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Rapid depot-specific activation of adipocyte precursor cells at the onset of obesity
Open accessAbstract
Excessive accumulation of white adipose tissue (WAT) is the defining characteristic of obesity. WAT mass is composed primarily of mature adipocytes, which are generated through the proliferation and differentiation of adipocyte precursors (APs). Although the production of new adipocytes contributes to WAT growth in obesity, little is known about the cellular and molecular mechanisms underlying adipogenesis in vivo. Here, we show that high-fat diet feeding in mice rapidly and transiently induces proliferation of APs within WAT to produce new adipocytes. Importantly, the activation of adipogenesis is specific to the perigonadal visceral depot in male mice, consistent with the patterns of obesogenic WAT growth observed in humans. Furthermore, we find that in multiple models of obesity, the activation of APs is dependent on the phosphoinositide 3-kinase (PI3K)-AKT2 pathway; however, the development of WAT does not require AKT2. These data indicate that developmental and obesogenic adipogenesis are regulated through distinct molecular mechanisms.
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“Male mice develop diet-induced obesity primarily though visceral fat hyperplasia, while female mice do so via both visceral and subcutaneous fat hyperplasia (70, 71) with sex steroids playing a major role (70, 72).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [71]
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Citations
Cites
The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
A global double-fluorescent Cre reporter mouse
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L., & Luo, L. (2007) · genesis · doi:10.1002/dvg.20335 · Cited by 3,491
Global burden of obesity in 2005 and projections to 2030
Kelly, T., Yang, W., Chen, C.-S., Reynolds, K., & He, J. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.102 · Cited by 3,319
Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome
Wajchenberg, B. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0415 · Cited by 2,961
What we talk about when we talk about fat
Rosen, E. D., & Spiegelman, B. M. (2014) · Cell · doi:10.1016/j.cell.2013.12.012 · Cited by 2,373
Dynamics of fat cell turnover in humans
Spalding, K. L., Arner, E., Westermark, P. O., Bernard, S., Buchholz, B. A., Bergmann, O., Blomqvist, L., Hoffstedt, J., Näslund, E., Britton, T., et al. (2008) · Nature · doi:10.1038/nature06902 · Cited by 2,357
Fat and Beyond: The Diverse Biology of PPARγ
Tontonoz, P., & Spiegelman, B. M. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061307.091829 · Cited by 2,085
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,860
Forming functional fat: a growing understanding of adipocyte differentiation
Cristancho, A. G., & Lazar, M. A. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3198 · Cited by 1,382
The nuts and bolts of AGC protein kinases
Pearce, L. R., Komander, D., & Alessi, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2822 · Cited by 1,294
Tracking adipogenesis during white adipose tissue development, expansion and regeneration
Wang, Q. A., Tao, C., Gupta, R. K., & Scherer, P. E. (2013) · Nature Medicine · doi:10.1038/nm.3324 · Cited by 1,262
Wang, Y., Rimm, E. B., Stampfer, M. J., Willett, W. C., & Hu, F. B. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.3.555 · Cited by 1,127
Identification of White Adipocyte Progenitor Cells In Vivo
Rodeheffer, M. S., Birsoy, K., & Friedman, J. M. (2008) · Cell · doi:10.1016/j.cell.2008.09.036 · Cited by 980
Self-citationCho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., & Birnbaum, M. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100462200 · Cited by 959
Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 genePreprint
Chen, W. S., Xu, P.-Z., Gottlob, K., Chen, M.-L., Sokol, K. A., Shiyanova, T., Roninson, I. B., Weng, W., Suzuki, R., Tobe, K., et al. (2001) · Genes & Development · doi:10.1101/gad.913901 · Cited by 941
Beneficial Effects of Subcutaneous Fat Transplantation on Metabolism
Tran, T. T., Yamamoto, Y., Gesta, S., & Kahn, C. R. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.04.004 · Cited by 731
Garofalo, R. S., Orena, S. J., Rafidi, K., Torchia, A. J., Stock, J. L., Hildebrandt, A. L., Coskran, T., Black, S. C., Brees, D. J., Wicks, J. R., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16885 · Cited by 726
Lee, Y., Petkova, A. P., Mottillo, E. P., & Granneman, J. G. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.009 · Cited by 710
Characterization of the adipocyte cellular lineage in vivo
Berry, R., & Rodeheffer, M. S. (2013) · Nature Cell Biology · doi:10.1038/ncb2696 · Cited by 566
Self-citationA Family with Severe Insulin Resistance and Diabetes Due to a Mutation in AKT2
George, S., Rochford, J. J., Wolfrum, C., Gray, S. L., Schinner, S., Wilson, J. C., Soos, M. A., Murgatroyd, P. R., Williams, R. M., Acerini, C. L., et al. (2004) · Science · doi:10.1126/science.1096706 · Cited by 562
Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source
Chau, Y.-Y., Bandiera, R., Serrels, A., Martínez-Estrada, O. M., Qing, W., Lee, M., Slight, J., Thornburn, A., Berry, R., McHaffie, S., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb2922 · Cited by 518
Diet-induced adipocyte number increase in adult rats: a new model of obesity.
Faust, I. M., Johnson, P. R., Stern, J. S., & Hirsch, J. (1978) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1978.235.3.e279 · Cited by 514
Lipid accumulation in non-adipose tissue and lipotoxicity
van Herpen, N. A., & Schrauwen-Hinderling, V. B. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.11.049 · Cited by 500
The Akt kinases: Isoform specificity in metabolism and cancer
Gonzalez, E., & McGraw, T. E. (2009) · Cell Cycle · doi:10.4161/cc.8.16.9335 · Cited by 485
Adipose tissue cellularity in human obesity
Hirsch, J., & Batchelor, B. R. (1976) · Clinics in Endocrinology and Metabolism · doi:10.1016/s0300-595x(76)80023-0 · Cited by 441
Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism
Macotela, Y., Boucher, J., Tran, T. T., & Kahn, C. R. (2009) · Diabetes · doi:10.2337/db08-1054 · Cited by 401
Sixteen years and counting: an update on leptin in energy balance
Gautron, L., & Elmquist, J. K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45888 · Cited by 367
Increase in Cell Number as a Factor in the Growth of the Organs and Tissues of the Young Male Rat
Enesco, M., & Leblond, C. P. (1962) · Development · doi:10.1242/dev.10.4.530 · Cited by 346
Regulation of Tissue Growth through Nutrient Sensing
Hietakangas, V., & Cohen, S. M. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102108-134815 · Cited by 341
Cell Turnover and Adult Tissue Homeostasis: From Humans to Planarians
Pellettieri, J., & Alvarado, A. S. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130244 · Cited by 316
Lemonnier, D. (1972) · Journal of Clinical Investigation · doi:10.1172/jci107115 · Cited by 315
Joe, A. W., Yi, L., Even, Y., Vogl, A. W., & Rossi, F. M. V. (2009) · Stem Cells · doi:10.1002/stem.190 · Cited by 297
Insulin signalling mechanisms for triacylglycerol storage
Czech, M., Tencerová, M., Pedersen, D. J., & Aouadi, M. (2013) · Diabetologia · doi:10.1007/s00125-013-2869-1 · Cited by 289
Akt2 Is Required for Hepatic Lipid Accumulation in Models of Insulin Resistance
Leavens, K. F., Easton, R., Shulman, G. I., Previs, S. F., & Birnbaum, M. J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.10.004 · Cited by 289
Characterization of Structure and Cellular Components of Aspirated and Excised Adipose Tissue
Eto, H., Suga, H., Matsumoto, D., Inoue, K., Aoi, N., D, H. K. M., Araki, J., & Yoshimura, K. (2009) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0b013e3181b5a3f1 · Cited by 281
Lodhi, I. J., Yin, L., Jensen-Urstad, A. P. L., Funai, K., Coleman, T., Baird, J. H., Ramahi, M. K. E., Razani, B., Song, H., Hsu, F., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.013 · Cited by 253
Weighing in on Adipocyte Precursors
Berry, R., Jeffery, E. C., & Rodeheffer, M. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.003 · Cited by 246
Self-citationThe Influence of a Hypercaloric Diet on Gross Body and Adipose Tissue Composition in the Rat
Peckham, S. C., Entenman, C., & Carroll, H. W. (1962) · Journal of Nutrition · doi:10.1093/jn/77.2.187 · Cited by 222
Characterization of Cre recombinase models for the study of adipose tissue
Jeffery, E. C., Berry, R., CHURCH, C. D., Yu, S., Shook, B. A., Horsley, V., Rosen, E. D., & Rodeheffer, M. S. (2014) · Adipocyte · doi:10.4161/adip.29674 · Cited by 215
Self-citationThe spatiotemporal development of adipose tissue
Han, J., Lee, J.-E., Jin, J., Lim, J. S., Oh, N., Kim, K., Chang, S.-I., Shibuya, M., Kim, H., & Koh, G. Y. (2011) · Development · doi:10.1242/dev.067686 · Cited by 212
A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice
Grove, K. L., Fried, S. K., Greenberg, A. S., Xiao, X. Q., & Clegg, D. J. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.12 · Cited by 208
Adipose Depots Possess Unique Developmental Gene Signatures
Yamamoto, Y., Gesta, S., Lee, K. Y., Tran, T. T., Saadatirad, P., & Kahn, C. R. (2010) · Obesity · doi:10.1038/oby.2009.512 · Cited by 185
An Activating Mutation of AKT2 and Human Hypoglycemia
Hussain, K., Challis, B., Rocha, N., Payne, F., Minic, M., Thompson, A., Daly, A., Scott, C. L., Harris, J. R., Smillie, B. J. L., et al. (2011) · Science · doi:10.1126/science.1210878 · Cited by 181
The link between abdominal obesity and the metabolic syndrome
Phillips, L. K., & Prins, J. B. (2008) · Current Hypertension Reports · doi:10.1007/s11906-008-0029-7 · Cited by 178
Pref-1 Marks Very Early Mesenchymal Precursors Required for Adipose Tissue Development and Expansion
Hudak, C. S. S., Gulyaeva, О. N., Wang, Y., Park, S.-M., Lee, L. P., Kang, C., & Sul, H. S. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.06.060 · Cited by 125
Berry, R., CHURCH, C. D., Gericke, M. T., Jeffery, E. C., Colman, L., & Rodeheffer, M. S. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-411619-1.00004-5 · Cited by 123
Self-citationCharacterization of Cre Recombinase Activity for In Vivo Targeting of Adipocyte Precursor Cells
Krueger, K. C., Costa, M. J. D. C., Du, H., & Feldman, B. J. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.10.009 · Cited by 116
Isolation and Study of Adipocyte Precursors
CHURCH, C. D., Berry, R., & Rodeheffer, M. S. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-411619-1.00003-3 · Cited by 110
Self-citationBirsoy, K., Berry, R., Wang, T., Ceyhan, O., Tavazoie, S., Friedman, J. M., & Rodeheffer, M. S. (2011) · Development · doi:10.1242/dev.067710 · Cited by 109
Self-citationVariations in the Size of the Major Omentum Are Primarily Determined by Fat Cell Number
Arner, P., Andersson, D. P., Thörne, A., Wirén, M., Hoffstedt, J., Näslund, E. B., Thorell, A., & Rydén, M. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-4106 · Cited by 108
Studies of the number and volume of fat cells in adipose tissue
Steinberg, M., Zingg, W., Ángel, A., & Medovy, H. (1962) · The Journal of Pediatrics · doi:10.1016/s0022-3476(62)80282-0 · Cited by 87
[Metabolic difference between visceral fat and subcutaneous abdominal fat].
Björntorp, P. A. (2000) · PubMed · Cited by 60
Developmental changes in thymidine kinase, DNA, and fat cellularity in Zucker rats.
Cleary, M. P., Brasel, J. A., & Greenwood, M. R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.236.5.e508 · Cited by 42
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Ghaben, A. L., & Scherer, P. E. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0093-z · Cited by 1,395
Metabolism disrupting chemicals and metabolic disorders
Heindel, J. J., Blumberg, B., Cave, M., Machtinger, R., Mantovani, A., Mendez, M. A., Nadal, A., Palanza, P., Panzica, G., Sargis, R., et al. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.10.001 · Cited by 1,101
Adipose-tissue plasticity in health and disease
Sakers, A. P., Siqueira, M. K. D., Seale, P., & Villanueva, C. J. (2022) · Cell · doi:10.1016/j.cell.2021.12.016 · Cited by 1,124
A single-cell atlas of human and mouse white adipose tissue
Emont, M. P., Jacobs, C., Essene, A. L., Pant, D., Tenen, D., Colleluori, G., Di Vincenzo, A., Jørgensen, A. M., Dashti, H., Stefek, A., et al. (2022) · Nature · doi:10.1038/s41586-022-04518-2 · Cited by 840
The aetiology and molecular landscape of insulin resistance
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Metadata
- Authors
- Jeffery, E., Church, C. D., Holtrup, B., Colman, L., & Rodeheffer, M. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Rodeheffer, Matthew S.
- Venue
- Nature Cell Biology
- Published
- 2015-03-02
- Volume
- 17
- Issue
- 4
- Pages
- 376-385
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4380653
- OpenAlex
- W2000524154
- Cited by
- 404
- References
- 53
- Citations by year
- 2026: 14 · 2025: 26 · 2024: 29 · 2023: 44 · 2022: 42 · 2021: 39 · 2020: 39 · 2019: 42 · 2018: 37 · 2017: 40 · 2016: 35 · 2015: 16
- FWCI
- 33.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000142)
- National Institute of General Medical Sciences (T32GM007223)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK090489, R56DK090489, DK-045735, DK090489, P30DK045735)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adipocyte precursors, adipogenesis, obesity, white adipose tissue, high-fat diet, adipocyte proliferation
- MeSH terms
- Wortmannin, Phosphoinositide-3 Kinase Inhibitors, Androstadienes, Animals, Eating, Male, Mice, Inbred C57BL, Obesity, Random Allocation, Tamoxifen, Mice, Knockout, Phosphatidylinositol 3-Kinases, Cell Proliferation, Adipogenesis, Proto-Oncogene Proteins c-akt, Mice, Adipose Tissue, White, Adipocytes, White, Diet, High-Fat
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