Hypothalamic inflammation and somatic diseases
Authors:
B. Mravec; A. S. Černáčková
Authors‘ workplace:
Biomedicínske centrum SAV, Ústav experimentálnej endokrinológie, Slovenská akadémia vied, Bratislava
; Fyziologický ústav, LF UK v Bratislave
Published in:
Cesk Slov Neurol N 2018; 81(3): 278-283
Category:
Review Article
doi:
https://doi.org/10.14735/amcsnn2018278
Tato práca bola podporená grantom VEGA 2/ 0028/ 16 a grantom EÚ z programu cezhraničnej spolupráce Interreg V-A SK-AT V014 – NutriAging.
Overview
The hypothalamus represents a key structure involved in maintenance of homeostasis. Several factors, such as long-term increases in plasma levels of saturated fatty acids or pro-inflammatory cytokines, can induce hypothalamic inflammation. Hypothalamic inflammation disrupts homeostatic regulations and may contribute to the development of somatic diseases or may have a negative effect on the course of already existing somatic diseases. Hypothalamic inflammation plays a role in the etiopathogenesis of obesity, diabetes mellitus, hypertension, and cachexia. Understanding the causes and mechanisms involved in the development of hypothalamic inflammation allows for a more comprehensive view of the etiopathogenesis of somatic diseases and thus creates a basis for the introduction of new approaches in their treatment.
Keywords:
cytokines – diabetes mellitus – hypertension – hypothalamus – cachexia – obesity – ageing – stress – inflammation
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Sources
1. Billman GE. Homeostasis: the dynamic self-regulatory process that maintains health and buffers against disease. In: Sturmberg JP, Martin CM (eds). Handbook of systems and complexity in health. New York: Springer Science+Business Media 2013: 159– 170.
2. Chovatiya R, Medzhitov R. Stress, inflammation, and defense of homeostasis. Mol Cell 2014; 54(2): 281– 288. doi: 10.1016/ j.molcel.2014.03.030.
3. Graebner AK, Iyer M, Carter ME. Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states. Front Syst Neurosci 2015; 9: 111. doi: 10.3389/ fnsys.2015.00111.
4. Watts AG. 60 YEARS OF NEUROENDOCRINOLOGY: the structure of the neuroendocrine hypothalamus: the neuroanatomical legacy of Geoffrey Harris. J Endocrinol 2015; 226(2): T25– T39. doi: 10.1530/ JOE-15-0157.
5. de Git KC, Adan RA. Leptin resistance in diet-induced obesity: the role of hypothalamic inflammation. Obes Rev 2015; 16(3): 207– 224. doi: 10.1111/ obr.12243.
6. Burfeind KG, Michaelis KA, Marks DL. The central role of hypothalamic inflammation in the acute illness response and cachexia. Semin Cell Dev Biol 2016; 54: 42– 52. doi: 10.1016/ j.semcdb.2015.10.038.
7. Swaab DF. Chapter 20 Hypothalamic infections. Handb Clin Neurol 2004; 80: 91– 99. doi: 10.1016/ S0072-9752(04)80006-X.
8. Xanthos DN, Sandkuhler J. Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity. Nat Rev Neurosci 2014; 15(1): 43– 53. doi: 10.1038/ nrn3617.
9. Velickovic N, Drakulic D, Petrovic S et al. Time-course of hypothalamic-pituitary-adrenal axis activity and inflammation in juvenile rat brain after cranial irradiation. Cell Mol Neurobiol 2012; 32(7): 1175– 1185. doi: 10.1007/ s10571-012-9843-1.
10. Ballesteros-Zebadua P, Custodio V, Franco-Perez J et al. Whole-brain irradiation increases NREM sleep and hypothalamic expression of IL-1beta in rats. Int J RadiatBiol 2014; 90(2): 142– 148. doi: 10.3109/ 09553002.2014.859767.
11. Cai DS, Liu TW. Hypothalamic inflammation: a double-edged sword to nutritional diseases. Ann Ny Acad Sci 2011; 1243: E1– E39. doi: 10.1111/ j.1749-6632.2011.06388.x.
12. Zhang KZ, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature 2008; 454(7203): 455– 462. doi: 10.1038/ nature07203.
13. Pahl HL. Activators and target genes of Rel/ NF-kappaB transcription factors. Oncogene 1999; 18(49): 6853– 6866. doi: 10.1038/ sj.onc.1203239.
14. Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 2006; 25(51): 6680– 6684. doi: 10.1038/ sj.onc.1209954.
15. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011; 29: 415– 445. doi: 10.1146/ annurev-immunol-031210-101322.
16. Purkayastha S, Zhang G, Cai D. Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-beta and NF-kappaB. Nat Med 2011; 17(7): 883– 887. doi: 10.1038/ nm.2372.
17. Posey KA, Clegg DJ, Printz RL et al. Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. Am J Physiol Endocrinol Metab 2009; 296(5): E1003– E1012. doi: 10.1152/ ajpendo.90377.2008.
18. Zhang X, Zhang G, Zhang H et al. Hypothalamic IKKbeta/ NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008; 135(1): 61– 73. doi: 10.1016/ j.cell.2008.07.043.
19. Rahman MH, Bhusal A, Lee WH et al. Hypothalamic inflammation and malfunctioning glia in the pathophysiology of obesity and diabetes: Translational significance. Biochem Pharmacol 2018: pii: S0006-2952(18)30024. doi: 10.1016/ j.bcp.2018.01.024.
20. Thaler JP, Choi SJ, Schwartz MW et al. Hypothalamic inflammation and energy homeostasis: Resolving the paradox. Front Neuroendocrin 2010; 31(1): 79– 84. doi: 10.1016/ j.yfrne.2009.10.002.
21. Cesar HC, Pisani LP. Fatty-acid-mediated hypothalamic inflammation and epigenetic programming. J Nutr Biochem 2017; 42: 1– 6. doi: 10.1016/ j.jnutbio.2016.08.008.
22. Cardinale JP, Sriramula S, Mariappan N et al. Angiotensin II-Induced hypertension is modulated by nuclear factor-kappa B in the paraventricular nucleus. Hypertension 2012; 59(1): 113– 121. doi: 10.1161/ HYPERTENSIONAHA.111.182154.
23. Erdos B, Broxson CS, King MA et al. Acute pressor effect of central angiotensin II is mediated by NAD(P)H-oxidase-dependent superoxide production in the hypothalamic cardiovascular regulatory nuclei. J Hypertens 2006; 24(1): 109– 116.
24. Han C, Rice MW, Cai DS. Neuroinflammatory and autonomic mechanisms in diabetes and hypertension. Am J Physiol Endocrinol Metab 2016; 311(1): E32– E41. doi: 10.1152/ ajpendo.00012.2016.
25. Simonds SE, Pryor JT, Ravussin E et al. Leptin mediates the increase in blood pressure associated with obesity. Cell 2014; 159(6): 1404– 1416. doi: 10.1016/ j.cell.2014.10.058.
26. Li P, Cui BP, Zhang LL et al. Melanocortin 3/ 4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure. Exp physiol 2013; 98(2): 435– 443. doi: 10.1113/ expphysiol.2012.067256.
27. da Silva AA, do Carmo JM, Kanyicska B et al. Endogenous melanocortin system activity contributes to the elevated arterial pressure in spontaneously hypertensive rats. Hypertension 2008; 51(4): 884– 890. doi: 10.1161/ HYPERTENSIONAHA.107.100636.
28. Khor S, Cai DS. Hypothalamic and inflammatory basis of hypertension. Clin Sci 2017; 131(3): 211– 223. doi: 10.1042/ Cs20160001.
29. Braun TP, Zhu XX, Szumowski M et al. Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. J Exp Med 2011; 208(12): 2449– 2463. doi: 10.1084/ jem.20111020.
30. Ovadya Y, Krizhanovsky V. Senescent cells: SASPected drivers of age-related pathologies. Biogerontology 2014; 15(6): 627– 642. doi: 10.1007/ s10522-014-9529-9.
31. Lopez-Otin C, Blasco MA, Partridge L et al. The hallmarks of aging. Cell 2013; 153(6): 1194– 1217. doi: 10.1016/ j.cell.2013.05.039.
32. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol 2013; 75: 685– 705. doi: 10.1146/ annurev-physiol-030212-183653.
33. Franceschi C, Bonafe M, Valensin S et al. Inflammaging – an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000; 908: 244– 254.
34. Deleidi M, Jaggle M, Rubino G. Immune aging, dysmetabolism, and inflammation in neurological diseases. Front Neurosci 2015; 9: 172. doi: 10.3389/ fnins.2015.00172.
35. von Bernhardi R, Tichauer JE, Eugenín J. Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders. J Neurochem 2010; 112(5): 1099– 1114. doi: 10.1111/ j.1471-4159.2009.06537.x.
36. Ye SM, Johnson RW. An age-related decline in interleukin-10 may contribute to the increased expression of interleukin-6 in brain of aged mice. Neuroimmunomodulation 2001; 9(4): 183– 192. doi: 10.1159/ 000049025.
37. Jacobs AH, Tavitian B, consortium INMiND. Non-invasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab 2012; 32(7): 1393– 1415. doi: 10.1038/ jcbfm.2012.53.
38. Chauveau F, Boutin H, Van Camp N et al. Nuclear imaging of neuroinflammation: a comprehensive review of [C-11]PK11195 challengers. Eur J Nucl Med Mol Imagining 2008; 35(12): 2304– 2319. doi: 10.1007/ s00259-008-0908-9.
39. Arlicot N, Katsifis A, Garreau L et al. Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation. Eur J Nucl Med Mol Imagining 2008; 35(12): 2203– 2211. doi: 10.1007/ s00259-008-0834-x.
40. Shukuri M, Takashima-Hirano M, Tokuda K et al. In vivo expression of cyclooxygenase-1 in activated microglia and macrophages during neuroinflammation visualized by PET with C-11-ketoprofen methyl ester. J Nucl Med 2011; 52(7): 1094– 1101. doi: 10.2967/ jnumed.110.084046.
41. Dolle F, Luus C, Reynolds A et al. Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography. Curr Med Chem 2009; 16(22): 2899– 2923. doi: 10.2174/ 092986709788803150.
42. Pinas V, Windhorst A, Lammertsma A et al. Radiolabelled matrix metalloproteinase (Mmp) inhibitors for in vivo imaging of unstable plaques using PET and spect 1. J Labelled Comp Radiopharm 2009; 52(S1): S42– S42. doi: 10.1002/ jlcr.1627.
43. McAteer MA, Sibson NR, von zur Muhlen C et al. In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide. Nat Med 2007; 13(10): 1253– 1258. doi: 10.1038/ nm1631.
44. Shao X, Zhang HA, Rajian JR et al. I-125-Labeled gold nanorods for targeted imaging of inflammation. ACS Nano 2011; 5(11): 8967– 8973. doi: 10.1021/ nn203138t.
45. Saha GB, MacIntyre WJ, Go RT. Radiopharmaceuticals for brain imaging. Semin Nucl Med 1994; 24(4): 324– 349. doi: 10.1016/ S0001-2998(05)80022-4.
46. Quarantelli M. MRI/ MRS in neuroinflammation: methodology and applications. Clin Transl Imaging 2015; 3(6): 475– 489. doi: 10.1007/ s40336-015-0142-y.
47. Rigas A, Farmakis D, Papingiotis G et al. Hypothalamic dysfunction in heart failure: pathogenetic mechanisms and therapeutic implications. Heart Fail Rev 2018; 23(1): 55– 61. doi: 10.1007/ s10741-017-9659-7.
48. Ropelle ER, Flores MB, Cintra DE et al. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition. PLoS Biol 2010; 8(8): pii: e1000465. doi: 10.1371/ journal.pbio.1000465.
49. Cintra DE, Ropelle ER, Moraes JC et al. Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity. PLoS One 2012; 7(1): e30571. doi: 10.1371/ journal.pone.0030571.
50. Dragano NRV, Solon C, Ramalho AF et al. Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the hypothalamus and control energy homeostasis and inflammation. J Neuroinflammation 2017; 14(1): 91. doi: 10.1186/ s12974-017-0869-7.
51. Lira FS, Yamashita AS, Rosa JC et al. Hypothalamic inflammation is reversed by endurance training in anorectic-cachectic rats. Nutr Metab (Lond) 2011; 8(1): 60. doi: 10.1186/ 1743-7075-8-60.
52. al-Majid S, McCarthy DO. Resistance exercise training attenuates wasting of the extensor digitorum longus muscle in mice bearing the colon-26 adenocarcinoma. Biol Res Nurs 2001; 2(3): 155– 166. doi: 10.1177/ 109980040100200301.
53. DeBoer MD, Zhu XX, Levasseur P et al. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology 2007; 148(6): 3004– 3012. doi: 10.1210/ en.2007-0016.
54. Gonzalez PV, Cragnolini AB, Schioth HB et al. Interleukin-1 beta-induced anorexia is reversed by ghrelin. Peptides 2006; 27(12): 3220– 3225. doi: 10.1016/ j.peptides.2006.09.008.
55. Duxbury MS, Waseem T, Ito H et al. Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness. Biochem Biophys Res Commun 2003; 309(2): 464– 468. doi: 10.1016/ j.bbrc.2003.08.024.
56. Goldstein DS. Adrenal responses to stress.Cell Mol Neurobiol 2010; 30(8): 1433– 1440. doi: 10.1007/ s10571-010-9606-9.
Labels
Paediatric neurology Neurosurgery NeurologyArticle was published in
Czech and Slovak Neurology and Neurosurgery
2018 Issue 3
Most read in this issue
- Chronic inflammatory demyelinating polyradiculoneuropathy
- Factors affecting early diagnosis of amyotrophic lateral sclerosis
- Muscle biopsy in 10 key points
- Is essential tremor a disease or a syndrome?