Adipose tissue fibrosis, hypertrophy, and hyperplasia: Correlations with diabetes in human obesity
Open accessAbstract
OBJECTIVE: The relationship between adipose tissue fibrosis, adipocyte hypertrophy, and preadipocyte hyperplasia in the context of obesity and the correlation of these tissue-based phenomena with systemic metabolic disease are poorly defined. The goal of this study was to clarify the relationship between adipose tissue fibrosis, adipocyte hypertrophy, and preadipocyte hyperplasia in human obesity and determine the correlation of these adipose-tissue based phenomena with diabetes. METHODS: Visceral and subcutaneous adipose tissues from humans with obesity collected during bariatric surgery were studied with QRTPCR, immunohistochemistry, and flow cytometry for expression of collagens and fibrosis-related proteins, adipocyte size, and preadipocyte frequency. Results were correlated with clinical characteristics including diabetes status. RESULTS: Fibrosis was decreased, hypertrophy was increased, and preadipocyte frequency and fibrotic gene expression were decreased in adipose tissues from diabetic subjects compared to non-diabetic subjects. These differences were greater in visceral compared to subcutaneous adipose tissue. CONCLUSIONS: These data are consistent with the hypothesis that adipose tissue fibrosis in the context of human obesity limits adipocyte hypertrophy and is associated with a reciprocal increase in adipocyte hyperplasia, with beneficial effects on systemic metabolism. These findings suggest adipose tissue fibrosis as a potential target for manipulation of adipocyte metabolism.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hypertrophic adipocytes show a positive correlation with insulin resistance and the risk of CVD.
“Hypertrophic adipocytes show a positive correlation with insulin resistance and the risk of CVD”
From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Muir et al., 2016
The Discussion reports a positive correlation between adipocyte hypertrophy and diabetes in this study and cites prior findings linking adipocyte size with insulin resistance. The Results likewise show larger adipocytes in subjects with diabetes. The paper does not establish a correlation between hypertrophic adipocytes and CVD risk. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA recent human study comparing obese patients with and without type 2 diabetes found significantly less visceral adipose tissue fibrosis in the diabetic subjects.
“However, a recent human study compared obese patients with or without T2D and found significantly less fibrosis in the visceral AT of the diabetic subjects (122).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [122]
Less fibrosis is associated with adipocyte hypertrophy, reduced pre-adipocyte hyperplasia, and adipose tissue dysfunction.
“Less fibrosis was associated with adipocyte hypertrophy, reduced pre-adipocyte hyperplasia, and AT dysfunction (122).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [122]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hypoxia-Inducible Factor 1α Induces Fibrosis and Insulin Resistance in White Adipose Tissue
Halberg, N., Khan, T., Trujillo, M. E., Wernstedt-Asterholm, I., Attie, A. D., Sherwani, S., Wang, Z. V., Landskroner-Eiger, S., Dineen, S., Magalang, U. J., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00192-09 · Cited by 896 · see citing works
Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology
Arner, E., Westermark, P. O., Spalding, K. L., Britton, T., Rydén, M., Frisén, J., Bernard, S., & Arner, P. (2010) · Diabetes · doi:10.2337/db09-0942 · Cited by 645 · see citing works
Divoux, A., Tordjman, J., Lacasa, D., Veyrie, N., Hugol, D., Aissat, A., Basdevant, A., Guerre-Millo, M., Poitou, C., Zucker, J., et al. (2010) · Diabetes · doi:10.2337/db10-0585 · Cited by 620 · see citing works
Henegar, C., Tordjman, J., Achard, V., Lacasa, D., Cremer, I., Guerre-Millo, M., Poitou, C., Basdevant, A., Stich, V., Viguerie, N., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-1-r14 · Cited by 471 · see citing works
Spencer, M., Yao-Borengasser, A., Unal, R., Rasouli, N., Gurley, C. M., Zhu, B., Peterson, C. A., & Kern, P. A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00329.2010 · Cited by 439 · see citing works
Regional differences in cellular mechanisms of adipose tissue gain with overfeeding
Tchoukalova, Y. D., Votruba, S. B., Tchkonia, T., Giorgadze, N., Kirkland, J. L., & Jensen, M. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005259107 · Cited by 377 · see citing works
Impaired Preadipocyte Differentiation in Human Abdominal Obesity
Isakson, P., Hammarstedt, A., Gustafson, B., & Smith, U. (2009) · Diabetes · doi:10.2337/db08-1770 · Cited by 369 · see citing works
Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction
Sun, K., Park, J., Gupta, O. T., Holland, W. L., Auerbach, P., Zhang, N., Goncalves Marangoni, R., Nicoloro, S. M., Czech, M. P., Varga, J., et al. (2014) · Nature Communications · doi:10.1038/ncomms4485 · Cited by 364 · see citing works
Lacasa, D., Taleb, S., Keophiphath, M., Miranville, A., & Clement, K. (2007) · Endocrinology · doi:10.1210/en.2006-0687 · Cited by 334 · see citing works
Goossens, G. H., Bizzarri, A., Venteclef, N., Essers, Y., Cleutjens, J. P., Konings, E., Jocken, J. W. E., Čajlaković, M., Ribitsch, V., Clément, K., et al. (2011) · Circulation · doi:10.1161/circulationaha.111.027813 · Cited by 324 · see citing works
Cellular hypoxia and adipose tissue dysfunction in obesity
Wood, I. S., de Heredia, F. P., Wang, B., & Trayhurn, P. (2009) · Proceedings of The Nutrition Society · doi:10.1017/s0029665109990206 · Cited by 290 · see citing works
Identification of an Adipogenic Niche for Adipose Tissue Remodeling and Restoration
Lee, Y., Petkova, A. P., & Granneman, J. G. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.003 · Cited by 274 · see citing works
Jiang, C., Qu, A., Matsubara, T., Chanturiya, T., Jou, W., Gavrilova, O., Shah, Y. M., & Gonzalez, F. J. (2011) · Diabetes · doi:10.2337/db11-0174 · Cited by 269 · see citing works
Sengenès, C., Lolmède, K., Zakaroff‐Girard, A., Busse, R., & Bouloumié, A. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20381 · Cited by 250 · see citing works
Kim, S. M., Lun, M., Wang, M., Senyo, S. E., Guillermier, C., Patwari, P., & Steinhauser, M. L. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.010 · Cited by 244 · see citing works
Hypertrophy and hyperplasia of abdominal adipose tissues in women
Drolet, R., Richard, C., Sniderman, A. D., Mailloux, J. R., Fortier, M. P., Huot, C., Rhéaume, C., & Tchernof, A. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803708 · Cited by 243 · see citing works
Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes
Tchkonia, T., Giorgadze, N., Pirtskhalava, T., Thomou, T., DePonte, M., Koo, A., Forse, R. A., Chinnappan, D., Martin-Ruiz, C. M., von Zglinicki, T., et al. (2006) · Diabetes · doi:10.2337/db06-0540 · Cited by 226 · see citing works
The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity
O'Connell, J., Lynch, L., Cawood, T. J., Kwasnik, A., Nolan, N., Geoghegan, J., McCormick, A., O'Farrelly, C., & O'Shea, D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009997 · Cited by 211 · see citing works
Landgraf, K., Rockstroh, D., Wagner, I. V., Weise, S., Tauscher, R., Schwartze, J. T., Löffler, D., Bühligen, U., Wojan, M., Till, H., et al. (2014) · Diabetes · doi:10.2337/db14-0744 · Cited by 188 · see citing works
Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells
O’Rourke, R. W., White, A. E., Metcalf, M. D., Olivas, A., Mitra, P., Larison, W. G., Cheang, E. C., Varlamov, O., Corless, C. L., Roberts, C. T., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2103-y · Cited by 177 · see citing works
Self-citationVila, I. K., Badin, P.-M., Marques, M.-A., Monbrun, L., Lefort, C., Mir, L., Louche, K., Bourlier, V., Roussel, B., Gui, P., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.062 · Cited by 165 · see citing works
Veilleux, A., Caron-Jobin, M., Noël, S., Laberge, P. Y., & Tchernof, A. (2011) · Diabetes · doi:10.2337/db10-1039 · Cited by 155 · see citing works
Johannsen, D. L., Tchoukalova, Y. D., Tam, C. S., Covington, J. D., Xie, W., Schwarz, J., Bajpeyi, S., & Ravussin, É. (2014) · Diabetes Care · doi:10.2337/dc14-0761 · Cited by 145 · see citing works
Cotillard, A., Poitou, C., Torcivia, A., Bouillot, J., Dietrich, A., Klöting, N., Grégoire, C., Lolmède, K., Blüher, M., & Clément, K. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1074 · Cited by 139 · see citing works
Abdennour, M., Reggio, S., Naour, G. L., Liu, Y., Poitou, C., Aron‐Wisnewsky, J., Charlotte, F., Bouillot, J., Torcivia, A., Sasso, M., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3253 · Cited by 138 · see citing works
Henninger, A. M. J., Eliasson, B., Jenndahl, L. E., & Hammarstedt, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105262 · Cited by 125 · see citing works
Rydén, M., Andersson, D. P., Bergström, I. B., & Arner, P. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1526 · Cited by 124 · see citing works
Maumus, M., Sengenès, C., Decaunes, P., Zakaroff‐Girard, A., Bourlier, V., Lafontan, M., Galitzky, J., & Bouloumié, A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0044 · Cited by 123 · see citing works
Lu, J., Shi, J., Li, M., Gui, B., Fu, R., Yao, G., Duan, Z., Lv, Z., Yang, Y., Chen, Z., et al. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.01.042 · Cited by 119 · see citing works
JAK3/STAT6 Stimulates Bone Marrow–Derived Fibroblast Activation in Renal Fibrosis
Yan, J., Zhang, Z., Yang, J., Mitch, W. E., & Wang, Y. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014070717 · Cited by 112 · see citing works
Profibrotic Role for Interleukin-4 in Cardiac Remodeling and Dysfunction
Peng, H., Sarwar, Z., Yang, X.-P., Peterson, E. L., Xu, J., Janic, B., Rhaleb, N., Carretero, O. A., & Rhaleb, N. (2015) · Hypertension · doi:10.1161/hypertensionaha.115.05627 · Cited by 111 · see citing works
Lackey, D. E., Burk, D. H., Ali, M. R., Mostaedi, R., Smith, W. H., Park, J., Scherer, P. E., Seay, S. A., McCoin, C. S., Bonaldo, P., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00476.2013 · Cited by 111 · see citing works
Dankel, S. N., Svärd, J., Matthä, S., Claussnitzer, M., Klöting, N., Glunk, V., Fandalyuk, Z., Grytten, E., Solsvik, M. H., Nielsen, H., et al. (2014) · Obesity · doi:10.1002/oby.20758 · Cited by 95 · see citing works
Bourlier, V., Sengenès, C., Zakaroff‐Girard, A., Decaunes, P., Wdziekonski, B., Galitzky, J., Villageois, P., Estève, D., Chiotasso, P., Dani, C., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031274 · Cited by 92 · see citing works
Hogling, D. E., Andersson, D. P., Bäckdahl, J., Hoffstedt, J., Rössner, S. M., Thorell, A., Arner, P., Arner, P., & Rydén, M. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.18 · Cited by 77 · see citing works
Hauner, H., Wabitsch, M., & Pfeiffer, E. F. (1988) · PubMed · Cited by 67 · see citing works
Zhang, W., Wu, R., Zhang, F., Xu, Y.-Z., Liu, B., Yang, Y., Zhou, H., Wang, L., Wan, K., Xiao, X., et al. (2012) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12020 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis.
Crewe, C., An, Y. A., & Scherer, P. E. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88883 · Cited by 732 · see citing works
Mechanisms of weight regain after weight loss — the role of adipose tissue
van Baak, M. A., & Mariman, E. C. M. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0148-4 · Cited by 203 · see citing works
The regulation of adipose tissue health by estrogens
Steiner, B. M., & Berry, D. C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.889923 · Cited by 171 · see citing works
Adipose Tissue Dysfunction in Polycystic Ovary Syndrome
Bril, F., Ezeh, U., Amiri, M., Hatoum, S., Pace, L., Chen, Y.-H., Bertrand, F., Gower, B., & Azziz, R. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad356 · Cited by 123 · see citing works
Kolnes, K. J., Petersen, M. H., Lien-Iversen, T., Højlund, K., & Jensen, J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.737709 · Cited by 112 · see citing works
Adipose tissue aging is regulated by an altered immune system
Zhang, Y.-X., Ou, M.-Y., Yang, Z.-H., Sun, Y., Li, Q.-F., & Zhou, S.-B. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1125395 · Cited by 62 · see citing works
Varlamov, O., Bishop, C. V., Handu, M., Takahashi, D., Srinivasan, S., White, A., & Roberts, C. T. (2017) · Human Reproduction · doi:10.1093/humrep/dex244 · Cited by 34 · see citing works
Association of omental adipocyte hypertrophy and fibrosis with human obesity and type 2 diabetes
Liu, F., He, J., Liu, B., Zhang, P., Wang, H., Sun, X., Chu, X., Guan, W., Feng, W., Bi, Y., et al. (2021) · Obesity · doi:10.1002/oby.23155 · Cited by 9 · see citing works
Defective Visceral Adipose Tissue Adaptation in Gestational Diabetes Mellitus
McElwain, C. J., Manna, S., Musumeci, A., Sylvester, I., Rouchon, C., O'Callaghan, A. M., Ebad, M. A. B., McCarthy, F. P., & McCarthy, C. M. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad699 · Cited by 7 · see citing works
- Authors
- Muir, L. A., Neeley, C. K., Meyer, K. A., Baker, N. A., Brosius, A. M., Washabaugh, A. R., Varban, O. A., Finks, J. F., Zamarron, B. F., Flesher, C. G., Chang, J. S., DelProposto, J. B., Geletka, L., Martinez‐Santibanez, G., Kaciroti, N., Lumeng, C. N., & O'Rourke, R. W.
- Affiliations
- University of Michigan (US)
- Department of Pediatrics and Communicable Diseases University of Michigan Medical School Ann Arbor Michigan USA
- Department of Surgery University of Michigan Medical School Ann Arbor Michigan USA
- ORCID
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2016-02-25
- Volume
- 24
- Issue
- 3
- Pages
- 597-605
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC4920141
- OpenAlex
- W2284433125
- Cited by
- 367
- References
- 37
- Citations by year
- 2026: 20 · 2025: 29 · 2024: 47 · 2023: 46 · 2022: 52 · 2021: 53 · 2020: 33 · 2019: 23 · 2018: 36 · 2017: 21 · 2016: 7
- FWCI
- 27.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000433)
- National Institute of General Medical Sciences (T32GM007315)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034933, R01DK090262, DK090262, R01DK097449, T32DK094775, T32DK101357)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- adipose tissue fibrosis, adipocyte hypertrophy, type 2 diabetes, visceral adipose tissue, subcutaneous adipose tissue, collagen expression, adipocyte size, bariatric surgery
- MeSH terms
- Adipose Tissue, Diabetes Mellitus, Type 2, Female, Fibrosis, Humans, Hyperplasia, Hypertrophy, Male, Middle Aged, Obesity, Adipocytes, Bariatric Surgery, Subcutaneous Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
