diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM10251diaendo-10251Research ArticleОбзорыReviewРоль внутриклеточных жировых включений в возникновении сахарного диабета 2 типаThe role of lipid droplets in the emergence of diabetes mellitus type 2https://orcid.org/0000-0002-3174-1560АстаховаЛидия ВалентиновнаAstakhovaL. V.

м.н.с.

junior research associate

astahovalidiya@mail.ruhttps://orcid.org/0000-0001-6780-1820КацеровДмитрий СергеевичKatserovD. S.

аспирант 

PhD student

dkatze39@gmail.comhttps://orcid.org/0000-0002-3174-1560МацковаЛюдмила ВалентиновнаMatskovaL. V.

в.н.с.

PhD, leading research associate

liudmila.matskova@ki.seБалтийский федеральный университет им. Иммануила КантаРоссияImmanuel Kant Baltic Federal UniversityRussian FederationБалтийский федеральный университет им. Иммануила Канта; Каролинский институт; Каролинский институтРоссияImmanuel Kant Baltic Federal University; Karolinska InstitutetRussian Federation202010082020233267274Copyright © Астахова Л.В., Кацеров Д.С., Мацкова Л.В., 20202020Астахова Л.В., Кацеров Д.С., Мацкова Л.В.Astakhova L.V., Katserov D.S., Matskova L.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/10251

Темпы роста распространенности сахарного диабета (CД) во всем мире и в России, в частности, и сопутствующих ему патологий, а также недостаточная эффективность антидиабетической терапии свидетельствуют о пробелах в понимании механизмов возникновения и течения этого заболевания. Известно, что метаболические нарушения, являющиеся причиной возникновения СД 2 типа (СД2), обусловлены нарушениями в митохондриальной активности и, как следствие, нарушениями окисления жирных кислот и уровня триглицеридов, что может приводить к накоплению внутриклеточных жировых включений (ЖВ) и инсулинорезистентности. В обзоре представлено текущее состояние знаний о новых клеточных структурах, ЖВ как сопутствующем признаке СД2. Дается биохимическая и функциональная характеристика ЖВ. Обсуждается их возможная роль в возникновении и развитии СД2. Рассматривается взаимовлияние ЖВ и митохондрий, влияние ЖВ на нервную систему. Особое внимание уделяется освещению влияния микробиоты желудочно-кишечного тракта (ЖКТ) на динамику возникновения ЖВ. Микробиота ЖКТ играет важную роль в развитии и течении многих заболеваний человека, связанных с нарушениями метаболизма. Знание взаимосвязей между микробиотой ЖКТ и динамикой возникновения ЖВ позволит выявить скрытые аспекты молекулярного механизма функционирования митохондрий, что дает перспективу превентивным подходам в лечении ожирения, метаболических нарушений и СД2.

The increased incidence of diabetes mellitus type 2 (DM2T) all over the world and in Russia in particular, indicates a lack of effectiveness of antidiabetic therapy and suggests the existence of gaps in the understanding of the mechanisms of onset and clinical course of this disease as well as a concomitant lack of effectiveness of antidiabetic therapy. It is known that metabolic disorders that cause DM2T are caused by disturbances in mitochondrial activity resulting in increased cellular fatty acid inclusions and insulin resistance. The present review presents the current state of knowledge about new cellular structures, fat inclusions or, using a more conventional term, lipid droplets (LDs), as a pathological feature accompanying the occurrence of DM2T. The review describes the biochemical and functional characteristics of LDs and their possible role in the onset and development of diabetes. The interrelationship of LDs and mitochondria and the effect of LDs on the nervous system are considered. Particular attention is paid to highlighting the effect of the microbiota of the gastrointestinal tract on the dynamics of the emergence of LDs. The GIT microbiota plays an important role in the development and course of many human diseases associated with metabolic disorders. Further knowledge of the relationship between the gastrointestinal microbiota and the dynamics of LD emergence will uncover new aspects of the molecular mechanism of mitochondrial function, which gives the prospect of preventive approaches in the treatment of obesity, metabolic disorders and diabetes.

сахарный диабетжировые включениямитохондриимикробиотаинсулинметаболическая болезньdiabetes mellitusfatty inclusionslipid dropletsmitochondriamicrobiotainsulinmetabolic diseaseReferencesGross DA, Silver DL. Cytosolic lipid droplets: from mechanisms of fat storage to disease. Crit Rev Biochem Mol Biol. 2014;49(4):304–326. doi: https://doi.org/10.3109/10409238.2014.931337Gross DA, Silver DL. Cytosolic lipid droplets: from mechanisms of fat storage to disease. Crit Rev Biochem Mol Biol. 2014;49(4):304–326. doi: https://doi.org/10.3109/10409238.2014.931337Walther TC, Farese RV Jr. Lipid droplets and cellular lipid metabolism. Annu Rev Biochem. 2012;81:687–714. doi: https://doi.org/10.1146/annurev-biochem-061009-102430Walther TC, Farese RV Jr. Lipid droplets and cellular lipid metabolism. Annu Rev Biochem. 2012;81:687–714. doi: https://doi.org/10.1146/annurev-biochem-061009-102430Saka HA, Valdivia R. Emerging roles for lipid droplets in immunity and host-pathogen interactions. Annu Rev Cell Dev Biol. 2012;28:411–437. doi: https://doi.org/10.1146/annurev-cellbio-092910-153958Saka HA, Valdivia R. Emerging roles for lipid droplets in immunity and host-pathogen interactions. Annu Rev Cell Dev Biol. 2012;28:411–437. doi: https://doi.org/10.1146/annurev-cellbio-092910-153958Pol A, Gross SP, Parton RG. Review: biogenesis of the multifunctional lipid droplet: lipids, proteins, and sites. J Cell Biol. 2014;204(5):635–646. doi: https://doi.org/10.1083/jcb.201311051Pol A, Gross SP, Parton RG. Review: biogenesis of the multifunctional lipid droplet: lipids, proteins, and sites. J Cell Biol. 2014;204(5):635–646. doi: https://doi.org/10.1083/jcb.201311051Guo Y, Cordes KR, Farese RV Jr, Walther TC. Lipid droplets at a glance. J Cell Sci. 2009;122(Pt 6):749–752. doi: https://doi.org/10.1242/jcs.037630Guo Y, Cordes KR, Farese RV Jr, Walther TC. Lipid droplets at a glance. J Cell Sci. 2009;122(Pt 6):749–752. doi: https://doi.org/10.1242/jcs.037630Onal G, Kutlu O, Gozuacik D, Dokmeci Emre S. Lipid droplets in health and disease. Lipids Health Dis. 2017;16(1):128. doi: https://doi.org/10.1186/s12944-017-0521-7Onal G, Kutlu O, Gozuacik D, Dokmeci Emre S. Lipid droplets in health and disease. Lipids Health Dis. 2017;16(1):128. doi: https://doi.org/10.1186/s12944-017-0521-7Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365(9467):1333–1346. doi: https://doi.org/10.1016/S0140-6736(05)61032-XStumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365(9467):1333–1346. doi: https://doi.org/10.1016/S0140-6736(05)61032-XKassan A, Herms A, Fernández-Vidal A, et al. Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains. J Cell Biol. 2013;203(6):985–1001. doi: https://doi.org/10.1083/jcb.201305142Kassan A, Herms A, Fernández-Vidal A, et al. Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains. J Cell Biol. 2013;203(6):985–1001. doi: https://doi.org/10.1083/jcb.201305142Wilfling F, Wang H, Haas JT, et al. Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets. Dev Cell. 2013;24(4):384–399. doi: https://doi.org/10.1016/j.devcel.2013.01.013Wilfling F, Wang H, Haas JT, et al. Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets. Dev Cell. 2013;24(4):384–399. doi: https://doi.org/10.1016/j.devcel.2013.01.013Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133–2223. doi: https://doi.org/10.1152/physrev.00063.2017Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133–2223. doi: https://doi.org/10.1152/physrev.00063.2017Jeukendrup AE. Regulation of fat metabolism in skeletal muscle. Ann N Y Acad Sci. 2002;967:217–235. doi: https://doi.org/10.1111/j.1749-6632.2002.tb04278.xJeukendrup AE. Regulation of fat metabolism in skeletal muscle. Ann N Y Acad Sci. 2002;967:217–235. doi: https://doi.org/10.1111/j.1749-6632.2002.tb04278.xOlofsson SO, Andersson L, Håversen L, et al. The formation of lipid droplets: possible role in the development of insulin resistance/type 2 diabetes. Prostaglandins Leukot Essent Fatty Acids. 2011;85(5):215–218. doi: https://doi.org/10.1016/j.plefa.2011.04.019Olofsson SO, Andersson L, Håversen L, et al. The formation of lipid droplets: possible role in the development of insulin resistance/type 2 diabetes. Prostaglandins Leukot Essent Fatty Acids. 2011;85(5):215–218. doi: https://doi.org/10.1016/j.plefa.2011.04.019Kaushik S, Cuervo AM. “AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA”. Autophagy. 2016;12(2):432–438. doi: https://doi.org/10.1080/15548627.2015.1124226Kaushik S, Cuervo AM. “AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA”. Autophagy. 2016;12(2):432–438. doi: https://doi.org/10.1080/15548627.2015.1124226Zechner R, Zimmermann R, Eichmann TO, et al. Signals-lipases and lipolysis in lipid metabolism and signaling. Cell Metab. 2012;15(3):279–291. doi: https://doi.org/10.1016/j.cmet.2011.12.018Zechner R, Zimmermann R, Eichmann TO, et al. Signals-lipases and lipolysis in lipid metabolism and signaling. Cell Metab. 2012;15(3):279–291. doi: https://doi.org/10.1016/j.cmet.2011.12.018Singh R, Kaushik S, Wang Y, et al. Autophagy regulates lipid metabolism. Nature. 2009;458(7242):1131–1135. doi: https://doi.org/10.1038/nature07976Singh R, Kaushik S, Wang Y, et al. Autophagy regulates lipid metabolism. Nature. 2009;458(7242):1131–1135. doi: https://doi.org/10.1038/nature07976Aramburu J, Drews-Elger K, Estrada-Gelonch A, et al. Regulation of the hypertonic stress response and other cellular functions by the Rel-like transcription factor NFAT5. Biochem Pharmacol. 2006;72(11):1597–1604. doi: https://doi.org/10.1016/j.bcp.2006.07.002Aramburu J, Drews-Elger K, Estrada-Gelonch A, et al. Regulation of the hypertonic stress response and other cellular functions by the Rel-like transcription factor NFAT5. Biochem Pharmacol. 2006;72(11):1597–1604. doi: https://doi.org/10.1016/j.bcp.2006.07.002Jambunathan S, Yin J, Khan W, et al. FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation. PLoS One. 2011;6(12):e28614. doi: https://doi.org/10.1371/journal.pone.0028614Jambunathan S, Yin J, Khan W, et al. FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation. PLoS One. 2011;6(12):e28614. doi: https://doi.org/10.1371/journal.pone.0028614Gong J, Sun Z, Wu L, et al. Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites. J Cell Biol. 2011;195(6):953–963. doi: https://doi.org/10.1083/jcb.201104142Gong J, Sun Z, Wu L, et al. Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites. J Cell Biol. 2011;195(6):953–963. doi: https://doi.org/10.1083/jcb.201104142Ueno M, Shen WJ, Patel S, et al. Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress. J Lipid Res. 2013;54(3):734–743. doi: https://doi.org/10.1194/jlr.M033365Ueno M, Shen WJ, Patel S, et al. Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress. J Lipid Res. 2013;54(3):734–743. doi: https://doi.org/10.1194/jlr.M033365Uzbekov R, Roingeard P. Nuclear lipid droplets identified by electron microscopy of serial sections. BMC Res Notes. 2013;6:386. doi: https://doi.org/10.1186/1756-0500-6-386Uzbekov R, Roingeard P. Nuclear lipid droplets identified by electron microscopy of serial sections. BMC Res Notes. 2013;6:386. doi: https://doi.org/10.1186/1756-0500-6-386Haemmerle G, Moustafa T, Woelkart G, et al. ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1. Nat Med. 2011;17(9):1076–1085. doi: https://doi.org/10.1038/nm.2439Haemmerle G, Moustafa T, Woelkart G, et al. ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1. Nat Med. 2011;17(9):1076–1085. doi: https://doi.org/10.1038/nm.2439Lefebvre P, Chinetti G, Fruchart JC, Staels B. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest. 2006;116(3):571–580. doi: https://doi.org/10.1172/JCI27989Lefebvre P, Chinetti G, Fruchart JC, Staels B. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest. 2006;116(3):571–580. doi: https://doi.org/10.1172/JCI27989Supruniuk E, Mikłosz A, Chabowski A. The Implication of PGC-1α on Fatty Acid Transport across Plasma and Mitochondrial Membranes in the Insulin Sensitive Tissues. Front Physiol. 2017;8:923. doi: https://doi.org/10.3389/fphys.2017.00923Supruniuk E, Mikłosz A, Chabowski A. The Implication of PGC-1α on Fatty Acid Transport across Plasma and Mitochondrial Membranes in the Insulin Sensitive Tissues. Front Physiol. 2017;8:923. doi: https://doi.org/10.3389/fphys.2017.00923Shaw CS, Jones DA, Wagenmakers AJ. Network distribution of mitochondria and lipid droplets in human muscle fibres. Histochem Cell Biol. 2008;129(1):65–72. doi: https://doi.org/10.1007/s00418-007-0349-8Shaw CS, Jones DA, Wagenmakers AJ. Network distribution of mitochondria and lipid droplets in human muscle fibres. Histochem Cell Biol. 2008;129(1):65–72. doi: https://doi.org/10.1007/s00418-007-0349-8Tarnopolsky MA, Rennie CD, Robertshaw HA, et al. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am J Physiol Regul Integr Comp Physiol. 2007;292(3):R1271–1278. doi: https://doi.org/10.1152/ajpregu.00472.2006Tarnopolsky MA, Rennie CD, Robertshaw HA, et al. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity. Am J Physiol Regul Integr Comp Physiol. 2007;292(3):R1271–1278. doi: https://doi.org/10.1152/ajpregu.00472.2006Amati F. Revisiting the diacylglycerol-induced insulin resistance hypothesis. Obes. Rev. 2012;13:40–50. doi: https://doi.org/10.1111/j.1467-789X.2012.01036.xAmati F. Revisiting the diacylglycerol-induced insulin resistance hypothesis. Obes. Rev. 2012;13:40–50. doi: https://doi.org/10.1111/j.1467-789X.2012.01036.xEiden M, Koulman A, Hatunic M, et al. Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes. Genome Med. 2015;7:63. doi: https://doi.org/10.1186/s13073-015-0179-6Eiden M, Koulman A, Hatunic M, et al. Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes. Genome Med. 2015;7:63. doi: https://doi.org/10.1186/s13073-015-0179-6Sergi D, Naumovski N, Heilbronn LK, et al. Mitochondrial (Dys)function and insulin resistance: from pathophysiological molecular mechanisms to the impact of diet. Front Physiol. 2019;10:532. doi: https://doi.org/10.3389/fphys.2019.00532Sergi D, Naumovski N, Heilbronn LK, et al. Mitochondrial (Dys)function and insulin resistance: from pathophysiological molecular mechanisms to the impact of diet. Front Physiol. 2019;10:532. doi: https://doi.org/10.3389/fphys.2019.00532Gordaliza-Alaguero I, Cantó C, Zorzano A. Metabolic implications of organelle-mitochondria communication. EMBO Rep. 2019;20(9):e47928. doi: https://doi.org/10.15252/embr.201947928Gordaliza-Alaguero I, Cantó C, Zorzano A. Metabolic implications of organelle-mitochondria communication. EMBO Rep. 2019;20(9):e47928. doi: https://doi.org/10.15252/embr.201947928Skuratovskaia D, Litvinova L, Vulf M, et al. From normal to obesity and back: the associations between mitochondrial DNA copy number, gender, and body mass index. Cells. 2019;8(5):430. doi: https://doi.org/https://doi.org/10.3390/cells8050430Skuratovskaia D, Litvinova L, Vulf M, et al. From normal to obesity and back: the associations between mitochondrial DNA copy number, gender, and body mass index. Cells. 2019;8(5):430. doi: https://doi.org/https://doi.org/10.3390/cells8050430Gordaliza-Alaguero I, Cantó C, Zorzano A. Metabolic implications of organelle-mitochondria communication. EMBO Rep. 2019;20(9):e47928. doi: https://doi.org/10.15252/embr.201947928Gordaliza-Alaguero I, Cantó C, Zorzano A. Metabolic implications of organelle-mitochondria communication. EMBO Rep. 2019;20(9):e47928. doi: https://doi.org/10.15252/embr.201947928Hoppins S. The regulation of mitochondrial dynamics. Curr Opin Cell Biol. 2014;29:46–52. doi: https://doi.org/10.1016/j.ceb.2014.03.005Hoppins S. The regulation of mitochondrial dynamics. Curr Opin Cell Biol. 2014;29:46–52. doi: https://doi.org/10.1016/j.ceb.2014.03.005Olzmann JA, Carvalho P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 2019;20(3):137–155. doi: https://doi.org/10.1038/s41580-018-0085-zOlzmann JA, Carvalho P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 2019;20(3):137–155. doi: https://doi.org/10.1038/s41580-018-0085-zRambold AS, Cohen S, Lippincott-Schwartz J. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis,autophagy, and mitochondrial fusion dynamics. Dev Cell. 2015;32(6):678–692. doi: https://doi.org/10.1016/j.devcel.2015.01.029Rambold AS, Cohen S, Lippincott-Schwartz J. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis,autophagy, and mitochondrial fusion dynamics. Dev Cell. 2015;32(6):678–692. doi: https://doi.org/10.1016/j.devcel.2015.01.029Li Z, Thiel K, Thul PJ, et al. Lipid droplets control the maternal histone supply of drosophila embryos. Curr Biol. 2012;22(22):2104–2113. doi: https://doi.org/10.1016/j.cub.2012.09.018Li Z, Thiel K, Thul PJ, et al. Lipid droplets control the maternal histone supply of drosophila embryos. Curr Biol. 2012;22(22):2104–2113. doi: https://doi.org/10.1016/j.cub.2012.09.018Strauss JA, Shaw CS, Bradley H, et al. Immunofluorescence microscopy of SNAP23 in human skeletal muscle reveals colocalization with plasma membrane, lipid droplets, and mitochondria. Physiol Rep. 2016;4(1). pii: e12662. doi: https://doi.org/10.14814/phy2.12662Strauss JA, Shaw CS, Bradley H, et al. Immunofluorescence microscopy of SNAP23 in human skeletal muscle reveals colocalization with plasma membrane, lipid droplets, and mitochondria. Physiol Rep. 2016;4(1). pii: e12662. doi: https://doi.org/10.14814/phy2.12662Wang H, Sreenivasan U, Hu H, et al. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J Lipid Res. 2011;52(12):2159–2168. doi: https://doi.org/10.1194/jlr.M017939Wang H, Sreenivasan U, Hu H, et al. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J Lipid Res. 2011;52(12):2159–2168. doi: https://doi.org/10.1194/jlr.M017939Granneman JG, Moore HP, Mottillo EP, et al. Interaction of perilipin-5(Plin5) with adipose triglyceride lipase. J Biol Chem. 2011;286(7)5126–5135. doi: https://doi.org/10.1074/jbc.M110.180711Granneman JG, Moore HP, Mottillo EP, et al. Interaction of perilipin-5(Plin5) with adipose triglyceride lipase. J Biol Chem. 2011;286(7)5126–5135. doi: https://doi.org/10.1074/jbc.M110.180711Boutant M, Kulkarni SS, Joffraud M, et al. Mfn2 is critical for brown adipose tissue thermogenic function. EMBO J. 2017;36(11):1543–1558. doi: https://doi.org/10.15252/embj.201694914Boutant M, Kulkarni SS, Joffraud M, et al. Mfn2 is critical for brown adipose tissue thermogenic function. EMBO J. 2017;36(11):1543–1558. doi: https://doi.org/10.15252/embj.201694914Cermelli S, Guo Y, Gross SP, Welte MA. The lipid-droplet proteome reveals that droplets are a protein-storage depot. Curr Biol. 2006;16(18):1783–1795. doi: https://doi.org/10.1016/j.cub.2006.07.062Cermelli S, Guo Y, Gross SP, Welte MA. The lipid-droplet proteome reveals that droplets are a protein-storage depot. Curr Biol. 2006;16(18):1783–1795. doi: https://doi.org/10.1016/j.cub.2006.07.062Herms A, Bosch M, Ariotti N, et al. Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce lipotoxicity. Curr Biol. 2013;23(15):1489–1496. doi: https://doi.org/10.1016/j.cub.2013.06.032Herms A, Bosch M, Ariotti N, et al. Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce lipotoxicity. Curr Biol. 2013;23(15):1489–1496. doi: https://doi.org/10.1016/j.cub.2013.06.032Ioannou MS, Liu Z, Lippincott-Schwartz J. A neuron-glia co-culture system for studying intercellular lipid transport. Curr Protoc Cell Biol. 2019;84(1):e95. doi: https://doi.org/10.1002/cpcb.95Ioannou MS, Liu Z, Lippincott-Schwartz J. A neuron-glia co-culture system for studying intercellular lipid transport. Curr Protoc Cell Biol. 2019;84(1):e95. doi: https://doi.org/10.1002/cpcb.95Liu Y, Chen X, Zhang Y, Liu J. Advancing single-cell proteomics and metabolomics with microfluidic technologies. Analyst. 2019;144(3):846–858. doi: https://doi.org/10.1039/c8an01503aLiu Y, Chen X, Zhang Y, Liu J. Advancing single-cell proteomics and metabolomics with microfluidic technologies. Analyst. 2019;144(3):846–858. doi: https://doi.org/10.1039/c8an01503aDavletov B, Montecucco C. Lipid function at synapses. Curr Opin Neurobiol. 2010;20(5):543–549. doi: https://doi.org/10.1016/j.conb.2010.06.008Davletov B, Montecucco C. Lipid function at synapses. Curr Opin Neurobiol. 2010;20(5):543–549. doi: https://doi.org/10.1016/j.conb.2010.06.008Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014;15(12):771–785. doi: https://doi.org/10.1038/nrn3820Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014;15(12):771–785. doi: https://doi.org/10.1038/nrn3820Cole NB, Murphy DD, Grider T, et al. Lipid droplet binding and oligomerization properties of the Parkinson’s disease protein alpha-synuclein. J Biol Chem. 2002;277(8):6344–6352. doi: https://doi.org/10.1074/jbc.M108414200Cole NB, Murphy DD, Grider T, et al. Lipid droplet binding and oligomerization properties of the Parkinson’s disease protein alpha-synuclein. J Biol Chem. 2002;277(8):6344–6352. doi: https://doi.org/10.1074/jbc.M108414200Gavgiotaki E, Filippidis G, Kalognomou M, et al. Third Harmonic Generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of BV-2 microglia cells. J Struct Biol. 2015;189(2):105–113. doi: https://doi.org/10.1016/j.jsb.2014.11.011Gavgiotaki E, Filippidis G, Kalognomou M, et al. Third Harmonic Generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of BV-2 microglia cells. J Struct Biol. 2015;189(2):105–113. doi: https://doi.org/10.1016/j.jsb.2014.11.011Liu L, Zhang K, Sandoval H, et al. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015;160(1-2):177–190. doi: https://doi.org/10.1016/j.cell.2014.12.019Liu L, Zhang K, Sandoval H, et al. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015;160(1-2):177–190. doi: https://doi.org/10.1016/j.cell.2014.12.019Walpole GF, Grinstein S, Westman J. The role of lipids in host–pathogen interactions. IUBMB Life. 2018;70(5):384–392. doi: https://doi.org/10.1002/iub.1737Walpole GF, Grinstein S, Westman J. The role of lipids in host–pathogen interactions. IUBMB Life. 2018;70(5):384–392. doi: https://doi.org/10.1002/iub.1737Herker E, Ott M. Unique ties between hepatitis C virus replication and intracellular lipids. Trends Endocrinol Metab. 2011;22(6):241–248. doi: https://doi.org/10.1016/j.tem.2011.03.004Herker E, Ott M. Unique ties between hepatitis C virus replication and intracellular lipids. Trends Endocrinol Metab. 2011;22(6):241–248. doi: https://doi.org/10.1016/j.tem.2011.03.004Hinson ER, Cresswell P. The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic alpha-helix. Proc Natl Acad Sci U S A. 2009;106(48):20452–20457. doi: https://doi.org/10.1073/pnas.0911679106Hinson ER, Cresswell P. The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic alpha-helix. Proc Natl Acad Sci U S A. 2009;106(48):20452–20457. doi: https://doi.org/10.1073/pnas.0911679106Jan HM, Chen YC, Shih YY, et al. Metabolic labelling of cholesteryl glucosides in Helicobacter pylori reveals how the uptake of human lipids enhances bacterial virulence. Chem Sci. 2016;7(9):6208–6216. doi: https://doi.org/10.1039/c6sc00889eJan HM, Chen YC, Shih YY, et al. Metabolic labelling of cholesteryl glucosides in Helicobacter pylori reveals how the uptake of human lipids enhances bacterial virulence. Chem Sci. 2016;7(9):6208–6216. doi: https://doi.org/10.1039/c6sc00889eAnand P, Cermelli S, Li Z, et al. A novel role for lipid droplets in the organismal antibacterial response. Elife. 2012;1:e00003. doi: https://doi.org/10.7554/eLife.00003Anand P, Cermelli S, Li Z, et al. A novel role for lipid droplets in the organismal antibacterial response. Elife. 2012;1:e00003. doi: https://doi.org/10.7554/eLife.00003Sheng Y, Ren H, Limbu SM, et al. The presence or absence of intestinal microbiota affects lipid deposition and related genes expression in zebrafish (danio rerio). Front Microbiol. 2018;9:1124. doi: https://doi.org/10.3389/fmicb.2018.01124Sheng Y, Ren H, Limbu SM, et al. The presence or absence of intestinal microbiota affects lipid deposition and related genes expression in zebrafish (danio rerio). Front Microbiol. 2018;9:1124. doi: https://doi.org/10.3389/fmicb.2018.01124Zanni E, Laudenzi C, Schifano E, et al. Impact of a complex food microbiota on energy metabolism in the model organism caenorhabditis elegans. Biomed Res Int. 2015;2015:621709. doi: https://doi.org/10.1155/2015/621709Zanni E, Laudenzi C, Schifano E, et al. Impact of a complex food microbiota on energy metabolism in the model organism caenorhabditis elegans. Biomed Res Int. 2015;2015:621709. doi: https://doi.org/10.1155/2015/621709Russell WR, Hoyles L, Flint HJ, Dumas ME. Colonic bacterial metabolites and human health. Curr Opin Microbiol. 2013;16(3):246–254. doi: https://doi.org/10.1016/j.mib.2013.07.002Russell WR, Hoyles L, Flint HJ, Dumas ME. Colonic bacterial metabolites and human health. Curr Opin Microbiol. 2013;16(3):246–254. doi: https://doi.org/10.1016/j.mib.2013.07.002Xiao C, Stahel P, Carreiro AL, et al. Recent advances in triacylglycerol mobilization by the gut. Trends Endocrinol Metab. 2018;29(3):151–163. doi: https://doi.org/10.1016/j.tem.2017.12.001Xiao C, Stahel P, Carreiro AL, et al. Recent advances in triacylglycerol mobilization by the gut. Trends Endocrinol Metab. 2018;29(3):151–163. doi: https://doi.org/10.1016/j.tem.2017.12.001

The authors declare that there are no conflicts of interest present.