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Autophagy: a molecular switch to regulate adipogenesis and lipolysis

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Abstract

Obesity is a complex epidemic disease caused by an imbalance of adipose tissue function that results in hyperglycemia, hyperlipidemia and insulin resistance which further develop into type 2 diabetes, cardiovascular disease and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Adipose tissue is responsible for fat storage; white adipose tissue stores excess energy as fat for availability during starvation, whereas brown adipose tissue regulates thermogenesis through fat oxidation using uncoupling protein 1. However, hypertrophic fat storage results in inflammation and increase the chances for obesity which triggers autophagy genes and lipolytic enzymes to regulate lipid metabolism. Autophagy degrades cargo molecule with the help of lysosome and redistributes the energy back to the cell. Autophagy regulates adipocyte differentiation by modulating master regulators of adipogenesis. Adipogenesis is the process which stores excessive energy in the form of lipid droplets. Lipid droplets (LD) are dynamic cellular organelles that store toxic free-fatty acids into neutral triglycerides in adipose tissue. LD activates both lipolysis and lipophagy to degrade excess triglycerides. In obese tissue, autophagy is activated via pro-inflammatory cytokines produced by surplus fat stored in the adipose tissue. This review focused on the process of autophagy and adipogenesis and the transcription factors that regulate lipogenesis and lipolysis in the adipose tissue. We have also discussed about the importance of autophagic regulation within adipose tissue which controls the onset of obesity and its associated diseases.

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References

  1. Caballero B (2007) The global epidemic of obesity: an overview. Epidemiol Rev 29(1):1–5

    Article  PubMed  Google Scholar 

  2. Unamuno X, Gómez-Ambrosi J, Rodríguez A et al (2018) Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Invest 48(9):e12997

    Article  PubMed  Google Scholar 

  3. Fuster JJ, Ouchi N, Gokce N, Walsh K (2016) Obesity-induced changes in adipose tissue microenvironment and their impact on cardiovascular disease. Circ Res 118:1786–1807. https://doi.org/10.1161/CIRCRESAHA.115.306885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Longo M, Zatterale F, Naderi J et al (2019) Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int J Mol Sci. https://doi.org/10.3390/ijms20092358

    Article  PubMed  PubMed Central  Google Scholar 

  5. Vishvanath L, Gupta RK (2019) Contribution of adipogenesis to healthy adipose tissue expansion in obesity. J Clin Invest 129(10):4022–4031

    Article  PubMed  PubMed Central  Google Scholar 

  6. Al-Sulaiti H, S. Dömling A, A. Elrayess M (2019) Mediators of impaired adipogenesis in obesity-associated insulin resistance and T2DM. In: Adipose tissue—an update

  7. Engin A (2017) The definition and prevalence of obesity and metabolic syndrome. In: Advances in experimental medicine and biology

  8. Gao M, Liu D (2019) Controlling obesity and metabolic diseases by hydrodynamic delivery of a fusion gene of exendin-4 and α1 antitrypsin. Sci Rep. https://doi.org/10.1038/s41598-019-49757-y

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lee M-W, Lee M, Oh K-J (2019) Adipose tissue-derived signatures for obesity and type 2 diabetes: adipokines, batokines and MicroRNAs. J Clin Med. https://doi.org/10.3390/jcm8060854

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lee YH, Mottillo EP, Granneman JG (2014) Adipose tissue plasticity from WAT to BAT and in between. Biochim Biophys Acta 3:358–369

    Article  Google Scholar 

  11. Yau WW, Singh BK, Lesmana R et al (2019) Thyroid hormone (T3) stimulates brown adipose tissue activation via mitochondrial biogenesis and MTOR-mediated mitophagy. Autophagy. https://doi.org/10.1080/15548627.2018.1511263

    Article  PubMed  Google Scholar 

  12. Bódis K, Roden M (2018) Energy metabolism of white adipose tissue and insulin resistance in humans. Eur J Clin Invest 48(11):e13017

    Article  PubMed  Google Scholar 

  13. Lehnig AC, Stanford KI (2018) Exercise-induced adaptations to white and brown adipose tissue. J Exp Biol 221(Suppl_1), jeb161570

  14. Zhang K, Yang X, Zhao Q, et al (2020) Review article molecular mechanism of stem cell differentiation into adipocytes and adipocyte differentiation of malignant tumor. Stem Cells Int

  15. Tang QQ, Lane MD (2012) Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem 81:715–736. https://doi.org/10.1146/annurev-biochem-052110-115718

    Article  CAS  PubMed  Google Scholar 

  16. Obregon MJ (2014) Adipose tissues and thyroid hormones. Front Physiol 5:479

    Article  PubMed  PubMed Central  Google Scholar 

  17. Axe EL, Walker SA, Manifava M et al (2008) Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 182:685–701. https://doi.org/10.1083/jcb.200803137

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hurley JH, Young LN (2017) Mechanisms of autophagy initiation. Annu Rev Biochem. https://doi.org/10.1146/annurev-biochem-061516-044820

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tardelli M, Bruschi FV, Trauner M (2020) The role of metabolic lipases in the pathogenesis and management of liver disease. Hepatology. https://doi.org/10.1002/hep.31250

    Article  PubMed  Google Scholar 

  20. Parzych KR, Klionsky DJ (2014) An overview of autophagy: morphology, mechanism, and regulation. Antioxidants Redox Signal 20:460–473. https://doi.org/10.1089/ars.2013.5371

    Article  CAS  Google Scholar 

  21. Zorzano A (2019) Role of autophagy in the regulation of adipose tissue biology. Cell Cycle 18:1435–1445. https://doi.org/10.1080/15384101.2019.1624110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Deng Z, Purtell K, Lachance V et al (2017) Autophagy receptors and neurodegenerative diseases. Trends Cell Biol 27:491–504. https://doi.org/10.1016/j.tcb.2017.01.001

    Article  CAS  PubMed  Google Scholar 

  23. Bialik S, Dasari SK, Kimchi A (2018) Autophagy-dependent cell death—where, how and why a cell eats itself to death. J Cell Sci 131(18):jcs215152.

  24. Russell RC, Yuan HX, Guan KL (2014) Autophagy regulation by nutrient signaling. Cell Res 24(1):42–57

    Article  CAS  PubMed  Google Scholar 

  25. Birgisdottir ÅB, Lamark T, Johansen T (2013) The LIR motif—crucial for selective autophagy. J Cell Sci 126:3237–3247. https://doi.org/10.1242/jcs.126128

    Article  CAS  PubMed  Google Scholar 

  26. Nakamura S, Yoshimori T (2017) New insights into autophagosome-lysosome fusion. J Cell Sci 130:1209–1216. https://doi.org/10.1242/jcs.196352

    Article  CAS  PubMed  Google Scholar 

  27. Di Malta C, Cinque L, Settembre C (2019) Transcriptional regulation of autophagy: mechanisms and diseases. Front Cell Dev Biol 7:1–10. https://doi.org/10.3389/fcell.2019.00114

    Article  Google Scholar 

  28. Baerga R, Zhang Y, Chen PH et al (2009) Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a cellular model and in mice. Autophagy. https://doi.org/10.4161/auto.5.8.9991

    Article  PubMed  Google Scholar 

  29. Zhang Y, Goldman S, Baerga R et al (2009) Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Natl Acad Sci USA 106:19860–19865. https://doi.org/10.1073/pnas.0906048106

    Article  PubMed  PubMed Central  Google Scholar 

  30. Guo L, Huang J-X, Liu Y et al (2013) Transactivation of Atg4b by C/EBPβ promotes autophagy to facilitate adipogenesis. Mol Cell Biol 33:3180–3190. https://doi.org/10.1128/mcb.00193-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ahmed M, Lai TH, Hwang JS et al (2019) Transcriptional regulation of autophagy genes via stage-specific activation of CEBPB and PPARG during adipogenesis: a systematic study using public gene expression and transcription factor binding datasets. Cells. https://doi.org/10.3390/cells8111321

    Article  PubMed  PubMed Central  Google Scholar 

  32. Goldman SJ, Zhang Y, Jin S (2011) Autophagic degradation of mitochondria in white adipose tissue differentiation. Antioxid Redox Signaling 14(10):1971–1978. https://doi.org/10.1089/ars.2010.3777

  33. Martinez-Lopez N, Garcia-Macia M, Sahu S et al (2016) Autophagy in the CNS and periphery coordinate lipophagy and lipolysis in the brown adipose tissue and liver. Cell Metab. https://doi.org/10.1016/j.cmet.2015.10.008

    Article  PubMed  Google Scholar 

  34. Zhang Y, Zeng X, Jin S (2012) Autophagy in adipose tissue biology. Pharmacol Res 66:505–512. https://doi.org/10.1016/j.phrs.2012.09.004

    Article  CAS  PubMed  Google Scholar 

  35. Clemente-Postigo M, Tinahones A, El BR et al (2020) The role of Autophagy in white adipose tissue function: implications for metabolic health. Metabolites 10:1–29. https://doi.org/10.3390/metabo10050179

    Article  CAS  Google Scholar 

  36. Kosacka J, Kern M, Klöting N et al (2015) Autophagy in adipose tissue of patients with obesity and type 2 diabetes. Mol Cell Endocrinol. https://doi.org/10.1016/j.mce.2015.03.015

    Article  PubMed  Google Scholar 

  37. O’Neill LAJ, Grahame Hardie D (2013) Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493(7432):346–355. https://doi.org/10.1038/nature11862

  38. You Z, Xu Y, Wan W et al (2019) TP53INP2 contributes to autophagosome formation by promoting LC3-ATG7 interaction. Autophagy. https://doi.org/10.1080/15548627.2019.1580510

    Article  PubMed  PubMed Central  Google Scholar 

  39. Romero M, Sabaté-Pérez A, Francis VA et al (2018) TP53INP2 regulates adiposity by activating β-catenin through autophagy-dependent sequestration of GSK3β. Nat Cell Biol 20:443–454. https://doi.org/10.1038/s41556-018-0072-9

    Article  CAS  PubMed  Google Scholar 

  40. Glick D, Barth S, Macleod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221:3–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Yim WWY, Mizushima N (2020) Lysosome biology in autophagy. Cell Discov 6:6. https://doi.org/10.1038/s41421-020-0141-7

  42. Rubinsztein DC, Shpilka T, Elazar Z (2012) Mechanisms of autophagosome biogenesis. Curr Biol 22:R29–R34. https://doi.org/10.1016/j.cub.2011.11.034

    Article  CAS  PubMed  Google Scholar 

  43. Roberts R, Ktistakis NT (2013) Omegasomes: PI3P platforms that manufacture autophagosomes. Essays Biochem 55:17–27. https://doi.org/10.1042/BSE0550017

    Article  CAS  PubMed  Google Scholar 

  44. Yu L, Chen Y, Tooze SA (2018) Autophagy pathway: cellular and molecular mechanisms. Autophagy 14:207–215. https://doi.org/10.1080/15548627.2017.1378838

    Article  CAS  PubMed  Google Scholar 

  45. Eskelinen EL (2008) To be or not to be? Examples of incorrect identification of autophagic compartments in conventional transmission electron microscopy of mammalian cells. Autophagy 4(2):257–260. https://doi.org/10.4161/auto.5179

  46. Berg TO, Fengsrud M, Strømhaug PE et al (1998) Isolation and characterization of rat liver amphisomes: evidence for fusion of autophagosomes with both early and late endosomes. J Biol Chem. https://doi.org/10.1074/jbc.273.34.21883

    Article  PubMed  Google Scholar 

  47. Fader CM, Sánchez D, Furlán M, Colombo MI (2008) Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in K562 cells. Traffic. https://doi.org/10.1111/j.1600-0854.2007.00677.x

    Article  PubMed  Google Scholar 

  48. Pankiv S, Alemu EA, Brech A et al (2010) FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end—directed vesicle transport. J Cell Biol. https://doi.org/10.1083/jcb.200907015

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wijdeven RH, Janssen H, Nahidiazar L et al (2016) Cholesterol and ORP1L-mediated ER contact sites control autophagosome transport and fusion with the endocytic pathway. Nat Commun. https://doi.org/10.1038/ncomms11808

    Article  PubMed  PubMed Central  Google Scholar 

  50. Eijkelenboom A, Burgering BMT (2013) FOXOs: signalling integrators for homeostasis maintenance. Nat Rev Mol Cell Biol 14(2):83–97. https://doi.org/10.1038/nrm3507

  51. Feng Y, Yao Z, Klionsky DJ (2015) How to control self-digestion: transcriptional, post-transcriptional, and post-translational regulation of autophagy. Trends Cell Biol 25(6):354–363. https://doi.org/10.1016/j.tcb.2015.02.002

  52. Greer EL, Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24:7410–7425. https://doi.org/10.1038/sj.onc.1209086

    Article  CAS  PubMed  Google Scholar 

  53. Zhao Y, Hu X, Liu Y et al (2017) ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway. Mol Cancer 16(1):79. https://doi.org/10.1186/s12943-017-0648-1

  54. Zhao Y, Yang J, Liao W et al (2010) Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol 12:665–675. https://doi.org/10.1038/ncb2069

    Article  CAS  PubMed  Google Scholar 

  55. Lapierre LR, Kumsta C, Sandri M et al (2015) Transcriptional and epigenetic regulation of autophagy in aging. Autophagy 11:867–880. https://doi.org/10.1080/15548627.2015.1034410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Steingrímsson E, Copeland NG, Jenkins NA (2004) Melanocytes and the microphthalmia transcription factor network. Annu Rev Genet. https://doi.org/10.1146/annurev.genet.38.072902.092717

    Article  PubMed  Google Scholar 

  57. Napolitano G, Ballabio A (2016) TFEB at a glance. J Cell Sci 129:2475–2481. https://doi.org/10.1242/jcs.146365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hemesath TJ, Steingrímsson E, McGill G et al (1994) microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev. https://doi.org/10.1101/gad.8.22.2770

    Article  PubMed  Google Scholar 

  59. Palmieri M, Impey S, Kang H et al (2011) Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum Mol Genet. https://doi.org/10.1093/hmg/ddr306

    Article  PubMed  Google Scholar 

  60. Sakamaki JI, Long JS, New M et al (2018) Emerging roles of transcriptional programs in autophagy regulation. Transcription 9:131–136. https://doi.org/10.1080/21541264.2017.1372045

    Article  CAS  PubMed  Google Scholar 

  61. Sardiello M, Palmieri M, Di RA et al (2009) A gene network regulating lysosomal biogenesis and function. Science (80-). https://doi.org/10.1126/science.1174447

    Article  Google Scholar 

  62. Settembre C, Di Malta C, Polito VA et al (2011) TFEB links autophagy to lysosomal biogenesis. Science (80-). https://doi.org/10.1126/science.1204592

    Article  Google Scholar 

  63. Sancak Y, Bar-Peled L, Zoncu R et al (2010) Ragulator-rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell. https://doi.org/10.1016/j.cell.2010.02.024

    Article  PubMed  PubMed Central  Google Scholar 

  64. Kenzelmann Broz D, Mello SS, Bieging KT et al (2013) Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key p53 responses. Genes Dev. https://doi.org/10.1101/gad.212282.112

    Article  PubMed  PubMed Central  Google Scholar 

  65. Füllgrabe J, Ghislat G, Cho DH, Rubinsztein DC (2016) Transcriptional regulation of mammalian autophagy at a glance. J Cell Sci 129:3059–3066. https://doi.org/10.1242/jcs.188920

    Article  CAS  PubMed  Google Scholar 

  66. Jiang H, Martin V, Gomez-Manzano C et al (2010) The RB-E2F1 pathway regulates autophagy. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-10-1604

    Article  PubMed  PubMed Central  Google Scholar 

  67. Rosen ED, Spiegelman BM (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444:847–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Coelho M, Oliveira T, Fernandes R (2013) Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci 9(2):191–200. https://doi.org/10.5114/aoms.2013.33181

  69. Tan CY, Vidal-Puig A (2008) Adipose tissue expandability: the metabolic problems of obesity may arise from the inability to become more obese. In: Biochemical Society Transactions 36(Pt 5), 935–940. https://doi.org/10.1042/BST0360935

  70. Lafontan M, Langin D (2009) Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res 48(5):275–297. https://doi.org/10.1016/j.plipres.2009.05.001

  71. da Silva C, Durandt C, Kallmeyer K et al (2020) The role of pref-1 during adipogenic differentiation: an overview of suggested mechanisms. Int J Mol Sci 21:1–25. https://doi.org/10.3390/ijms21114104

    Article  CAS  Google Scholar 

  72. Luo L, Liu M (2016) Adipose tissue in control of metabolism. J Endocrinol 231:R77–R99. https://doi.org/10.1530/JOE-16-0211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Gao Q, Goodman JM (2015) The lipid droplet-a well-connected organelle. Front Cell Dev Biol 3:49. https://doi.org/10.3389/fcell.2015.00049

  74. Walther TC, Farese RV (2012) Lipid droplets and cellular lipid metabolism. Annu Rev Biochem. https://doi.org/10.1146/annurev-biochem-061009-102430

    Article  PubMed  PubMed Central  Google Scholar 

  75. Ibrahim MM (2010) Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 11:11–18. https://doi.org/10.1111/j.1467-789X.2009.00623.x

    Article  PubMed  Google Scholar 

  76. Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7:885–896

    Article  CAS  PubMed  Google Scholar 

  77. Ali AT, Hochfeld WE, Myburgh R, Pepper MS (2013) Adipocyte and adipogenesis. Eur J Cell Biol 92:229–236. https://doi.org/10.1016/j.ejcb.2013.06.001

    Article  CAS  PubMed  Google Scholar 

  78. Huang H, Song TJ, Li X et al (2009) BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci USA 106:12670–12675. https://doi.org/10.1073/pnas.0906266106

    Article  PubMed  PubMed Central  Google Scholar 

  79. Lee MJ (2018) Transforming growth factor beta superfamily regulation of adipose tissue biology in obesity. Biochim Biophys Acta Molecular basis disease 1864(4 Pt A), 1160–1171. https://doi.org/10.1016/j.bbadis.2018.01.025

  80. Tzeng J, Byun J, Park JY et al (2015) An ideal PPAR response element bound to and activated by PPARα. PLoS ONE. https://doi.org/10.1371/journal.pone.0134996

    Article  PubMed  PubMed Central  Google Scholar 

  81. Lefterova MI, Lazar MA (2009) New developments in adipogenesis. Trends Endocrinol Metab 20:107–114. https://doi.org/10.1016/j.tem.2008.11.005

    Article  CAS  PubMed  Google Scholar 

  82. de sá PM, Richard AJ, Hang H, Stephens JM, (2017) Transcriptional regulation of adipogenesis. Compr Physiol 7:635–674. https://doi.org/10.1002/cphy.c160022

    Article  Google Scholar 

  83. Moseti D, Regassa A, Kim WK (2016) Molecular regulation of adipogenesis and potential anti-adipogenic bioactive molecules. Int J Mol Sci 17:1–24. https://doi.org/10.3390/ijms17010124

    Article  CAS  Google Scholar 

  84. Lamichane S, Lamichane BD, Kwon SM (2018) Pivotal roles of peroxisome proliferator-activated receptors (PPARs) and their signal cascade for cellular and whole-body energy homeostasis. Int J Mol Sci 19(4):949. https://doi.org/10.3390/ijms19040949

  85. Tyagi S, Gupta P, Saini A et al (2011) The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J Adv Pharm Technol Res 2(4):236–240. https://doi.org/10.4103/2231-4040.90879

  86. Kersten S (2002) Peroxisome proliferator activated receptors and obesity. Eur J Pharmacol. https://doi.org/10.1016/S0014-2999(02)01431-0

    Article  PubMed  Google Scholar 

  87. Ma X, Wang D, Zhao W, Xu L (2018) Deciphering the roles of PPARγ in adipocytes via dynamic change of transcription complex. Front Endocrinol (Lausanne). 9:473. https://doi.org/10.3389/fendo.2018.00473

  88. Qi C, Zhu Y, Reddy JK (2000) Peroxisome proliferator-activated receptors, coactivators, and downstream targets. Cell Biochem Biophys. https://doi.org/10.1385/CBB:32:1-3:187

    Article  PubMed  Google Scholar 

  89. Chandra V, Huang P, Hamuro Y et al (2008) Structure of the intact PPAR-γ-RXR-α nuclear receptor complex on DNA. Nature. https://doi.org/10.1038/nature07413

  90. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM (2000) Transcriptional regulation of adipogenesis. Genes Dev 14(11):1293–1307. https://doi.org/10.1101/gad.14.11.1293

  91. Guo L, Li X, Tang QQ (2015) Transcriptional regulation of adipocyte differentiation: a central role for CCAAT/ enhancer-binding protein (C/EBP) β. J Biol Chem 290:755–761. https://doi.org/10.1074/jbc.R114.619957

    Article  CAS  PubMed  Google Scholar 

  92. Lefterova MI, Zhang Y, Steger DJ et al (2008) PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev 22:2941–2952. https://doi.org/10.1101/gad.1709008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Birsoy K, Chen Z, Friedman J (2008) Transcriptional regulation of adipogenesis by KLF4. Cell Metab. https://doi.org/10.1016/j.cmet.2008.02.001

    Article  PubMed  PubMed Central  Google Scholar 

  94. Oishi Y, Manabe I, Tobe K et al (2005) Krüppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab. https://doi.org/10.1016/j.cmet.2004.11.005

    Article  PubMed  Google Scholar 

  95. Mori T, Sakaue H, Iguchi H et al (2005) Role of krüppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem. https://doi.org/10.1074/jbc.M410515200

    Article  PubMed  Google Scholar 

  96. Komiya Y, Habas R (2008) WNT signal transduction pathways. Organogenesis 4(2):68–75. https://doi.org/10.4161/org.4.2.5851

  97. Liu X, Klionsky DJ (2015) TP53INP2/DOR protein chaperones deacetylated nuclear LC3 to the cytoplasm to promote macroautophagy. Autophagy. https://doi.org/10.1080/15548627.2015.1074373

    Article  PubMed  PubMed Central  Google Scholar 

  98. Olzmann JA, Carvalho P (2019) Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol 20:137–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Kloska A, Węsierska M, Malinowska M et al (2020) Lipophagy and lipolysis status in lipid storage and lipid metabolism diseases. Int J Mol Sci 21:1–33

    Google Scholar 

  100. Bickel PE, Tansey JT, Welte MA (2009) PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochim Biophys Acta 1791:419–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Singh R, Cuervo AM (2012) Lipophagy: connecting autophagy and lipid metabolism. Int J Cell Biol 2012:282041. https://doi.org/10.1155/2012/282041

  102. Zechner R, Zimmermann R, Eichmann TO et al (2012) FAT SIGNALS - lipases and lipolysis in lipid metabolism and signaling. Cell Metab 15:279–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Osuga JI, Ishibashi S, Oka T et al (2000) Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci U S A 97:787–792. https://doi.org/10.1073/pnas.97.2.787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Casado ME, Pastor O, García-Seisdedos D et al (2016) Hormone-sensitive lipase deficiency disturbs lipid composition of plasma membrane microdomains from mouse testis. Biochim Biophys Acta 1861:1142–1150. https://doi.org/10.1016/j.bbalip.2016.06.018

    Article  CAS  PubMed  Google Scholar 

  105. Zechner R, Madeo F, Kratky D (2017) Cytosolic lipolysis and lipophagy: two sides of the same coin. Nat Rev Mol Cell Biol 18:671–684

    Article  CAS  PubMed  Google Scholar 

  106. Kiss RS, Nilsson T (2014) Rab proteins implicated in lipid storage and mobilization. J Biomed Res 28:169–177. https://doi.org/10.7555/JBR.28.20140029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kimmel AR, Sztalryd C (2016) The perilipins: major cytosolic lipid droplet-associated proteins and their roles in cellular lipid storage, mobilization, and systemic homeostasis. Annu Rev Nutr 36:471–509

    Article  CAS  PubMed  Google Scholar 

  108. Kaushik S, Cuervo AM (2016) AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA. Autophagy 12:432–438. https://doi.org/10.1080/15548627.2015.1124226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Kaushik S, Cuervo AM (2015) Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. Nat Cell Biol 17:759–770. https://doi.org/10.1038/ncb3166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Schulze RJ, Sathyanarayan A, Mashek DG (2017) Breaking fat: the regulation and mechanisms of lipophagy. Biochim Biophys Acta 1862:1178–1187

    Article  CAS  PubMed Central  Google Scholar 

  111. Li Z, Schulze RJ, Weller SG et al (2016) A novel rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets. Sci Adv 2:1601470. https://doi.org/10.1126/sciadv.1601470

    Article  CAS  Google Scholar 

  112. Lettieri Barbato D, Tatulli G, Aquilano K, Ciriolo MR (2013) FoxO1 controls lysosomal acid lipase in adipocytes: implication of lipophagy during nutrient restriction and metformin treatment. Cell Death Dis 4:e861. https://doi.org/10.1038/cddis.2013.404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Ng F, Tang BL (2013) Sirtuins’ modulation of autophagy. J Cell Physiol 228:2262–2270. https://doi.org/10.1002/jcp.24399

    Article  CAS  PubMed  Google Scholar 

  114. Nuñez CE, Rodrigues VS, Gomes FS et al (2013) Defective regulation of adipose tissue autophagy in obesity. Int J Obes. https://doi.org/10.1038/ijo.2013.27

    Article  Google Scholar 

  115. Soussi H, Cl K, Dugail I (2016) Adipose tissue autophagy status in obesity : Expression and fl ux—two faces of the picture. Autophagy 12:588–589. https://doi.org/10.1080/15548627.2015.1106667

    Article  CAS  PubMed  Google Scholar 

  116. Kovsan J, Blüher M, Tarnovscki T et al (2011) Altered autophagy in human adipose tissues in obesity. J Clin Endocrinol Metab. https://doi.org/10.1210/jc.2010-1681

    Article  PubMed  Google Scholar 

  117. Öst A, Svensson K, Ruishalme I et al (2010) Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes. Mol Med. https://doi.org/10.2119/molmed.2010.00023

    Article  PubMed  PubMed Central  Google Scholar 

  118. Jansen HJ, Van Essen P, Koenen T et al (2012) Autophagy activity is up-regulated in adipose tissue of obese individuals and modulates proinflammatory cytokine expression. Endocrinology. https://doi.org/10.1210/en.2012-1625

    Article  PubMed  Google Scholar 

  119. Ji J, Petropavlovskaia M, Khatchadourian A et al (2019) Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in β-cells. J Cell Mol Med. https://doi.org/10.1111/jcmm.14172

    Article  PubMed  PubMed Central  Google Scholar 

  120. Haim Y, Blüuher M, Slutsky N et al (2015) Elevated autophagy gene expression in adipose tissue of obese humans: a potential non-cell-cycle-dependent function of E2F1. Autophagy. https://doi.org/10.1080/15548627.2015.1094597

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the Indian Council of Medical Research (ICMR) and the Vellore Institute of Technology (VIT), India.

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This work was funded by the Indian Council of Medical Research (ICMR) (5/9/1171/2015-NUT) and the Vellore Institute of Technology (VIT), India.

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MS made the first draft, followed by refinement by KT. Both authors were involved in subsequent fine tuning of the paper along with the design and development of figures.

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Correspondence to Kavitha Thirumurugan.

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Sekar, M., Thirumurugan, K. Autophagy: a molecular switch to regulate adipogenesis and lipolysis. Mol Cell Biochem 477, 727–742 (2022). https://doi.org/10.1007/s11010-021-04324-w

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