Intracellular ATP in balance of pro- and anti-inflammatory cytokines in adipose tissue with and without tissue expansion
Open accessAbstract
Objectives To understand the mechanism of white fat expansion in the presence of inflammation, we examined the balance of pro- and anti-inflammatory cytokines in epididymal fat during weight gain in diet-induced obese mice.Methods The pro- and anti-inflammatory cytokines were examined in white fat of diet-induced obese mice and lean mice. The mechanism of gene expression was investigated with a focus on intracellular ATP (iATP). ATP activity was tested in cellular and non-cellular systems in activation of serine kinases (IKKβ, JNK and ERK).Results The pro- (tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), IL-6, monocyte chemoattractant protein 1, interferon gamma and osteopontin) and the anti-inflammatory cytokines (IL-10, IL-1Ra, IL-13, soluble TNF receptor 2, pigment epithelium-derived factor and adiponectin) were increased at the same time during the weight gain. The balance was observed even in the absence of tissue expansion upon feeding in lean and obese mice. The iATP levels were positively associated with the cytokine elevation in the adipose tissue. In macrophages, induction of iATP with lauric acid stimulated the expression. Inhibition of iATP with β-oxidation inhibitor (Etomoxir) or mitochondrial uncoupler (2,4-dinitrophenol, DNP) suppressed the expression. ATP exhibited an activity in the activation of inflammatory kinases (IKKβ, JNK and ERK) in the living cells and cell lysate. The kinase activation was blocked in the cells by ATP inhibition.Conclusions The data suggest that the pro- and anti-inflammatory cytokines are dynamically balanced in the white adipose tissue by iATP.
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?
Proinflammatory adipokine release (TNF-α, IL-1β, IL-6, MCP-1, and IFNγ) seems to be decreased by high DNP concentrations (100 μM) in isolated murine RAW 264.7 macrophages.
“Proinflammatory adipokine release (TNF-α, IL-1β, IL-6, MCP-1, and IFNγ) also seems to be decreased by high DNP concentrations (100 μM) in isolated murine RAW 264.7 macrophages [271].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [271]
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
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 · see citing works
Metabolic Endotoxemia Initiates Obesity and Insulin Resistance
Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., et al. (2007) · Diabetes · doi:10.2337/db06-1491 · Cited by 6,638 · see citing works
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664 · see citing works
Type 2 diabetes as an inflammatory disease
Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737 · see citing works
The complexity of NF-κB signaling in inflammation and cancer
Hoesel, B., & Schmid, J. A. (2013) · Molecular Cancer · doi:10.1186/1476-4598-12-86 · Cited by 3,194 · see citing works
Macrophages, inflammation, and insulin resistance
Olefsky, J. M., & Glass, C. K. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135846 · Cited by 2,733 · see citing works
Özcan, U., Yilmaz, E., Özcan, L., Furuhashi, M., Vaillancourt, E., Smith, R. O., Görgün, C. Z., & Hotamisligil, G. S. (2006) · Science · doi:10.1126/science.1128294 · Cited by 2,413 · see citing works
Macrophage-specific PPARγ controls alternative activation and improves insulin resistance
Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., Eagle, A. R., Vats, D., Brombacher, F., Ferrante, A. W., et al. (2007) · Nature · doi:10.1038/nature05894 · Cited by 2,107 · see citing works
Adipose tissue remodeling and obesity
Sun, K., Kusminski, C. M., & Scherer, P. E. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45887 · Cited by 1,941 · see citing works
Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity
Brestoff, J. R., Kim, B. S., Saenz, S. A., Stine, R. R., Monticelli, L. A., Sonnenberg, G. F., Thome, J. J., Farber, D. L., Lutfy, K., Seale, P., et al. (2015) · Nature · doi:10.1038/nature14115 · Cited by 968 · see citing works
Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase
Talukdar, S., Oh, D. Y., Bandyopadhyay, G. K., Li, D., Xu, J., McNelis, J., Lu, M. M., Li, P., Yan, Q., Zhu, Y., et al. (2012) · Nature Medicine · doi:10.1038/nm.2885 · Cited by 966 · see citing works
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
Qiu, Y., Nguyen, K. D., Odegaard, J. I., Cui, X., Tian, X., Locksley, R. M., Palmiter, R. D., & Chawla, A. (2014) · Cell · doi:10.1016/j.cell.2014.03.066 · Cited by 869 · see citing works
Ye, J., Gao, Z., Yin, J., & He, Q. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00435.2007 · Cited by 840 · see citing works
Endoplasmic Reticulum Stress Activates Cleavage of CREBH to Induce a Systemic Inflammatory Response
Zhang, K., Shen, X., Wu, J., Sakaki, K., Saunders, T. L., Rutkowski, D. T., Back, S. H., & Kaufman, R. J. (2006) · Cell · doi:10.1016/j.cell.2005.11.040 · Cited by 819 · see citing works
Kang, K., Reilly, S. M., Karabacak, V., Gangl, M. R., Fitzgerald, K., Hatano, B., & Lee, C.-H. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.04.002 · Cited by 699 · see citing works
Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling
Wernstedt Asterholm, I., Tao, C., Morley, T. S., Wang, Q. A., Delgado-Lopez, F., Wang, Z. V., & Scherer, P. E. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.05.005 · Cited by 668 · see citing works
Inflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance
Lee, Y. S., Li, P., Huh, J. Y., Hwang, I. J., Lu, M., Kim, J. I., Ham, M., Talukdar, S., Chen, A., Lu, W. J., et al. (2011) · Diabetes · doi:10.2337/db11-0194 · Cited by 566 · see citing works
Berberine suppresses proinflammatory responses through AMPK activation in macrophages
Jeong, H. W., Hsu, K. C., Lee, J.-W., Ham, M., Huh, J. Y., Shin, H. J., Kim, W. S., & Kim, J. B. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90599.2008 · Cited by 454 · see citing works
Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue.
Yin, J., Gao, Z., He, Q., Zhou, D., Guo, Z., & Ye, J. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90760.2008 · Cited by 319 · see citing works
Self-citationCacicedo, J. M., Yagihashi, N., Keaney, J. F., Ruderman, N. B., & Ido, Y. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.09.177 · Cited by 233 · see citing works
Regulation of energy balance by inflammation: Common theme in physiology and pathology
Wang, H., & Ye, J. (2014) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-014-9306-8 · Cited by 173 · see citing works
Inflammation during obesity is not all bad: evidence from animal and human studies
Ye, J., & McGuinness, O. P. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00266.2012 · Cited by 173 · see citing works
Ye, J., & Keller, J. N. (2010) · Aging · doi:10.18632/aging.100155 · Cited by 171 · see citing works
Immunoregulation through extracellular nucleotides
Vitiello, L., Gorini, S., Rosano, G., & la Sala, A. (2012) · Blood · doi:10.1182/blood-2012-01-406496 · Cited by 135 · see citing works
Sun, S., Xia, S., Ji, Y., Kersten, S., & Qi, L. (2012) · Diabetes · doi:10.2337/db11-1389 · Cited by 75 · see citing works
Gao, Z., Wang, Z., Zhang, X., Butler, A. A., Zuberi, A. R., Gawrońska‐Kozak, B., Lefevre, M., York, D., Ravussin, É., Berthoud, H., et al. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00178.2006 · Cited by 66 · see citing works
The Adenosine A2b Receptor: Its Role in Inflammation
Ham, J., & Rees, D. (2008) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/187153008786848303 · Cited by 51 · see citing works
Interplay of pro- and anti-inflammatory cytokines to determine lipid accretion in adipocytes
Wang, Y., Wang, H., Hegde, V. K., Dubuisson, O. S., Gao, Z., Dhurandhar, N. V., & Ye, J. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.9 · Cited by 33 · see citing works
Zhang, Y., Zhao, Z., Ke, B., Wan, L., Wang, H., & Ye, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150454 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
Demine, S., Renard, P., & Arnould, T. (2019) · Cells · doi:10.3390/cells8080795 · Cited by 476 · see citing works
Zinc regulates vascular endothelial cell activity through zinc-sensing receptor ZnR/GPR39
Zhu, D., Su, Y., Zheng, Y., Fu, B. M., Tang, L., & Qin, Y. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00279.2017 · Cited by 120 · see citing works
Mechanism of insulin resistance in obesity: a role of ATP
Ye, J. (2021) · Frontiers of Medicine · doi:10.1007/s11684-021-0862-5 · Cited by 70 · see citing works
Posicionamento sobre o Consumo de Gorduras e Saúde Cardiovascular – 2021
Izar, M. C. D. O., Lottenberg, A. M., Giraldez, V. Z. R., Santos, R. D., Machado, R. M., Bertolami, A., Assad, M. H. V., Saraiva, J. F. K., Faludi, A. Á., Moreira, A. S. B., et al. (2021) · Arquivos Brasileiros de Cardiologia · doi:10.36660/abc.20201340 · Cited by 65 · see citing works
Regulation of microbiota–GLP1 axis by sennoside A in diet-induced obese mice
Le, J., Zhang, X., Jia, W., Zhang, Y., Luo, J., Sun, Y., & Ye, J. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.01.014 · Cited by 58 · see citing works
Lauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophages
Tham, Y. Y., Choo, Q.-C., Muhammad, T. S. T., & Chew, C.-H. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-06019-9 · Cited by 48 · see citing works
Dang, C. P., Issara-Amphorn, J., Charoensappakit, A., Udompornpitak, K., Bhunyakarnjanarat, T., Saisorn, W., Sae‐khow, K., & Leelahavanichkul, A. (2021) · Journal of Innate Immunity · doi:10.1159/000516348 · Cited by 45 · see citing works
Wu, K., Luan, G., Xu, Y., Shen, S., Qian, S., Zhu, Z., Zhang, X., Yin, S., & Ye, J. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.02.160 · Cited by 34 · see citing works
Liu, C., Deng, Z., Du, E., & Xu, C. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8601 · Cited by 26 · see citing works
He, S., Chen, X.-X., Ge, W., Yang, S., Chen, J., Niu, J.-W., Xia, L., & Chen, G. (2021) · Nature and Science of Sleep · doi:10.2147/nss.s312272 · Cited by 25 · see citing works
The mechanisms of nucleotide actions in insulin resistance
Liu, K., Jin, X., Zhang, X., Lian, H., & Ye, J. (2022) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2022.01.006 · Cited by 25 · see citing works
Liaudanskaya, V., Jgamadze, D., Berk, A. N., Bischoff, D. J., Gu, B. J., Hawks-Mayer, H., Whalen, M. J., Chen, H. I., & Kaplan, D. L. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.11.031 · Cited by 23 · see citing works
de Sá, R. D. C. D. C., Simão, J. D. J., da Silva, V. S., Farias, T. M., Cruz, M. M., Antraco, V. J., Armelin‐Correa, L., & Alonso‐Vale, M. I. C. (2021) · Nutrients · doi:10.3390/nu13030754 · Cited by 21 · see citing works
Qin, X., Xu, Y., Peng, S., Qian, S., Zhang, X., Shen, S., Yang, J., & Ye, J. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.04.133 · Cited by 17 · see citing works
The Purinergic Landscape of Type 2 Diabetes Mellitus
García-Jacobo, R. E., Bergamin, L. S., Vultaggio-Poma, V., Thorstenberg, M. L., Tarantini, M., García-Hernández, M. H., & Virgilio, F. D. (2022) · Molecules · doi:10.3390/molecules27061838 · Cited by 16 · see citing works
Qian, S., Ma, L., Peng, S., Xu, Y., Wu, K., Shen, S., Zhang, X., Sun, Y., & Ye, J. (2020) · Bioscience Reports · doi:10.1042/bsr20200665 · Cited by 13 · see citing works
Effects of hypnotic bromovalerylurea on microglial BV2 cells
Kawasaki, S., Abe, N., Ohtake, F., Islam, A., Choudhury, M. E., Utsunomiya, R., Kikuchi, S., Nishihara, T., Kuwabara, J., Yano, H., et al. (2017) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2017.05.007 · Cited by 12 · see citing works
Cao, X., Ye, X., Zhang, S., Wang, L., Xu, Y., Peng, S., Zhou, Y., Peng, Y., Li, J., Zhang, X., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.663530 · Cited by 10 · see citing works
Type 2 diabetes: a sacrifice program handling energy surplus
Ye, J., & Yin, J. (2024) · Life Metabolism · doi:10.1093/lifemeta/loae033 · Cited by 9 · see citing works
Jamali, F., Mousavi, S., Rad, A. H., Meshkini, A., Alikhah, H., Houshyar, J., Moghadam, S. K., Yaghoubi, S. M., Asghari, K. M., Ilkhchi, M. T., et al. (2025) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10513-6 · Cited by 6 · see citing works
Stachulski, A. V., Rossignol, J., Pate, S., Taujanskas, J., Robertson, C. M., Aerts, R., Pascal, E., Piacentini, S., Frazia, S. L., Santoro, M., et al. (2021) · Future Medicinal Chemistry · doi:10.4155/fmc-2021-0055 · Cited by 6 · see citing works
Cabezas, R., Sahebkar, A., Echeverrı́a, V., Santos, J. G., Ashraf, G. M., & Barreto, G. E. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-64872-5_29 · Cited by 5 · see citing works
Failure of inflammation hypothesis in the pathogenesis of type 2 diabetes
Ye, J. (2024) · Obesity Medicine · doi:10.1016/j.obmed.2024.100565 · Cited by 3 · see citing works
Obesity-Associated Chronic Inflammation: A Protective Mechanism against Type 2 Diabetes
Ye, J. (2025) · Immune discovery. · doi:10.70322/immune.2025.10007 · Cited by 1 · see citing works
Obesity, adipokines and their relationship with insulin resistance
García-Ortega, W. A., Angulo-Camacho, J. Á., & Ibarra-Sánchez, A. (2023) · Ciencia Latina Revista Científica Multidisciplinar · doi:10.37811/cl_rcm.v6i6.4335 · Cited by 1 · see citing works
Yasen, M., Jiang, L., Sharofova, M. U., Xin, X., Nuraliev, Y., Ye, J., & Aisa, H. A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.28.316349 · Cited by 1 · see citing works
ATPIF1 inactivation promotes antitumor immunity through metabolic reprogramming of CD8 + T cellsPreprint
Zhong, G., Wang, Y., Zhang, J., Wang, Y., Li, Y., Guan, Y., Shen, S., Zhang, X., Cao, X., Wu, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.23.310979
Rossignol, J., Tijsma, A. S. L., & van Baalen, C. A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.30.454324
- Authors
- Lee, J. H., Zhang, Y., Zhao, Z., Ye, X., Zhang, X., Wang, H., & Ye, J.
- Affiliations
- Pennington Biomedical Research Center (US)
- Peking University (CN)
- Shanghai Sixth People's Hospital (CN)
- Henan Medical University (CN)
- Corresponding author
- Ye, J
- Venue
- International Journal of Obesity
- Published
- 2017-02-07
- Volume
- 41
- Issue
- 4
- Pages
- 645-651
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- PMC
- PMC5380535
- OpenAlex
- W2579519901
- Cited by
- 30
- References
- 30
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 9 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 2
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK068036, R01DK085495, R01DK068036, P30DK072476)
- 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
- intracellular ATP, adipose tissue inflammation, diet-induced obesity, pro- and anti-inflammatory cytokines, epididymal adipose tissue, macrophages, lauric acid, mitochondrial beta-oxidation, etomoxir, 2,4-dinitrophenol, IKKβ, JNK, ERK, adiponectin, TNF-α, IL-1β, interleukin-6
- MeSH terms
- Pigment Epithelium-Derived Factor, Adenosine Triphosphate, Adipose Tissue, Animals, Disease Models, Animal, Eye Proteins, Gene Expression Regulation, Inflammation, Insulin Resistance, Male, Mice, Inbred C57BL, Mice, Obese, Nerve Growth Factors, Obesity, Tumor Necrosis Factor-alpha, Blotting, Western, Signal Transduction, Tissue Expansion, Serpins, Cytokines, Interleukin-10, 3T3-L1 Cells, Mice, Adiponectin, Adipose Tissue, White, Real-Time Polymerase Chain Reaction
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
