Fatty acids are novel nutrient factors to regulate mTORC1 lysosomal localization and apoptosis in podocytes
Open accessAbstract
Podocyte apoptosis is a potent mechanism of proteinuria in diabetic nephropathy. More detailed mechanistic insight into podocyte apoptosis is needed to better understand the pathogenesis of diabetic nephropathy. An elevated level of serum free fatty acid (FFA), as well as hyperglycemia, is a clinical characteristic in diabetes, although its causal role in podocyte apoptosis remains unclear. This study examined the effect of three types of FFAs, saturated, monounsaturated and polyunsaturated FFAs, on podocyte apoptosis. Palmitate, a saturated FFA, induced endoplasmic reticulum (ER) stress-dependent apoptosis in podocytes. Oleate, a monounsaturated FFA, and eicosapentaenoic acid (EPA), an ω-3 polyunsaturated FFA did not induce apoptosis; rather, they antagonized palmitate-induced apoptosis. Palmitate activated mammalian target of rapamycin (mTOR) complex 1 (mTORC1), a nutrient-sensing kinase regulating a wide range of cell biology. Furthermore, inhibition of mTORC1 activity by rapamycin or siRNA for Raptor, a component of mTORC1, ameliorated palmitate-induced ER stress and apoptosis in podocytes. Activity of mTORC1 is regulated by upstream kinases and Rag/Ragulator-dependent recruitment of mTOR onto lysosomal membranes. Palmitate activated mTORC1 by enhancing recruitment of mTOR onto lysosomal membranes, which was inhibited by co-incubation with oleate or EPA. Inhibition of mTOR translocation onto lysosomes by transfection with dominant-negative forms of Rag ameliorated palmitate-induced apoptosis. This study suggests that saturated and unsaturated FFAs have opposite effects on podocyte apoptosis by regulating mTORC1 activity via its translocation onto lysosomal membranes, and the results provide a better understanding of the pathogenesis in diabetic nephropathy and a novel role of mTORC1 in cell apoptosis.
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Dietary palmitic acid activates both the NLRP3 inflammasome and mTORC1.
“and activates both the NLRP3 inflammasome and mTORC116,17”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [16]
Section 3.2 reports that palmitate activated mTORC1 signaling in cultured podocytes, and Section 3.4 links this to mTOR translocation onto lysosomal membranes (page numbers unavailable). The cited paper does not establish that dietary palmitic acid activates mTORC1, and the passages do not address NLRP3 inflammasome activation. (LLM, conf=0.88)
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Cites
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154 · see citing works
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107 · see citing works
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · see citing works
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · see citing works
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941 · see citing works
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849 · see citing works
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083 · see citing works
Roles of CHOP/GADD153 in endoplasmic reticulum stress
Oyadomari, S., & Mori, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401373 · Cited by 2,833 · see citing works
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · see citing works
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464 · see citing works
Laplante, M., & Sabatini, D. (2009) · Journal of Cell Science · doi:10.1242/jcs.051011 · Cited by 2,317 · see citing works
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193 · see citing works
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911 · see citing works
mTOR is a key modulator of ageing and age-related disease
Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013) · Nature · doi:10.1038/nature11861 · Cited by 1,676 · see citing works
Hara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., BELHAM, C. M., & Avruch, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14484 · Cited by 1,370 · see citing works
Regulation of TORC1 by Rag GTPases in nutrient response
Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., & Guan, K.-L. (2008) · Nature Cell Biology · doi:10.1038/ncb1753 · Cited by 1,349 · see citing works
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311 · see citing works
Lipotoxicity in the Pathogenesis of Obesity-Dependent NIDDM: Genetic and Clinical Implications
Unger, R. H. (1995) · Diabetes · doi:10.2337/diab.44.8.863 · Cited by 1,100 · see citing works
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes & Development · doi:10.1101/gad.995802 · Cited by 1,093 · see citing works
Podocyte loss and progressive glomerular injury in type II diabetes.
Pagtalunan, M. E., Miller, P. L., Jumping-Eagle, S., Nelson, R. G., Myers, B. D., Rennke, H. G., Coplon, N. S., Sun, L., & Meyer, T. W. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119163 · Cited by 1,088 · see citing works
Floegel, A., Stefan, N., Yu, Z., Mühlenbruch, K., Drogan, D., Joost, H.-G., Fritsche, A., Häring, H.-U., Hrabě de Angelis, M., Peters, A., et al. (2013) · Diabetes · doi:10.2337/db12-0495 · Cited by 988 · see citing works
Dysregulation of the TSC-mTOR pathway in human disease
Inoki, K., Corradetti, M. N., & Guan, K. (2004) · Nature Genetics · doi:10.1038/ng1494 · Cited by 970 · see citing works
DeFronzo, R. A. (2010) · Diabetologia · doi:10.1007/s00125-010-1684-1 · Cited by 889 · see citing works
Mundel, P. H., Reiser, J., Zúñiga, A., Pavenstädt, H., Davidson, G. R., Kriz, W., & Zeller, R. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3739 · Cited by 876 · see citing works
Glutaminolysis Activates Rag-mTORC1 Signaling
Durán, R. V., Oppliger, W., Robitaille, A. M., Heiserich, L., Skendaj, R., Gottlieb, E., & Hall, M. N. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.043 · Cited by 723 · see citing works
Zhou, Y. P., & Grill, V. E. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117042 · Cited by 677 · see citing works
Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes
Narita, M., Young, A. R. J., Arakawa, S., Samarajiwa, S. A., Nakashima, T., Yoshida, S., Hong, S., Berry, L. S., Reichelt, S., Ferreira, M., et al. (2011) · Science · doi:10.1126/science.1205407 · Cited by 594 · see citing works
Role of mTOR in podocyte function and diabetic nephropathy in humans and mice
Gödel, M., Hartleben, B., Herbach, N., Liu, S., Zschiedrich, S., Lu, S., Debreczeni-Mór, A., Lindenmeyer, M. T., Rastaldi, M.-P., Hartleben, G., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44774 · Cited by 547 · see citing works
mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice
Inoki, K., Mori, H., Wang, J., Suzuki, T., Hong, S., Yoshida, S., Blattner, S. M., Ikenoue, T., Rüegg, M. A., Hall, M. N., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44771 · Cited by 538 · see citing works
Saturated Fatty Acid and TLR Signaling Link β Cell Dysfunction and Islet Inflammation
Eguchi, K., Manabe, I., Tanaka, Y., Ohsugi, M., Kono, N., Ogata, F., Yagi, N., Ohto, U., Kimoto, M., Miyake, K., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.023 · Cited by 519 · see citing works
Self-citationRegulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival
Efeyan, A., Zoncu, R., Chang, S. H., Gumper, I., Snitkin, H., Wolfson, R. L., Kirak, O., Sabatini, D. M., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11745 · Cited by 457 · see citing works
Proteinuria in diabetic kidney disease: a mechanistic viewpoint.
Jefferson, J., Shankland, S., & Pichler, R. (2008) · Kidney International · doi:10.1038/ki.2008.128 · Cited by 425 · see citing works
Oleate Reverses Palmitate-induced Insulin Resistance and Inflammation in Skeletal Muscle Cells
Coll, T., Eyre, E., Rodríguez-Calvo, R., Palomer, X., Sánchez, R. M., Merlos, M., Laguna, J. C., & Vázquez-Carrera, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708700200 · Cited by 347 · see citing works
Nada, S., Hondo, A., Kasai, A., Koike, M., Saito, K., Uchiyama, Y., & Okada, M. (2009) · The EMBO Journal · doi:10.1038/emboj.2008.308 · Cited by 341 · see citing works
mTORC1 serves ER stress-triggered apoptosis via selective activation of the IRE1–JNK pathway
Kato, H., Nakajima, S., Saito, Y., Takahashi, S., Katoh, R., & Kitamura, M. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.98 · Cited by 273 · see citing works
Platat, C., Drai, J., Oujaa, M., Schlienger, J.-L., & Simon, C. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/82.6.1178 · Cited by 263 · see citing works
Kume, S., Haneda, M., Kanasaki, K., Sugimoto, T., Araki, S., Isshiki, K., Isono, M., Uzu, T., Guarente, L., Kashiwagi, A., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605904200 · Cited by 231 · see citing works
Self-citationAKT2 is essential to maintain podocyte viability and function during chronic kidney disease
Canaud, G., Bienaimé, F., Viau, A., Treins, C., Baron, W., Nguyen, C., Burtin, M., Bérissi, S., Giannakakis, K., Muda, A. O., et al. (2013) · Nature Medicine · doi:10.1038/nm.3313 · Cited by 222 · see citing works
Regulation of podocyte survival and endoplasmic reticulum stress by fatty acids
Sieber, J., Lindenmeyer, M. T., Kampe, K., Campbell, K. N., Cohen, C. D., Hopfer, H., Mundel, P., & Jehle, A. W. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00196.2010 · Cited by 203 · see citing works
Progression of diabetic nephropathy
Kikkawa, R., Koya, D., & Haneda, M. (2003) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2003.50077 · Cited by 193 · see citing works
Self-citationFenofibrate, a PPARα agonist, has renoprotective effects in mice by enhancing renal lipolysis
Tanaka, Y., Kume, S., Araki, S., Isshiki, K., Chin‒Kanasaki, M., Sakaguchi, M., Sugimoto, T., Koya, D., Haneda, M., Kashiwagi, A., et al. (2011) · Kidney International · doi:10.1038/ki.2010.530 · Cited by 190 · see citing works
Self-citationInhibition of MTOR Disrupts Autophagic Flux in Podocytes
Cinà, D. P., Onay, T., Paltoo, A., Li, C., Maezawa, Y., De Arteaga, J., Jurisicova, A., & Quaggin, S. E. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2011070690 · Cited by 172 · see citing works
Sestrin2 integrates Akt and mTOR signaling to protect cells against energetic stress-induced death
Ben‐Sahra, I., Dirat, B., Laurent, K., Puissant, A., Auberger, P., Budanov, A. V., Tanti, J., & Bost, F. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2012.157 · Cited by 157 · see citing works
Nutrient Sensing, Autophagy, and Diabetic Nephropathy
Kume, S., Thomas, M. C., & Koya, D. (2011) · Diabetes · doi:10.2337/db11-0555 · Cited by 157 · see citing works
Self-citationYoshida, S., Hong, S., Suzuki, T., Nada, S., Mannan, A. M., Wang, J., Okada, M., Guan, K., & Inoki, K. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.238014 · Cited by 155 · see citing works
mTOR and rapamycin in the kidney: signaling and therapeutic implications beyond immunosuppression
Huber, T. B., Walz, G., & Kuehn, E. W. (2010) · Kidney International · doi:10.1038/ki.2010.457 · Cited by 155 · see citing works
Metabolic memory and diabetic nephropathy: potential role for epigenetic mechanisms
Tonna, S. J., El‐Osta, A., Cooper, M. E., & Tikellis, C. (2010) · Nature Reviews Nephrology · doi:10.1038/nrneph.2010.55 · Cited by 152 · see citing works
mToR inhibitors-induced proteinuria: mechanisms, significance, and management
Letavernier, E., & Legendre, C. M. (2008) · Transplantation Reviews · doi:10.1016/j.trre.2007.12.001 · Cited by 141 · see citing works
Bachar-Wikström, E., Ariav, Y., Ketzinel‐Gilad, M., Cerasi, E., Kaiser, N., & Leibowitz, G. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004954 · Cited by 140 · see citing works
Mammalian Target of Rapamycin Regulates Nox4-Mediated Podocyte Depletion in Diabetic Renal Injury
Eid, A. A., Ford, B. M., Bhandari, B. K., Cavaglieri, R. D. C., Block, K. L., Barnes, J. L., Gorin, Y. C., Choudhury, G. G., & Abboud, H. E. (2013) · Diabetes · doi:10.2337/db12-1504 · Cited by 139 · see citing works
Overview of Glucose Signaling in Mesangial Cells in Diabetic Nephropathy
Haneda, M., Koya, D., Isono, M., & Kikkawa, R. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000064500.89551.76 · Cited by 117 · see citing works
Self-citationmTOR regulates expression of slit diaphragm proteins and cytoskeleton structure in podocytes
Vollenbröker, B., George, B., Wolfgart, M., Saleem, M. A., Pavenstädt, H., & Weide, T. (2008) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.90319.2008 · Cited by 116 · see citing works
Kang, Y. J., Lü, M., & Guan, K.-L. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.82 · Cited by 115 · see citing works
Soumura, M., Kume, S., Isshiki, K., Takeda, N., Araki, S., Tanaka, Y., Sugimoto, T., Chin‒Kanasaki, M., Nishio, Y., Haneda, M., et al. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.10.012 · Cited by 81 · see citing works
Self-citationClore, J. N., Allred, J., White, D., Li, J., & Stillman, J. (2002) · Metabolism · doi:10.1053/meta.2002.35202 · Cited by 80 · see citing works
Role of TSC–mTOR pathway in diabetic nephropathy
Inoki, K. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.09.028 · Cited by 68 · see citing works
Mammalian target of rapamycin signaling in the podocyte
Inoki, K., & Huber, T. B. (2012) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e3283520f38 · Cited by 38 · see citing works
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Tagawa, A., Yasuda, M., Kume, S., Yamahara, K., Nakazawa, J., Chin-Kanasaki, M., Araki, H., Araki, S.-I., Koya, D., Asanuma, K., et al. (2016) · Diabetes · doi:10.2337/db15-0473 · Cited by 315 · see citing works
Self-citationMann, G., Mora, S., Madu, G., & Adegoke, O. A. J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.702826 · Cited by 271 · see citing works
Linking diet to acne metabolomics, inflammation, and comedogenesis: an update
Melnik, B. (2015) · Clinical, Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s69135 · Cited by 259 · see citing works
Breaking fat: The regulation and mechanisms of lipophagy
Schulze, R. J., Sathyanarayan, A., & Mashek, D. G. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2017.06.008 · Cited by 240 · see citing works
Lipids, lysosomes, and autophagy
Jaishy, B. P., & Abel, E. D. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r067520 · Cited by 229 · see citing works
Acne vulgaris: The metabolic syndrome of the pilosebaceous follicle
Melnik, B. C. (2017) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2017.09.006 · Cited by 197 · see citing works
Impaired β-Oxidation and Altered Complex Lipid Fatty Acid Partitioning with Advancing CKD
Afshinnia, F., Rajendiran, T. M., Soni, T., Byun, J., Wernisch, S., Sas, K. M., Hawkins, J. J., Bellovich, K. A., Gipson, D., Michailidis, G. C., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2017030350 · Cited by 187 · see citing works
CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress
Hua, W., Huang, H., Tan, L.-T., Wan, J., Gui, H.-B., Zhao, L., Ruan, X. Z., Chen, X., & Du, X. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127507 · Cited by 163 · see citing works
Sebaceous-immunobiology is orchestrated by sebum lipids
Lovászi, M., Szegedi, A., Zouboulis, C. C., & Törőcsik, D. (2017) · Dermato-Endocrinology · doi:10.1080/19381980.2017.1375636 · Cited by 151 · see citing works
van Vliet, S., Shy, E. L., Abou Sawan, S., Beals, J. W., West, D. W., Skinner, S. K., Ulanov, A. V., Li, Z., Paluska, S. A., Parsons, C. M., et al. (2017) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.159855 · Cited by 141 · see citing works
Lipin proteins and glycerolipid metabolism: Roles at the ER membrane and beyond
Zhang, P., & Reue, K. (2017) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2017.04.007 · Cited by 145 · see citing works
Endoplasmic reticulum stress in kidney function and disease
Taniguchi, M., & Yoshida, H. (2015) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000141 · Cited by 132 · see citing works
Burd, N. A., Beals, J. W., Martinez, I. G., Salvador, A. F., & Skinner, S. K. (2019) · Sports Medicine · doi:10.1007/s40279-018-1009-y · Cited by 127 · see citing works
A lysosome-centered view of nutrient homeostasis
Mony, V. K., Benjamin, S. B., & O'Rourke, E. (2016) · Autophagy · doi:10.1080/15548627.2016.1147671 · Cited by 113 · see citing works
Afshinnia, F., Nair, V., Lin, J., Rajendiran, T. M., Soni, T., Byun, J., Sharma, K., Fort, P. E., Gardner, T. W., Looker, H. C., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.130317 · Cited by 122 · see citing works
Madak‐Erdogan, Z., Band, S., Zhao, Y. C., Smith, B. P., Kulkoyluoglu‐Cotul, E., Zuo, Q., Casiano, A. S., Wrobel, K., Rossi, G., Smith, R. L., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2849 · Cited by 114 · see citing works
Monteyne, A. J., Coelho, M. O., Porter, C., Abdelrahman, D. R., Jameson, T. S., Jackman, S. R., Blackwell, J. R., Finnigan, T. J., Stephens, F. B., Dirks, M. L., et al. (2020) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa092 · Cited by 110 · see citing works
Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy
Liu, K., Qiu, D., Liang, X., Huang, Y., Wang, Y., Jia, X., Li, K., Zhao, J., Du, C., Qiu, X., et al. (2021) · Autophagy · doi:10.1080/15548627.2021.1961072 · Cited by 110 · see citing works
Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation
Melnik, B. C. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160817048 · Cited by 108 · see citing works
Eicosapentaenoic acid attenuates renal lipotoxicity by restoring autophagic flux
Yamamoto, T., Takabatake, Y., Minami, S., Sakai, S., Fujimura, R., Takahashi, A., Namba‐Hamano, T., Matsuda, J., Kimura, T., Matsui, I., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1782034 · Cited by 102 · see citing works
Cellular Uptake, Metabolism and Sensing of Long-Chain Fatty Acids
He, Q., Chen, Y., Wang, Z., He, H., & Yu, P. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2801010 · Cited by 103 · see citing works
Lee, J., & Ridgway, N. D. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2019.03.010 · Cited by 93 · see citing works
Free Fatty Acids and Their Metabolism Affect Function and Survival of Podocytes
Sieber, J., & Jehle, A. W. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00186 · Cited by 88 · see citing works
Tian, N., Gao, Y., Wang, X., Wu, X., Zou, D., Zhu, Z., Han, Z., Wang, T., & Shi, Y. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s167405 · Cited by 85 · see citing works
TFEB–GDF15 axis protects against obesity and insulin resistance as a lysosomal stress response
Kim, J., Kim, S., Kang, H., Lee, S., Park, S., Cho, Y., Lim, Y.-M., Ahn, J. W., Kim, Y.-H., Chung, S., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00368-w · Cited by 86 · see citing works
Kwon, B., & Querfurth, H. W. (2015) · Biochimie · doi:10.1016/j.biochi.2015.09.006 · Cited by 73 · see citing works
Melnik, B. C., John, S. M., Carrera‐Bastos, P., & Schmitz, G. (2016) · Clinical and Translational Allergy · doi:10.1186/s13601-016-0108-9 · Cited by 71 · see citing works
Nutrients and Pathways that Regulate Health Span and Life Span
Pignatti, C., D’Adamo, S., Stefanelli, C., Flamigni, F., & Cetrullo, S. (2020) · Geriatrics · doi:10.3390/geriatrics5040095 · Cited by 64 · see citing works
Non-genetic mechanisms of diabetic nephropathy
Han, Q., Zhu, H., Chen, X., & Liu, Z. (2017) · Frontiers of Medicine · doi:10.1007/s11684-017-0569-9 · Cited by 65 · see citing works
Regulation of mTORC1 by amino acids in mammalian cells: A general picture of recent advances
Zhang, S.-Z., Lin, X.-Y., Hou, Q.-L., Hu, Z.-Y., Wang, Y., & Wang, Z.-H. (2021) · Animal Nutrition · doi:10.1016/j.aninu.2021.05.003 · Cited by 56 · see citing works
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Nakano, T., Watanabe, H., Imafuku, T., Tokumaru, K., Fujita, I., Arimura, N., Maeda, H., Tanaka, M., Matsushita, K., Fukagawa, M., et al. (2021) · Toxins · doi:10.3390/toxins13120909 · Cited by 61 · see citing works
Melnik, B. C. (2015) · Current Diabetes Reviews · doi:10.2174/1573399811666150114100653 · Cited by 58 · see citing works
Van Vliet, S., Beals, J. W., Martinez, I. G., Skinner, S. K., & Burd, N. A. (2018) · Nutrients · doi:10.3390/nu10020224 · Cited by 56 · see citing works
Melnik, B. C., John, S. M., & Schmitz, G. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-014-0377-9 · Cited by 56 · see citing works
Lysosomal dysfunction–induced autophagic stress in diabetic kidney disease
Zheng, H.-J., Zhang, X.-Q., Guo, J., Zhang, W., Ai, S.-N., Zhang, F., Wang, Y.-X., & Liu, W.-J. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15301 · Cited by 50 · see citing works
Impact of Diet and Nutrition in Patients with Acne Vulgaris
Ryguła, I., Pikiewicz, W., & Kaminiów, K. (2024) · Nutrients · doi:10.3390/nu16101476 · Cited by 70 · see citing works
Weikel, K., Ruderman, N. B., & Cacicedo, J. M. (2016) · Metabolism · doi:10.1016/j.metabol.2016.01.005 · Cited by 49 · see citing works
Xiao, J., Zhu, S., Guan, H., Zheng, Y., Li, F., Zhang, X., Guo, H., Wang, X., & Ye, Z. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0254-y · Cited by 46 · see citing works
Su, Y., Chen, Q., Ma, K., Ju, Y., Ji, T., Wang, Z., Li, W., & Li, W. (2018) · Pharmacological Reports · doi:10.1016/j.pharep.2018.12.008 · Cited by 45 · see citing works
Clătici, V. G., Voicu, C., Voaideṣ, C., Roșeanu, A., Icriverzi, M., & Jurcoane, Ș. (2018) · Europe PMC (PubMed Central) · doi:10.26574/maedica.2018.13.4.273 · Cited by 45 · see citing works
Metabolomics in asthma: A platform for discovery
Xu, S., Panettieri, R. A., & Jude, J. A. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100990 · Cited by 43 · see citing works
Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor
Nicastro, R., Brohée, L., Alba, J., Nüchel, J., Figlia, G., Kipschull, S., Gollwitzer, P., Romero-Pozuelo, J., Fernandes, S. A., Lamprakis, A., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01198-6 · Cited by 36 · see citing works
Srikanth, M. P., Jones, J. W., Kane, M. A., Awad, O., Park, T. S., Zambidis, E. T., & Feldman, R. A. (2021) · Stem Cells Translational Medicine · doi:10.1002/sctm.20-0386 · Cited by 42 · see citing works
Yuan, Z., Cao, A., Liu, H., Guo, H., Zang, Y., Wang, Y., Wang, Y., Wang, H., Yin, P., & Peng, W. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25930 · Cited by 42 · see citing works
Melnik, B. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031059 · Cited by 42 · see citing works
Melnik, B. C. (2021) · Biomolecules · doi:10.3390/biom11030404 · Cited by 42 · see citing works
Metformin: An Inhibitor of mTORC1 Signaling
Melnik, B. C., & Schmitz, G. (2014) · Cited by 39 · see citing works
Afshinnia, F., Rajendiran, T. M., He, C., Byun, J., Montemayor, D., Darshi, M., Tůmová, J., Kim, J., Limonte, C. P., Miller, R. G., et al. (2021) · Diabetes Care · doi:10.2337/dc21-0737 · Cited by 39 · see citing works
Transcriptional and Translational Modulation of myo-Inositol Oxygenase (Miox) by Fatty Acids
Tominaga, T., Dutta, R. K., Joladarashi, D., Doi, T., Reddy, J. K., & Kanwar, Y. S. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.698191 · Cited by 38 · see citing works
Aljohani, A., Khan, M. I., Syed, D. N., Bonneville, A., Lewis, S., Neill, L. O., Mukhtar, H., & Ntambi, J. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-52339-7 · Cited by 36 · see citing works
Dorotea, D., Jiang, S., Pak, E. S., Son, J. B., Choi, H. G., Ahn, S., & Ha, H. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00810-3 · Cited by 35 · see citing works
The potential mechanistic link between allergy and obesity development and infant formula feeding
Melnik, B. C. (2014) · Allergy Asthma and Clinical Immunology · doi:10.1186/1710-1492-10-37 · Cited by 35 · see citing works
PACSIN2 accelerates nephrin trafficking and is up‐regulated in diabetic kidney disease
Dumont, V., Tolvanen, T. A., Kuusela, S., Wang, H., Nyman, T. A., Lindfors, S., Tienari, J., Nísen, H., Suetsugu, S., Plomann, M., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201601265r · Cited by 34 · see citing works
Kim, J., Wilbon, S. S., & Fornoni, A. (2021) · Kidney360 · doi:10.34067/kid.0006152020 · Cited by 36 · see citing works
West, S., Monteyne, A. J., Whelehan, G., Abdelrahman, D. R., Murton, A. J., Finnigan, T. J. A., Blackwell, J. R., Stephens, F. B., & Wall, B. T. (2022) · British Journal Of Nutrition · doi:10.1017/s0007114522003087 · Cited by 35 · see citing works
Kuwagata, S., Kume, S., Chin‒Kanasaki, M., Araki, H., Araki, S., Nakazawa, J., Sugaya, T., Koya, D., Haneda, M., Maegawa, H., et al. (2016) · Kidney International · doi:10.1016/j.kint.2016.06.036 · Cited by 33 · see citing works
Self-citationDifferential network enrichment analysis reveals novel lipid pathways in chronic kidney disease
Ma, J., Karnovsky, A., Afshinnia, F., Wigginton, J. E., Rader, D. J., Natarajan, L., Sharma, K., Porter, A. C., Rahman, M., He, J., et al. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz114 · Cited by 32 · see citing works
Bagheri, R., Moghadam, B. H., Jo, E., Tinsley, G. M., Stratton, M. T., Ashtary‐Larky, D., Eskandari, M., & Wong, A. (2020) · British Journal Of Nutrition · doi:10.1017/s0007114520002238 · Cited by 32 · see citing works
A nutrigeroscience approach: Dietary macronutrients and cellular senescence
Calubag, M. F., Robbins, P. D., & Lamming, D. W. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.025 · Cited by 32 · see citing works
Enhanced insulin receptor, but not PI3K, signalling protects podocytes from ER stress
Garner, K., Betin, V. M. S., Pinto, V., Graham, M., Abgueguen, E., Barnes, M., Bedford, D. C., McArdle, C. A., & Coward, R. J. (2018) · Scientific Reports · doi:10.1038/s41598-018-22233-9 · Cited by 31 · see citing works
Fatty acids: Adiposity and breast cancer chemotherapy, a bad synergy?
Mentoor, I., Engelbrecht, A., & Nell, T. A. (2018) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2018.11.009 · Cited by 30 · see citing works
Tagaya, M., Kume, S., Yasuda‒Yamahara, M., Kuwagata, S., Yamahara, K., Takeda, N., Tanaka, Y., Chin‒Kanasaki, M., Nakae, Y., Yokoi, H., et al. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2022.166368 · Cited by 30 · see citing works
Self-citationMonteyne, A. J., Coelho, M. O., Porter, C., Abdelrahman, D. R., Jameson, T. S., Finnigan, T. J., Stephens, F. B., Dirks, M. L., & Wall, B. T. (2020) · The Journal of Nutrition · doi:10.1093/jn/nxaa251 · Cited by 29 · see citing works
Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases
Li, G., Kidd, J. M., & Li, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051559 · Cited by 29 · see citing works
Denhez, B., Rousseau, M., Spino, C., Dancosst, D.-A., Dumas, M.-È., Guay, A., Lizotte, F., & Geraldes, P. (2020) · Scientific Reports · doi:10.1038/s41598-020-78376-1 · Cited by 29 · see citing works
Lian, C.-Y., Yang, H., Zhai, Z., Li, Z., Han, D., & Wang, L. (2020) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2020.111231 · Cited by 28 · see citing works
Sugahara, S., Kume, S., Chin‒Kanasaki, M., Tomita, I., Yasuda‒Yamahara, M., Yamahara, K., Takeda, N., Osawa, N., Yanagita, M., Araki, S., et al. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018090950 · Cited by 26 · see citing works
Self-citationMilk Fat Intake and Telomere Length in U.S. Women and Men: The Role of the Milk Fat Fraction
Tucker, L. A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/1574021 · Cited by 25 · see citing works
The Effect of Whole Egg Intake on Muscle Mass: Are the Yolk and Its Nutrients Important?
Santos, H. O., Gomes, G. K., Schoenfeld, B. J., & de Oliveira, E. P. (2021) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2021-0086 · Cited by 24 · see citing works
Guo, W., Zhong, W. H., Hao, L., Sun, X., & Zhou, Z. (2021) · Cells · doi:10.3390/cells10102730 · Cited by 24 · see citing works
Szczuko, M., Kaczkan, M., Drozd, A., Maciejewska, D., Palma, J., Owczarzak, A., Marczuk, N., Rutkowski, P., & Małgorzewicz, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071719 · Cited by 24 · see citing works
Arshad, Z., Rezapour-Firouzi, S., Ebrahimifar, M., Mosavi-Jarrahi, A., & Mohammadian, M. (2019) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2019.20.4.1005 · Cited by 22 · see citing works
Lipotoxicity dysregulates the immunoproteasome in podocytes and kidneys in type 2 diabetes
Lee, H. S., Suh, J. Y., Kang, B. C., & Lee, E. (2021) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00509.2020 · Cited by 23 · see citing works
Oleic Acid in the Diet and What It Does: Implications for Diabetes and Its Complications
Granado-Casas, M., & Mauricio, D. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813822-9.00014-x · Cited by 23 · see citing works
Amin, N. G., Rahim, A. A., Rohoma, K. H., Elwafa, R. A., Dabees, H. M. F., & Elrahmany, S. M. (2024) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01450-5 · Cited by 21 · see citing works
Yao, Y., Wang, J., Yoshida, S., Nada, S., Okada, M., & Inoki, K. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015010032 · Cited by 21 · see citing works
Targeting the lysosome: Mechanisms and treatments for nonalcoholic fatty liver disease
Pu, J. (2022) · Journal of Cellular Biochemistry · doi:10.1002/jcb.30274 · Cited by 21 · see citing works
Lipotoxicity, Nutrient-Sensing Signals, and Autophagy in Diabetic Nephropathy
Kume, S., & Maegawa, H. (2020) · JMA Journal · doi:10.31662/jmaj.2020-0005 · Cited by 20 · see citing works
Self-citationMonteyne, A. J., West, S., Stephens, F. B., & Wall, B. T. (2024) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2024.04.032 · Cited by 20 · see citing works
Su, Y., Chen, Q., Ju, Y., Li, W., & Li, W. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2020.158793 · Cited by 19 · see citing works
Lv, J., Yu, H., Du, S., Xu, P., Zhao, Y., Qi, W., & Wang, X. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06076-3 · Cited by 18 · see citing works
Wang, J., Chen, Y., Song, Q., Griffiths, A., & Song, Z. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220928276 · Cited by 18 · see citing works
Angiopoietin-Like Protein 2 Promotes the Progression of Diabetic Kidney Disease
Ishii, T., Furuya, F., Takahashi, K., Shikata, M., Takamura, T., Kobayashi, H., Miyazaki, A., Morinaga, J., Terada, K., Oike, Y., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-02705 · Cited by 18 · see citing works
Aslan, İ., Özcan, F., Karaarslan, T., Kıraç, E., & Aslan, M. (2016) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2016.12.001 · Cited by 17 · see citing works
Arshad, Z., Rezapour-Firouzi, S., Mohammadian, M., & Ebrahimifar, M. (2018) · Europe PMC (PubMed Central) · doi:10.22034/apjcp.2018.19.9.2391 · Cited by 15 · see citing works
Dairy consumption and hepatocellular carcinoma risk
Melnik, B. C. (2021) · Annals of Translational Medicine · doi:10.21037/atm-2020-ubih-06 · Cited by 15 · see citing works
Ketone Body Metabolism in Diabetic Kidney Disease
Yamahara, K., Yasuda‒Yamahara, M., Kuwagata, S., Chin‒Kanasaki, M., & Kume, S. (2024) · Kidney360 · doi:10.34067/kid.0000000000000359 · Cited by 15 · see citing works
Self-citationFutatsugi, K., Tokuyama, H., Shibata, S., Naitoh, M., Kanda, T., Minakuchi, H., Yamaguchi, S., Hayashi, K., Minamishima, Y. A., Yanagita, M., et al. (2016) · Scientific Reports · doi:10.1038/srep36533 · Cited by 15 · see citing works
Geng, Y., Arroyave-Ospina, J. C., Buist‐Homan, M., Plantinga, J. A., Olinga, P., Reijngoud, D., van Vilsteren, F. G. I., Blokzijl, H., Kamps, J. A. A. M., & Moshage, H. J. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109255 · Cited by 14 · see citing works
Inositol-requiring enzyme 1α links palmitate-induced mTOR activation and lipotoxicity in hepatocytes
Chen, Y., Griffiths, A., Wang, J., Zhang, T., Song, Q., & Song, Z. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00165.2020 · Cited by 14 · see citing works
Translational Aspects of the Mammalian Target of Rapamycin Complexes in Diabetic Nephropathy
Daher, A. A., Alkhansa, S., Azar, W. S., Rafeh, R. W., Ghadieh, H. E., & Eid, A. A. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0217 · Cited by 12 · see citing works
The Lipid-Oxidative Stress Axis: Novel Therapeutic Targets for Podocytopathy
Liu, Y., Zou, M., & Wang, Y. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s530737 · Cited by 13 · see citing works
Sós, L., Garabuczi, É., Sághy, T., Mocsár, G., & Szondy, Z. (2022) · Cells · doi:10.3390/cells11213502 · Cited by 11 · see citing works
Tsap, M. I., & Shcherbata, H. R. (2025) · Progress in Lipid Research · doi:10.1016/j.plipres.2025.101341 · Cited by 11 · see citing works
Kayampilly, P. P., Roeser, N. F., Rajendiran, T. M., Pennathur, S., & Afshinnia, F. (2022) · Metabolites · doi:10.3390/metabo12100940 · Cited by 10 · see citing works
Imafuku, T., Watanabe, H., Satoh, T., Matsuzaka, T., Inazumi, T., Kato, H., Tanaka, S., Nakamura, Y., Nakano, T., Tokumaru, K., et al. (2020) · Kidney360 · doi:10.34067/kid.0000772019 · Cited by 10 · see citing works
Tsap, M. I., Yatsenko, A. S., Hegermann, J., Beckmann, B., Tsikas, D., & Shcherbata, H. R. (2024) · eLife · doi:10.7554/elife.98020 · Cited by 8 · see citing works
Dietary modulation of large extracellular vesicles: the good and the bad for human health
Monfoulet, L., & Martínez, M. C. (2021) · Nutrition Reviews · doi:10.1093/nutrit/nuab106 · Cited by 7 · see citing works
A novel therapeutic target for kidney diseases: Lessons learned from starvation response
Yamahara, K., Yasuda‒Yamahara, M., & Kume, S. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108590 · Cited by 7 · see citing works
Self-citationTanaka, Y., Kume, S., Maeda, S., Osawa, N., Takeda, N., Chin‒Kanasaki, M., Isshiki, K., Ugi, S., Oshima, I., Uzu, T., et al. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.11.145 · Cited by 7 · see citing works
Self-citation
- Authors
- Yasuda, M., Tanaka, Y., Kume, S., Morita, Y., Chin-Kanasaki, M., Araki, H., Isshiki, K., Araki, S.-I., Koya, D., Haneda, M., Kashiwagi, A., Maegawa, H., & Uzu, T.
- Affiliations
- Shiga University of Medical Science (JP)
- Kanazawa Medical University (JP)
- Asahikawa Medical University (JP)
- Corresponding author
- Kume, Shinji
- ORCID
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 1842
- Issue
- 7
- Pages
- 1097-1108
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2033453768
- Cited by
- 123
- References
- 57
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 20 · 2020: 16 · 2019: 14 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 5
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science (25713033, 24890089)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- podocyte apoptosis, mTORC1, free fatty acids, palmitate, oleate, eicosapentaenoic acid, endoplasmic reticulum stress, lysosomal translocation, raptors, diabetic nephropathy, proteinuria, saturated fatty acids, omega-3 fatty acids
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Cell Line, Diabetic Nephropathies, Fatty Acids, Food, Humans, Lysosomes, Palmitates, Eicosapentaenoic Acid, Apoptosis, Oleic Acid, Multiprotein Complexes, Podocytes, Mice, HEK293 Cells, TOR Serine-Threonine Kinases, Endoplasmic Reticulum Stress
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