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Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62
Open accessAbstract
Signaling cascades that control adipogenesis are essential in the regulation of body weight and obesity. The adaptor p62 controls pathways that modulate cell differentiation. We report here that p62(-/-) mice develop mature-onset obesity, leptin resistance, as well as impaired glucose and insulin intolerance. The metabolic rate was significantly reduced in p62(-/-) nonobese mice, which displayed increased mRNA levels of PPAR-gamma and reduced levels of UCP-1 in adipose tissue. Basal activity of ERK was enhanced in fat from nonobese mutant mice. Embryo fibroblasts from p62(-/-) mice differentiated better than the wild-type controls into adipocytes, which was abrogated by pharmacological inhibition of the ERK pathway. p62 is induced during adipocyte differentiation and inhibits ERK activation by direct interaction. We propose that p62 normally antagonizes basal ERK activity and adipocyte differentiation and that its loss leads to the hyperactivation of ERK that favors adipogenesis and obesity.
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“sqstm1-knockout mice display reduced numbers of osteoclasts as well as cognitive impairment and anxiety, associated with hyperphosphorylated MAPT/tau and neurofibrillary tangles [134–136].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [136]
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1 retracted
Cytokines suppress adipogenesis and PPAR-γ function through the TAK1/TAB1/NIK cascade
Suzawa, M., Takada, I., Yanagisawa, J., Ohtake, F., Ogawa, S., Yamauchi, T., Kadowaki, T., Takeuchi, Y., Shibuyà, H., Gotoh, Y., et al. (2003) · Nature Cell Biology · doi:10.1038/ncb942 · Cited by 292
RetractedA central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J., & Shoelson, S. E. (2005) · Nature Medicine · doi:10.1038/nm1166 · Cited by 2,245
IKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677
Self-citationBile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
渡辺, 光., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., Moore, D. D., & Auwerx, J. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21025 · Cited by 1,398
Self-citationPhosphorylation and Functional Inactivation of TSC2 by Erk
Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005) · Cell · doi:10.1016/j.cell.2005.02.031 · Cited by 1,268
TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signalingPreprint
Lomaga, M. A., Yeh, W., Sarosi, I., Duncan, G. S., Furlonger, C. L., Ho, A. P., Morony, S., Capparelli, C., Van, G. Y., Kaufman, S., et al. (1999) · Genes & Development · doi:10.1101/gad.13.8.1015 · Cited by 1,265
Flier, J. S. (2004) · Cell · doi:10.1016/s0092-8674(03)01081-x · Cited by 1,122
Inhibition of Adipogenesis Through MAP Kinase-Mediated Phosphorylation of PPARγ
Hu, E., Kim, J. B., Sarraf, P., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.274.5295.2100 · Cited by 1,051
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Self-citationKratz, M., Coats, B. R., Hisert, K. B., Hagman, D. K., Mutskov, V. J., Peris, E., Schoenfelt, K. Q., Kuzma, J. N., Larson, I. A., Billing, P. S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.08.010 · Cited by 865
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Tanti, J.-F., & Jager, J. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.07.004 · Cited by 430
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Shin, S., Wakabayashi, N., Misra, V., Biswal, S., Lee, G., Agoston, E., Yamamoto, M., & Kensler, T. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00915-07 · Cited by 355
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Self-citationp62/SQSTM1/A170: Physiology and pathology
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“In line with these findings, others found that mice deficient in the signaling adapter p62, an ERK inhibitor protein, develop obesity and insulin resistance associated with enhanced basal level of ERK activity (Rodriguez et al. 2006).”
Resultp62/SQSTM1 – steering the cell through health and disease
Sánchez‐Martín, P., & Komatsu, M. (2018) · Journal of Cell Science · doi:10.1242/jcs.222836 · Cited by 287
“Indeed, in mice, loss of Sqstm1 causes insulin resistance and impaired glucose tolerance due to hyperactivation of ERK1 signaling (Rodriguez et al., 2006).”
BackgroundPankiv, S., Lamark, T., Bruun, J., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.039925 · Cited by 266
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“As p62 deficiency leads to mature-onset obesity (Rodriguez et al. 2006) and there is a recognized correlation between obesity, T2DM, aging, and cognitive impairment (Craft 2005), we hypothesize that the p62-deficient mice constitute an invaluable model to analyze the relations between tau modification and neurodegener…”
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BackgroundSelf-citationImplication of inflammatory signaling pathways in obesity-induced insulin resistance
Tanti, J., Ceppo, F., Jager, J., & Berthou, F. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00181 · Cited by 255
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BackgroundInfluentialSelf-citationAssurance of mitochondrial integrity and mammalian longevity by the p62–Keap1–Nrf2–Nqo1 cascade
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BackgroundInfluentialEmerging role of p62/sequestosome-1 in the pathogenesis of Alzheimer's disease
Salminen, A., Kaarniranta, K., Haapasalo, A., Hiltunen, M., Soininen, H., & Alafuzoff, I. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.11.005 · Cited by 153
Rivera, J. F., Gurlo, T., Daval, M., Huang, C. J., Matveyenko, A. V., Butler, P. C., & Costes, S. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.111 · Cited by 136
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“targeting of poly-ubiquitinated proteins destined for degradation by autophagy and proteasomal pathways [54–56].”
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“In mice, the knock out of Sqstm1 leads to matureonset obesity, leptine resistance, and impaired glucose tolerance and insulin resistance potentially mediated by disturbed regulation of adipocyte differentiation due to enhanced basal ERK activity.(22) Furthermore, the chronic absence of Sqstm1/p62 promotes mature-onset…”
BackgroundApoptosis and autophagy: Targeting autophagy signalling in cancer cells –‘trick or treats’?
Corcelle–Termeau, E., Puustinen, P., & Jäättelä, M. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07332.x · Cited by 124
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Simon, D. N., & Rout, M. P. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4899-8032-8_13 · Cited by 121
Livingston, M. J., Zhang, M., Kwon, S., Chen, J., Li, H., Manicassamy, S., & Dong, Z. (2023) · Autophagy · doi:10.1080/15548627.2023.2281156 · Cited by 120
“Previous studies suggest that during adipogenesis SQSTM1/p62 may sequester MAPK/ERK into cytoplasmic aggregates to prevent the access of MAPK/ERK to its upstream kinase for phosphorylation and activation [32].”
BackgroundResultp62/SQSTM1 synergizes with autophagy for tumor growth in vivoPreprint
Wei, H., Wang, C., Croce, C. M., & Guan, J. (2014) · Genes & Development · doi:10.1101/gad.237354.113 · Cited by 120
“2006), p62-null mice can survive for more than 1 year but with defects in adult mice such as adult-onset obesity and diabetes (Rodriguez et al. 2006).”
BackgroundUse of p62/SQSTM1 antibodies for neuropathological diagnosis
Kuusisto, E., Kauppinen, T., & Alafuzoff, I. I. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00884.x · Cited by 113
The Pathways Underlying the Multiple Roles of p62 in Inflammation and Cancer
Hennig, P., Fenini, G., Filippo, M. D., Karakaya, T., & Beer, H. (2021) · Biomedicines · doi:10.3390/biomedicines9070707 · Cited by 122
Milan, E., Perini, T., Resnati, M., Orfanelli, U., Oliva, L., Raimondi, A., Cascio, P., Bachi, A., Marcatti, M., Ciceri, F., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1052928 · Cited by 116
p62/ SQSTM 1—Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer
Taniguchi, K., Yamachika, S., He, F., & Karin, M. (2016) · FEBS Letters · doi:10.1002/1873-3468.12301 · Cited by 116
“adipogenesis [16, 288] although it was also reported that absence of p62 in the brain causes”
BackgroundHepatic ERK activity plays a role in energy metabolism
Jiao, P., Feng, B., Li, Y., He, Q., & Xu, H. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.05.021 · Cited by 112
“Deficiency of the signaling adaptor p62, a protein that antagonizes basal ERK activity, promotes adipogenesis in vitro and mature-onset obesity and insulin resistance in vivo (Rodriguez et al., 2006).”
BackgroundHuang, J., Durán, Á., Reina‐Campos, M., Valencia, T., Castilla, E. A., Müller, T. D., Tschöp, M. H., Moscat, J., & Díaz-Meco, M. T. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.001 · Cited by 111
“…tissue from non-tumor-bearing p62Adipo mice showed a significant increase in crown-like structure (CLS) compared with WT mice (Figures 6A and 6B), consistent with the enhanced inflammation previously reported in the adipose tissue of these mutant mice (Muller et al., 2013; Rodriguez et al., 2006).”
InfluentialSelf-citationKao, C., Chao, A., Tsai, C.-L., Chuang, W.-C., Huang, W.-P., Chen, G., Lin, C.-Y., Th, W., Wang, H., & Lai, C. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.468 · Cited by 109
“P62/ SQSTM1 was also shown to inhibit ERK phosphorylation, and the knockout of p62 was shown to enhance ERK activation in vivo.(47) On the other hand, ERK knockdown has been shown to induce autophagy,(48) and sustained ERK activation may inhibit the autophagic flux.”
BackgroundAutophagy as an emerging target in cardiorenal metabolic disease: From pathophysiology to management
Zhang, Y., Whaley‐Connell, A. T., Sowers, J. R., & Ren, J. T. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.06.004 · Cited by 109
“Global deletion of p62 promotes insulin resistance along with increased body fat mass (Rodriguez et al., 2006).”
A functional role for the p62–ERK1 axis in the control of energy homeostasis and adipogenesis
Lee, S. J., Pfluger, P. T., Kim, J. Y., Nogueiras, R., Durán, Á., Pagès, G., Pouysségur, J., Tschöp, M. H., Díaz-Meco, M. T., & Moscat, J. (2010) · EMBO Reports · doi:10.1038/embor.2010.7 · Cited by 108
“Interestingly, activation of ERK during in vitro adipogenesis has been reported to be biphasic (Sale et al, 1995).”
BackgroundSelf-citationSergin, I., Bhattacharya, S., Emanuel, R., Esen, E., Stokes, C. J., Evans, T. D., Arif, B., Curci, J. A., & Razani, B. (2016) · Science Signaling · doi:10.1126/scisignal.aad5614 · Cited by 108
Nucleophagy: from homeostasis to disease
Papandreou, M., & Tavernarakis, N. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-018-0266-5 · Cited by 107
Age-associated oxidative damage to the p62 promoter: implications for Alzheimer disease
Du, Y., Wooten, M. C., Gearing, M., & Wooten, M. W. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.11.003 · Cited by 108
“Knockout mice (p62) were generated as described previously [25].”
Wu, Z., Jiao, P., Huang, X., Feng, B., Feng, Y., Yang, S., Hwang, P. W., Du, J., Nie, Y., Xiao, G., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43250 · Cited by 99
Transactivation of Atg4b by C/EBPβ Promotes Autophagy To Facilitate Adipogenesis
Guo, L., Huang, J.-X., Liu, Y., Li, X., Zhou, S.-R., Qian, S.-W., Liu, Y., Zhu, H., Huang, H.-Y., Dang, Y., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00193-13 · Cited by 100
Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis
Kulkarni, A., Muralidharan, C., May, S. C., Tersey, S. A., & Mirmira, R. G. (2022) · Endocrinology · doi:10.1210/endocr/bqac184 · Cited by 95
Cardioprotection requires taking out the trash
Gottlieb, R. A., Finley, K. D., & Mentzer, R. M. (2009) · Basic Research in Cardiology · doi:10.1007/s00395-009-0011-9 · Cited by 97
“Interestingly, genetic deletion of murine p62 results in viable adult mice that develop insulin resistance and obesity as early as 4 months of age [83].”
Shen, Y., Yang, J., Zhao, J., Xiao, C., Xu, C., & Xiang, Y. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.04.010 · Cited by 92
Lattante, S., de Calbiac, H., Le Ber, I., Brice, A., Ciura, S., & Kabashi, E. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddu580 · Cited by 90
Mitochondrial homeostasis in adipose tissue remodeling
Altshuler-Keylin, S., & Kajimura, S. (2017) · Science Signaling · doi:10.1126/scisignal.aai9248 · Cited by 91
Linares, J. F., Amanchy, R., Díaz-Meco, M. T., & Moscat, J. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00620-10 · Cited by 89
“The protein scaffold and signaling regulator p62 has been implicated in critical cellular functions such as bone homeostasis (2), obesity (20), and cancer (1) through the regulation of important signaling intermediaries like TRAF6/NF- B (23), the atypical protein kinase C isoforms (23), caspase-8 (4), ERK1 (10), and t…”
BackgroundSelf-citationSequestosome-1/p62 Is the Key Intracellular Target of Innate Defense Regulator Peptide
Yu, H. B., Kielczewska, A., Rozek, A., Takenaka, S., Li, Y., Thorson, L., Hancock, R. E. W., Guarna, M. M., North, J. R., Foster, L. J., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.c109.073627 · Cited by 81
Huang, H., Zhu, J., Li, Y., Zhang, L., Gu, J., Xie, Q., Jin, H., Che, X., Li, J., Huang, C., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1196313 · Cited by 82
A role for sequestosome 1/p62 in mitochondrial dynamics, import and genome integrity
Seibenhener, M. L., Du, Y., Díaz-Meco, M. T., Moscat, J., Wooten, M. C., & Wooten, M. W. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.11.004 · Cited by 85
“Glucose tolerance tests in aged p62−/− mice have also shown to be defective in glucose uptake and insulin tolerance [4] indicative of glycolytic defects.”
Self-citationWhitehouse, C. A., Waters, S., Marchbank, K., Horner, A. A., McGowan, N. W. A., Jovanovic, J. V., Xavier, G. M., Kashima, T. G., Cobourne, M. T., Richards, G. O., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913058107 · Cited by 83
“p62 null mice show defects in osteoclastogenesis in vitro because of reduced receptor activator for nuclear factorκ B ligand (RANKL)–stimulated NF-κB signaling and develop mature-onset obesity and insulin resistance through hyperactivation of ERK and adipogenesis (4).”
BackgroundForced lipophagy reveals that lipid droplets are required for early embryonic development in mouse
Tatsumi, T., Takayama, K., Ishii, S., Yamamoto, A., Hara, T., Minami, N., Miyasaka, N., Kubota, T., Matsuura, A., Itakura, E., et al. (2018) · Development · doi:10.1242/dev.161893 · Cited by 81
“Although we used the p62T352A mutant to prevent secondary effects of p62, we were still concerned that p62 overexpression alone might induce lipophagy, largely because p62 plays multiple roles in cell signaling, including lipid metabolism (Rodriguez et al., 2006).”
MethodEmerging role of epigenetics and miRNA in diabetic cardiomyopathy
Asrih, M., & Steffens, S. (2012) · Cardiovascular Pathology · doi:10.1016/j.carpath.2012.07.004 · Cited by 81
“On the other hand, reduced availability of FFA also disturbs myocardial bioenergetics and contraction/relaxation coupling [40].”
BackgroundMoscat, J., Díaz-Meco, M. T., & Wooten, M. W. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.119 · Cited by 86
“data showing the negative regulation of ERK by p62 and its role in obesity in p62-deficient mice.(137) Consistent with the notion that p62 is a ‘signaling organizer’ rather than ‘garbage disposal’ are the very recent data from the Ashkenazi laboratory.”
BackgroundSelf-citationChoe, J., Jung, H., Park, K.-Y., & Kim, S.-K. (2014) · Rheumatology · doi:10.1093/rheumatology/ket474 · Cited by 81
Accumulation of p62 is associated with poor prognosis in patients with triple-negative breast cancer
Yuan, Z.-Y., Luo, Li, M., Xi, S., Fu, J., & He (2013) · OncoTargets and Therapy · doi:10.2147/ott.s46222 · Cited by 84
Target acquired: Selective autophagy in cardiometabolic disease
Evans, T. D., Sergin, I., Zhang, X., & Razani, B. (2017) · Science Signaling · doi:10.1126/scisignal.aag2298 · Cited by 74
Cundy, T. (2018) · Metabolism · doi:10.1016/j.metabol.2017.06.010 · Cited by 76
Metadata
- Authors
- Rodriguez, A., Durán, A., Selloum, M., Champy, M.-F., Diez-Guerra, F. J., Flores, J. M., Serrano, M., Auwerx, J., Diaz-Meco, M. T., & Moscat, J.
- Affiliations
- Phénotypage et ingénierie précliniques des systèmes d’organismes modèles (FR)
- Universidad Complutense de Madrid (ES)
- Spanish National Cancer Research Centre (ES)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Moscat, Jorge
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 3
- Issue
- 3
- Pages
- 211-222
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2096738869
- Cited by
- 290
- References
- 34
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 14 · 2021: 19 · 2020: 14 · 2019: 14 · 2018: 24 · 2017: 17 · 2016: 19 · 2015: 14 · 2014: 22 · 2013: 26 · 2012: 21
- FWCI
- 9.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- p62, insulin resistance, leptin resistance, adipogenesis, ERK signaling, PPARγ, UCP1, metabolic rate, adipose tissue, impaired glucose tolerance
- MeSH terms
- Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Embryo, Mammalian, Fibroblasts, HeLa Cells, Humans, Insulin Resistance, RNA, Messenger, Transcription Factors, Signal Transduction, Adipocytes, Mice, Knockout, 3T3-L1 Cells, Extracellular Signal-Regulated MAP Kinases, Adipogenesis, Mice, Transcription Factor TFIIH
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