. 2009;119:2577–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Milanski M, Arruda AP, Coope A, Ignacio-Souza LM, Nunez CE, Roman EA, et al. Inhibition of hypothalamic inflammation reverses diet-induced insulin resistance in the liver. Diabetes. 2012;61:1455–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Araujo EP, de Souza CT, Velloso LA. Atypical transforming growth factor-beta signaling in the hypothalamus is linked to diabetes. Nat Med. 2014;20:985–7.

    CAS  PubMed  Google Scholar 

  47. Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, et al. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature. 2013;497:211–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Cavadas C, Aveleira CA, Souza GF, Velloso LA. The pathophysiology of defective proteostasis in the hypothalamus - from obesity to ageing. Nat Rev Endocrinol. 2016;12:723–33.

    CAS  PubMed  Google Scholar 

  49. Bombassaro B, Ramalho AFS, Fioravante M, Solon C, Nogueira G, Nogueira PAS, et al. CD1 is involved in diet-induced hypothalamic inflammation in obesity. Brain Behav Immun. 2019;78:78–90.

    CAS  PubMed  Google Scholar 

  50. Hetz C, Chevet E, Oakes SA. Proteostasis control by the unfolded protein response. Nat Cell Biol. 2015;17:829–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Hetz C, Papa FR. The unfolded protein response and cell fate control. Mol Cell. 2018;69:169–81.

    CAS  PubMed  Google Scholar 

  52. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140:900–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Salvado L, Palomer X, Barroso E, Vazquez-Carrera M. Targeting endoplasmic reticulum stress in insulin resistance. Trends Endocrinol Metabol. 2015;26:438–48.

    CAS  Google Scholar 

  54. Won JC, Jang PG, Namkoong C, Koh EH, Kim SK, Park JY, et al. Central administration of an endoplasmic reticulum stress inducer inhibits the anorexigenic effects of leptin and insulin. Obesity. 2009;17:1861–5.

    CAS  PubMed  Google Scholar 

  55. Williams KW, Liu T, Kong X, Fukuda M, Deng Y, Berglund ED, et al. Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis. Cell Metabol. 2014;20:471–82.

    CAS  Google Scholar 

  56. Cakir I, Cyr NE, Perello M, Litvinov BP, Romero A, Stuart RC, et al. Obesity induces hypothalamic endoplasmic reticulum stress and impairs proopiomelanocortin (POMC) post-translational processing. J Biol Chem. 2013;288:17675–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Contreras C, Gonzalez-Garcia I, Martinez-Sanchez N, Seoane-Collazo P, Jacas J, Morgan DA, et al. Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance. Cell Rep. 2014;9:366–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Contreras C, Gonzalez-Garcia I, Seoane-Collazo P, Martinez-Sanchez N, Linares-Pose L, Rial-Pensado E, et al. Reduction of hypothalamic endoplasmic reticulum stress activates browning of white fat and ameliorates obesity. Diabetes. 2017;66:87–99.

    CAS  PubMed  Google Scholar 

  59. Nasrallah CM, Horvath TL. Mitochondrial dynamics in the central regulation of metabolism. Nat Rev Endocrinol. 2014;10:650–8.

    CAS  PubMed  Google Scholar 

  60. Shadel GS, Horvath TL. Mitochondrial ROS signaling in organismal homeostasis. Cell. 2015;163:560–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Eisner V, Picard M, Hajnoczky G. Mitochondrial dynamics in adaptive and maladaptive cellular stress responses. Nat Cell Biol. 2018;20:755–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Ni HM, Williams JA, Ding WX. Mitochondrial dynamics and mitochondrial quality control. Redox Biol. 2015;4:6–13.

    CAS  PubMed  Google Scholar 

  63. Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, et al. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature. 2008;454:846–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature. 2007;449:228–32.

    CAS  PubMed  Google Scholar 

  65. Santoro A, Campolo M, Liu C, Sesaki H, Meli R, Liu ZW, et al. DRP1 suppresses leptin and glucose sensing of POMC neurons. Cell Metabol. 2017;25:647–60.

    CAS  Google Scholar 

  66. Ramirez S, Gomez-Valades AG, Schneeberger M, Varela L, Haddad-Tovolli R, Altirriba J, et al. Mitochondrial dynamics mediated by mitofusin 1 is required for POMC neuron glucose-sensing and insulin release control. Cell Metabol. 2017;25:1390–9 e6.

    CAS  Google Scholar 

  67. Paeger L, Pippow A, Hess S, Paehler M, Klein AC, Husch A, et al. Energy imbalance alters Ca(2+) handling and excitability of POMC neurons. Elife. 2017;6:e25641. pii

    PubMed  PubMed Central  Google Scholar 

  68. Ravanan P, Srikumar IF, Talwar P. Autophagy: the spotlight for cellular stress responses. Life Sci. 2017;188:53–67.

    CAS  PubMed  Google Scholar 

  69. Jacob JA, Salmani JMM, Jiang Z, Feng L, Song J, Jia X, et al. Autophagy: an overview and its roles in cancer and obesity. Clin Chim Acta. 2017;468:85–89.

    CAS  PubMed  Google Scholar 

  70. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2014;20:460–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Kaushik S, Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, et al. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metabol. 2011;14:173–83.

    CAS  Google Scholar 

  72. Kaushik S, Arias E, Kwon H, Lopez NM, Athonvarangkul D, Sahu S, et al. Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO Rep. 2012;13:258–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Malhotra R, Warne JP, Salas E, Xu AW, Debnath J. Loss of Atg12, but not Atg5, in pro-opiomelanocortin neurons exacerbates diet-induced obesity. Autophagy. 2015;11:145–54.

    PubMed  PubMed Central  Google Scholar 

  74. Meng Q, Cai D. Defective hypothalamic autophagy directs the central pathogenesis of obesity via the IkappaB kinase beta (IKKbeta)/NF-kappaB pathway. J Biol Chem. 2011;286:32324–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Coupe B, Ishii Y, Dietrich MO, Komatsu M, Horvath TL, Bouret SG. Loss of autophagy in pro-opiomelanocortin neurons perturbs axon growth and causes metabolic dysregulation. Cell Metabol. 2012;15:247–55.

    CAS  Google Scholar 

  76. Portovedo M, Ignacio-Souza LM, Bombassaro B, Coope A, Reginato A, Razolli DS, et al. Saturated fatty acids modulate autophagy’s proteins in the hypothalamus. PLoS ONE. 2015;10:e0119850.

    PubMed  PubMed Central  Google Scholar 

  77. Reginato A, de Fante T, Portovedo M, da Costa NF, Payolla TB, Miyamotto JE, et al. Autophagy proteins are modulated in the liver and hypothalamus of the offspring of mice with diet-induced obesity. J Nutr Biochem. 2016;34:30–41.

    CAS  PubMed  Google Scholar 

  78. Hipp MS, Kasturi P, Hartl FU. The proteostasis network and its decline in ageing. Nat Rev Mol Cell Biol. 2019;20:421–35.

    CAS  PubMed  Google Scholar 

  79. Akhurst RJ, Hata A. Targeting the TGFbeta signalling pathway in disease. Nat Rev Drug Discov. 2012;11:790–811.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Anderson P, Kedersha N. RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol. 2009;10:430–6.

    CAS  PubMed  Google Scholar 

  81. Mendoza J. Eating rewards the gears of the clock. Trends Endocrinol Metabol. 2019;30:299–311.

    CAS  Google Scholar 

  82. 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.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The Laboratory of Cell Signaling is supported by funding provided by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. The Laboratories of Cell Signaling belongs to the Obesity and Comorbidities Research Center and the National Institute of Science and Technology – Neuroimmunomodulation

Author information

Authors and Affiliations

  1. Laboratory of Cell Signaling, Obesity and Comorbidities Center University of Campinas, Campinas, São Paulo, 13084-970, Brazil

    Daniela S. Razolli, Alexandre Moura-Assis, Bruna Bombassaro & Licio A. Velloso

Authors
  1. Daniela S. Razolli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandre Moura-Assis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruna Bombassaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Licio A. Velloso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Licio A. Velloso.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

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

The laboratory of Cell Signaling belongs to the National Institute of Science and Technology in Neuroimmunomodulation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Razolli, D.S., Moura-Assis, A., Bombassaro, B. et al. Hypothalamic neuronal cellular and subcellular abnormalities in experimental obesity. Int J Obes 43, 2361–2369 (2019). https://doi.org/10.1038/s41366-019-0451-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-019-0451-8

This article is cited by

Search

Advanced search

Quick links