CoChat
Sign Up
Cited by 270Lipid metabolism and biosynthesisNeurological diseases and metabolismNeuroinflammation and Neurodegeneration Mechanisms

Lipid droplets in neurodegenerative disorders

Open access
Farmer, Brandon C., Walsh, Adeline E., Kluemper, Jude C., Johnson, Lance A.·2020·Frontiers in Neuroscience
DOI 10.3389/fnins.2020.00742PMC PMC7403481
Open this paper in CoChat — free accountOpen PDF

Abstract

Knowledge of lipid droplets (LDs) has evolved from simple depots of lipid storage to dynamic and functionally active organelles involved in a variety of cellular functions. Studies have now informed significant roles for LDs in cellular signaling, metabolic disease, and inflammation. While lipid droplet biology has been well explored in peripheral organs such as the liver and heart, LDs within the brain are relatively understudied. The presence and function of these dynamic organelles in the central nervous system has recently gained attention, especially in the context of neurodegeneration. In this review, we summarize the current understanding of LDs within the brain, with an emphasis on their relevance in neurodegenerative diseases.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fnins.2020.00742

Cites

13 of 13 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Excess lipid droplet accumulation is associated with several diseases, including Alzheimer's disease.

    “It is well documented that several diseases are associated with excessive LDs, including but not limited to obesity, atherosclerosis, cancer, type 2 diabetes, and Alzheimer’s disease (AD) (Farmer et al., 2020; Dalhaimer, 2019)”

    From APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses (2025) · cites this paper as Farmer et al., 2020

    The Alzheimer’s Disease section (page unavailable) reports increased lipid-droplet formation in both human AD samples and an AD mouse model. The Introduction also links lipid droplets to obesity-related dysfunction and insulin resistance. The cited passages do not establish the sentence’s additional associations with atherosclerosis, cancer, or specifically type 2 diabetes. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Altered lipid droplet biology has been linked to both brain aging and neurodegenerative diseases.

    “Altered lipid droplet biology has been linked to both brain aging and neurodegenerative diseases10–24.”

    From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [14]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 123

  1. Aditi K. Shakarad M. N. Agrawal N. (2016). Altered lipid metabolism in Drosophila model of Huntington’s disease. Sci. Rep. 6: 31411. PMC4979013 27506601
  2. Ahdab-Barmada M. Moossy J. Nemoto E. M. Lin M. R. (1986). Hyperoxia produces neuronal necrosis in the rat. J. Neuropathol. Exp. Neurol. 45 233– 246. 10.1097/00005072-198605000-00006 3958757 · DOI
  3. Alzheimer A. Stelzmann R. A. Schnitzlein H. N. Murtagh F. R. (1995). An English translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde”. Clin. Anat. 8 429– 431. 10.1002/ca.980080612 8713166 · DOI · Paper page
  4. Andreone B. J. Chow B. W. Tata A. Lacoste B. Ben-Zvi A. Bullock K. (2017). Blood-brain barrier permeability is regulated by lipid transport-dependent suppression of caveolae-mediated transcytosis. Neuron 94 581– 594.e585. 28416077 PMC5474951
  5. Arrese E. L. Saudale F. Z. Soulages J. L. (2014). Lipid droplets as signaling platforms linking metabolic and cellular functions. Lipid Insights 7 7– 16. 25221429 PMC4161058
  6. Arribat Y. Grepper D. Lagarrigue S. Qi T. Cohen S. Amati F. (2020). Spastin mutations impair coordination between lipid droplet dispersion and reticulum. PLoS Genet. 16: e1008665. 10.1371/journal.pgen.1008665 32315314 PMC7173978 · DOI
  7. Bailey A. P. Koster G. Guillermier C. Hirst E. M. A. Macrae J. I. Lechene C. P. (2015). Antioxidant role for lipid droplets in a stem cell niche of Drosophila. Cell 163 340– 353. 10.1016/j.cell.2015.09.020 26451484 PMC4601084 · DOI
  8. Benstead T. J. Dyck P. J. Sangalang V. (1989). Inner perineurial cell vulnerability in ischemia. Brain Res. 489 177– 181. 10.1016/0006-8993(89)90021-8 2743147 · DOI
  9. Bouab M. Paliouras G. N. Aumont A. Forest-Berard K. Fernandes K. J. (2011). Aging of the subventricular zone neural stem cell niche: evidence for quiescence-associated changes between early and mid-adulthood. Neuroscience 173 135– 149. 10.1016/j.neuroscience.2010.11.032 21094223 · DOI
  10. Bozza P. T. Bakker-Abreu I. Navarro-Xavier R. A. Bandeira-Melo C. (2011). Lipid body function in eicosanoid synthesis: an update. Prostaglandins Leukot. Essent. Fatty Acids 85 205– 213. 10.1016/j.plefa.2011.04.020 21565480 · DOI
  11. Branchu J. Boutry M. Sourd L. Depp M. Leone C. Corriger A. (2017). Loss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration. Neurobiol. Dis. 102 21– 37. 10.1016/j.nbd.2017.02.007 28237315 PMC5391847 · DOI
  12. Brawer J. R. Walsh R. J. (1982). Response of tanycytes to aging in the median eminence of the rat. Am. J. Anat. 163 247– 256. 10.1002/aja.1001630305 7091013 · DOI
  13. Bruce K. D. Zsombok A. Eckel R. H. (2017). Lipid processing in the brain: a key regulator of systemic metabolism. Front. Endocrinol. 8: 60. 10.3389/fendo.2017.00060 28421037 PMC5378716 · DOI
  14. Cabirol-Pol M. J. Khalil B. Rival T. Faivre-Sarrailh C. Besson M. T. (2018). Glial lipid droplets and neurodegeneration in a Drosophila model of complex I deficiency. Glia 66 874– 888. 10.1002/glia.23290 29285794 · DOI
  15. Cabodevilla A. G. Sanchez-Caballero L. Nintou E. Boiadjieva V. G. Picatoste F. Gubern A. (2013). Cell survival during complete nutrient deprivation depends on lipid droplet-fueled beta-oxidation of fatty acids. J. Biol. Chem. 288 27777– 27788. 10.1074/jbc.m113.466656 23940052 PMC3784694 · DOI
  16. Calderon-Garciduenas L. Azzarelli B. Acuna H. Garcia R. Gambling T. M. Osnaya N. (2002). Air pollution and brain damage. Toxicol. Pathol. 30 373– 389. 12051555
  17. Ceafalan L. C. Fertig T. E. Gheorghe T. C. Hinescu M. E. Popescu B. O. Pahnke J. (2019). Age-related ultrastructural changes of the basement membrane in the mouse blood-brain barrier. J. Cell. Mol. Med. 23 819– 827. 10.1111/jcmm.13980 30450815 PMC6349169 · DOI · Paper page
  18. Chali F. Milior G. Marty S. Morin-Brureau M. Le Duigou C. Savary E. (2019). Lipid markers and related transcripts during excitotoxic neurodegeneration in kainate-treated mice. Eur. J. Neurosci. 50 1759– 1778. 30767299
  19. Cingolani F. Czaja M. J. (2016). Regulation and functions of autophagic lipolysis. Trends Endocrinol. Metab. 27 696– 705. 10.1016/j.tem.2016.06.003 27365163 PMC5035575 · DOI
  20. Cohen S. (2018). Lipid droplets as organelles. Int. Rev. Cell Mol. Biol. 337 83– 110. 10.1016/bs.ircmb.2017.12.007 29551163 PMC6241319 · DOI
  21. Cole N. B. Murphy D. D. Grider T. Rueter S. Brasaemle D. Nussbaum R. L. (2002). Lipid droplet binding and oligomerization properties of the Parkinson’s disease protein alpha-synuclein. J. Biol. Chem. 277 6344– 6352. 10.1074/jbc.m108414200 11744721 · DOI
  22. Cornett D. S. Reyzer M. L. Chaurand P. Caprioli R. M. (2007). MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nat. Methods 4 828– 833. 10.1038/nmeth1094 17901873 · DOI
  23. Crespo D. Verduga R. Fernandez-Viadero C. Megias M. (1995). Structural changes induced by cytidine-5’-diphosphate choline (CDP-choline) chronic treatment in neurosecretory neurons of the supraoptic nucleus of aged CFW-mice. Mech. Ageing Dev. 84 183– 193. 10.1016/0047-6374(95)01654-6 8788774 · DOI
  24. Croce K. R. Yamamoto A. (2019). A role for autophagy in Huntington’s disease. Neurobiol. Dis. 122 16– 22. 30149183 PMC6364695
  25. de Estable-Puig R. F. Estable-Puig J. F. (1973). Intraneuronal lipid droplets in irradiated nervous tissue. Virchows Arch. B Cell. Pathol. 14 117– 125. 4358915
  26. de Souza P. V. S. De Rezende Pinto W. B. V. De Rezende Batistella G. N. Bortholin T. Oliveira A. S. B. (2017). Hereditary spastic paraplegia: clinical and genetic hallmarks. Cerebellum 16 525– 551. 27271711
  27. Derk J. Bermudez Hernandez K. Rodriguez M. He M. Koh H. Abedini A. (2018). Diaphanous 1 (DIAPH1) is highly expressed in the aged human medial temporal cortex and upregulated in myeloid cells during Alzheimer’s disease. J. Alzheimers Dis. 64 995– 1007. 10.3233/jad-180088 29966194 PMC6082178 · DOI
  28. Dichlberger A. Schlager S. Kovanen P. T. Schneider W. J. (2016). Lipid droplets in activated mast cells - a significant source of triglyceride-derived arachidonic acid for eicosanoid production. Eur. J. Pharmacol. 785 59– 69. 10.1016/j.ejphar.2015.07.020 26164793 · DOI
  29. Doetsch F. Garcia-Verdugo J. M. Alvarez-Buylla A. (1997). Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci. 17 5046– 5061. 10.1523/jneurosci.17-13-05046.1997 9185542 PMC6573289 · DOI
  30. Doetsch F. Garcia-Verdugo J. M. Alvarez-Buylla A. (1999). Regeneration of a germinal layer in the adult mammalian brain. Proc. Natl. Acad. Sci. U.S.A. 96 11619– 11624. 10.1073/pnas.96.20.11619 10500226 PMC18083 · DOI
  31. Edwards T. L. Clowes V. E. Tsang H. T. H. Connell J. W. Sanderson C. M. Luzio J. P. (2009). Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5. Biochem. J. 423 31– 39. 10.1042/bj20082398 19580544 PMC2762690 · DOI
  32. Eriksson L. Westermark P. (1990). Age-related accumulation of amyloid inclusions in adrenal cortical cells. Am. J. Pathol. 136 461– 466. 2305837 PMC1877396
  33. Etschmaier K. Becker T. Eichmann T. O. Schweinzer C. Scholler M. Tam-Amersdorfer C. (2011). Adipose triglyceride lipase affects triacylglycerol metabolism at brain barriers. J. Neurochem. 119 1016– 1028. 10.1111/j.1471-4159.2011.07498.x 21951135 · DOI
  34. Fanning S. Selkoe D. Dettmer U. (2020). Parkinson’s disease: proteinopathy or lipidopathy? NPJ Parkinsons Dis. 6: 3. PMC6941970 31909184
  35. Fuchs B. Süss R. Schiller J. (2010). An update of MALDI-TOF mass spectrometry in lipid research. Prog. Lipid Res. 49 450– 475. 10.1016/j.plipres.2010.07.001 20643161 · DOI
  36. Gajkowska B. Zareba-Kowalska A. (1989). [Effect of ischemia on the ultrastructure of the hypothalamo-hypophyseal system in rats]. Neuropatol. Pol. 27 367– 381. 2639291
  37. Gao G. Chen F. J. Zhou L. Su L. Xu D. Xu L. (2017). Control of lipid droplet fusion and growth by CIDE family proteins. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1862 1197– 1204. 10.1016/j.bbalip.2017.06.009 28648584 · DOI
  38. Hamilton J. A. Hillard C. J. Spector A. A. Watkins P. A. (2007). Brain uptake and utilization of fatty acids, lipids and lipoproteins: application to neurological disorders. J. Mol. Neurosci. 33 2– 11. 10.1007/s12031-007-0060-1 17901539 · DOI
  39. Hamilton L. K. Aumont A. Julien C. Vadnais A. Calon F. Fernandes K. J. (2010). Widespread deficits in adult neurogenesis precede plaque and tangle formation in the 3xTg mouse model of Alzheimer’s disease. Eur. J. Neurosci. 32 905– 920. 10.1111/j.1460-9568.2010.07379.x 20726889 · DOI
  40. Hamilton L. K. Dufresne M. Joppe S. E. Petryszyn S. Aumont A. Calon F. (2015). Aberrant lipid metabolism in the forebrain niche suppresses adult neural stem cell proliferation in an animal model of Alzheimer’s disease. Cell Stem Cell 17 397– 411. 10.1016/j.stem.2015.08.001 26321199 · DOI · Paper page
  41. Hamilton L. K. Fernandes K. J. L. (2018). Neural stem cells and adult brain fatty acid metabolism: lessons from the 3xTg model of Alzheimer’s disease. Biol. Cell 110 6– 25. 10.1111/boc.201700037 28980327 · DOI
  42. Han X. Zhu J. Zhang X. Song Q. Ding J. Lu M. (2018). Plin4-dependent lipid droplets hamper neuronal mitophagy in the MPTP/p-induced mouse model of Parkinson’s disease. Front. Neurosci. 12: 397. 10.3389/fnins.2018.00397 29967574 PMC6015897 · DOI · Paper page
  43. Harris C. A. Haas J. T. Streeper R. S. Stone S. J. Kumari M. Yang K. (2011). DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes. J. Lipid Res. 52 657– 667. 10.1194/jlr.m013003 21317108 PMC3284159 · DOI
  44. Hooper C. Puttamadappa S. S. Loring Z. Shekhtman A. Bakowska J. C. (2010). Spartin activates atrophin-1-interacting protein 4 (AIP4) E3 ubiquitin ligase and promotes ubiquitination of adipophilin on lipid droplets. BMC Biol. 8: 72. 10.1186/1741-7007-8-72 20504295 PMC2887783 · DOI
  45. Hulette C. M. Earl N. L. Anthony D. C. Crain B. J. (1992). Adult onset niemann-pick disease type C presenting with dementia and absent organomegaly. Clin. Neuropathol. 11 293– 297. 1473312
  46. Inloes J. M. Kiosses W. B. Wang H. Walther T. C. Farese R. V. Jr. Cravatt B. F. (2018). Functional contribution of the spastic paraplegia-related triglyceride hydrolase DDHD2 to the formation and content of lipid droplets. Biochemistry 57 827– 838. 10.1021/acs.biochem.7b01028 29278326 PMC5854151 · DOI
  47. Islam A. Kagawa Y. Miyazaki H. Shil S. K. Umaru B. A. Yasumoto Y. (2019). FABP7 protects astrocytes against ROS toxicity via lipid droplet formation. Mol. Neurobiol. 56 5763– 5779. 10.1007/s12035-019-1489-2 30680690 · DOI
  48. Jin Y. Tan Y. Chen L. Liu Y. Ren Z. (2018). Reactive oxygen species induces lipid droplet accumulation in HepG2 cells by increasing perilipin 2 expression. Int. J. Mol. Sci. 19: 3445. 10.3390/ijms19113445 30400205 PMC6274801 · DOI
  49. Johnson J. E. Jr. (1980). Fine structural alterations in the aging rat pineal gland. Exp. Aging Res. 6 189– 211. 10.1080/03610738008258357 6248343 · DOI
  50. Kalia L. V. Lang A. E. (2015). Parkinson’s disease. Lancet 386 896– 912. 25904081
  51. Kamada H. Sato K. Iwai M. Ohta K. Nagano I. Shoji M. (2003). Changes of free cholesterol and neutral lipids after transient focal brain ischemia in rats. Acta Neurochir. Suppl. 86 177– 180. 10.1007/978-3-7091-0651-8_38 14753430 · DOI
  52. Kamada H. Sato K. Iwai M. Zhang W. R. Nagano I. Manabe Y. (2002). Spatiotemporal changes of free cholesterol and neutral lipids after transient middle cerebral artery occlusion in rats. Ann. N. Y. Acad. Sci. 977 115– 122. 10.1111/j.1749-6632.2002.tb04805.x 12480740 · DOI
  53. Kassan A. Herms A. Fernández-Vidal A. Bosch M. Schieber N. L. Reddy B. J. N. (2013). Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains. J. Cell Biol. 203 985– 1001. 10.1083/jcb.201305142 24368806 PMC3871434 · DOI
  54. Kaushik S. Rodriguez-Navarro J. A. Arias E. Kiffin R. Sahu S. Schwartz G. J. (2011). Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metab. 14 173– 183. 10.1016/j.cmet.2011.06.008 21803288 PMC3148494 · DOI · Paper page
  55. Khatchadourian A. Bourque S. D. Richard V. R. Titorenko V. I. Maysinger D. (2012). Dynamics and regulation of lipid droplet formation in lipopolysaccharide (LPS)-stimulated microglia. Biochim. Biophys. Acta 1821 607– 617. 10.1016/j.bbalip.2012.01.007 22289388 · DOI · Paper page
  56. Kim S. Kim N. Park S. Jeon Y. Lee J. Yoo S. J. (2020). Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance. Autophagy 16 1200– 1220. 10.1080/15548627.2019.1659616 31469345 PMC7469491 · DOI
  57. Kis V. Barti B. Lippai M. Sass M. (2015). Specialized cortex glial cells accumulate lipid droplets in Drosophila melanogaster. PLoS One 10: e0131250. 10.1371/journal.pone.0131250 26148013 PMC4493057 · DOI
  58. Klemann C. Martens G. J. M. Sharma M. Martens M. B. Isacson O. Gasser T. (2017). Integrated molecular landscape of Parkinson’s disease. NPJ Parkinsons Dis. 3: 14. PMC5460267 28649614
  59. Kwon Y. H. Kim J. Kim C. S. Tu T. H. Kim M. S. Suk K. (2017). Hypothalamic lipid-laden astrocytes induce microglia migration and activation. FEBS Lett. 591 1742– 1751. 10.1002/1873-3468.12691 28542876 · DOI · Paper page
  60. Lass A. Zimmermann R. Haemmerle G. Riederer M. Schoiswohl G. Schweiger M. (2006). Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab. 3 309– 319. 10.1016/j.cmet.2006.03.005 16679289 · DOI
  61. Lee J. Homma T. Kurahashi T. Kang E. S. Fujii J. (2015). Oxidative stress triggers lipid droplet accumulation in primary cultured hepatocytes by activating fatty acid synthesis. Biochem. Biophys. Res. Commun. 464 229– 235. 10.1016/j.bbrc.2015.06.121 26116535 · DOI
  62. Lee L. L. Aung H. H. Wilson D. W. Anderson S. E. Rutledge J. C. Rutkowsky J. M. (2017). Triglyceride-rich lipoprotein lipolysis products increase blood-brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress. Am. J. Physiol. Cell Physiol. 312 C500– C516. 28077357 PMC5407020
  63. Lee S. C. Moore G. R. Golenwsky G. Raine C. S. (1990). Multiple sclerosis: a role for astroglia in active demyelination suggested by class II MHC expression and ultrastructural study. J. Neuropathol. Exp. Neurol. 49 122– 136. 10.1097/00005072-199003000-00005 2307980 · DOI · Paper page
  64. Lee S.-J. Zhang J. Choi A. M. K. Kim H. P. (2013). Mitochondrial dysfunction induces formation of lipid droplets as a generalized response to stress. Oxid. Med. Cell. Longev. 2013: 327167. PMC3794647 24175011
  65. Libby A. E. Wang H. Mittal R. Sungelo M. Potma E. Eckel R. H. (2015). Lipoprotein lipase is an important modulator of lipid uptake and storage in hypothalamic neurons. Biochem. Biophys. Res. Commun. 465 287– 292. 10.1016/j.bbrc.2015.08.026 26265042 PMC4565155 · DOI
  66. Liberski P. P. Yanagihara R. Gibbs C. J. Jr. Gajdusek D. C. (1989). White matter ultrastructural pathology of experimental Creutzfeldt-Jakob disease in mice. Acta Neuropathol. 79 1– 9. 10.1007/bf00308949 2686336 · DOI
  67. Liu L. Mackenzie K. R. Putluri N. Maletic-Savatic M. Bellen H. J. (2017). The glia-neuron lactate shuttle and elevated ROS promote lipid synthesis in neurons and lipid droplet accumulation in Glia via APOE/D. Cell Metab. 26 719– 737.e716. 28965825 PMC5677551
  68. Liu Y. Wang T. Ji Y. J. Johnson K. Liu H. Johnson K. (2018). A C9orf72-CARM1 axis regulates lipid metabolism under glucose starvation-induced nutrient stress. Genes Dev. 32 1380– 1397. 10.1101/gad.315564.118 30366907 PMC6217731 · DOI
  69. Lo Giudice T. Lombardi F. Santorelli F. M. Kawarai T. Orlacchio A. (2014). Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms. Exp. Neurol. 261 518– 539. 10.1016/j.expneurol.2014.06.011 24954637 · DOI
  70. Lucken-Ardjomande Hasler S. Vallis Y. Jolin H. E. Mckenzie A. N. Mcmahon H. T. (2014). GRAF1a is a brain-specific protein that promotes lipid droplet clustering and growth, and is enriched at lipid droplet junctions. J. Cell Sci. 127 4602– 4619. 10.1242/jcs.147694 25189622 PMC4215711 · DOI
  71. Marasigan S. M. Sato M. Miyoshi K. (1986). Experimental striatal degeneration induced by kainic acid administration: relevance to morphological changes in Huntington’s disease. Jpn. J. Psychiatry Neurol. 40 113– 121. 10.1111/j.1440-1819.1986.tb01618.x 2945956 · DOI
  72. Marcos A. L. Corradi G. R. Mazzitelli L. R. Casali C. I. Fernandez Tome M. D. C. Adamo H. P. (2019). The Parkinson-associated human P5B-ATPase ATP13A2 modifies lipid homeostasis. Biochim. Biophys. Acta Biomembr. 1861: 182993. 10.1016/j.bbamem.2019.05.015 31132336 · DOI
  73. McColgan P. Tabrizi S. J. (2018). Huntington’s disease: a clinical review. Eur. J. Neurol. 25 24– 34. 28817209
  74. Meng H. Wang M. Liu H. Liu X. Situ A. Wu B. (2015). Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice. ACS Nano 9 3540– 3557. 10.1021/acsnano.5b00510 25776964 PMC4415452 · DOI
  75. Meyers A. Chourey K. Weiskittel T. M. Pfiffner S. Dunlap J. R. Hettich R. L. (2017). The protein and neutral lipid composition of lipid droplets isolated from the fission yeast, Schizosaccharomyces pombe. J. Microbiol. 55 112– 122. 10.1007/s12275-017-6205-1 28120187 · DOI
  76. Missaglia S. Coleman R. A. Mordente A. Tavian D. (2019). Neutral lipid storage diseases as cellular model to study lipid droplet function. Cells 8: 187. 10.3390/cells8020187 30795549 PMC6406896 · DOI
  77. Miyazu K. Kobayashi K. Fukutani Y. Nakamura I. Hasegawa H. Yamaguchi N. (1991). Membranous lipodystrophy (Nasu-Hakola disease) with thalamic degeneration: report of an autopsied case. Acta Neuropathol. 82 414– 419. 10.1007/bf00296554 1722609 · DOI
  78. Montesinos J. Guardia-Laguarta C. Area-Gomez E. (2020). The fat brain. Curr. Opin. Clin. Nutr. Metab. Care 23 68– 75. 32004239
  79. Murphy R. C. Hankin J. A. Barkley R. M. (2009). Imaging of lipid species by MALDI mass spectrometry. J. Lipid Res. 50 S317– S322. 19050313 PMC2674737
  80. Nakai Y. Shioda S. Tashiro N. Honma Y. (1979). Fine structures of the cerebrospinal fluid-contacting neurons in the hypothalamus of the lamprey, Lampetra japonica. Arch. Histol. Jpn. 42 337– 353. 10.1679/aohc1950.42.337 539889 · DOI
  81. Nakajima S. Gotoh M. Fukasawa K. Murakami-Murofushi K. Kunugi H. (2019). Oleic acid is a potent inducer for lipid droplet accumulation through its esterification to glycerol by diacylglycerol acyltransferase in primary cortical astrocytes. Brain Res. 1725: 146484. 10.1016/j.brainres.2019.146484 31562840 · DOI
  82. Nguyen T. B. Louie S. M. Daniele J. R. Tran Q. Dillin A. Zoncu R. (2017). DGAT1-dependent lipid droplet biogenesis protects mitochondrial function during starvation-induced autophagy. Dev. Cell 42 9– 21.e25. 28697336 PMC5553613
  83. Ogrodnik M. Zhu Y. Langhi L. G. P. Tchkonia T. Kruger P. Fielder E. (2019). Obesity-induced cellular senescence drives anxiety and impairs neurogenesis. Cell Metab. 29: 1233. 10.1016/j.cmet.2019.01.013 31067450 PMC6509279 · DOI · Paper page
  84. Olzmann J. A. Carvalho P. (2019). Dynamics and functions of lipid droplets. Nat. Rev. Mol. Cell Biol. 20 137– 155. 10.1038/s41580-018-0085-z 30523332 PMC6746329 · DOI · Paper page
  85. Outeiro T. F. Lindquist S. (2003). Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 302 1772– 1775. 10.1126/science.1090439 14657500 PMC1780172 · DOI
  86. Ozsvar A. Szipocs R. Ozsvar Z. Baka J. Barzo P. Tamas G. (2018). Quantitative analysis of lipid debris accumulation caused by cuprizone induced myelin degradation in different CNS areas. Brain Res. Bull. 137 277– 284. 10.1016/j.brainresbull.2018.01.003 29325992 · DOI
  87. Papadopoulos C. Orso G. Mancuso G. Herholz M. Gumeni S. Tadepalle N. (2015). Spastin binds to lipid droplets and affects lipid metabolism. PLoS Genet. 11: e1005149. 10.1371/journal.pgen.1005149 25875445 PMC4395272 · DOI
  88. Paula-Barbosa M. M. Cardoso R. M. Guimaraes M. L. Cruz C. (1980). Dendritic degeneration and regrowth in the cerebral cortex of patients with Alzheimer’s disease. J. Neurol. Sci. 45 129– 134. 10.1016/s0022-510x(80)80014-1 7359162 · DOI
  89. Pennetta G. Welte M. A. (2018). Emerging links between lipid droplets and motor neuron diseases. Dev. Cell 45 427– 432. 10.1016/j.devcel.2018.05.002 29787708 PMC5988256 · DOI
  90. Puchkov D. Haucke V. (2013). Greasing the synaptic vesicle cycle by membrane lipids. Trends Cell Biol. 23 493– 503. 10.1016/j.tcb.2013.05.002 23756446 · DOI
  91. Puri V. Konda S. Ranjit S. Aouadi M. Chawla A. Chouinard M. (2007). Fat-specific protein 27, a novel lipid droplet protein that enhances triglyceride storage. J. Biol. Chem. 282 34213– 34218. 10.1074/jbc.m707404200 17884815 · DOI
  92. Puri V. Ranjit S. Konda S. Nicoloro S. M. Straubhaar J. Chawla A. (2008). Cidea is associated with lipid droplets and insulin sensitivity in humans. Proc. Natl. Acad. Sci. U.S.A. 105 7833– 7838. 10.1073/pnas.0802063105 18509062 PMC2409392 · DOI
  93. Rambold A. S. Cohen S. Lippincott-Schwartz J. (2015). Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev. Cell 32 678– 692. 10.1016/j.devcel.2015.01.029 25752962 PMC4375018 · DOI · Paper page
  94. Rawish E. Nickel L. Schuster F. Stolting I. Frydrychowicz A. Saar K. (2020). Telmisartan prevents development of obesity and normalizes hypothalamic lipid droplets. J. Endocrinol. 244 95– 110. 10.1530/joe-19-0319 31585441 · DOI
  95. Renvoisé B. Stadler J. Singh R. Bakowska J. C. Blackstone C. (2012). Spg20-/- mice reveal multimodal functions for Troyer syndrome protein spartin in lipid droplet maintenance, cytokinesis and BMP signaling. Hum. Mol. Genet. 21 3604– 3618. 10.1093/hmg/dds191 22619377 PMC3406757 · DOI
  96. Saka H. A. Valdivia R. (2012). Emerging roles for lipid droplets in immunity and host-pathogen interactions. Annu. Rev. Cell Dev. Biol. 28 411– 437. 10.1146/annurev-cellbio-092910-153958 22578141 · DOI
  97. Sanhueza M. Chai A. Smith C. Mccray B. A. Simpson T. I. Taylor J. P. (2015). Network analyses reveal novel aspects of ALS pathogenesis. PLoS Genet. 11: e1005107. 10.1371/journal.pgen.1005107 25826266 PMC4380362 · DOI
  98. Scherzer C. R. Feany M. B. (2004). Yeast genetics targets lipids in Parkinson’s disease. Trends Genet. 20 273– 277. 10.1016/j.tig.2004.05.005 15219388 · DOI
  99. Scherzer C. R. Jensen R. V. Gullans S. R. Feany M. B. (2003). Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson’s disease. Hum. Mol. Genet. 12 2457– 2466. 10.1093/hmg/ddg265 12915459 · DOI
  100. Shimabukuro M. K. Langhi L. G. P. Cordeiro I. Brito J. M. Batista C. M. D. C. Mattson M. P. (2016). Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes. Sci. Rep. 6: 23795. PMC4814830 27029648
  101. Simpson E. P. Henry Y. K. Henkel J. S. Smith R. G. Appel S. H. (2004). Increased lipid peroxidation in sera of ALS patients: a potential biomarker of disease burden. Neurology 62 1758– 1765. 10.1212/wnl.62.10.1758 15159474 · DOI
  102. Smialek M. Gajkowska B. Ostrowski R. P. Piotrowski P. (1997). Experimental squalene encephaloneuropathy in the rat. Folia Neuropathol. 35 262– 264. 9833408
  103. Stokreef J. C. Reifel C. W. Shin S. H. (1986). A possible phagocytic role for folliculo-stellate cells of anterior pituitary following estrogen withdrawal from primed male rats. Cell Tissue Res. 243 255– 261. 3948235
  104. Stoll E. A. Makin R. Sweet I. R. Trevelyan A. J. Miwa S. Horner P. J. (2015). Neural stem cells in the adult subventricular zone oxidize fatty acids to produce energy and support neurogenic activity. Stem Cells 33 2306– 2319. 10.1002/stem.2042 25919237 PMC4478223 · DOI
  105. Sturrock R. R. (1980). A comparative quantitative and morphological study of ageing in the mouse neostriatum, indusium griseum and anterior commissure. Neuropathol. Appl. Neurobiol. 6 51– 68. 10.1111/j.1365-2990.1980.tb00204.x 7374912 · DOI
  106. Sturrock R. R. (1983). A light microscopic and scanning electron microscopic study of intraventricular macrophages in the brains of aged mice. J. Anat. 136 761– 771. 6885627 PMC1171959
  107. Sturrock R. R. (1988). An ultrastructural study of intraventricular macrophages in the brains of aged mice. Anat. Anz. 165 283– 290. 3400892
  108. Sztalryd C. Brasaemle D. L. (2017). The perilipin family of lipid droplet proteins: gatekeepers of intracellular lipolysis. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1862 1221– 1232. 10.1016/j.bbalip.2017.07.009 28754637 PMC5595658 · DOI
  109. Tambini M. D. Pera M. Kanter E. Yang H. Guardia-Laguarta C. Holtzman D. (2016). ApoE4 upregulates the activity of mitochondria-associated ER membranes. EMBO Rep. 17 27– 36. 10.15252/embr.201540614 26564908 PMC4718413 · DOI · Paper page
  110. Ueno M. Sakamoto H. Kanenishi K. Onodera M. Akiguchi I. Hosokawa M. (2001). Ultrastructural and permeability features of microvessels in the hippocampus, cerebellum and pons of senescence-accelerated mice (SAM). Neurobiol. Aging 22 469– 478. 10.1016/s0197-4580(01)00213-5 11378254 · DOI
  111. Urbanczyk A. Enz R. (2011). Spartin recruits PKC-ζ via the PKC-ζ-interacting proteins ZIP1 and ZIP3 to lipid droplets. J. Neurochem. 118 737– 748. 10.1111/j.1471-4159.2011.07367.x 21707618 · DOI
  112. Vandoorne T. De Bock K. Van Den Bosch L. (2018). Energy metabolism in ALS: an underappreciated opportunity? Acta Neuropathol. 135 489– 509. 10.1007/s00401-018-1835-x 29549424 PMC5978930 · DOI
  113. Walther T. C. Chung J. Farese R. V. Jr. (2017). Lipid droplet biogenesis. Annu. Rev. Cell Dev. Biol. 33 491– 510. 28793795 PMC6986389
  114. Walther T. C. Farese R. V. Jr. (2012). Lipid droplets and cellular lipid metabolism. Annu. Rev. Biochem. 81 687– 714. 22524315 PMC3767414
  115. Wang H. Bell M. Sreenivasan U. Hu H. Liu J. Dalen K. (2011). Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a lipid droplet-associated protein. J. Biol. Chem. 286 15707– 15715. 21393244 PMC3091179
  116. Welte M. A. (2015). Expanding roles for lipid droplets. Curr. Biol. 25 R470– R481. 26035793 PMC4452895
  117. Wilfling F. Wang H. Haas J. T. Krahmer N. Gould T. J. Uchida A. (2013). Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets. Dev. Cell 24 384– 399. 23415954 PMC3727400
  118. Yagi T. Ito D. Nihei Y. Ishihara T. Suzuki N. (2011). N88S seipin mutant transgenic mice develop features of seipinopathy/BSCL2-related motor neuron disease via endoplasmic reticulum stress. Hum. Mol. Genet. 20 3831– 3840. 21750110
  119. Yin C. Ackermann S. Ma Z. Mohanta S. K. Zhang C. Li Y. (2019). ApoE attenuates unresolvable inflammation by complex formation with activated C1q. Nat. Med. 25 496– 506. 30692699 PMC6420126
  120. Zechner R. Zimmermann R. Eichmann T. O. Kohlwein S. D. Haemmerle G. Lass A. (2012). FAT SIGNALS–lipases and lipolysis in lipid metabolism and signaling. Cell Metab. 15 279– 291. 22405066 PMC3314979
  121. Zehmer J. K. Huang Y. Peng G. Pu J. Anderson R. G. W. Liu P. (2009). A role for lipid droplets in inter-membrane lipid traffic. Proteomics 9 914– 921. 19160396 PMC2676673
  122. Zhang J. Liu Q. (2015). Cholesterol metabolism and homeostasis in the brain. Protein Cell 6 254– 264. 25682154 PMC4383754
  123. Zhu Y. Chen C. Y. Li J. Cheng J. X. Jang M. Kim K. H. (2018). In vitro exploration of ACAT contributions to lipid droplet formation during adipogenesis. J. Lipid Res. 59 820– 829. 29549095 PMC5928425

Cited by

Sorted by citations

Authors
Farmer, B. C., Walsh, A. E., Kluemper, J. C., & Johnson, L. A.
Affiliations
University of Kentucky (US)
Corresponding author
Johnson, Lance A.
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2020-07-29
Volume
14
Pages
742-742
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2020.00742
PMC
PMC7403481
OpenAlex
W3046107762
Cited by
270
References
13
Citations by year
2026: 48 · 2025: 49 · 2024: 58 · 2023: 37 · 2022: 49 · 2021: 22 · 2020: 7
FWCI
2.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute on Aging (F30AG063422, R01AG062550, R01AG060056)
  • National Institute of General Medical Sciences (GM-103527, P20GM103527)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
lipid droplets, neurodegenerative diseases, lipid metabolism, signal transduction, inflammation, central nervous system, neurodegeneration

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review