Adipose tissue, insulin action and vascular disease: inflammatory signals
Abstract
Insulin resistance, both in nondiabetic and diabetic subjects, is frequently associated with obesity, particularly an excess of central fat. Many of the features that have been ascribed to the metabolic or insulin-resistance syndrome are also more commonly found in obese subjects. These phenotypes include diabetic dyslipidaemia, elevation of levels of plasminogen activator inhibitor-1, microalbuminuria and endothelial dysfunction. More recently, features of acute-phase activation and low-grade inflammation, including elevated levels of fibrinogen, C-reactive protein and interleukin-6, have been associated with (central) obesity. Adipose tissue generation of cytokines has been shown in vitro and in vivo, and a number of novel cytokine-like molecules, collectively termed adipocytokines, have been identified as adipocyte products. While several of these, such as tumour necrosis factor-alpha, may act predominantly in autocrine or paracrine fashion, others are released into the systemic circulation, acting as signalling molecules to remote tissues, including liver, skeletal muscle and endothelium. A clearer understanding of adipose tissue signalling, and its contribution to the state of low-grade inflammation of obesity, will require physiological, as well as cellular and molecular, studies.
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Chronic low-grade inflammation is associated with poor iron status in obese persons.
“past and emerging evidence indicates that chronic low-grade inflammation is associated with poor Fe status in obese persons (716 -721) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [717]
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“Second, white adipose tissue (WAT) is responsible for the production of factors that stimulate the production of inflammatory markers from the liver other organs; this may well be the case of CRP, where it is argued that hepatic and extra hepatic production are stimulated by increased IL-6 from the expanded fat mass o…”
BackgroundMicrovascular Endothelial Dysfunction in Human Obesity: Role of TNF-α
Virdis, A., Colucci, R., Bernardini, N., Blandizzi, C., Taddei, S., & Masi, S. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00512 · Cited by 84 · see citing works
“Moreover, leptin can stimulate the secretion of TNF-α and interleukin-6 (IL-6) which, in turn, may induce endothelial dysfunction (27).”
BackgroundInfluentialCalabrò, P., & Yeh, E. T. H. (2008) · Current Hypertension Reports · doi:10.1007/s11906-008-0008-z · Cited by 84 · see citing works
Glucose-Free Dialysis Solutions: Inductors of Inflammation or Preservers of Peritoneal Membrane?
Martikainen, T., Teppo, A., Grönhagen‐Riska, C., et al. (2005) · Peritoneal Dialysis International · doi:10.1177/089686080502500509 · Cited by 83 · see citing works
“There are also other recent reports that assume features of low-grade inflammation may be associated with obesity (23,24).”
BackgroundRole of nutrition on anemia in elderly
Bianchi, V. E. (2015) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2015.09.003 · Cited by 85 · see citing works
Association of Midlife Inflammatory Markers With Cognitive Performance at 10-Year Follow-up
Kipinoinen, T., Toppala, S., Rinne, J. O., Viitanen, M. H., Jula, A., & Ekblad, L. L. (2022) · Neurology · doi:10.1212/wnl.0000000000201116 · Cited by 81 · see citing works
CCAAT/Enhancer Binding Proteinβin relation to ER Stress, Inflammation, and Metabolic Disturbances
van der Krieken, S. E., Popeijus, H. E., Mensink, R. P., & Plat, J. (2015) · BioMed Research International · doi:10.1155/2015/324815 · Cited by 81 · see citing works
“Typically, elevated concentrations of C-reactive protein, various cytokines, prothrombotic molecules, and adhesionmolecules are present in this inflammatory state [4– 6] which play an essential role in the development of atherosclerosis and insulin resistance [7, 8].”
BackgroundNordic Diet and Inflammation—A Review of Observational and Intervention Studies
Lankinen, M. A., Uusitupa, M. I. J., & Schwab, U. (2019) · Nutrients · doi:10.3390/nu11061369 · Cited by 80 · see citing works
Gastric Bypass and Sleeve Gastrectomy: the Same Impact on IL-6 and TNF-α. Prospective Clinical Trial
Viana, E. C., Araujo-Dasilio, K. L., Miguel, G. P. S., Bressan, J., Lemos, E. M., Moysés, M. R., Abreu, G. R., Azevedo, J. L. M. C., de Carvalho, P. S., Passos‐Bueno, M. R. S., et al. (2013) · Obesity Surgery · doi:10.1007/s11695-013-0894-2 · Cited by 78 · see citing works
“These proteins may represent a link between obesity and associated co-morbidities, including cardiovascular diseases, type 2 diabetes, and certain cancers, among other conditions [6–8].”
BackgroundPCR arrays identify metallothionein-3 as a highly hypoxia-inducible gene in human adipocytes
Wang, B., Wood, I. S., & Trayhurn, P. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.01.036 · Cited by 78 · see citing works
β-cell failure in type 2 diabetes mellitus
Lencioni, C., Lupi, R., & Prato, S. D. (2008) · Current Diabetes Reports · doi:10.1007/s11892-008-0031-0 · Cited by 79 · see citing works
Chang, H. M., Lee, H. J., Park, H. S., Kang, J., Kim, K. S., Song, Y. S., & Jang, Y. J. (2010) · Obesity · doi:10.1038/oby.2010.60 · Cited by 76 · see citing works
“In addition to storing excess energy, adipose tissue secretes several bioactive peptides that exert paracrine and endocrine effects and play an important role in metabolic regulation (3,4).”
BackgroundThe study of anti-metabolic syndrome effect of puerarin in vitro
Xu, M., Xiao, S.-Z., Sun, Y., Zheng, X., Ou-yang, Y., & Chen, G. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.03.036 · Cited by 76 · see citing works
Burgeiro, A., Fuhrmann, A., Cherian, S., Espinoza, D., Jarak, I., Carvalho, R. A., Loureiro, M., Patrício, M., Antunes, M., & Carvalho, E. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00384.2015 · Cited by 76 · see citing works
“Given the importance of inflammation in heart pathophysiology and metabolism, including diabetes (41, 78, 79, 87), we tested the proinflammatory markers IL6, TNFA, IL8, and SERPINE1 gene expression and observed that although there were no differences for IL6 and TNFA, both IL8 and SERPINE1 were significantly decreased…”
MethodCohen, E., Margalit, I., Shochat, T., Goldberg, E., & Krause, I. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s294368 · Cited by 75 · see citing works
A microarray analysis of the hypoxia-induced modulation of gene expression in human adipocytes
Mazzatti, D. J., Lim, F.-L., O'Hara, A., Wood, I. S., & Trayhurn, P. (2012) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2012.654611 · Cited by 73 · see citing works
“The expansion of white adipose tissue mass in obesity induces a state of inflammation in the tissue which is considered to underpin the development of the associated diseases, particularly the metabolic syndrome and type 2 diabetes (Hotamisligil, 2006; Rosen & Spiegelman, 2006; Yudkin, 2003).”
BackgroundImpact of oxygen availability on body weight management
Quintero, P., Milagro, F. I., Campión, J., & Martínez, J. A. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.10.022 · Cited by 72 · see citing works
“On the other hand, obese subjects present a chronic inflammation of the adipose tissue [9], which is potentially considered to play an important role in the initiation and development of obesity-related diseases [10,11], and to enhance the oxidative stress of fat tissue [12–14].”
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“Adipose tissue secretion of IL-6 may constitute up to a third of its plasma concentration [34].”
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“Other molecules, such as interleukin-6, that affect lipid metabolism (Yudkin, 2003) are associated with increased level of C-reactive protein production, which changes inversely to serum OT levels (Qian et al.”
BackgroundExcessive visceral fat accumulation in advanced chronic obstructive pulmonary disease
Kida, K., Furutate, R., Ishii, I., Wakabayashi, Motegi, Yamada, & Gemma (2011) · International Journal of COPD · doi:10.2147/copd.s22885 · Cited by 74 · see citing works
“C-reactive protein, and interleukin (IL)-6, are particularly associated with central or visceral obesity.(11) Adiponectin is an anti-inflammatory cytokine that is believed to control cardiovascular diseases.”
Morand, J.-P. F., Macri, J., & Adeli, K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413343200 · Cited by 70 · see citing works
Wood, I. S., Stezhka, T., & Trayhurn, P. (2011) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-0985-7 · Cited by 65 · see citing works
“As adipose tissue mass expands in obesity, an inflammatory response is initiated in the tissue and this is associated both with the increased release of inflammatory adipokines and by the recruitment of macrophages [7, 11, 37, 39, 44].”
BackgroundCirculating IL-18 and the risk of type 2 diabetes in women
Hivert, M., Sun, Q., Shrader, P., Mantzoros, C. S., Meigs, J. B., & Hu, F. B. (2009) · Diabetologia · doi:10.1007/s00125-009-1455-z · Cited by 67 · see citing works
Wu, J. T., & Wu, L. (2005) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.10.016 · Cited by 62 · see citing works
- Authors
- Yudkin, J. S.
- Affiliations
- University College London (GB)
- Corresponding author
- Yudkin, J S
- ORCID
- Yudkin, J S
- Venue
- International Journal of Obesity
- Published
- 2003-11-14
- Volume
- 27
- Issue
- S3
- Pages
- S25-S28
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2087706636
- Cited by
- 311
- References
- 0
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 14 · 2018: 6 · 2017: 5 · 2016: 9 · 2015: 11 · 2014: 19 · 2013: 17 · 2012: 22
- FWCI
- 15.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- adipose tissue, insulin resistance, abdominal obesity, low-grade inflammation, adipokines, cytokines, TNF-α, interleukin-6, C-reactive protein, fibrinogen, endothelial dysfunction, microalbuminuria, plasminogen activator inhibitor-1, diabetic dyslipidemia, metabolic syndrome, vascular disease
- MeSH terms
- Adipose Tissue, Animals, Endothelium, Vascular, Humans, Inflammation, Insulin Resistance, Vascular Diseases, Signal Transduction
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